San Diego State University

1.0  SDSU Institutional Review Board (IRB) General Information

 

1.1  Institutional Responsibility

San Diego State University assumes responsibility for the protection of the rights and welfare of human subjects in compliance with federal regulations as documented within SDSU's Assurance issued by the U.S. Department of Health and Human Services Office of Human Research Protections.  SDSU's assurance states requirements and procedures for human subjects protections to ensure that all research conducted within its jurisdiction complies with the Code of Federal Regulations pertaining to human subjects (DHHS Policy - 45 CFR 46; FDA Policy 21 CFR 50 and 56).

1.2  University Administrative Support

Administrative support for the SDSU Institutional Review Board is provided through Graduate and Research Affairs’ Division of Research Administration and Technology Services.  This office is also responsible  for establishing and maintaining a program in support of ethical and responsible human subjects research conducted under the auspices of SDSU.  This is accomplished through proactive oversight of approved research (Continuing Review Program), Internet access to relevant resources, ongoing education and training, and periodic assessment of resources dedicated in support of these activities.

1.3  IRB Responsibility

The Institutional Review Board (IRB) at SDSU implements a review process established within the Code of Federal Regulations (45 CFR 46) to ensure that human subjects research complies with federal regulations, institutional policies and ethical standards. The IRB serves to protect the rights and ensure the safety of people involved as participants in research. The IRB also provides assistance to the investigator in complying with federal and state regulations and institutional standards for human subjects research.  The IRB is guided by the ethical principles as set forth in the Ethical Principles and Guidelines for the Protection of Human Subjects of Research also known as the Belmont Report.

1.4  IRB and Institutional Authority

The IRB may approve research reviewed or may require that modifications to the protocol be made to secure approval to conduct the research.  The IRB may also disapprove research.  Decisions made by the IRB are communicated in writing to the investigator (45 CFR 46.109).   The IRB may also suspend or terminate approval of research that is not conducted in accordance with the approved protocol or that has been associated with unexpected serious harm to subjects (45 CFR 46.113).  Actions taken by the IRB to suspend or terminate approval will be documented in writing and reported to the investigator, institutional officials and to the Office for Human Research Protections (OHRP).

Research that is approved by the IRB may be subject to further review by the officials of the institution.  Authorized institutional officials may approve or disapprove research planned by an employee, student or agent of the University.  The institutional officials may not approve research involving human subjects that has not been approved by the IRB (45 CFR 46.112).

1.5  IRB Jurisdiction

The IRB reviews research when procedures are proposed to obtain information about a living individual through the use of a survey, interview, observation, experimentation, or the analysis of human tissues, records, samples or other data previously collected from human subjects. All research involving human subjects must be reviewed and approved by the Institutional Review Board (IRB) in advance of study initiation (45 CFR 46.109).

An IRB review must occur when SDSU is engaged in human subjects research.  For example:

SDSU or SDSU Foundation employees or agents, in connection with his/her institutional responsibilities, intervene or interact with human subjects for purposes of research or obtain individually identifiable private information about human subjects for purposes of research; or

SDSU or SDSU Foundation receives a direct federal award to conduct human subject research, even where all activities involving human subjects are carried out by a subcontractor or collaborator.

Research that involves the use of SDSU’s non-public information to identify or contact human research subjects or prospective subjects or utilizes any SDSU property or facilities in connection with human subjects research. 

1.6  IRB Membership

1.6.1  IRB Composition

The IRB members are appointed annually for a renewable one-year term by the Associate Vice President for Research in accordance with federal requirements (45 CFR 46.107).  The IRB is composed of members representing the University faculty, staff and local community. Membership includes at least one individual whose primary concerns are in the nonscientific areas and at least one member not otherwise affiliated with the institution and who is not part of the immediate family of a person affiliated with the institution. The faculty members represent a variety of disciplines representative of the research reviewed.

1.6.2  Selection/Appointments

The IRB Chair or IRB Administrator will confirm that IRB membership is in compliance with regulations (46.107).  If an additional member(s) is needed, several methods are used to identify candidates. The existing members may be asked to provide recommendations to the Chair.  Department Chairs may be contacted to suggest faculty who are available and interested.  Faculty who are active in the research community may be contacted directly to discuss service to the committee. The Chair and the IRB Administrator forward recommendations to the Assistant Vice President for Research. Appointment to the IRB is made by the Associate Vice President for Research.  Reappointment may occur on an annual basis provided the member demonstrates an interest in research ethics, knowledge of regulations and ethical standards in ascertaining the acceptability of proposed research, and has the time to devote to associated responsibilities.  

1.6.3  Alternate Member

An alternate member may be appointed to the Committee to serve in the absence of a member.  The alternate is selected based on the expertise and perspective he/she can bring to the review process.  Due to the diversity in an individual's academic and/or professional training as well as experience, an alternate member is selected to represent an absent member (if needed) using the following criteria: scientist/M.D., scientist/non M.D.; nonscientist, or community member (45 CFR 46.107).

1.7  IRB Member Responsibilities

1.7.1  Member Training

IRB members participate in initial and continuing education by reviewing relevant materials on issues, regulations and guidance concerning human subjects protections (45 CFR 46.107). Successful completion of the IRB tutorial assessment is a mechanism for the SDSU research community, including IRB members, to demonstrate a basic understanding of both federal and SDSU-specific ethical principles and regulatory compliance practices.  In addition to the IRB tutorial, IRB members are familiar with the Institutional Review Board Guidebook (http://ohrp.osophs.dhhs.gov/irb/irb_guidebook.htm), Code of Federal Regulations (45 CFR 46) (http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm), the Belmont Report Ethical Principles and Guidelines for the Protection of Human Subjects of Research (http://ohrp.osophs.dhhs.gov/humansubjects/guidance/belmont.htm), Office for Human Research Protections - Policy and Guidance (http://ohrp.osophs.dhhs.gov/polasur.htm#REG), and the U.S. Food and Drug Administration (FDA) INFORMATION SHEETS Guidance for Institutional Review Boards and Clinical Investigators, 1998 Update (http://www.fda.gov/oc/oha/IRB/toc.html).

1.7.2  Reviewer Expertise (Research Involving Children, Prisoners, etc.)

The IRB membership includes those familiar with the type of research routinely conducted in the social and behavioral sciences.  Two members are licensed medical doctors to assist with the review of clinical trials and studies that may involve more than minimal risk of physical injury.  The IRB recognizes that additional expertise may be necessary when reviewing a protocol (45 CFR 46.107).  The IRB may request consultation from an individual with competence in a specific area when issues relevant to a protocol require expertise above or beyond that available on the IRB.  Individuals invited to comment due to their expertise may not vote on a motion.

1.7.3  Primary Reviewer Process

The primary reviewer is responsible for presenting an in-depth review of all protocol documents submitted to the IRB members during the scheduled meeting and identifies areas of the research that require elaboration prior to securing approval. A committee member is identified as a primary reviewer based on his or her expertise in the discipline in which the research is taking place as long as he or she does not have a conflicting interest with the study.  Assignment as a primary reviewer is indicated on the meeting agenda. This process is used for initial and continuing review as well as proposed protocol modifications not eligible for expedited review.

1.7.4  Documents Reviewed by the IRB

1.7.4.1  Primary Reviewer

The primary reviewer reviews the entire application packet including the protocol, consent documents, grant application (if funded by the Department of Health and Human Services), recruitment materials and other supporting documents (verification of informed consent process/procedures forms, investigators' assurance form, faculty sponsor's assurance [students]). If the study is a clinical trial, the primary reviewer will also review the investigator's brochure. 

For continuing review conducted during the convened committee, the primary reviewer receives the Report of Progress and Review Request along with the consent form(s) and an abstract of the study.  The Report of Progress and Review Request includes the number of subjects intended for study, the number of subjects accrued, a summary of any significant adverse events or unexpected problems, a summary of protocol revisions approved by the IRB since the last review, current literature that may influence the conduct of the study and an update of financial interests (if applicable). The primary reviewer may also access to the protocol file prior to the convened meeting either electronically or through the Division of Research Administration during routine office hours. Materials describing proposed protocol modifications are accessible to the primary reviewer as a standard practice.

1.7.4.2  IRB Members

Each IRB member may access the entire initial review application packet including the protocol, consent documents, recruitment materials and other supporting documents (verification of informed consent process/procedures forms, investigators' assurance form, faculty sponsor's assurance [students]) ,the investigator’s brochure or the grant proposal if applicable.  In addition, each member completes a review sheet to document comments specific to a protocol and each member documents any conflict of interest related to a specific research protocol.

For continuing review, all members may access the Report of Progress and Review Request along with the consent form(s) and an abstract of the study. 

1.8  Subcommittee Procedures

A subcommittee of the IRB is defined as one or more experienced IRB members designated by the IRB Chair or IRB Administrator to act on behalf of the committee when action by the full board is not required (45 CFR 46.110). 

1.9  Review of Significant Adverse Events (SAE)           

The investigator files an SAE report within five days of the event.  The Division of Research Administration forwards reports received to a member of the IRB for review and comment. IRB members may access a report identifying projects reporting an SAE at the convened meeting.

1.10  Quorum and Voting Requirements (46.107 and 46.108)

To convene a meeting of the IRB, a majority of the voting members of the IRB must be present. The committee may not convene without a member whose primary concerns are nonscientific.  If the quorum fails during the meeting (early departures, loss of nonscientist, excused for conflict) the meeting will be terminated until the quorum can be restored.  Any action taken without a quorum present is considered invalid.

An alternate member may be assigned to replace a member who is not able to attend the convened meeting. The alternate may vote only when in attendance to replace a voting member.   Individuals designated as non-voting members may contribute to discussion; however, may not serve as a primary reviewer, propose a motion or vote on a motion. In order for a motion to pass, it must receive the approval of a majority of voting members present at the meeting. 

1.11  IRB Member Conflict of Interest

Regulations stipulate that a IRB member may not participate in the initial or continuing review of a project in which the member has a conflicting interest except in response to information requested by the committee (45 CFR 46.107e).  If a member has a conflict of interest (personal, professional or financial), he/she will leave the meeting room while discussion and voting occurs. This will be documented on the review documents as well as in the meeting minutes. If the quorum should fail due to the absence of the member in conflict, the IRB Chair will determine whether the member may remain present and abstain from the vote in order to retain the quorum.


2.0  When is a Review Required?

An IRB review is required when a study meets the criteria as defined by the federal regulations as human subjects research.

2.1  Definitions

In determining whether or not a project requires review by the IRB, the first step is to determine if the project is research and to then identify whether the people involved are also human subjects.  The IRB only reviews activities that involve the participation of human subjects in research. The definitions used by the IRB in determining the need for review follow:

2.1.1  Research

The Department of Health and Human Services (DHHS) Code of Federal Regulations (45 CFR 46.102d) has defined research as, "A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge." As described in the Belmont Report, "...the term 'research' designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships).

2.1.2  Human Subject

A human subject is defined as "a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction, or (2) identifiable private information (45 CFR 46.102f)"

2.1.3  Generalizable Knowledge

The IRB considers generalizable knowledge to include the dissemination of research findings beyond the boundaries of the institution (e.g., publication (including thesis or dissertation) or presentation or use outside the specific instructional setting.  The exception to the parameters defined occurs when a report of findings is issued to an agency that has contracted with the university to acquire programmatic information (e.g., needs assessment, program evaluation, quality control).

For more human subjects research-related definitions, please visit the Office for Human Research Protections (OHRP) website: [LINK] http://ohrp.osophs.dhhs.gov/irb/irb_glossary.htm.

2.2  When is IRB Review Required?

IRB review is required when SDSU is engaged  (link to http://ohrp.osophs.dhhs.gov/humansubjects/assurnace/engage.htm) in human subjects research.  This occurs when an agent or employee:

Intervenes with a living individual for research purposes (e.g., to draw/collect blood or other biological samples, dispense drugs, administer treatments, use physical sensors, test sensory acuity, collect information by survey, interview oral history).

Manipulates an individual’s environment for research purposes (control environmental light, sound, temperature, social interactions).

Interacts with an individual for research purposes (obtain consent, conduct interviews, screen potential subjects).  Please note: Employees who make information available about a study and/or obtain permission from an individual to release contact information to an investigator but do not consent individuals nor act on behalf of the investigator are not engaged in research.

Releases individually identifiable private information or allows an investigator to obtain an individual’s private information without the individuals written consent (release of patient’s name to investigators for recruitment, allowing access to an individuals academic or medical record).

Obtains, receives or possesses private information that is individually identifiable (with or without coding system) for research purposes.

Obtains, receives or possesses individually identifiable private information for use in maintaining a statistical center for a multi-site research program

Receives a direct HHS award to conduct human subjects research that will be carried out by a subcontractor or collaborator.

2.3  More Information on When IRB Review is Necessary

2.3.1  SDSU Sponsored Research

Regardless of where the research activity will occur, the IRB is required to review all research involving human subjects that is sponsored by SDSU, the SDSU Foundation or its ancillaries. 

2.3.2  SDSU Involvement

All research projects that involve human subjects conducted by or under the direction of any employee, student, or agent of SDSU or SDSU Foundation in connection with his or her institutional responsibilities or that utilizes any property or facility of this institution, whether funded or not funded, are subject to the federal regulations governing such research (see 45 CFR 46 and The Belmont Report), and to the policies and procedures outlined in the University's Assurance of Compliance.  IRB review and approval must occur in advance of study initiation.

2.3.3  Collaborative Research  

Research conducted in collaboration with other universities, research institutions, or hospitals must be reviewed and approved by the IRB when the research is conducted by or under the direction of an SDSU employee, student or agent.  Studies in which the duties of the principal investigator are formally contracted to a non-SDSU performance site must obtain approval from an IRB designated for that institution in addition to review requirements imposed by the SDSU IRB.

2.3.4  Consultant

The IRB is required to review all research conducted by or under the direction of an agent of SDSU unless the researcher is hired on his/her own time, does not utilize SDSU resources, and will not reference SDSU in documents or publications associated with any reported outcomes.

2.3.5  Students Enrolled in Joint Doctoral Program

The IRB is required to review all research conducted by or under the direction of an SDSU employee, student or agent performing research related activities as part of their responsibilities at this institution.  The requirement to obtain approval from the IRB is in addition to review requirements imposed by the other institution with which the investigator is affiliated.  This will apply primarily to students who are fulfilling degree requirements for a doctoral degree and who are enrolled in two academic institutions.

2.3.6  Research in Foreign Countries

Research conducted in a foreign country by or under the direction of an SDSU-affiliated researcher must be approved by the IRB and adhere to University and federal/state guidelines. The standards for ethical conduct in research must be incorporated into the research design.  Any proposed variations to ethical practices endorsed by the institution and federal regulations (recruitment procedures, consent process, confidentiality practices) that result from cultural, political or social issues unique to the country in which the research will occur must be supported by the investigator within the protocol submitted for review. 

2.3.7  Pilot Studies

Studies that meet the definition of research that involve human subjects must receive IRB review and approval prior to initiation. Pilot or feasibility studies may include as few as one person, however, the same federal, state and institutional requirements to protect human subjects in research regardless of the number of subjects involved. 

2.3.8  Secondary or Existing Data Analysis

Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, must be reviewed by the IRB. It is likely that this type of research will meet the criteria for exemption and can be verified through an administrative review (45 CFR 46.101).  Please note: All data included in the request to analyze existing data must exist at the time the research is proposed.  This category does not apply to prospective collection of materials.

2.3.9  Nonaffiliated Investigator 

Persons not affiliated with SDSU who plan to conduct research that involves the use of SDSU facilities and/or students must obtain clearance from the Vice President of Business Services prior to conducting the study.  IRB may also review the study to ensure ethical practices are implemented when conducting the research.

2.3.10  Access of SDSU Non-public Information

Research that involves the use of SDSU non-public information to identify or contact human research subjects or prospective subjects must be approved by the IRB in advance of initiating the research.  

2.4  When is IRB Review Not Required?

SDSU is not engaged in research when an employee or agent of the university:

Consults on research but at no time obtains, receives, or possesses identifiable private information (e.g., a consultant analyzes data that cannot be linked to individual subjects, either directly or indirectly through coding systems, by any member of the research team).

Performs commercial services for the investigators (or performs other genuinely non-collaborative services meriting neither professional recognition nor publication privileges), and (ii) adheres to commonly recognized professional standards for maintaining privacy and confidentiality (e.g., an appropriately qualified laboratory performs analyses of blood samples for investigators solely on a commercial basis).

Releases anonymous (no codes, links or identifiers) individual information or specimens to an investigator.

Releases identifiable private information to a State or Local Health Department for public health purposes (no research component to the activity).

Releases private identifiable information to an investigator when written permission of the subject has been obtained and is documented.

2.5  More Information on when IRB Review May Not be Necessary

IRB review may not be required in the following situations:

2.5.1  Program Evaluation, Needs Assessment and Quality Control

Studies conducted for the purpose of program evaluation, needs assessment, or quality control in which findings are solely intended for use in internal program planning and development and are not designed to contribute to generalizable knowledge (publication or presentation) are not subject to IRB review.

2.5.2  Consultation

Employee consults on research but does not receive or possess identifiable and private information about persons participating in the study.

Employee is engaged in research as a consultant through a non-institutional contract.  Research activities will occur outside of his/her SDSU employment and he/she will not reference SDSU in documents or publications associated with any reported outcomes

2.5.3  Research Methods Courses/Class Assignments

The primary purpose of providing training in research methods is for the student to become more knowledgeable about the research process.  Instructors may assign a project, in conjunction with the course, in which students design a study, recruit participants, collect and analyze data and report their findings in the form of a final paper. Since the intent of the project/assignment is to train students, the assignment is not considered to be research as defined within the federal regulations and is not subject to IRB review.  The course instructor is responsible for including information about ethical research practices and providing direct supervision of each project.  Projects conducted for this purpose should not exceed minimal risk, or target special populations or include sensitive subject matter.

If the assignment results in findings that the student may want to present or publish, it is recommended that the study be replicated and conducted under a IRB-approved protocol.  The IRB does not have the authority to approve research that has occurred.

2.5.4  Research Not Involving Human Subjects

Although an activity may be considered research (…systematic investigation designed to contribute to generalizable knowledge…), it may not involve human subjects (…a living individual about whom information is obtained through intervention or interaction).  Persons involved in a research activity are not considered to be human subjects when the following apply:

The information collected is not about the individual. That is, the person interviewed/surveyed is asked to provide information specific to his/her expertise or profession as opposed to personal information about him/herself (opinions, thoughts, or perceptions).  For example, a welder asked to describe the composite of shielding gas, shielding gas flow rate, and formation of the weld bead is not disclosing information about him/herself and, as such, is not a research subject.  Likewise, an entomologist who describes the varieties of pesticide used to control a specific pest and to identify the types of pesticides that are used most frequently is contributing his/her expertise rather than information about him/herself.

The person is asked to wear a devise to measure something external to the person (air quality, environmental toxins).  No data are collected about the person.

The information must be about a living individual to qualify as a human subject. Review of death records does not involve human subjects. However, analyses of biologic specimen (blood, tissues) or nonpublic records do require IRB review and approval before analysis may begin.

3.0  Review Process and Procedures

3.1  Review Procedures

The Institutional Review Board  (IRB) will review research involving human subjects to assure that the protocol meets with federal, state and institutional regulations. Activity involving human subjects (identification of prospective subjects, recruitment, etc.) may not be initiated until the study has been reviewed and approved by the IRB.

There are three different procedures that are used to review an application (Exempt, Expedited and Convened Committee). The appropriate review procedure is determined by federal regulations and applied based on how human subjects are involved in the research. The type of review is based on risk associated with participation in the research, the study intervention/interaction and how informed consent is obtained and documented. A research protocol, informed consent statement and additional supporting documents are required for all research projects submitted for review. 

3.2 Web-based Application Submission

The principal investigator may use SDSU’s web-based application system to create, modify or renew an IRB protocol.  The investigator may also submit a response to conditions, adverse event report or other relevant reports electronically using the web-based application system.

3.3  Administrative Review

Research that is considered minimal risk and that meets federal criteria for an exempt or expedited review (e.g., use of existing data; some survey or interview procedures) may be eligible for review through administrative procedures (45 CFR 46.101 & 45 CFR 46.110). The research protocol is evaluated to determine whether criteria are met to justify an exempt or expedited review.  The Division of Research Administration, in consultation with the IRB, will review and verify new protocols that are identified as exempt.  Notification of concurrence with the exempt status, including citation of the specific exemption category, will be conveyed in writing or electronically to the investigator.  All nonexempt research will be reviewed through IRB subcommittee (expedited) or by convened committee. Studies receiving an exempt or expedited review are reviewed on a first come first serve basis. Review notification is available to investigators approximately three weeks following application submission for an administrative review.

3.3.1  Exempt Review

The majority of studies that involve data collection from adults using a survey or interview format are exempt unless the questions deal with a sensitive aspect of a subject's behavior such as illegal conduct, drug use, sexual behavior, or the use of alcohol. Surveys and interviews of children are not exempt; however, children can be included if the research meets the criteria of category one described in 45 CFR 46.101 [http://gra.sdsu.edu/cphs/exempt.htm]. Research involving pregnant women and/or fetuses, prisoners, or the institutionalized mentally disabled cannot be exempt.

If the subject's identity is not recorded (anonymous) and/or the interview/survey questions are considered non-sensitive, then the research will probably be exempt. If the subject's response to the questions would pose a risk to that person if disclosed, then the research would receive an expedited review rather than an exempt review.

For all research, the investigator is required to provide adequate information about the research to potential subjects so that an informed decision can be made regarding participation. In research that meets the criteria for exemption, the investigator can deliver this information verbally or both verbally and in writing based on an IRB approved script or consent statement. 

The following types of research qualifies for an exempt review (45 CFR 46.101):

(1) Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as

(i) research on regular and special education instructional strategies, or

(ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

(2) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:

(i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and

(ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.

(3) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (2), if

(i) the human subjects are elected or appointed public officials or candidates for public office;or

(ii) Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.

(4) Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.

(5) Research and demonstration projects which are conducted by or subject to the approval of the federal department or agency heads, and which are designed to study, evaluate or otherwise examine:

(i) public benefit or service programs,

(ii) procedures for obtaining benefits or services under those programs,

(iii) possible changes in or alternatives to those programs or procedures,

(iv) possible changes in methods or levels of payment for benefits or services under those programs.

(6) Taste and food quality evaluation and consumer acceptance studies,

(i) if wholesome foods without additives are consumed or

(ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

Additional Information:

Categories 2 and 3 are not exempt if the research deals with a sensitive aspect of a subject's behavior such as illegal conduct, drug use, sexual behavior, or the use of alcohol.

Surveys and interviews of children are not exempt.

Observation of children is exempt if the investigator does not participate in the activities being observed.

Research involving pregnant women and/or fetuses, prisoners, or the institutionalized mentally disabled is not exempt.

3.3.2  Existing Data

The research may qualify for an exemption if it involves the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens if: these data sources are publicly available or the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects (45 CFR 46.101(b)(4)).

3.3.3  Expedited Review

The IRB Chair or one or more experienced IRB members designated by the IRB Chair may review research that qualifies for an expedited review using criteria listed in 46.110 [http://gra.sdsu.edu/IRB/expedite.htm] below. When conducting an expedited review, the designated reviewer(s) has the authority to act on behalf of the IRB with the exception of disapproving the research.  During the initial review process, questions may arise that require the investigator to provide additional information or clarification about the protocol.  Questions developed during the initial review are communicated to the investigator via electronic or standard mail or by telephone within three weeks of application submission.  The investigator is given a 90-day timeframe during which the protocol file will be held in a “pending status” and he/she may respond to the stipulations posed by the IRB reviewer(s).  Upon receipt and acceptance of by the IRB representative(s) of the investigators response, approval to conduct the research is communicated to the investigator by standard mail or electronic correspondence.  If the investigator does not respond to the stipulations for project approval within the 90-day time frame, the protocol is identified as inactive within the database and the hard copy or electronic documents are destroyed. IRB members are informed of initial and continuing review and protocol modifications reviewed using expedited procedures at the appropriate convened committee meeting.

To determine if the research is eligible for an expedited review, please review the following federal requirements for expedited review:

(A) Research activities that (1) present no more than minimal risk to human subjects, and (2) involve only procedures listed in one or more of the following categories, may be reviewed by the IRB through the expedited review procedure authorized by 45 CFR 46.110 and 21 CFR 56.110. The activities listed should not be deemed to be of minimal risk simply because they are included on this list. Inclusion on this list merely means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human subjects.

(B) The categories in this list apply regardless of the age of subjects, except as noted.

(C) The expedited review procedure may not be used where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.

(D) The expedited review procedure may not be used for classified research involving human subjects.

(E) IRBs are reminded that the standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review--expedited or convened--utilized by the IRB.

(F) Categories one (1) through seven (7) pertain to both initial and continuing IRB review.

Research Categories

(1) Clinical studies of drugs and medical devices only when condition (a) or (b) is met.

(a) Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.)

(b) Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

(2) Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows

(a) from healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, the amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more frequently than 2 times per week; or

(b) from other adults and children2, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and collection may not occur more frequently than 2 times per week. 

(3) Prospective collection of biological specimens for research purposes by noninvasive means.

Examples: (a) hair and nail clippings in a nondisfiguring manner; (b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction;(c) permanent teeth if routine patient care indicates a need for extraction; (d) excreta and external secretions (including sweat); (e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax or by applying a dilute citric solution to the tongue; (f) placenta removed at delivery; (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) supra-and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collected after saline mist nebulization.

(4) Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.)

Examples: (a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject's privacy; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.

(5) Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)

(6) Collection of data from voice, video, digital, or image recordings made for research purposes.

(7) Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies. (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.)

(8) Continuing review of research previously approved by the convened IRB as follows: (a) where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or (b) where no subjects have been enrolled and no additional risks have been identified; or (c) where the remaining research activities are limited to data analysis.

(9) Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

_____________________

1 An expedited review procedure consists of a review of research involving human subjects by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB in accordance with the requirements set forth in 45 CFR 46.110.

2 Children are defined in the HHS regulations as "persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted." 45CFR 46.402(a).

3.4  Convened Committee Review

If the research is not eligible for an exempt or expedited review (e.g., involves more than minimal risk; an experimental design; subjects considered to be vulnerable [children, prisoners, cognitively impaired]; and/or deception) the protocol must be reviewed by the convened IRB membership at the monthly meeting. Research protocols to be reviewed during the convened monthly meeting are accessible to the IRB members approximately 10 days in advance of the meeting.  Therefore, protocols submitted for convened committee review must be received on or before the posted deadline date, which is usually two weeks before the scheduled convened committee meeting.   A primary reviewer is identified to present a specific protocol to other members in attendance.  Following presentation and discussion, the committee will vote on a motion to either: 1) approve the protocol as it stands; 2) request revisions to the protocol to secure approval; 3) request that additional information be provided prior to further review by the convened committee; or 4) disapprove the protocol.

3.5  Review Time Period

The research protocol may qualify for an administrative (exempt or expedited) review (45 CFR 46.101 & 45 CFR 46.110). Completion of this review process may take three to four weeks.  If the research requires review by the convened committee, the investigator will be notified by either standard mail or electronic correspondence of the review decision within one week following the monthly meeting date. Protocols that require review by the convened committee must be submitted on or before the posted monthly deadline date.  Deadline dates pertain only to protocols that require review by the convened committee. Administrative reviews are conducted in the order received. Completed protocols eligible for an administrative review should be submitted as soon as possible to receive the timeliest review.

3.6  Approval Criteria

For approval of a research protocol, the following federal requirements must be satisfied (45 CFR 46.111):

Risks to subjects are minimized by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk.

Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.

Selection of subjects is equitable.

Informed consent will be sought from each prospective subject or the subject's legally authorized representative.

The research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

When some or all of the subjects are likely to be vulnerable to coercion or undue influence (such as children, prisoners, pregnant women, the cognitively impaired, or economically or educationally disadvantaged) additional safeguards have been included in the study to protect the rights and welfare of these subjects.

3.7  Delay of Approval

The most common reason for delay is an incomplete application or an inadequate consent form. To avoid unnecessary delay, the IRB application instructions should be followed when writing the protocol, acquiring or assembling supporting documents or developing a consent form. Prior to submitting the IRB application, investigators are encouraged to review the IRB Checklist [http://gra.sdsu.edu/IRB/checklist.htm] to ensure all necessary documents are included.

3.8  Funded Research

The investigator must append the narrative section of the grant proposal (if DHHS) to his/her IRB protocol application (45 CFR 46.103f).  In addition, the title of the IRB application must be consistent with the grant that the protocol represents.  If an award is received, the SDSU Foundation will not release funds until IRB approval is secured. The SDSU Foundation has access to IRB review status for research receiving extramural funding.

3.9  Approval in Principle

If the research lacks definite plans for involvement of human subjects, an Approval in Principle may be appropriate (45 CFR 46.118).  This process allows for the investigator to disclose plans to conduct research and to demonstrate understanding that human involvement in the research cannot occur until the IRB approval is secured. This occurs when the research plan has not been completely developed or material development will occur prior to any involvement with subjects.

45 CFR 46.118: Certain types of applications for grants, cooperative agreements, or contracts are submitted to departments or agencies with the knowledge that subjects may be involved within the period of support, but definite plans would not normally be set forth in the application or proposal. These include activities such as institutional type grants when selection of specific projects is the institution's responsibility; research training grants in which the activities involving subjects remain to be selected; and projects in which human subjects' involvement will depend upon completion of instruments, prior animal studies, or purification of compounds. These applications need not be reviewed by an IRB before an award may be made. No human subjects may be involved in any project supported by these awards until the project has been reviewed and approved by the IRB, as provided in this policy, and certification submitted, by the institution, to the Department or Agency.

3.10  Review Decisions

“An IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities (45 CFR 46.109).”

3.10.1  Research Approved

If the research is approved, an electronic letter from the IRB stating the approval date and terms of approval will be sent to the investigator. In addition, a master of the IRB-approved and stamped informed consent document will be sent to the investigator. If the investigator is requesting monetary support to conduct the research, the SDSU Foundation will have access to the review outcome.

3.10.2  Revisions Required to Secure Approval

A conditional approval or approval with stipulations is awarded if there are correctable problems found in the protocol. In this situation, a letter (delivered electronically) is sent to the investigator detailing the areas that the IRB has identified for the investigator to address. Research may not commence until the stipulations have been addressed and accepted by an IRB representative. The investigator is provided with a 90-day time period within which the stipulated conditions must be addressed. The IRB determines, upon initial review, whether the investigator’s response to stipulations will require subsequent review by the convened committee or can be reviewed via subcommittee. 

3.10.3  Insufficient Information to Complete Review

If a determination for approval cannot be made due to pertinent information missing from the protocol, the investigator is informed of information needed by the IRB to complete the review. Research activity may not commence until the investigator has provided the information and the IRB has reviewed and accepted the response.

3.10.4  Disapproval (45 CFR 46.109)

If the research is disapproved, the investigator may not conduct the research. The IRB will provide the investigator with the reason for its decision. The investigator may resubmit a protocol to the IRB for review if the reasons given for disapproval can be corrected and addressed.

3.11  Approval Period (45 CFR 46.109(c))

IRB approval is valid for up to one year from the date of initial review (45 CFR 46.109).  The length and terms of approval is determined by the IRB based on project complexity, degree or type of risk associated with participation, and the investigator’s history of compliance with ethical practices.  Protocols that are verified as exempt may be valid for a longer period of time provided no changes are made to the protocol.

3.12  Determining Risk

The IRB determines whether the proposed research exceeds minimal risk on a case-by-case basis with consideration to the procedures proposed and subject population to be involved in the research.  

3.13  Appeal of IRB Decision

If the investigator is not satisfied with the decision of the IRB, or with the process by which a decision is rendered, an appeal process may be enacted. To initiate the appeal of a IRB decision, the investigator must submit a statement to the IRB noting areas of contention. If the issue is not resolved through the IRB, the appeal will be forwarded to the Assistant Vice President of Research, Graduate and Research Affairs - Division of Research Administration and Technology Services.

3.14  Communication with Investigators

All communication between the investigator and the IRB are conducted through the Division of Research Administration and Technology Services.  The investigator will receive an electronic message from the IRB office to indicate that the protocol was received and to notify the investigator of the assigned protocol number that can be used to track protocol review status.  The investigator may log onto the IRB website for an update of preliminary protocol status. Once the protocol has been adequately reviewed, the investigator will receive notification of the review outcome by electronic correspondence.  Once the investigator has received notification that the protocol is approved, research may begin. If a conditional approval is granted, the correspondence will detail the topics that require a response. Upon IRB review and approval of the response, the investigator will receive correspondence indicating Committee approval.  Approximately six weeks prior to the protocol expiration date, the IRB office will advise the investigator to complete a ”Report of Progress and Request for Renewal” which must be reviewed and approved by the IRB prior to the protocol expiration date. It is the investigator’s responsibility to submit this report.

4.0  Protocol Development

4.1  Where to Begin?

This section provides guidance that may be useful in preparing a protocol and informed consent document for review by the IRB. 

Prior to developing a protocol, review Ethical Principles and Guidelines for the Protection of Human Subjects of Research also known as the Belmont Report (http://www.ohrp.osophs.dhhs.gov/humansubjects/guidance/belmont.htm) and complete the IRB Human Subjects Tutorial (gra.sdsu.edu/IRB/tutorial).

To enter the web based IRB application to begin to write a protocol, please go back to the main menu and click on Electronic IRB Application Submission.

4.2  Protocol Guidance

The Institutional Review Board reviews the study protocol to determine study benefit and to assess risk and risk management procedures. This guidance is for use by investigators in creating a protocol for their specific research studies.  The protocol is the most important section of the IRB application as it outlines the specific procedures that will be followed during the course of the study. One of the most common reasons for delay of IRB approval is due to an incomplete protocol. Please do not assume that members of the committee understand the proposed research well enough to infer details about the study—be explicit, yet concise about the study details according to the guidance provided within each section. 

4.3  Study Abstract

The IRB uses the study abstract to gain a general understanding of the scope of the research and to verify the type of review that is needed (e.g. exempt, expedited, or convened committee). The abstract should provide the IRB member with a basic understanding of why the study is being conducted, how it will be carried out, how the results will be interpreted and how risks will be managed.  Specifically, the abstract should include a one-paragraph summary of the protocol that includes a brief description of the study purpose/objective, methods, subjects, planned analyses, potential benefits, potential risks, and risk management procedures. 

4.4  Statement of Purpose and Background

One of the major responsibilities of the IRB is to assess the risks and benefits of proposed research. Part of the process of risk/benefit analysis includes reviewing what has been done in the past and what should be done in the future in order to gain a better understanding of the phenomenon under study.  Therefore, the IRB must review a summary of the literature and other background information (e.g. pre-clinical/animal data if relevant or other facts) in order to justify approval of the proposed human subjects research study.

Within this section, investigators should briefly discuss the relevant background information and literature reviewed to provide the rationale for the proposed research. State the relevance of this research to and potential for contribution to the field of study. Provide justification for involving humans in the research. If relevant, include a summary of pre-clinical/animal data that have been obtained through other research. Provide a reference list/bibliography at the end of the protocol.

4.5  Subjects

The IRB is required to evaluate whether subject selection procedures for a given research study are fair to ensure that the burdens of research participation are distributed equitably across groups of people.  Therefore, information regarding the characteristics of subjects that will be involved in the proposed study are needed to conduct an adequate IRB review.  Additionally, the IRB must consider recruitment procedures for the proposed study to ensure that a broad cross-section of research subjects are included in the research and to evaluate the procedures that will be established to protect subject privacy during the recruitment phase,

4.6  Subject Characteristics

Within this section, define the group of subjects that are appropriate for use in the research study and provide a description of subject characteristics (e.g., type of population, number of subjects, gender, age range, etc. The application will include prompts to indicate the specific type of subject group(s) to be included in the research.  Investigators will be required and prompted to provide additional information to justify inclusion of special populations in the research where ability to acquire informed consent may be limited.

4.7  For studies involving Special Populations or Vulnerable Subjects

Special populations or vulnerable subjects include children, pregnant women, prisoners, physically or cognitively challenged, economic or socially disadvantaged, subordinate individuals (e.g. students and employees), and fetuses.  Additional safeguards for all subjects that are likely to be vulnerable to coercion or undue influence must be included in the study to protect the rights and welfare of these subjects (45 CFR 46.111(7)(b)). Specify what additional safeguards are included to protect these participants.

The degree to which these potential subjects are vulnerable is directly related to the degree to which these individuals are capable of volunteering or providing informed consent to research participation. There are specific federal regulations (45 CFR 46 Subparts B - D) that apply to conducting research with vulnerable populations which assures that the risks associated with participation are minimal or that the research is of direct benefit to the subjects.  Special considerations will be made by the IRB in reviewing protocols that include vulnerable subjects.

4.7.1  Children

The Code of Federal Regulations (45 CFR 46.401 Subpart D - http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm#subpartd) describes additional protections for children involved as subjects in research.  A child is defined by the State of California as a person who is under the age of 18 years and is not legally emancipated (link to state law on emancipation. http://www.leginfo.ca.gov/cgi-bin/displaycode?section=fam&group=06001-07000&file=7000-7002).

The IRB may only approve research involving children when all conditions of this subpart are satisfied as follows:

The research does not involve more than minimal risk (i.e. does not expose the child to greater risk than encountered in daily life).

The research involves greater than minimal risk, however the individual subject may receive direct benefit from participating in the research.

The research involves greater than minimal risk and no prospect of direct benefit to the participant, however, the results of the research will contribute to generalizable knowledge about the subject's disorder or condition.

The research, while otherwise not approvable presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children.

4.7.1.1  Involving Children in Research at School

The IRB must determine if it is appropriate to involve school children in a research study.  School children can be involved in research when the data collected will be used to assess classroom instructional strategies/techniques, curricula development, or classroom management techniques.  Discuss whether class time is used or if children are participating outside of structured class time (address nonparticipating students, supervision of non participants, procedures used to pull out children/subjects during class time, etc.).

4.7.2  Fetuses, Pregnant Women, and Human In Vitro Fertilization

The Code of Federal Regulations (45 CFR 46.401 Subpart B - http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm#subpartb) provides additional safeguards for research that involves fetuses, pregnant women, and human in vitro fertilization.  Pregnant women or fetuses may be involved in research if all of the following conditions are met:

(a) Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on nonpregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;

(b) The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means;

(c) Any risk is the least possible for achieving the objectives of the research;

(d) If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means, her consent is obtained in accord with the informed consent provisions of subpart A of this part;

(e) If the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with the informed consent provisions of subpart A of this part, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest.

(f) Each individual providing consent under paragraph (d) or (e) of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;

(g) For children as defined in Sec. 46.402(a) who are pregnant, assent and permission are obtained in accord with the provisions of subpart D of this part;

(h) No inducements, monetary or otherwise, will be offered to terminate a pregnancy;

(i) Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and

(j) Individuals engaged in the research will have no part in determining the viability of a neonate

The IRB must determine that all aspects of the research comply with this subpart.  The IRB must give special consideration to subject selection, monitoring and oversight of informed consent, and monitoring the research as needed.  For more guidance on research involving fetuses and human in vitro fertilization please review the Office for Human Research Protections (OHRP) IRB Guidebook: http://ohrp.osophs.dhhs.gov/irb/irb_chapter6.htm#g2.  For more information on inclusion of pregnant women in research, please go to: http://ohrp.osophs.dhhs.gov/irb/irb_chapter6.htm#g3.

4.7.3  Cognitively Impaired (45 CFR 46.111(b))

When recruiting participants who are cognitively impaired, the investigator must evaluate whether the potential subject is capable of making an informed choice to participate in the research. The process used by the investigator to determine participant autonomy must be described in the protocol. If the individual is deemed competent to make an informed choice, it may be necessary to include additional procedures during the consent process to ensure that the prospective subject understands the information presented about the study.  The investigator may consider including questions at the end of each section of the consent document to use in assessing participant comprehension of the consent content.  This mechanism allows for the investigator to clarify the participant's understanding of specific aspects of the study as the consent process occurs (e.g. After the Description of the Study section, include questions such as: Do you understand what will happen during the testing phase? The training phase?).  If the individual is not legally able to consent for him/herself, the person who is legally authorized to serve as the individuals advocate and caretaker is responsible for determining whether the proposed study is appropriate. 

4.7.4  Prisoners

The Code of Federal Regulations 45 CFR 46.401 Subpart C (http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm#subpartc) allows the IRB to review and approve research that includes prisoners when the following conditions are met: The study does not place the subject at more than minimal risk and the investigation pertains to possible causes, effects and processes of incarceration and of criminal behavior or the investigation pertains to prisons as institutional structures or of prisoners as incarcerated individuals or the investigation pertains to conditions that affect prisoners as a class of people (e.g. vaccine trials, research on disease that is more prevalent in prisoners than other groups and research on social and psychological problems of prisoners such as alcoholism, drug addiction and sexual assaults) or the study has the likelihood of improving the health or well-being of the prisoner.

4.7.5  Women and Minorities

Federal guidelines require that NIH-funded studies incorporate a research design that is sufficient to elicit information about individuals of both sexes/genders and diverse racial and ethnic groups to examine differential effects of research procedures on such groups. For more information on this topic, please go to: http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm

4.7.6  College Students 

The IRB tries to estimate the degree of situational coercion and, through guidelines, assist researchers to reduce the pressure that a student may experience when recruited to participate in research. The IRB encourages investigators to follow recruitment procedures intended to create the opportunity for students to participate in research while reducing the possibility of unintended coercion. For example, avoid one-on-one solicitations of students by faculty, graduate assistants or other students. If research participation is a course requirement, offer an equitable alternative to participation in a study as a method of obtaining course credit (e.g., summarize a journal article, attend a research lecture, and assist with data collection) and conduct data collection outside of the scheduled class time.

4.7.7  Employees

The IRB must consider the potential for coercion or undue influence and breeches of confidentiality when employees are recruited as research subjects. State how voluntary participation will be ensured if the subjects under study are recruited by their employer.  Recruitment procedures should allow for employees to participate in the study without jeopardizing their job status, their pay or their relationship with their supervisors.

4.8  Selection Criteria

The IRB must review the criteria by which subjects will be selected for study participation to determine whether subject selection practices are equitable and justified.  The research protocol should include the rationale to support the selection criteria. In order for the IRB to know that subjects will be selected appropriately, the protocol should include a description of how the inclusion/exclusion criteria will be assessed and by whom (include a description of the assessor’s professional qualifications/credentials if relevant).

4.9  Screening Procedures

The IRB is concerned about protecting subject confidentiality and for ensuring that a prospective subject has given informed consent before disclosing private information. In certain cases, investigators are interested in screening individuals before they are formally enrolled into the study to determine whether they meet the basic study selection criteria. This process can often lead to disclosure of private information prior to obtaining and documenting informed consent.  Therefore, if a screening procedure will be used, the IRB requires information about how screening will take place (e.g. interview, survey, records review) and how data collected during screening will be handled if the person is found to be ineligible (e.g. used as research data or destroyed).  If individuals will disclose private information, the IRB will review the procedures used to obtain consent from the person in advance of implementing screening procedures. If the protocol identifies specific inclusion and exclusion requirements to determine subject eligibility (e.g., age, physical or psychological condition), the IRB will review a screening checklist in which specific inclusion and exclusion criteria are listed and defined. The IRB will review the procedures used to document appropriate screening of subjects. For example, it is recommended that a screening checklist is completed for each subject enrolled and that a checklist is maintained in the study master file or in individual subject files.  

4.10  Recruitment

The IRB requires a description of how and by whom potential subjects will be identified and recruited. If records are accessed to identify potential subjects, the IRB will review a description of procedures used to ensure that records are only accessed by those with consent from the individual.

4.10.1  Advertisement/Announcements/Flyers/Scripts

Advertising a research study for the purpose of recruiting participants is part of the informed consent process. Printed or electronic media intended for use in subject recruitment are reviewed by the IRB to ensure that the procedures proposed for informing potential subjects are not coercive and do not state or imply an outcome or other benefit beyond what is outlined in the consent documents and the protocol.

Recruitment advertisements, such as flyers, postcards, brochures, newspaper advertisements, press releases, or postings on the Internet are reviewed for the accuracy and presentation of information the prospective subject needs to determine their eligibility and interest. This includes the review of content, language, and design. Information should not be misleading to subjects, as such, the use of words that appear neutral as opposed to sensational are encouraged. Attention should be paid to the use of appropriate graphics, font size and format/design, and to accurate spelling and punctuation. The following information should be included in recruitment materials: 

1.  name and address of the principal investigator and/or research facility;

2.  concise description of the purpose of the research;

3.  eligibility criteria for subject participation;

4.  time or other commitment required of the subjects; and

5.  location of the research and person to contact for further information.

Please note:  

In medical studies, advertisement materials should make no claims, either explicitly or implicitly, that the research activity is safe, effective, equivalent, or superior to any other current practice.

Reference to incentives offered may include that subjects will be paid but should not emphasize the payment or the amount to be paid.

4.10.2  Legitimate Access to Records

A primary concern of the IRB specific to subject recruitment involves protecting the privacy and confidentiality of prospective subjects.  Recruitment procedures in which names of individuals are released from private sources to an investigator are generally not endorsed by the IRB.  Recruitment procedures should allow for the individual to consent to the release of information in advance of being contacted directly by an investigator. 

Established Legal/Ethical Protections:

The IRB advises against the release of identifiable private information from a source to an unaffiliated researcher without the permission of the potential subject where legal and ethical guidelines prohibit the source from doing so.

An example of when this may occur is when a researcher is attempting to identify prospective subject according to specific eligibility criteria for recruitment to a study by accessing private files through a hospital or medical clinic.

To obtain permission to access private and identifiable information about a prospective subject, the researcher will need to propose procedures to obtain consent from the individuals involved. This may be in the form of a release form used by the source to document permission to release information to the researcher.  The consent statement should include information about what information is requested, how it will be used and to whom it will be given. Review and acceptance of this consent document by the IRB is required in advance of its use.

No Established Legal/Ethical Protections.

The IRB recommends against the release of information about an individual where the individual about whom information is to be released may normally consider the information to be private - although not protected by law or the ethics of a specific profession.

The IRB advises against procedures that involve a person or organization providing information about another individual/potential subject without his/her permission for the purpose of recruitment.

The IRB recommends procedures that allow for an organization or an enrolled subject to provide information about the study to a prospective subject (flyer, postcard or other announcement) that allows for the prospective subject to initiate contact if he/she would like additional information about the study.

Please note: Research that involves the collection or study of existing data, documents, records or specimens where the sources are either publicly available or recorded in a manner that subjects cannot be identified, directly or through identifiers linked to the subject may meet the criteria for exempt review.

4.10.3  Recruitment Incentives – Finder’s Fees and Bonus Payments

Any remuneration (in cash or in kind) for patient referral is considered unethical and is not permitted as it may compromise the provider-patient relationship.  The policy set forth by the American Medical Association Code of Ethics states: “Payment by or to a physician solely for the referral of a patient is fee splitting and is unethical." Referral incentives may include, but are not limited to monetary compensation, stock options, material goods or other incentives such as food or entertainment. In addition, bonus payments to the investigator, study coordinator or provider for the purpose of encouraging recruitment of subjects to the study may compromise the judgment of the research team and is not acceptable.

The IRB does not endorse practices that involve remuneration of any kind to a provider for patient referrals or bonus payments to members of the research team for purposes of subject recruitment.

Please visit the American Medical Association web site for more information on this topic.  http://www.ama-assn.org/ethic/ceja.65b.pdf

4.11  Informed Consent Process

“Informed consent is one of the primary ethical requirements underpinning research with human subjects; it reflects the basic principle of respect for persons. It is too often forgotten that informed consent is an ongoing process, not a piece of paper or a discrete moment in time. Informed consent assures that prospective human subjects will understand the nature of the research and can knowledgeably and voluntarily decide whether or not to participate. This assurance protects all parties - both the subject, whose autonomy is respected, and the investigator, who otherwise faces legal hazards. The "proxy consent" of someone other than the subject is not the same as the subject's own consent, although it may be an acceptable substitute when a subject is unable to give informed consent.” (OHRP IRB Guidebook, Available: http://ohrp.osophs.dhhs.gov/irb/irb_chapter3.htm#e2).

Within this section, the IRB will review the procedures that will be followed during the informed consent process. The IRB will review the process used to introduce the informed consent document and procedures used by the investigator to ensure full disclosure of the research (i.e., purpose of the study, study description risks, benefits, confidentiality, investigator's telephone number to call for questions, etc.). The IRB will also review procedures developed by the investigator that will enhance the potential subject's understanding of the research (e.g. use of audio/visual materials or reiterating complex information in lay terminology).  It is important to include a description of the person who will make initial contact with the potential subject to demonstrate that this individual is knowledgeable about the study, can present the information to laypeople and will promote voluntary participation. The IRB will also consider how and where the research will be introduced to the subject to assess whether the timing and setting of the informed consent process is conducive to objective decision making.  If minor children are involved in the study, the IRB will review the process used to obtain parental consent as well as assent from the minor child.  The IRB will review the consent document(s) for use in obtaining and documenting consent from study participants.  Consent forms must adequately describe the study using language appropriate for the target audience.  If relevant, the investigator will be asked to translate consent documents into the subject’s primary language after the English version of the consent form has received IRB approval. 

4.11.1  Waiver of Consent Requirements

If waiver of consent, alteration of consent content or waiver of consent documentation is requested, the IRB must review justification to support the request. 

As per 45 CFR 46 116 (c), the IRB may waive the requirement to obtain informed consent or approve a consent procedure which alters some of the consent content if the IRB finds and documents that:

a. The research is designed to evaluate a public benefit or service program and the research could not be carried out without the waiver or alteration or

b.  The research involves no more than minimal risk to the subject;

c.  The research could not be carried out without the waiver or alteration and

d.  When appropriate, the subjects are provided with additional information after participation.

4.11.2  Waiver of Consent Documentation

The IRB may waive requirements to document voluntary participation via a signed consent form if the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context (45 CFR 46.117 (c)).

4.11.3  Assent from Children (45 CFR 46.408)

Assent is demonstrated by a child's agreement to participate in research. In California, a child is a person who is under the age of 18 years (unless legally emancipated).  It is required that the researcher makes adequate provisions to solicit assent from children unless the IRB waives this requirement. 

The IRB will review a description of the process and procedures for obtaining assent from the child.  To determine whether the child is able to assent depends on the child's age and maturity.   If the child is considered to be capable of providing assent, whether or not assent is documented is also determined by the IRB. Generally, children are able to read and write to some extent by age 7.  As such, documenting assent by having the child sign an assent form is usually a procedure that is incorporated for children age 7 – 17. When documentation is not required, the IRB requires that the investigator conduct the assent process through a verbal interaction and the IRB will review a script of what will be said during the verbal consent process. Click here for information on what to include within a child assent document or within a verbal presentation to obtain child assent [http://gra.sdsu.edu/IRB/assent.htm].

4.11.4  Parental Permission  (45 CFR 46.408)

If a child will be involved as a study participant, the IRB will review procedures used to obtain and document permission from the parent or guardian. To develop a Parental Permission/Consent document, click here [http://gra.sdsu.edu/IRB/parentalconsent.htm].

4.11.5  Non English Speaking Subjects

If non-English speaking persons will be recruited, the IRB will review a description of the qualifications of the person who will conduct the translated consent process (verbal and written).  The IRB must review the English version of the consent document first before approving the translated version.  After the English version has been approved by the IRB, the investigator will be required to forward a copy of the translated document so that it may bear the IRB stamp of approval.

4.12  Potential Problems

Address any potential problems involving subject identification, recruitment or data collection that may negatively effect the ability to conduct this study.

4.13   Research Design and Methods

The IRB evaluates the research design to weigh the potential benefits of the study as compared to the potential risks. The IRB protocol must include adequate information about the research design for the IRB to make an informed judgment that the design will result in meaningful and valid data.  The IRB will review a description of the research design, the scientific rationale underlying the proposed research and the statistical basis for the structure of the investigation. The IRB will also review the specific aims of the research the hypotheses to be tested, the questions to answer and the type of data to be gathered and tested.

Note that the IRB Guidelines from the Federal Government state, “The value of research depends upon the integrity of the study results. One of the ethical justifications for research involving human subjects is the social value of advancing scientific understanding and promoting human welfare by improving health care. But if a research study is so methodologically flawed that little or no reliable information will result, it is unethical to put subjects at risk or even to inconvenience them through participation in such a study.”

If the IRB determines that the experimental designs or statistical methods are inappropriate, the investigator will be asked to make revisions so that review of the protocol may continue.  Some common issues to consider include the appropriate number of subjects, the power of the study (effect size estimates), the type of statistical procedure (e.g., parametric versus nonparametric), and the type of study.

4.13.1  Tasks Associated with Participation

The IRB will review the tasks that subjects will be asked to complete during the course of a study.  Specifically, you should the protocol should describe what subjects will do during their involvement and the amount of time that participation in each aspect of the study will take. The protocol should also discuss any investigational, experimental, or special procedures that will involve the subject (medical devices, electrical equipment, etc.). If the research involves exercise testing, blood draws or DEXA scans, review the Exercise Protocols section of this guidance.

4.13.2  Tests, Questionnaires, and Interview Guides

The IRB reviews all research instruments such as surveys, interviews or questionnaires planned for use in data collection. As such, the investigator is asked to Include all interview schedules and survey instruments with the completed protocol application. The investigator may submit draft versions of study instruments for review; however, the IRB must review the final instruments prior to approving the use of those instruments for data collection.

4.13.3  Deception or Incomplete Disclosure

Deception involves not fully informing subjects of the real purpose of the study or providing false information about the study to subjects.  This may be appropriate and justifiable in some circumstances, particularly in social and behavioral research.  If the protocol involves deception, the IRB must review a complete description how deception will be used. The IRB will need adequate justification for the inclusion of deception and possible alternatives to the use of deception. In studies involving deception, the protocol should include procedures to debrief subjects following participation. . The debriefing statement should be presented both orally and in writing and include a description of the deception involved and an explanation about the true purpose of the research.  In addition, this statement should inform subjects of their right to withdraw their data from the study, if they feel upset or uncomfortable with the deception involved, and still receive any incentives offered to participants.

4.13.4  Study Location

The IRB will determine the appropriateness of the location and the setting where subjects will participate in this research. The protocol should address any special considerations associated with recruitment or data collection at the location (e.g. identifying potential subjects, obtaining voluntary participation, confidentiality of data and privacy concerns).   Performance Sites: If the research is supported by federal funds and persons not affiliated with SDSU will conduct the study, it is necessary for the investigator to document that the facility has an assurance with OHRP and that a local IRB has reviewed the study for conduct at the performance site.

4.14  Potential Benefits

The IRB must determine that conducting the proposed study will result in a benefit either to science/society or to the individual participant. Therefore, the investigator must provide the IRB with a clear description of the anticipated benefits that will be derived from this study. 

4.15  Risks

Research subjects may be exposed to risks as a result of participation in a study. When recruiting participants for research, information about the types of risks associated with study participation must be presented to each prospective subject. The Office Human Research Protections (OHRP) has provided the following descriptions of risks that may be associated with research participation. Physical harm is often associated with research involving medical procedures; however, it can also be related to research testing aspects of physical fitness or public health concerns. Minor pain and discomfort, as well as drug side effects or injury resulting from an invasive procedure should be considered when evaluating exposure to physical harm. The physical risk may be minor and transient; however, some procedures may result in adverse events that may be considered serious and possibly permanent. Psychological harm may occur when subjects are asked to disclose or think about personal feelings and/or behaviors or are involved in an experiment that involves a manipulation of the environment or deception. The subject may experience changes in awareness, thought processes and emotion as a result. Social or Economic harm is associated with research where sensitive information about the subject (e.g., alcohol and other drug abuse, mental illness, illegal activities, etc.) is obtained. A breach in the confidentiality of this information may lead to the individual being labeled in a way that could affect their reputation, insurance eligibility, or employment.

4.15.1  Data Safety Monitoring Board (DSMB)

“Monitoring of the research by the researcher is important because preliminary data may signal the need to change the research design, change the information presented to subjects, or even to terminate the project before the scheduled end date.” (OHRP IRB Guidebook, Available: http://ohrp.osophs.dhhs.gov/irb/irb_chapter3.htm#e5),   When applicable the IRB will review the process used to monitor data collected to ensure the safety of subjects (e.g., clinical trial studies) (45 CFR 46.111(a)(6)). Note that all Phase III randomized clinical trials supported or performed by the National Cancer Institute (NCI) require monitoring by a DSMB. For more information on DSMBs, please visit the NCI website at: http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm.

4.15.2  Assessment of Risk

The IRB will review information provided by the investigator to assess whether the risks and inconveniences associated with the research are reasonable in relation to the anticipated benefits to the subjects and in relation to the knowledge that may reasonably be expected to result from this research (45 CFR 46.111).

4.16 Confidentiality Procedures

To maintain confidentiality of research data, the investigator should protect information obtained from the subject to avoid the unintentional access by others (45 CFR 46.111(a)(7)). A federal Certificate of Confidentiality may be issued to protect sensitive data from being subpoenaed by a court of law.  The IRB may determine that documentation of informed consent be waived if this process increases the risk of a breach of confidentiality. Subjects should be provided with information about the procedures used to protect confidentiality.

Guidelines for developing procedures to address confidentiality include:

Limit the personal information recorded to that, which is essential to the research;

Store personally identifiable data securely and limit access to the principal investigator and authorized staff;

Code data as early in the research as possible and dispose of the code linking the data to individual subjects when data have been processed;

Do not disclose personally identifiable data to anyone other than the research team without the written consent of the subjects or their legal representative. (Exceptions may be made in case of emergency need for intervention or as required by regulatory agencies).

If the data are considered to be sensitive (e.g., sexual preference or practices, use of alcohol or other drugs, illegal conduct, psychological or metal health records, etc.) and place the subject at legal risk more elaborate measures to protect confidentiality may need to be implemented. In some cases, it may be appropriate to apply for a federal Certificate of Confidentiality  http://grants.nih.gov/grants/policy/coc/index.htm. For more information about the purpose and use of a federal Certificate of Confidentiality, please visit the NIH Office of Extramural Research website: http://grants1.nih.gov/grants/policy/coc/.

4.16.1  Anonymity and Confidentiality

Anonymity means that the identity of the subject is never recorded or associated with the data collected. Maintaining confidentiality involves recording but concealing the subject’s identity or codes linked to the individual’s identity. The IRB will review the procedures used to maintain either anonymous or confidential data.  If the subject’s identity will be recorded or a code will be created which is linked to the subject’s identity, the IRB will review the rationale for doing so. If it is necessary to track information over time, consider using a coding strategy that is not linked to the subject’s identity if at all possible. 

4.16.2  Reportable Disclosures

State law and mandated reporting requirements may limit the extent to which the investigator is able to protect the subject’s confidentiality.  If through interview or measurement, the subject is likely to disclose illegal or dangerous behavior (e.g. if the subject reports any kind of abuse or serious harm to self or others) the investigator must disclose whether and to whom information will be reported. Include a description of the limits to confidentiality within the consent document.

4.16.3  Coding Data for Tracking Purposes

In survey research, an investigator may wish to code data that would otherwise remain anonymous in order to track respondents.  The investigator may wish to track respondents for the purpose of contacting non-respondents at a later time or to publish information about non-respondents to describe the study sample.  The IRB considers these tactics appropriate as long as individuals are informed at the beginning of the study during the informed consent process that their identity will be linked to a code and that they may be contacted at a later time.  If coding will be used for tracking purposes, the IRB will review a description of the coding scheme used to track respondents and non-respondents to ensure that confidentiality is maintained.  If the individual's identity is linked to the code, the IRB will review how this information will be used once data collection is complete.

4.16.4  Image and Voice Recording

The IRB will review where the subject’s image or voice will be presented and to whom if the study involves the use of the audio or video recordings.  The subject should be informed about how images may be used within the consent document. If the investigator would like permission to present the recorded image for purpose other that the specific research for which the subject is consenting, an addendum to the consent is used to obtain this authorization.

4.16.5  Record Storage and Access

In an effort to further protect subject privacy, the IRB will review where and for how long research records will be stored and who will have access to the study data (hard copy or electronic files) once data have been collected and filed. The IRB will review procedures used to dispense of research records, samples/specimens upon completion of the research activity.

4.16.6  Release of Test Results

Data collected for research purposes may also be relevant to the participant’s physician or other professional. In some cases, it may also be appropriate to disclose test results to the participant.  This may depend on the investigator’s training in accurately interpreting the results of a test that has been used for research purposes and the implications of imparting this information to the subject (e.g. access to healthcare or mental health counseling services).  The protocol should address the collection of data that may also have clinical relevance and describe whether this information will be disclosed to the participant and/or to a clinical professional determined by the participant.

4.16.7  Transportation of Data

If data are collected at an off-site location,  the protocol should include procedures to ensure that data will be transported in a manner that minimizes risks associated with the inadvertent loss or theft of data. 

4.16.8  Certificate of Confidentiality

If the research includes disclosure of potentially sensitive or illegal information, additional measures to protect the participant’s privacy and confidentiality may be needed. A Federal Certificate of Confidentiality provides additional protection for the subject in that the data would be protected from subpoena by a court of law. To initiate the process to obtain a Certificate of Confidentiality for this study, contact:

Olga Boikess, National Institute of Mental Health, 6001 Executive Boulevard, Room 8102, MSC 9653,
Bethesda, MD 20892-9653, Phone: 301-443-3877, Fax: 301-443-2578, Email: oboikess@mail.nih.gov .  Upon receipt of the Certificate, forward a copy to the IRB.  Visit the NHI Office of Extramural Research website at http://grants1.nih.gov/grants/policy/coc/ for more information.

4.17  Costs

“Participation in research may result in additional actual costs to individuals. Any anticipated costs to research participants should be described to prospective subjects during the consent process.” (OHRP IRB Guidebook, Available: http://ohrp.osophs.dhhs.gov/irb/irb_chapter3.htm#e5 ). If this study exceeds minimal risk, state how costs pertaining to any injury incurred due to study participation will be covered and by whom. A study that exceeds minimal risk means that the probability or magnitude of harm or discomfort anticipated in the research are greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests (45 CFR 46.102).

4.18  Compensation and Incentives

To assist in subject recruitment, an incentive may be offered. The IRB considers the appropriateness of study compensation/incentives when reviewing protocols. The incentive should be reasonable compared to the burden or inconvenience incurred by study participants. It is important that the incentive be awarded for participation in the study rather than for completing a specific task.  The purpose of the incentive is to encourage participation. By awarding the incentive only when a task is completed, it may create an undue influence that does not allow for the participant to discontinue if uncomfortable.  The amount and type of incentive should not coerce or unduly influence the prospective subject into participating. The incentive is not contingent on study completion. Potential participants should understand what incentives will be offered before agreeing to participate in the study.  The terms of the incentive should be described within the consent form. Incentives may also be described on recruitment materials, but should not be sensationalized or exaggerated.

4.18.1  Prorating

The IRB encourages the use of a prorated incentive payment system. This allows for the subject to be paid as the study progresses and does not create the perception of a penalty for discontinuing participation.  In some cases, the incentive structure involves graduated payments over the course of the study to encourage continuation without creating an undue influence for participation.  The IRB may accept procedures to pay the incentive in one payment at the end of the study when there is a direct benefit to the subject and a complete data set (all sessions, all interviews, all surveys) must be acquired in order to draw any conclusions.

4.18.2  Coercion/Undue Influence

IRBs may approve research studies that minimize the possibility of coercion or undue influence. To do so, the IRB reviews incentives to determine if they are appropriate given the potential for risk or significant discomfort that research participants may experience. 

4.18.3  Lottery

If a lottery incentive will be used, the participant informed consent include an estimated timeline for when the information about the drawing will occur, how the person will be notified, how many prizes will be offered and the chances for winning one of the prizes (e.g. You have a one in five chance of winning a prize in the drawing.)

4.18.4  Amount

The IRB will consider the value of the incentive in order to determine its appropriateness and to minimize the potential for coercion.

4.18.5  Payment Type

IRBs must determine whether paid research participants are paid appropriately.   If a monetary incentive will be offered, the investigator must consider how subjects will be paid – either through cash, check/money order or other type of redeemable coupon.  The investigator must consider potential breeches in confidentiality if payment type is provided in a form other than cash.

4.18.6  Staggered Schedule

The investigator may want to consider compensating participants for each task in the study that is completed. A payment schedule allows for subjects to receive partial payment even if they do not complete all study activities.  The amount of the incentive may change depending on the nature of the task that the participant is asked to complete.  The investigator may want to consider increasing the amount of compensation each time the subject completes a study task to promote continued study participation (for example, if the study is longitudinal).    The IRB will review the payment schedule to determine that the incentive schedule does not appear coercive to unduly influence the subject’s decision to participate.

4.19  Investigator Experience

The IRB considers the investigator’s experience in the area of research to be undertaken to ensure that the research will be carried out appropriately.  The IRB will review a brief summary of the investigator's relevant research experience/training. If the investigator is a student, the IRB will also review a summary of the faculty member’s experience responsible for the research.           

4.20  Conflict of Interest

The IRB considers the investigator's financial interests when evaluating the protection of human subjects. If a financial interest is reported, the IRB will assess the investigator's objectivity in communicating risks, selecting subjects, promoting informed consent, and gathering, analyzing and reporting data. The SDSU Conflict of Interest committee may also review disclosures where a financial interest is reported. The IRB will review whether the investigator (including the investigator’s spouse or dependent child) or any person affiliated with the project has any financial interest, financial relationship, governance or administrative affiliation with any entity that is providing funds for or which has rights to intellectual property resulting from this study.  If a financial interest is reported, the investigator  must complete and attach the Financial Interest Disclosure form to the protocol.

4.20.1  Identification and Management of Potential Conflict (missing paragraph)

4.20.2  Disclosure within Consent Form

If the investigator has disclosed a financial interest in the research, the consent form should describe the financial interest as well as how the interest has been managed to avoid the possibility of a conflict in the conduct of the research.

4.21  Special Considerations

There are certain types of studies that require the PI to submit specific information to the IRB. These studies include, but are not limited to exercise testing, genetic testing, testing of non-FDA approved substances, studies conducted over the Internet and studies involving women of child-bearing potential.

4.21.1  Exercise Testing

Tests routinely conducted in exercise research protocols have been reviewed by the IRB to ensure that the researcher knows standardized procedures, appropriate risk management techniques are employed and that required training is received.  Investigators who plan to collect data that involves Maximal Aerobic Power (VO2max); Endurance Test Protocols; Hydrostatic Weighing; Venipuncture; Bone Mineral Density (DEXA Scan); Lactate Threshold; or Exercise in the Heat must review each exercise testing protocol in advance of including the procedure in a research protocol that is reviewed by the IRB. 

Each of the exercise protocols are included below in sections 4.21.1.1 to 4.21.1.7.   The investigator will be required to verify compliance with the IRB approved exercise protocol that is planned for use in a research study upon submission of the electronic IRB application.

The exercise protocols also provide the text to include within the informed consent document. The consent text provides a description of the test procedures, associated risks and risk management strategies that may be used by a potential subject to make an informed choice about study participation.  Incorporate the content, as appropriate, within the consent document that will be used to inform the subject and document voluntary participation.

It is likely that some of the content provided in this text will need to be edited if several tests are planned for use that, for example, have similar risks and/or risk management procedures.  Please remember, the purpose of informed consent is to provide information about the study in a format (oral and written) to enhance the prospective subjects comprehension of the information and their ability to make a decision about participation.  The consent form is also used to document voluntary participation.  When developing the consent form, use language that the subject is likely to understand (avoid technical terminology, adjust for educational background and age groups, provide translations for non-English speaking subjects).

4.21.1.1  Exercise Protocol: Maximal Aerobic Power (VO2max)

Appropriate Applications

The testing of maximal aerobic power through direct measurement of maximal oxygen consumption (VO2max) is considered the best measure of cardiovascular fitness.  VO2max has been assessed in a wide range of subjects, from children to the elderly, both fit and unfit, including cardiac patients.  It is often used in studies to determine the effects of exercise training on fitness, both from short-term training, e.g., several weeks to longitudinal studies of a year or longer.

For older subjects (e.g., men >40 years; women >50 years), a standard three-channel ECG will be used where adequate monitoring and recording of the heart activity can be attained.  The use of ECG with other individuals will be restricted to studies that require quantification and qualification of heart rate, including any abnormal beats.  For the majority of testing conditions requiring an ECG, a single lead will be used for monitoring and recording the ECG. 

Test Description

VO2max assessments are conducted in the Exercise Physiology Laboratory (ENS 255) and Annex Exercise Physiology Laboratory (ENS 111) at SDSU and in the Fitness Lab at 9245 Sky Park Court.  Each subject will be screened for cardiovascular disease using the Physical Activity Readiness Questionnaire (PAR-Q).  Any individual who answers “yes” to any of the PAR-Q questions will be excluded from the study.  Subjects who meet specific study criteria and who do not report cardiovascular disease or its symptomology will undergo a maximal graded exercise test on a selected ergometer (treadmill, cycle, rowing machine, hand-crank cycle).  Guidelines of the American College of Sports Medicine (ACSM) are adhered to regarding physician supervision of tests.  That is, all women over 50 years and all men over 40 years, and those with two or more major CVD risk factors must have physician supervision for maximal testing (this guideline does not apply to submaximal testing).

To determine VO2max, subjects undergo a maximal graded exercise test to voluntary exhaustion.  This means that the subject makes the decision when the test is over.  On a cycle ergometer, the test is terminated when the subject can no longer turn the cranks at the desired frequency; on the treadmill, the test is terminated when the subject can no longer run at the treadmill speed and stands straddling the treadmill belt while holding on the railing.  In addition, the subject is spotted at his/her side to prevent a possible fall.  When testing an athlete, in particular, he/she is coached to proceed as long as possible.  Untrained individuals, older subjects, and children are encouraged to “give a hard effort,” but not coached to continue to their absolute physical limits.  Following a test, the subject goes through a cool-down at a self-selected intensity until recovered.

Test protocols vary somewhat in terms of duration of each stage (1-3 minutes) and increments in intensity, but all begin with a 5-10 minute warm-up followed by a gradual increase in work effort until volitional exhaustion.  Typically, a graded exercise test takes 8-12 minutes, excluding warm-up and cool-down.  Throughout the test, the subject breathes through a rubber mouthpiece on a two-way re-breathing valve that is connected by low-resistance tubing to a metabolic measurement system.  A computer permits analysis of the expired air for oxygen consumption and carbon dioxide production.  Heart rates are monitored continuously, usually with a heart rate monitor that obtains a signal from a transmitter strapped around the chest.  Older, nonactive subjects are also monitored for heart arrhythmias and/or ischemic changes using a standard 3-lead ECG.  Blood pressure is also monitored and recorded at each stage with older subjects.  Only technicians trained in exercise ECG and blood pressure monitoring are permitted to test older and/or higher-risk subjects.

ECG assessment requires the placement of at least three electrodes, and possibly six, on the skin surface of the subject’s chest.  Each electrode surface site is prepared to ensure that the electrode remains on the skin during exercise.  The preparation process requires that the technician rub the electrode site with gauze until slightly red and to cleanse the area with alcohol prior to placing individual electrode pads.  This process must be performed to remove natural body oil that can interfere with the electrical signal and ECG assessment.

As follows ACSM guidelines, general indications that will be used for stopping an exercise test include:

Onset of angina or angina-like symptoms;

Significant drop (>20 mm Hg) in systolic blood pressure or a failure of the systolic blood pressure to rise with an increase in exercise intensity;

Excessive rise in blood pressure:  systolic pressure >260 mm Hg or diastolic pressure > 115 mm Hg;

Signs of poor perfusion:  lightheadedness, confusion, ataxia, pallor, cyanosis, nausea, or cold and clammy skin;

Failure of heart rate to increase with increased exercise intensity;

Noticeable change in heart rhythm;

Subject request to stop;

Physical or verbal manifestations of severe fatigue;

Failure of the testing equipment.

Training/Supervision Required

Technicians or investigators need to be knowledgeable and trained in two specific areas: 1) administration of graded exercise tests, including ability to conduct pre-test health screenings, and knowledge and recognition of signs and symptoms of cardiovascular disease; and, 2) procedures for conducting metabolic measures.  These procedures require academic preparation in exercise science.  Graduate students in the M.S. program in Exercise Physiology have taken coursework and had lab experiences to prepare them for these assessments.  In addition, before they are allowed to collect data they must demonstrate to their faculty supervisor that they are competent in all these procedures.

All staff will be properly trained in application of electrodes and their respective monitoring and recording.  Proper skin preparation is essential for good ECG tracings and staff will be trained.  Rubbing of the skin and cleansing it with alcohol may be necessary to place electrode pads on the chest of the subject.  Once trained, minimal supervision will be necessary.  Students conducting these procedures require academic preparation in exercise science.  Graduate students in the M.S. program in Exercise Physiology will have taken coursework and had lab experiences to prepare them for these procedures. 

Risks

Maximal exercise testing may produce light-headedness, fatigue, nausea, and delayed-onset muscle soreness.  These side effects are usually minimal in fit subjects.  They are also minimized by having a gradual warm-up as well as cool-down (at least 5 minutes each) and by having the subject refrain from eating for at least 2-3 hours before their test.  For treadmill testing, there is also a small risk of falling.  This risk is managed by having at least one spotter at the subject’s side.

There is also a risk of a cardiac event, such as a heart attack, cardiac arrest, or dangerous arrhythmia.  This risk is less than 1 occurrence in 12,000 tests of healthy subjects, and approximately 1-2 occurrences in 10,000 tests of higher risk and diseased subjects.

There are minimal risks associated with an ECG.  The most common is the debriding of the skin in preparation of ECG recording.  In order to get a good ECG tracing, the skin must be properly prepared which will cause some reddening of the area where the electrodes are placed on the chest surface.

Risk Management

All test personnel are required to have current CPR certification and to be trained in emergency procedures for the particular lab.  A telephone is located within 20 feet of the ergometers.  Individuals with probable CVD, as screened with the PAR-Q, are not tested at SDSU or at the Sky Park lab.  Subjects are warmed up and cooled down gradually, which has been shown to decrease the incidence of cardiac arrhythmias during and after stress testing.  In instances when ECG is monitored, only the necessary amount of skin preparation will be debrided, which minimizes perceived subject discomfort.


The mouthpiece and valves fall into the semi-critical device category.  This device will come into contact with mucus membranes, but will not penetrate body surface.  High-level disinfection using liquid glutaraldehyde disinfectants (e.g. Cidex) is acceptable according CDC recommendations.  We use EPA-registered sterlants for this purpose in our laboratory. 

Older is defined as men over 40 and women over 50 years of age, according to guidelines of the American College of Sports Medicine.  Partial CVD risk is determined by the PAR-Q, i.e., subjects are asked about symptomology and whether they are hypertensive.  Thus, a subject is screened out of studies if he/she reports symptoms indicative of CVD.  However, if a subject reports high blood pressure, depending on the particular study, he/she would not necessarily excluded from participating.  The investigator will take BP of anyone self-reporting hypertension; if BP is >160/90, he/she will be excluded from studies involving high intensity or maximal exercise unless the study is specifically recruiting this population in which case a physician will monitor the exercise test.

ECG monitoring is normally conducted only in studies of older men (>40 yr) and women (>50) with diabetes or hypertension, who, in addition to their age, are at higher than average risk for cardiovascular complications during a maximal exercise test.  Since all maximal tests for men and women in these age categories must have medical supervision, the attending physician will be responsible for interpreting the ECG.  Typically, the physician is accompanied by research assistants or faculty trained to recognize arrhythmias and possible ischemic responses.  ECG will not be monitored in studies of low risk individuals and in those for which the investigator has no expertise in this procedure.

Exercise ECG will be used to determine possible ischemic responses to exercise, as well as dysrhythmias.  Since, under most circumstances, a physician is supervising a maximal test in which ECG is being monitored, the physician will communicate test results to the subject.  If an investigator is monitoring ECG without the presence of a physician, a suspected abnormal response, not including PACs or infrequent PVCs, will be criteria to terminate a test prematurely.  If this occurs, the subject will be told that the test was stopped “because your ECG response was not completely normal.  I will make a copy of this test for you and I recommend that you show it to your physician.  Since I am not a physician, I cannot answer specific questions about your test, therefore, it is best if you call your doctor to discuss this with him/her.” 

All female subjects will be asked whether they are more than 3 months pregnant; if so, they will be excluded from maximal exercise testing.

Potential Benefits

Subjects receive a summary of their results.  Measuring VO2max is a frequent request by athletes and coaches for they believe it will aid in planning and monitoring the athletes' training.  Labs that conduct such testing often charge $150-300.  In instances where an ECG is measured, it will provide the staff a better means of assessing the qualitative (rhythm) and quantitative (rate) heart function during and after exercise.

Consent Form Content (Description of the Study section)

Prior to undergoing a maximal exercise test, we will conduct a brief health screening to determine whether testing would put you at increased risk for an abnormal cardiac event such as a dangerous rhythm disturbance or a heart attack.  If you are not at increased risk, you will be asked to report to the lab well rested; we recommend that you do no high-intensity exercise for 48 hours before your scheduled test.  Also, please do not eat at least 2-3 hours before your test, but continue to drink water during this time.

For the VO2max test, you will be fitted with a mouthpiece and nose-clip.  The mouthpiece will be connected by flexible tubing to the electronic instruments, which will monitor the amount of oxygen you consume and carbon dioxide you produce.  You will be able to breathe normally through your mouth, but not through your nose.  After a 5-10 minute warm-up, we will increase the work effort every 2 minutes until you no longer feel you can continue.  Every 2 minutes during the test, we will ask you to rate your perceived exertion, on a scale of 1-10. This helps us determine when you are getting close to your maximal effort.

 (If ECG is to be monitored)

You will have specific sites on the surface of your chest prepared for electrode placement.  During the preparation process, the technician will rub several sites with a gauze pad and then cleanse the area with alcohol prior to placing individual electrode pads on the area.  This preparation process may be slightly uncomfortable.  You will keep these electrodes on your skin until the end of the exercise, or until the technician indicates to you to remove them.

Consent Form Content (Risks and Discomforts section)

You are being asked to perform high-intensity maximal exercise that may lead to physical discomforts (e.g. fatigue and nausea).  These risks associate with participating in this study may include muscle cramps, muscle strain and/or joint injury, delayed muscle soreness, lightheadedness, and fatigue.  You may feel delayed muscle soreness (24-48 hours) after exercise.  There is a risk of a cardiovascular event (approximately 1 in 12,000 people) such as a heart attack or rhythm disturbance, since the exercise will be very high intensity.  To manage possible risks, there will be at least one CPR-certified investigator present at the testing, as well as a telephone available should an emergency arise.  If at any time during the test you want to stop, you can signal as instructed and we will stop the test.  You will feel very tired at the end of the test, but should recover within a few minutes.  We recommend that when you leave the lab that you do no strenuous exercise for the rest of the day.

Compensation for Injury section (If injury is not covered by the study)

If any complications arise, we will assist you in obtaining appropriate attention. If you need treatment or hospitalization because of being in this study, you are responsible for payment of the cost for that care. If you have insurance, you may bill your insurance company.  You will have to pay any costs not covered by your insurance. San Diego State University will not pay for any care, lost wages, or provide other financial compensation [include San Diego State University Foundation if this research is funded].  However, if you feel you have a claim that you wish to file against the State [or the Foundation], please contact Graduate and Research Affairs - Division of Research Administration at (619) 594-6622 to obtain the appropriate claim forms.

Compensation for Injury section (If injury is covered by the study)

If you need any treatment or hospitalization as a result of being in this study, all reasonable and customary medical expenses above what your insurance will cover will be paid by ________________ as long as:  you have followed all of the directions of the study investigator, you have notified the investigator immediately of the injury, you have followed medical advice regarding the injury, and you have not deliberately caused the injury.

4.21.1.2  Exercise Protocol: Endurance Tests

Appropriate Applications

Endurance tests may be used to study cardiorespiratory and/or metabolic effects at various intensities of effort.  They can also be used to collect data in thermoregulatory and altitude studies and in other studies examining the effects of endurance exercise on blood concentrations of hormones, electrolytes, etc.  The exercise intensity used in a protocol is usually determined as a percent of one’s VO2max; if so, VO2max must be determined before the endurance test can be performed.  These two procedures, under almost all circumstances, are not conducted on the same day.  According to ACSM guidelines, three categories of intensity are suggested: 1) light/low (<60% VO2max); 2) moderate (60-80% VO2max); and 3) heavy/high (>80% VO2max).  However, individual investigators may propose variations of these guidelines in their own protocols.

Test Description

After selection of the desired intensity, the subject warms up for 5-10 minutes, after which the ergometer is set to the selected intensity.  For example, if the investigator selects 70% of VO2max as the intensity for a treadmill study, the speed and grade are adjusted until the subject reaches 70% of his/her VO2max.  A variation that is frequently used for cycle ergometry testing is to conduct the endurance test at a given percent of each subject’s peak or maximum power output.  For a test, the subject is asked to continue exercising either for a pre-determined time or until volitional exhaustion.  Typically, heart rate is also monitored throughout the test using a heart rate monitor that takes its signal from a transmitter strapped around the chest with an elastic band. 

Training/Supervision Required

Technicians or investigators need to be knowledgeable and trained in administering exercise tests, including the ability to conduct a pre-test health screening, and knowledge and recognition of possible signs and symptoms of cardiovascular disease.  Technicians must also be familiar with the specific ergometer they propose to use in their study.  If students are taking metabolic measures, i.e., collecting expired gases and analyzing for O2 consumption and CO2 production, they must first demonstrate this competency to the satisfaction of their faculty sponsor.  These procedures require academic preparation in exercise science courses.  Graduate students in the M.S. program in Exercise Physiology take coursework and have lab experiences to prepare them for these assessments. 

Risks

The risk of a cardiac event is lower than it would be for maximal testing, however, the exact risk is not known.  Any exercise bout may produce light-headedness, fatigue, possibly nausea, and delayed-onset muscle soreness.  These side effects are usually minimal in fit subjects.  They are also minimized by having a gradual warm-up as well as cool-down (at least 5 minutes each) and by having the subject refrain from eating for at least 2-3 hours before their test.  For treadmill testing, there is also a small risk of falling.  This risk is managed by having at least one spotter at the subject’s side.

Risk Management

Lactate threshold assessments are conducted in the Exercise Physiology Laboratory (ENS 255) and Annex Exercise Physiology Laboratory (ENS 111) at SDSU and in the Fitness Lab at 9245 Sky Park Court.  All test personnel are required to have current CPR certification and trained in emergency procedures for the particular lab.  A telephone is located within a few feet of the ergometers.  Individuals with probable cardiovascular disease, as screened with the PAR-Q, are not tested at SDSU or at the Sky Park lab.

The mouthpiece and valves fall into the semi-critical device category.  This device will come into contact with mucus membranes, but will not penetrate body surface.  High-level disinfection using liquid glutaraldehyde disinfectants (e.g. Cidex) is acceptable according CDC recommendations.  We use EPA-registered sterlants for this purpose in our laboratory. 

Potential Benefits

There may be no direct benefits to subjects.  However, depending on the specific protocol, subjects may receive the results of their testing, which could possibly benefit them in their training.

Consent Form Content (Description of the Study section)

Prior to undergoing the exercise protocol, we will conduct a brief health screening to determine whether testing you would put you at risk for an abnormal cardiac event such as a dangerous rhythm disturbance or a heart attack.  If you are not at risk, you will be asked to report to the lab well rested; we recommend that you do no high-intensity exercise for 48 hours before your scheduled test.  Also, please do not eat at least 2-3 hours before your test, but continue to drink water during this time.

For this endurance test, you will run (walk) on the treadmill (or cycle ergometer) at a workload that is equal to (XX) percent of your VO2max.  We want you to continue to exercise as long as you can (or for a specified time period).

Consent Form Content (Risks and Risks Management section)

(For needle sticks or venipuncture)  Procedures that require blood samples to be collected have the risk of soreness, bruising and/or swelling at the collection site.  Prior to each finger stick, the area will be cleaned with an alcohol swab.  After the stick, you will be instructed to maintain slight pressure on the area to minimize additional bleeding. 

(If high intensity exercise is included) If you are asked to perform high-intensity exercise you may experience physical discomforts that may include muscle cramps, muscle strain and/or joint injury, delayed muscle soreness, lightheadedness, and fatigue. It is likely that you will feel significant delayed muscle soreness (24-48 hours) after.  There is also a risk of a cardiovascular event (less than that associated with maximal testing of 1 in 12,000 people) such as a heart attack or rhythm disturbance when participating in high intensity exercise. To manage possible risks, there will be at least one CPR-certified investigator present at the testing, as well as a cellular phone available should an emergency arise.

4.21.1.3 Exercise Protocol: Hydrostatic Weighing

Appropriate Applications 

This test is used to determine body density and estimate body composition.

Test Description

This procedure utilizes the difference in densities of the fat and non-fat masses to determine overall body density, which can be used to estimate body fat percent.  Briefly, the subject is placed in a water tank and weighed after maximally exhaling.  Differences in the dry and underwater weights are used to calculate body density.  However, an allowance must be made for residual lung volume–the air that remains in the lungs after a maximal exhalation–as this air increases a subject's buoyancy.  Residual lung volume can be either measured or estimated.  In our laboratory, residual lung volume is usually indirectly measured using an oxygen-dilution technique (Wilmore et al., 1980).  A 5-L Douglas re-breathing bag fitted with a two-way breathing valve is flushed and filled with 100% oxygen.  While in a seated position and fitted with the mouthpiece on the Douglass bag and a nose clip, the subject takes several normal breaths of ambient air.  Afterwards, the subject performs a maximal inhalation followed by a maximal exhalation and briefly holds his/her breath at the end of the exhalation.  At this point, the mouthpiece valve is turned so that the subject begins rebreathing from the 100% oxygen.  The subject takes 6-8 deep breaths after which the valve is closed and the subject removed from the Douglas bag.  At least two, but sometimes three trials are performed with several minutes between trials. 

The most accurate estimate of body composition by hydrostatic weighing requires residual lung volume to be measured.  There are, however, situations because of expediency or lack of equipment in which residual lung volume is estimated.  One way to estimate residual lung volume is from published tables that are based on age and weight.  Another method is to estimate residual volume from the measured vital capacity.  In this procedure, a seated subject, while fitted with a nose clip and connected to a spirometer, performs a maximal inhalation followed by a maximal exhalation.  Vital capacity is the volume of the maximal exhalation from which residual lung volume is estimated based on gender, as a percentage of the vital capacity. 

After having measured or estimated residual lung volume, the subject's dry weight is measured and then, wearing a swimming suit or running shorts, the subject climbs into the underwater weighing tank and sits in a seat that hangs from a force load-cell.  The procedure involves the subject performing a maximal exhalation and slowly leaning forward in the chair until the top of his/her head is under water.  After the underwater weight stabilizes (5-8 seconds), the subject is instructed, though yelling or pounding on the side of the tank, to return to an upright position.  During a weighing, the subject is always free to stand up or return to the upright position.  Four to eight trials are usually performed.

The non-skid steps up to the top of the tank where the subject enters are equipped with a handrail, and after climbing the steps, the subject climbs down a ladder into the water.  Depth of the water is approximately 54 inches, which is maintained between 30 and 34 °C.  While seated, the subject faces a clear plexiglas side to minimize feelings of claustrophobia.  After each testing session, the water is drained and the tank allowed to dry

Training/Supervision Needed

All test personnel are required to have current CPR certification and trained in emergency procedures for the particular lab.  A telephone is located within 30 feet of the underwater weighing tank. 

Risks

Other than risks of falling while getting into or out of the underwater weighing tank, there are no physical risks associated with this protocol.  Subjects not comfortable in water or in putting their head underwater may experience slight anxiety during the underwater weighing.

Risk Management

Subjects are encouraged to be careful while getting into or out of the underwater weighing tank.  For individuals who experience anxiety during the underwater weighing, the test administrator will go more slowly with the subject and encourage him/her to stand up in the water should the anxiety become too strong.

The mouthpiece and valves used for the measure of residual volume fall into the semi-critical device category.  This device will come into contact with mucus membranes, but will not penetrate body surface.  High-level disinfection using liquid glutaraldehyde disinfectants (e.g. Cidex) is acceptable according CDC recommendations.  We use EPA-registered sterilants for this purpose in our laboratory. 

Potential Benefits 

The subject obtains his/her body composition, which is an important component of overall personal fitness.

Consent Content  (Description of the Study section)

There are two parts to this procedure.  First, we will measure your residual volume, which is the amount of air that remains in your lungs after performing a maximal exhalation.  Afterwards, we'll weigh you underwater.  Together, this information will be used to estimate your body fat percentage. 

To measure your residual volume, you will perform 2-3 trials of breathing in and out of bag containing 100% oxygen.  In a seated position and wearing a nose clip, you'll be connected to a breathing mouthpiece connected to the bag of oxygen.  First, you'll take several normal breaths from the outside air and then perform a maximal exhalation.  At that time, a valve will be turned which will direct your breathing from the bag of oxygen.  You'll take 6-8 deep breaths after which you'll be removed from the valve.  After a couple of minutes, you'll repeat this 1-2 times. 

After you change into your bathing suit, you'll climb into the underwater weighing tank.  Briefly, you'll sit quietly on the hanging seat in the tank, and when instructed, perform a maximal exhalation and then slowly lean forward just to the point that your head is completely underwater.  You'll remain motionless for 5-8 seconds until instructed by the technician to come back to the surface.  It's very important that you blow all of the air out of your lungs and to remain as motionless as possible while underwater.  Should you develop any overpowering anxiety, you can always stand up before being instructed, as the depth of the water is only about 4½ feet.  We'll do at least four, but as many as eight, underwater weighings in all.  Afterwards, you’ll climb out of the tank, dry off and change back into your street clothes.

4.21.1.4 Exercise Protocol: Venipuncture

Appropriate Applications 

In various exercise studies, researchers may want to assess blood enzymes, blood lipids, hemoglobin, hormones, and serum parameters including glucose, electrolytes, or blood proteins that may be altered with physical exertion.  The venipuncture may be taken prior to, during (with the subject stopped) and after exercise.  For some studies that examine the graded effects of exercise on certain blood parameters, up to four blood samples may be taken via venipuncture (from different sites). 

Test Description

Venipuncture (also known as phlebotomy) refers to a procedure in which venous blood is drawn into a small tube via needle insertion and aspiration.  Steps taken by the phlebotomist to perform this procedure are to: wear safety (e.g. latex) gloves for reducing the likelihood of infection; position the subject in a seated position (unless blood is being taken from a subject standing on a treadmill stopped in the middle of an exercise protocol); clean the area (usually the antecubital fossa area) with alcohol and allow to air-dry; place an elastic band (tourniquet) around the upper arm to distend the veins; isolate the vein and insert the needle with a Vacutainer tube for aspiration.  Upon removal of the needle, sterile gauze will be placed over the insertion site secured by tape.  The subject will be encouraged to apply pressure to the site for several minutes to minimize bruising.  The needle will be discarded into a hazardous waste (Sharps) container, which will be properly disposed.

Training/Supervision Needed

Only staff who are California-certified phlebotomists are allowed to perform blood draws.  All certified phlebotomists will have had adequate experience to perform the blood draw without supervisory assistance; hence, no supervision will be necessary to perform a venipuncture.

Risks

Under normal conditions, there are minimal risks to the subject when performing venipuncture.  These risks include: bruising; perforation of the vein leading to hematoma under skin; light-headedness or dizziness due to fear of needles; and infection.

Risk Management

Whenever blood is drawn, there is a small risk of bruising.  Through this procedure, the risk for perforation of the vein is minimized.  To minimize the risk of light-headedness or dizziness, each subject will have blood drawn in a seated position.  Although infection is a risk with venipuncture, this is minimized by use of alcohol to cleanse the area prior to the blood draw, as well as the use safety (latex) gloves by the phlebotomist, in accordance with the bloodborne pathogens standard of OSHA.

Potential Benefits

From the blood analyses, we will be able to better understand the acute and/or chronic effects of exercise on hematological, enzymatic, and hormonal changes.  This information will aid in our understanding of exercise programs that can favorably modify, or yield deleterious effects to specific blood parameters.

Consent Content (Description of the Study section)

You will be asked to submit to a (or multiple) venous blood draw(s). All blood draws will be performed by certified technicians and follow established standard procedures. Usually, the amount of a single blood drawn is about 5-7 ml or ~1 tablespoon.

Consent Content (Risks and Discomforts section)

The risk in blood sampling is minimal, although there is the risk of soreness, bruising, and/or swelling at the collection site.  Risks will be minimized by employing a trained and certified technician who will follow standard procedures for safely drawing blood.

4.21.1.5 Exercise Protocol: Bone Mineral Density (DEXA Scan)

Applications

Dual-energy x-ray absorptiometry (DXA) measurements are used to measure bone mineral density (BMD) and body composition.  The National Osteoporosis Foundation recommends bone scans for the following persons:

All postmenopausal women under age 65 who have one or more additional risk factors for osteoporotic fracture (besides menopause);

All women aged 65 and older regardless of additional risk factors;

Postmenopausal women who present with fractures (to confirm diagnosis and determine disease severity);

Women who are considering therapy for osteoporosis, if BMD testing would facilitate the decision; and

Women who have been on hormone replacement therapy for prolonged periods.

Additional populations that may be studied are athletes and children, as well as men.  In addition, studies of body composition use the DXA technique as the new “gold standard” for determining lean tissue and fat mass.

Exclusion/Inclusion Criteria.  Criteria specific to each new protocol will be provided by the investigator.  The only general exclusion criterion is that pregnant women will not be scanned. 

Test Description

Bone mineral density (BMD, will be assessed by dual-energy x-ray absorptiometry (DXA) using a Lunar DPX-NT densitometer (Lunar/GE Corp).  All scans will be conducted in the fitness lab at the Center for Behavioral Epidemiology (C-BEACH), 9245 Sky Park Court, San Diego, CA.  The scan sites most often assessed include the spine (L1-L4), hip, and total body.  The DXA total body scans will be used to determine both total body BMD as well as body composition and regional fat distribution.  The average scan time for each of these is approximately 3, 4, and 10 minutes for the spine, hip, and total body, respectively.  The total time required for subject positioning and scanning is approximately 5, 8, and 12 minutes for the spine, hip, and total body, respectively.  A typical appointment, therefore, requires approximately 30 minutes per subject for all 3 scans, or approximately 20 minutes for spine and hip only.

Quality assurance (QA) tests will be performed each morning of use.  QA will be conducted using a standard with tissue-equivalent material with three bone-simulating chambers of known bone mineral content.  In vivo BMD precision is 0.6-1.2% for the spine, 0.6-1.7% for the femoral neck, 0.6-0.8% for total-body mineral, and less than 1.5% for total body soft tissue mass (Mazess, Br J Radiology 70:109-110, 1997).

Subjects are instructed, prior to the day of their scan, to dress with clothing free of any metal and not to wear jewelry.  Women are encouraged to wear a halter-top or something similar.  If subjects arrive with any metal on their clothing, they are asked to change into shorts and t-shirt.  A supply of these are kept in the fitness lab and laundered as needed.  The subject is shown the DXA machine and told that the scan arm will move above them while he/she lies on the table.  They are instructed to lie still and not to talk while the machine is scanning.  The following is a description of how the subject is positioned for each of the three scans:

Spine.  The subject lies supine with his/her hands on their shoulders (to keep the arms away from the lumbar spine).  The technician first straightens his/her body by gently pulling from the ankles (this is not done with older subjects or those who, when asked before proceeding, report back pain).  The scan arm is then brought to the start position.  The technician then asks the subject to bend his/her knees while a box is place beneath the lower legs.  This is done to insure that the spine is positioned correctly and kept in contact with the table.  The technician then locates the anatomical site for starting the scan, which is vertically aligned with the navel and 3-5 cm below it.  Prior to touching the subject, the technician tells him/her to point to their navel.  This is done to minimize the amount of palpation required by the technician.  The subject is then asked to remain still while the machine scans.

Hip.  The subject lies supine with his/her arms crossed over their chest.  The feet are strapped to a plastic device such that the hip joints are medially rotated.  The technician then locates the anatomical site for starting the scan, which is vertically aligned with the mid-thigh and approximately 7 inches below the anterior, superior iliac crest.  The subject is then asked to remain still while the machine scans.

Total Body. The subject lies supine with his/her arms by their sides.  Velcro straps are secured around the knees and ankles to hold the legs together.  The subject is then asked to remain still while the machine scans.

Females who are minors will be accompanied by a parent or another adult when scanned by a male technician.  The parent will sit just outside the door to the DXA room, but within clear view of the subject.  California law does not permit anyone other than the technician and patient in the room during scanning.

Training/Supervision Needed

All scans will be conducted by experienced technicians certified by the state of California.  California law requires all DXA facilities to be supervised by an M.D.  Jeffrey Dysart, M.D. in Family Practice, will serve as the C-BEACH medical advisor and licentiate.  He has ultimate responsibility for insuring safe and effective procedures regarding bone densitometry testing.  He is available to assist investigators in interpreting scans, should this be requested.  He is not required to be present during the scanning procedures.  Technicians certified by the state of California will conduct all preliminary analyses of scans, unless the Principal Investigator of a particular project indicates that he/she wants to receive unanalyzed data.  Some studies may have a designated reader at another site, but for analyses done at C-BEACH, any abnormal or questionable scans will be reviewed by both Dr Dysart and the technician, with Dr. Dysart making the final interpretation.

Risks

Skin entrance dose of radiation is approximately 20 µSv for a spine and hip scan, and 0.2 µSv for total body.  In practical terms, this is equivalent to the amount of radiation to which one is exposed during a cross-country airplane flight.  Since the long-term effects of exposure to a fetus are not known, pregnant women will not be scanned.  There are no other known risks associated with this procedure.

Risk Management

Only experienced and certified technicians are permitted to conduct scans.  Given the extremely low dose of radiation, the benefits far outweigh the risks for any population tested.  Young adults will have a baseline report for future comparison.  Menopausal women and older adults will have objective data regarding their risk for osteoporosis, thus allowing them to discuss with their physicians possible preventive treatment.  Since most insurance policies do not cover routine osteoporosis screening for persons younger than 65 years of age, participation in a research project in which BMD is assessed provides the participant with information that would otherwise cost between $150-300.  For studies involving female subjects, the investigator will include relevant screening questions (see below) as part of the consent content.

Screening for Pregnancy. To insure that a pregnant woman is not scanned, a female will be scheduled for testing within 14 days of her last period.  By including the following question in the screening process, relevant information can be obtained and used for scheduling without asking intrusive questions such as whether the subject is using birth control or whether she is sexually active.

Are you having menstrual cycles?  Yes                  No                 

If yes, what is the date of the first day of your last period?  __________

If you are in menopause, when did your periods stop completely?  ____________

Are you pregnant, or could you possibly be pregnant?  Yes                         No                 

The use of a pregnancy test is also an option for screening purposes.

Potential Benefits

The primary benefit is for women, particularly postmenopausal women, to assess and monitor bone mineral density and their risk of osteoporosis.  However, testing may also benefit males who are at risk.  Moreover, testing can detect the presence of fractures and determine the severity of osteoporosis.

Confidentiality of Data and Room Security

When not in use, the room in which the DXA is located is kept locked.  Other than Drs. Hovell and Nichols and the C-BEACH administrative assistant, only persons trained in DXA operation have keys to the room.  Data collected each day are removed from the hard drive and stored on diskettes, which are kept in a locked file in each investigator’s office.  Data transferred to a database for statistical analysis are coded; no identifying information will be used in data analysis.

Consent Content (Description of the Study section)

Dual-energy x-ray absorptiometry (DXA) measurements are used to measure bone mineral density (BMD) and body composition.  For the DXA measurement, it is necessary to dress with clothing free of any metal and not to wear jewelry.  We recommend that female participants wear a halter top or swim suit top, or something similar.  If you forget and arrive with any metal on your clothing, we will have spare pairs of sweat pants and several t-shirts that you can wear while being scanned.

The DXA machine consists of a table with a scan arm that moves over your body while you lie on the table with your arms by your sides and your knees and ankles held lightly together with Velcro straps.  You will be asked to lie still and not talk while the machine is scanning. The entire procedure takes approximately 12 minutes, while actual scan time is about 8 minutes.

Consent Content (Risks and Discomforts section)

The risk of harm from radiation with DXA machines is extremely small.  The actual amount of radiation emitted for a total body scan is 0.2 uSv, which, in practical terms, is much less than the amount received during a cross-country airplane trip.  However, the long-term effects of exposure to a fetus are not known, therefore, pregnant women are not scanned.  For females: To ensure that you are not pregnant, we will ask you to schedule your appointment within two weeks of your last period or to use a pregnancy test to confirm that you are not pregnant.

Parental consent text if the subject is a minor female child: The assent form explicitly states that if your daughter is pregnant or could possibly be pregnant because she is having sexual intercourse and not using birth control procedures, she cannot participate.  To avoid embarrassing your child we have indicated on the assent form that she should simply tell us she does not want to participate, without giving us a reason. If your daughter qualifies for the study we will ask her to tell us the date of her last menstrual period (if she has begun menstruating).  We will then schedule her for her scan and other measurements within 2 weeks of her last period, thus insuring that she could not possibly be pregnant when she is scanned.

Consent Content (Confidentiality of Data and Room Security section)

When not in use, the room in which the DXA is located is kept locked.  Other than Drs. Hovell and Nichols and the C-BEACH administrative assistant, only persons trained in DXA operation have keys to the room.  Data collected each day are removed from the hard drive and stored on diskettes, which are kept in a locked file in each investigator’s office.  Data transferred to a database for statistical analysis are coded; no identifying information will be used in data analysis.

4.21.1.6 Exercise Protocol: Lactate Threshold

Appropriate Applications

There are multiple reasons why the lactate threshold might want to be determined.  Identification of the lactate threshold is the best predictor of performance over a range of endurance distances.  Furthermore, training causes a shift in the exercise intensity at which the lactate threshold occurs, thus this test can be used to monitor training /detraining progression.  In addition, laboratory protocols may use an exercise intensity based that is relative to above or below the lactate threshold. 

Test Description

Briefly, the subject will perform a series of incremental exercise bouts during which ~50 mL of blood from a finger stick is analyzed for lactate concentration at the end of each bout.  As exercise intensity increases, blood lactate concentration increases in a curvilinear fashion, and the intent of this test is to identify the workload at which blood lactate concentration begins rising exponentially.  A brief (5-10 minutes) warm-up and cool-down are performed before and after a test.  The initial bout begins at a very low intensity, which progresses to a near-maximal intensity.  Each bout is usually 3-5 minutes in length, and depending upon the exercise mode, may be continuous or discontinuous.  During treadmill testing, subjects must be stopped in order to sample blood (a discontinuous protocol); with cycling protocols, however, blood can be sampled while a subject is exercising, thus the bouts could be continuous.  The number of bouts varies, but usually 5-8 bouts are performed. 

Blood is sampled from a finger stick that has been cleaned with an alcohol swab.  After allowing the finger to dry, a fingertip is lanced and the blood collected in one or two 50 mL heparin-coated capillary tubes.  The blood is transferred via a pipette to a lactate analyzer for determination of lactate concentration.  Sterile gauze is applied to the fingertip, and the subject instructed to maintain pressure for several minutes.  As multiple samples are required for this test, for subsequent samples, the fingertip is squeezed to determine whether blood can still be sampled from the same stick, and if so, reduces the number of finger sticks that must be performed.  Otherwise, additional finger sticks are performed on another site of the same finger or a different finger depending upon the subject's preferences.  Total blood drawn during this test is less than 0.5 mL

Training/Supervision Needed

Graduate students in the M.S. program in Exercise Physiology have taken coursework and had lab experiences to prepare them for these assessments. 

Risks

The risk of a cardiac event is lower than it would be for maximal testing, however, the exact risk is not known.  Any exercise bout may produce light-headedness, fatigue, possibly nausea, and delayed-onset muscle soreness.  These side effects are usually minimized in fit subjects.  They are also minimized by having a gradual warm-up as well as cool-down (at least 5 minutes each) and by having the subject refrain from eating for at least 2-3 hours before their test.

Under normal conditions, there are minimal risks to the subject when performing finger sticks that include:  bruising; light-headedness or dizziness due to fear of needles; and infection.

Risk Management

Lactate threshold assessments are conducted in the Exercise Physiology Laboratory (ENS 255) and Annex Exercise Physiology Laboratory (ENS 111) at SDSU and in the Fitness Lab at 9245 Sky Park Court.  Subjects who meet specific study criteria and who do not report cardiovascular disease or its symptomology, as screened with the Physical Activity Readiness Questionnaire (PAR-Q), will undergo an incremental exercise test on a selected ergometer (treadmill, cycle, rowing machine, hand-crank cycle). Mild exercise is used to warm-up and cool-down before and after exercise, which minimizes the risk of injury or a cardiac event from the exercise. 

Whenever blood is drawn, there is a small risk of bruising.  Although infection is a risk with finger sticks, this is minimized by use of alcohol to cleanse the area for the blood draw.  Latex gloves are worn by the technician at all times, and all contaminated materials are deposited in a biohazard container, in accordance with the bloodborne pathogens standard of OSHA.

Potential Benefits

If the intent of the test were to determine fitness level or predict endurance performance, this test would provide extremely valuable information to the subject.  However, if the test were used to determine exercise intensity of another exercise protocol, results of this test would likely be of little interest to the subject.

Consent Content (Description of the Study section)

You will first perform a 5-minute standardized warm-up at a low intensity.  Afterwards, you will perform several bouts of (treadmill or cycling) exercise, which increase in intensity.  Each intensity will be 3-5 minutes in length; the entire test will contain five to eight stages.  After each exercise bout, a small amount of blood will be sampled from a finger stick.  Prior to the finger stick, the fingertip will be cleaned with an alcohol swab.  The amount of blood drawn will be equivalent to only a few drops, and the total volume of blood taken will be less than a teaspoon. 

Consent Content (Risks and Risks Management section)

Procedures that require blood samples to be collected have the risk of soreness, bruising and/or swelling at the collection site.  Prior to each finger stick, the area will be cleaned with an alcohol swab.  After the stick, you will be instructed to maintain slight pressure on the area to minimize additional bleeding.

4.21.1.7 Exercise Protocol: Exercise in the Heat

Appropriate Applications

Testing of subjects in a warm, humid environment can provide insight into the acute and chronic effects of exercising in the heat.  Studies are performed to investigate the acute effects of exercise in the heat on the cardiovascular, metabolic, or thermoregulatory systems as well as the effects of acclimation on these systems to extreme environmental conditions. 

Test Description

Subjects may exercise in the environmental chamber in the SDSU exercise physiology laboratory (ENS 255) for up to 2 hours per day.  In heat acclimation studies, subjects may perform up to 10 days of exercise in the heated chamber.  Air temperature will range from 32 to 43 ºC (90 to 110 ºF) at a relative humidity of 30-80%.  During a test, heart rate, sweat rate, skin blood flow, sweat gland density, and core body temperature may be followed.  Heart rate is measured using a heart rate monitor received from a transmitter strapped around the chest.  Sweat rate is determined by pre- and post-exercise body weights.  Skin blood flow is estimated using either a laser Doppler technique or venous-occlusion plesmography.  A laser Doppler probe is positioned on a forearm from which the signal is converted to units of blood flow.  Venous-occlusion plesmography estimates blood flow from the tension measured from a strain gauge positioned around the forearm while applying a brood pressure cuff to the upper arm.  Sweat gland density is calculated by applying iodine-impregnated paper to the skin.  Core body temperature can be measured in a variety of ways: The three most commonly used methods in our laboratory are tympanic, rectal, and esophageal measurements.  Tympanic temperatures are measured with an infrared sensor inserted into the ear, although heat in the chamber may interfere with valid measurement of tympanic temperatures.  When tympanic temperatures are performed, though, the design of the sensor prevents it from being inserted too far and injuring the ear.  Rectal temperature is measured from a sanitized temperature probe inserted by the subject approximately 10 cm past the anal sphincter.  Esophageal temperature is measured using a single-use temperature probe inserted by the subject through a nostril to a length approximately 25% of the subject's height. 

Training/Supervision Needed

Graduate students in the M.S. program in Exercise Physiology have taken coursework and had lab experiences to prepare them for these assessments.  These individuals will have been prepared for giving instructions to subjects for inserting probes. 

Risks

The rectal or esophageal probe may produce mild discomfort while inserted.  The risk of a cardiac event from exercising n the heat is lower than it would be for maximal testing, however, the exact risk is not known.  Any exercise bout may produce light-headedness, fatigue, possibly nausea, and delayed-onset muscle soreness.  These side effects are usually minimized in fit subjects.  They are also minimized by having a gradual warm-up as well as cool-down (at least 5 minutes each) and by having the subject refrain from eating for at least 2-3 hours before their test.

Risk Management

Core body temperature will be monitored during the exercise test.  If a subject's core temperature exceeds 39.5 ºC, the test will be terminated and the subject removed from the environmental chamber.  Only single-use probes will be used to measure esophageal temperature. 

A negative pregnancy test is required of all female subjects before beginning an exercise experiment in the heat.  SDSU students may take a urine pregnancy test at the SDSU Student Health Center; she will need to provide the investigator with a copy of the test results.  If the subject is not a SDSU student, we will provide a urine pregnancy test that will be administered and read in the lab.

Potential Benefits

In heat acclimation studies, subjects may be able to exercise longer and with less fatigue and discomfort after becoming acclimated.

Consent Content (Description of the Study section)

You are being asked to exercise in the environmental chamber, which will be set to XX ºF and a relative humidity of  XX%, for XX minutes (and for XX consecutive days).  In order to monitor that you are not becoming overly heated, your tympanic (or rectal or esophageal) temperature will be followed.  Tympanic temperature is measured by inserted a temperature probe in the ear and holding it for a few seconds until the temperature is registered.  (Rectal temperature is measured with a probe inserted in your rectum.  You will do this yourself in the privacy of the changing room by inserting the probe to the mark indicated on the cable and/or esophageal temperature is measured with a probe inserted through a nostril into the esophagus to the point indicated on the cable.)  Before and after the exercise, your weight will be recorded.  To measure blood flow, a laser Doppler will be attached to your forearm and/or a strain gauge sensing devise will be placed around your forearm and a blood pressure cuff around the upper arm. 

Consent Content (Risks and Discomforts section)

You may experience discomfort and briefly gag when you insert the esophageal probe.  You may also experience mild irritation of the nose and throat both during and after the experiment.  Should your temperature exceed 39.5 ºC, we will terminate the test and remove you from the chamber.  If you feel uncomfortable during any part of this study, you may choose to terminate your participation.

4.21.1.8  Sweat Rate Via Pilocarpine Iontophoresis (consent content only)

Consent Content (Description of the Study section)

We will measure your forearm (or other body part) sweat rate using a Macroduct Sweat Collection System. This system works by stimulating sweat production in a small area (about 3 inches) of your forearm by using a small, nonshocking electrical current.  You may feel a mild tingling sensation, but nothing more. Many individuals report that they cannot feel anything. A total of approximately 10 drops of sweat will be collected from your forearm using a collection pad. The entire procedure, including prep time, takes about 30 minutes. 

4.21.2  Genetic Testing

If the study involves genetic testing, address issues pertaining to confidentiality of information collected. State whether or not the genetic information collected about the subject could pose a risk to them (e.g. denial of health insurance because of known predisposition to illness). State whether other genes will be studied in the DNA that may be shown at some point in the future to be related to illness. Describe how blood samples will be coded and stored. Explain whether or not any of the laboratory results will be made available to subjects, and whether the results will be added the subject’s medical record.

State whether the specimens collected the DNA obtained from that specimen will be used in additional research to be conducted and whether or not the DNA will have significant therapeutic or commercial value.  To protect subject privacy, all information that links the subject’s specimens and DNA to his/her identity must be removed prior to use in any research conducted outside of this specific study so that the sample that provided cannot be traced back to the individual subject. 

4.21.3  Non-FDA Approved Products

Address safety and efficacy concerns for studies that involve non-FDA regulated botanical products. Provide evidence to suggest that the product being tested is safe for use with humans at the dose level planned for use in this study.

4.21.4  Screening for Pregnancy

To insure that a pregnant woman is not included in research that may be harmful to her or her fetus, include procedures to screen for pregnancy.  The IRB has approved the following screening procedures:  Prior to testing, ask the female subject the start date or her last menstrual cycle.  If the participant has not menstruated within the last 14 days, the participant will need to schedule testing to occur within 14 days of the start of her next cycle.  The research investigator can make a urine pregnancy test kit available to participants to use as confirmation of pregnancy status.  If the pregnancy test indicates a negative result for pregnancy, the test may be conducted. If a positive pregnancy result is indicated, the subject is not eligible to participate in testing.

4.21.5  Internet Research

As Internet research has become more and more common, guidance to assist researchers in developing research protocols in compliance with the ethical standards applied to standard survey and observational research is needed.   Research conducted in the virtual world of the Internet is subject to the same IRB review process and human subjects protections as research conducted in the physical world.  The main concerns of the IRB for protecting subjects involved in research on the Internet are informed consent, protection of privacy and confidentiality.  These concerns pertain to survey and observational research conducted with human participants on the Internet.

4.21.5.1  Informed Consent

The informed consent process is reviewed by the IRB to determine whether appropriate information regarding the study (e.g., study purpose, participant involvement, risks, benefits, confidentiality) is provided to the prospective subjects.

Survey Research

Similar guidelines to obtaining consent for exempt research apply in anonymous, Internet survey research. A statement containing the following information to obtain consent for survey research conducted on the Internet will be reviewed by IRB:

Describe why the study is being conducted.

State who is being recruited and why they have been chosen.

Explain what each participant will be asked to do and estimate how long it will take to complete the task.

Emphasize that participation is voluntary.

Clarify whether participant's information will be anonymous (no identifiers, including on-line pseudonyms) or confidential. If confidential, indicate whether any information linked to the individual's identity (in the physical or virtual world) will be used.

Describe incentives/compensation offered or costs that may be incurred.

Explain added risks associated with privacy violations and strategies developed to reduce the risk of privacy loss or breech of confidentiality.

Provide contact information including the name of the investigator, department phone number and E-mail address for inquiries. Include the IRB telephone number and E-mail address (IRB@mail.sdsu.edu) for questions related to their rights as a participant in research.

Observational Research

Observational research conducted on the Internet is subject to IRB review. Examples of observational research include monitoring chat room discussions, tracking frequency of Internet use or following consumer patterns of behavior on the Internet. For Internet observational research, the IRB recommends the following procedures to obtain consent:

Prior to initiating observation or data collection from a particular site, the investigator will contact the domain host, webmaster or equivalent to provide a description of the study and request that information about the study be presented to the community.  Should the host agree, study information is presented to the community for discussion.  If the community indicates agreement to the host, the researcher is notified of permission to access the site.

New users that join once the research has begun must be informed of the research in the first welcome message from the domain host, webmaster or equivalent.

The user/prospective subject should have an opportunity to refuse participation in the observational research study.

NOTE: Deception in observational research, where the investigator identity is concealed or falsified on the Internet will be reviewed by the IRB on a case-by-case basis.

4.21.5.2  Privacy & Confidentiality

Survey Research

Confidentiality and privacy are of particular importance for Internet research, given that information may be stored and accessed for indefinite periods of time.  The investigator must assure the Committee that data collected will only be accessible to the investigator.

If there are plans to collect data via the Internet, efforts to enhance participant privacy and reduce risks associated with a breech to confidentiality of subject data must be considered.  Within the protocol, address the following issues as they pertain to data collection and submission procedures utilizing the Internet.

Privacy/Access. Describe procedures planned to protect participant identity when entering and submitting data via the Internet. For example, will the subject have a user name and/or password to gain access to the study site?  If so, develop instructions for the participant to use when creating a user name or password that enhances protection of her privacy (e.g., not using own name, not sharing password, etc.). Will data be transmitted in encrypted format? In an anonymous survey, will a name-blind survey URL be assigned to each individual survey to guarantee privacy?

Confidentiality of Data. Develop procedures to advise a participant on how to prevent another computer user from gaining access to his/her data. This concern focuses on accessing a computer for data entry that is shared with others (e.g. form autocomplete feature, Password Saving feature).  Caution the participant to finish the survey in one setting and to shut down the computer after the assessment is completed.

Secure Data Storage. Incorporate procedures to not include the participant’s name or identifiers within the database. Develop a coding scheme to protect subject privacy and confidentiality of data. Describe how/whether data will be backed-up and kept in a secure location, how long will it be stored, who will have access to the data collected.

Describe systems in place to prevent unauthorized persons (hackers) from accessing the database. For highly sensitive topics, IRB recommends that the subject have the option of printing out a blank copy of the survey and mailing it back to the investigator.

Observational Research

Investigators conducting observational research studies on the Internet must consider the perception that its members have regarding the privacy and confidentiality of the information that they disclose.  The investigator must also abide by rules that govern the on-line community regarding disclosure of information outside the realm of the group.  The investigator must consider the degree to which publication of information disclosed on the website could place subjects at risk. Given the search capabilities of the Internet, even direct, anonymous quotes from subjects could be linked back to the subject with a verbatim search of that direct quote.  Investigators must ensure the Committee that all possible precautions have been taken to ensure subject privacy and confidentiality.

These guidelines are evolving as Internet research becomes more prevalent.  Each research study is unique and poses different ethical issues and challenges for human subjects protections. Although Internet research may offer great benefit to science, it is imperative that human participants in these studies are adequately informed of the research and protected from associated risks.


5.0  Informed Consent Guidance

5.1  Consent Purpose

The Office for Human Research Protections (OHRP) states that “informed consent is one of the primary requirements underpinning research with human subjects; it reflects the basic principle of respect for persons."  Informed consent is the knowing consent of an individual or his/her legally authorized representative, which is obtained without undue inducement or element of force or coercion.  Obtaining informed consent does not end with a signature on a piece of paper.  It is a process in which the subject receives enough information about a study to make a decision about participation in the research. The subject should have up-to-date information about the requirements of the study during all phases of participation. The process involves reading, understanding and signing an informed consent document as well as discussing the details of study participation with a knowledgeable member of the research team.

5.2  Consent Process and Procedures

The following procedures should occur during the informed consent process (45 CFR 46.116):

The prospective subject is given adequate information to make an informed decision about participating in the proposed study.

The nature and expectations of the research including risks and benefits is explained to the subject.

The study is presented in a language that is clear and understandable.

The subject receives answers to questions that they may have about the study.

The study is explained in an appropriate setting and with enough time conducive to good decision-making. 

The prospective subject comprehends the information and can make a choice about whether they want to participate.

The prospective subject understands that he/she retains the right to refuse or withdraw from the study at any time without penalty.

The prospective subject and/or the parent or guardian is given copies of the approved consent form(s). 

The subject (or the parent/guardian when relevant) is provided with a copy of the Research Participant’s Bill of Rights to sign when the research involves medical experimentation.

Additionally, the investigator must retain the signed copies of the consent document and the Research Participant’s Bill of Rights (when applicable) for three years.

5.3  Alternative Consent Procedures (45 CFR 46.116 (6c))

The IRB may approve a consent procedure that does not include or changes the basic consent requirements or even waive the requirement to obtain informed consent when the following applies and can be documented:

(1) the research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs; and

(2) the research could not practicably be carried out without the waiver or alteration.

The IRB may also approve a consent procedure, which does not include or alters the basic consent requirements or even waive the requirement to obtain informed consent when the following applies and can be documented:

(1) the research involves no more than minimal risk to the subjects;

(2) the waiver or alteration will not adversely affect the rights and welfare of the subjects;

(3) the research could not practicably be carried out without the waiver or alteration;

Please note: The regulations referenced do not preempt any applicable Federal, State, or local laws which require additional information to be disclosed in order for informed consent to be legally effective.

5.4  Components of a Consent Form

The following information must be included in an informed consent document (45 CFR 46.116(a,b)):

Include a statement that the subject is being asked to participate in a research study.

Provide the name and degrees of all investigators involved in the study. Indicate the department and institution with which the investigator(s) is affiliated. If the investigator is a student, include the name of the person supervising the research.

Provide an explanation of what the study is designed to determine or assess using language that is clear to the target audience.

State the number of subjects being recruited for this study and the eligibility criteria used to identify prospective participants.

Describe the procedures that the subject will be asked to follow.

Indicate the location where the research will be conducted and the expected duration of the subject's participation. Be specific regarding the amount of time study participation will require of the subjects.

Provide a description of any risks or discomforts the subjects might encounter as a result of participation.

Describe the provisions made to address these risks or discomforts.

Include a statement to describe potential benefits to science and society that may result from this research. Provide a description of any benefits the subjects can expect as a result of participating in the study.

Describe the extent, if any, to which confidentiality of records identifying the subject will be maintained (include the procedures for using and storing data and include who will have access to the data).

If an incentive is offered to participants, describe what is being offered and what is required of the subject to obtain the incentive. If the subject is offered a payment, state the amount, formula for proration should the subject or investigator choose to discontinue participation, and when payment will occur. If an incentive is not offered, state that the participant will not be paid to participate in this study.

Identify any procedures that are experimental.

When applicable, inform subjects of appropriate alternative procedures or courses of treatment that might be available or advantageous to them.

Provide contact information of study personnel and IRB for the subject should he/she have questions or concerns about participation in the research.

State that the subject's participation in the study is voluntary. Explain that if the subject decides to participate, he/she can withdraw consent and stop participation at any time without penalty or loss of benefits allowed.

Unless a waiver of documentation of consent has been granted (see “Waiving Requirement to Document Consent” below), include a signature and date line for the participant and the investigator (or individual administering the consent form) to complete.  Label the signature lines as “subject” and “investigator” (or “study representative if the individual administering the consent form is not the principal investigator.) In addition, include space for the subject and the investigator (or individual administering the consent form) to print their name.

5.5  Structure of a Consent Form

The following points must be followed to ensure that the subject understands the nature and purpose of the research in which they are being asked to participate:

The consent should be written in 6th to 8th grade reading level avoiding technical jargon.

The consent document should be written in the second person (using the "you" pronoun).

Legible font size is used based on population targeted (11 or 12 point minimum).

Use of clear paragraph/section headings to allow the potential subject ease of access to specific study information.

Double spacing is used between paragraphs.

5.6  Obtaining Parental Permission (45 CFR 46.408)

Parental permission is required when recruiting children or minors as subjects in research. In California, a minor is identified as a person under the age of 18 years. Parental permission must be obtained in advance of enrolling a minor subject into a study. The Informed Consent format is used when developing a Parental Permission form. Text should reflect the activities that the child (and the parent, if they are also considered a subject) will be asked to participate in as a research subject. If the consent form is being developed to obtain parental permission only, the signature line is labeled "Parent or Guardian of Subject." The child subject's name is also printed to indicate the child for whom they are giving permission.

5.7  Obtaining Assent/Dissent from Minors (45 CFR 46.408)

Assent is demonstrated by a child's agreement to participate in research. In California, a child is a person who is under the age of 18 years (unless legally emancipated).  It is required that the researcher makes adequate provisions to solicit assent from children unless the IRB waives this requirement.  To determine whether the child is able to assent really depends on the child's age and maturity.   If the child is considered to be capable of providing assent, whether or not assent is documented is also determined by the IRB. When assent is obtained, an assent form should be constructed that targets the child's level of reading and language use. The assent should include basic information about the study and how the child will be involved. If the parent gives permission for the child to participate and the child assents to participate, then he/she may be enrolled in the study.

5.8  Disclosing a Financial Interest to Subjects

It is generally recognized that a research investigator has an ethical responsibility to disclose a possible conflict of interest to potential research subjects as part of the consent process. The IRB asks investigators to provide information within the protocol to indicate whether they or any other person responsible for the design, conduct, or reporting of this research has an economic interest in, or acts as an officer or a director of any outside entity whose financial interests would reasonably appear to be affected by, the research. If the investigator reports a financial interest with the study sponsor and the conflict can be managed, it is expected that the consent form will adequately inform subjects of the relationship as well as procedures used to minimize the effect the relationship may have on the study. (http://aspe.hhs.gov/sp/coi/refs.htm)

5.9  Documentation of Informed Consent (45 CFR 46.117)

In most cases, informed consent is documented by the use of a written consent form approved by the IRB and signed by the subject or the subject's legally authorized representative.

Unless the IRB has authorized revisions to the consent procedure, the consent form must include all elements identified within the IRB-approved consent template. The IRB-approved consent form may be read to the subject or to the subject's legally authorized representative in addition to allowing the potential subject an opportunity to review the consent document and ask questions before signing the consent document.

5.10  Waiving Requirement to Document Consent (45 CFR 46.117(c))

The IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either:

(1) That the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality.  If this is the case, the investigator will ask the subject whether he/she wants to sign the document that links him/her to the research.  The subject's wishes for documentation will dictate whether or not a signed consent form is needed.

(2) That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.

If the IRB approves waiving the requirement for documenting consent, the investigator may be required to provide the subject with a written statement regarding the research.

5.11 Signature of Project Representative

The project representative (principal investigator, study coordinator or designated project representative) also signs the consent to verify that the consent process is complete. When obtaining consent, the setting and timing of explaining the research must be conducive to good decision-making. The project representative should see that everything is done to enhance the prospective subjects’ comprehension of the information and their ability to make a choice. The person signing as the project representative should be knowledgeable about the study, able to present information using easily understood terminology, and one who can identify and resolve any remaining questions.

5.12  Short Form Written Consent (46.117(b)(2))

The regulations also allow for consent to be documented by signing a "short form" that states only that the required elements of informed consent have been presented orally to the subject or the subject's legally authorized representative. When this method is used, the IRB will approve a written description of the consent statement that is orally presented to the prospective subject.  In addition, a witness to the oral presentation is required. Following the oral presentation, the prospective subject/legal representative will sign the "short form" if he/she decides to participate in the research.  The witness verifies the consent process by also signing the "short form" and the consent statement that is presented orally to the subject. A copy of the consent statement is then given to the subject or the representative, in addition to a copy of the signed "short form."

5.13  Consent Translation

Both DHHS regulations (45 CFR 46.116) and FDA regulations (21 CFR 50.20) require that informed consent be obtained in language understandable to the subject (or the subject's legally authorized representative), and documented in writing (46.117 and 50.27, respectively). Non-English speaking subjects must be presented with and sign a consent form that is written in their primary language. The investigator must provide the IRB with a language appropriate translated consent document for review and approval prior to recruiting subjects.  It is recommended that the investigator secure IRB-approval of the English consent document prior to translating the consent form. The IRB does not require that a certified translator perform the document translation.  However, the IRB does not verify the accuracy of the translated consent document and the investigator must provide assurance to the IRB that the consent or assent form has been adequately translated. The IRB recommends that the investigator either hires a certified translator or verifies the translation using a "back-translation procedure." Translation of a document to Spanish using the back-translation method involves translation of the English document to a Spanish version. The Spanish version of the document is then converted back to English by another bilingual individual.  The original English version is then compared to the English version of the Spanish-translated document for accuracy. If the two documents are comparable, the translation would be considered adequate.

5.14  Special Considerations

5.14.1  Obtaining Consent of Non-English Speaking Persons

The consent document must be written in a language that is understandable to the subject.  If the subject does not speak English as their primary language, the consent form must be translated into the subject’s primary language.  It is recommended to submit the English version of the consent document to the IRB for review prior to submitting the translated document.  The Institutional Review Board (IRB) does not verify the accuracy of the translated document.  IRB approval of this document for use in subject recruitment will be based on the PI’s assurance that the translated document reflects the content of the IRB approved English version of the document.

5.14.2  Obtaining Consent from Cognitively Impaired Persons

If participants are identified as being cognitively impaired, it may be necessary to include additional procedures during the consent process to ensure that the prospective subject understands the information presented about the study.  Consider including questions at the end of each section of the consent document to use in assessing participant comprehension of the consent content.  This mechanism allows for the investigator to clarify the participant's understanding of specific aspects of the study as the consent process occurs (e.g. After the Description of the Study section,  include the following questions: Do you understand what will happen during the testing phase? The training phase?).

5.14.3  Internet Research

The consent form should explain added risks associated with privacy violations and strategies developed to reduce the risk of privacy loss or breech of confidentiality.  See the section entitled Internet Research for more information on this topic.

5.14.4  Deception or Incomplete Disclosure

In studies involving deception or incomplete disclosure, information about the details of the study hypothesis or research question to subjects may be abbreviated or withheld during the consent process. However, subjects should be provided with enough general information about the study or experiment to understand and make an informed decision about whether or not they want to complete the study tasks or expose themselves to potential risks involved in study participation.  Subjects should be debriefed about the true nature and purpose of the study after their participation has ended. 

5.14.5  Debriefing

In behavioral research involving deception, the IRB requires that subjects be debriefed after their participation. The debriefing statement should be presented both orally and in writing.  Debriefing procedures should include a written statement that will be summarized and then given to subjects to take home to read in more detail if they choose.  Along with a description of the deception involved and an explanation about the true purpose of the research, include a statement to inform subjects of their right to withdraw their data from the study and still receive course credit if they feel upset or uncomfortable with the deception involved.  Referral information should also be provided to the subject should participation in this study raise personal concerns that he/she would like to discuss with a clinical professional.

5.15  Sample Consent Forms

5.15.1 Adult Informed Consent

To view a sample of an Adult Informed Consent please click here [http://gra.sdsu.edu/IRB/consent.htm].

5.15.2  Parental Permission

To view a sample of an Parental Permission/Informed Consent please click here [http://gra.sdsu.edu/IRB/parentalconsent.htm].

5.15.3  Minor Assent/Dissent

To view a sample of a Minor Assent please click here. [http://gra.sdsu.edu/IRB/assent.htm]

5.15.4  Obtaining Consent in Exempt Research

A signed consent is generally not required for exempt research. The investigator will provide adequate information about the research to potential subjects so that an informed decision can be made. The investigator can deliver this information verbally or both verbally and in writing. The appropriate mode of delivery will depend on administration procedures.. The consent statement will include the information needed for a participant to make a decision regarding participation.  The statement will be written in a language easily understood by the target audience.

When applying for IRB review, submit the text to be used to obtain informed consent. Include the following information:

Identify who is conducting the study including institutional affiliation and academic status.

Describe why the study is being conducted.

State who is being recruited and why they have been chosen.

Explain what each participant will be asked to do and estimate how long it will take to complete the task.

Emphasize that participation is voluntary.

Clarify whether participant's information will be anonymous (no identifiers) or confidential. If confidential, indicate whether any information linked to the individual's identity will be used.

Describe incentives/compensation offered or costs that may be incurred.

Provide a department number and point of contact for telephone inquiries. Include the IRB telephone number for questions related to their rights as a participant in research.

5.15.5 Consent Forms with Collaborating Institutions

Investigators who have a joint appointment (e.g., joint doctoral students) may be required to obtain IRB approval from all institutions with which they are affiliated.  The IRB encourages investigators to work with each institution's IRB toward achieving a consent document that meets with both institutions’ requirement.  This is preferred to having two or more approved consent documents that are used to document informed consent from each subject.


6.0  Commencing Research

6.1  Investigator Responsibility

Protecting the rights and welfare of the research subject is a shared responsibility of the IRB and the investigator.  Ultimately, the investigator is responsible for the conduct of the study.  This includes the application and monitoring of ethical practices, compliance with state/federal regulations and institutional practices, and supervision/training of research staff.  Individuals conducting research under the auspices of SDSU are required to comply with all federal, state and institutional regulations and policies regulations for the protection of human research subjects. Investigators will document their  understanding of his/her responsibilities within during on-line IRB application process.,

6.2  Faculty Advisor’s Responsibility when Supervising Student Research

Student initiated research involving human subjects, whether dissertation, thesis or other research projects, must be supervised by an authorized faculty member to insure the compliance with procedures and regulations relating to the protection of human subjects.  Supervising faculty is responsible for the following aspect of the student's involvement in research:

Ensure that the student has reviewed and understands the federal regulations that govern research involving human subjects, the Belmont report and the institution's Assurance prior to developing a study that involves human subjects.

Meet with the student investigator to monitor the study progress.

Be available to the student investigator to supervise and to address problems should they arise.

Oversee the prompt reporting of any significant or untoward adverse effects within 5 days of occurrence.

Arrange for an alternate faculty sponsor to assume these duties when unavailable (vacation or sabbatical).

Monitor the research activity to insure that the protocol approved by the IRB is followed.

Students will verify that their faculty advisor will comply with the stated responsibilities during the online application process.

Master's students must receive human subjects approval if they are planning to sign up for the thesis course (799A) through the Graduate Division. Evaluators in the Graduate Division will verify the student’s IRB review status prior to releasing a schedule number to enroll in 799A. 

6.3  Institutional Responsibilities

SDSU’s assurance with the U.S. Department of Health and Human Services identifies responsibilities of the institution, the research investigator and the IRB related to human subjects protections issues.  The assurance authorizes the IRB to perform as the Institutional Review Board for this campus. [LINK- http://gra.sdsu.edu/IRB/mpa.htm]. 

6.4  Modifications & New Findings

Federal regulations require that any revision to previously approved research involving human subjects receive IRB approval in advance of implementation except when necessary to eliminate apparent immediate hazards to the subject (45 CFR 46.103 (b)(4)(iii)). A modification is defined by the IRB as a change that does not alter the overall character or purpose of the original project. Minor changes that do not adversely alter the overall risk-benefit profile of the study may receive an expedited review.  The convened committee reviews proposed changes that may affect the willingness of enrolled subjects to continue participation and/or increase the risk to research subjects.

Investigators may request to modify their protocol online. Within the modification request, the researcher is asked to provide a complete description of and rationale for the proposed modification and to address the effects of the modification on risks, benefits, management of risks, and informed consent.  Any new findings in the literature that may influence the study procedures, risks or benefits must also be reported to the IRB.

Changes to the consent document to inform subjects of new findings, changes in procedures, risks and benefits to study participation must also be approved by the IRB.  An IRB approval stamp will be applied to the revised and approved consent form when the modification approval is completed.  Procedures used to inform and document consent of previously enrolled subjects affected by the modification should be addressed. 

6.5  Adverse Event Reporting

The principal investigator of an IRB approved protocol must report any serious or unexpected adverse events experienced by a research subject that are associated with the study procedures.  Any undesirable experience associated with the research may be considered an adverse event.  The event is considered serious and should be reported when the subject experiences recurring problems, unanticipated side effects and/or death.  Failure to report an adverse event to the IRB may result in temporary or permanent suspension of the protocol approval.  The electronic application system allows investigator’s to report adverse events online.

6.6  Continuing Review of Approved Protocols (45 CFR 46.109(c))

Research projects must be reviewed at least annually. The initial IRB approval expires one year following its award, unless otherwise stipulated by the committee. Determination for more frequent review is based on the degree of risk associated with participation and/or the involvement of subjects that require additional protections as defined by the Department of Health and Human Services.

A continuation of approval is needed if: 1) subject recruitment and/or data collection is continuing or 2) data is being analyzed that was collected on this project. A final report is necessary if all procedures are completed that involve human subjects (e.g., recruitment, data collection and analysis). To apply for continuation of approval or to indicate a final report, the investigator must complete a Report of Progress and Review Request form online. Research that was initially reviewed by the convened committee will receive continuing review by the convened committee unless identified as not exceeding a minimal level of risk at the time of its initial review. Request for continued approval should be submitted in accordance with the appropriate deadline date as posted on the IRB schedule.

6.7  Site Monitoring

Continuing review may also involve a site visit by an IRB representative to the research facility. The goal of the site visit is to assess whether the protocol is being carried out as approved by the IRB.  A secondary goal is to provide assistance to the investigator and key personnel, as needed, to increase understanding of the ethical principles associated with human subjects protections and federal regulations. Specific areas targeted for review of the protocol includes: recruitment methods and materials; measures; eligibility criteria; compensation; informed consent procedures, IRB records; data management and record keeping. Relevant study materials (e.g., correspondence, recruitment materials, subject files, measures, etc.) are made available for review during the site visit (as required by 45 CFR 46.109 (e)). The IRB may recommend a site visit for research studies that involve vulnerable populations, a longitudinal design and/or procedures exceeding minimal risk. A site visit may also occur if a serious adverse event has occurred or a complaint has been registered.

6.8  Suspension or Termination of Approval

The IRB may suspend or terminate the approval of research that is not being conducted in accordance with the requirements set forth by the committee or that has been associated with unexpected serious harm to subjects (45 CFR 46.109(a)).