I. INTRODUCTION

> The purpose of consent form guidelines is to describe the procedure
> for reviewing consent forms submitted to the Army Surgeon General's
> Human Subjects Research Review Board (HSRRB). This review should
> ensure that the consent form is in compliance with applicable human
> subjects protection regulations and ethical guidelines. The review is
> documented on the HSRRB Consent Form Checklist, which should be used
> together with the Protocol Checklist for reviewing a protocol
> submission.

# II. 

# RESPONSIBILITIES

> A. All human subjects protection and regulatory affairs scientists in
> the Office of Regulatory Compliance and Quality (RCQ) are responsible
> for the review of consent forms in accordance with the procedure
> outlined in this SOP.
>
> B. For each protocol and consent form submitted to the HSRRB, the
> human subjects protection or regulatory affairs scientist who is
> assigned as the reviewer for the protocol is responsible for
> completing both the HSRRB Protocol and Consent Form Checklists. The
> reviewer is responsible for updating the consent form checklist when
> the Principal Investigator (PI) submits a revised consent form.
>
> C. The Acting Chair, HSRRB is responsible for approving the protocol
> and consent form review before recommendations are given to the PI and
> before the protocol and consent form are submitted to the HSRRB for
> review. The Acting Chair may delegate this duty to the Alternate
> Acting Chair or Vice Acting Chair as needed.

# III. PROCEDURES

> The reviewer should enter the HSRRB Log No., name of PI, and date
> checklist is completed or updated and sign in the space provided for
> "Reviewer's Signature." The reviewer should review each element of the
> checklist, check the appropriate box (Yes, No, or NA), and make
> written comments as needed. If a protocol submission contains more
> than one consent form, a separate checklist should be prepared for
> each consent form. If a revised consent form contains significant
> changes, a new checklist should be used to review the revised consent
> form. This checklist is designed to facilitate writing recommendations
> for changes to the consent form that the PI needs to make and/or
> additional information that needs to be provided. An explanation of
> each element of the checklist follows:
>
> A. Research Description. As appropriate, include the following:
>
> 1\. Title and Location of Study. The title and study location must be
> identified and consistent with those in the protocol. (AR 70-25,
> Appendix E-1; OTSG 15-2, Appendix B-1a.)
>
> 2\. Purpose. The consent form must clearly state and identify that the
> subject is participating in research. If the research is incorporated
> into standard care, research procedures must be clearly distinguished
> from standard care. Ensure that the purpose of the research is clearly
> described and accurately represented in the consent form in terms that
> the subject will understand. (32 C.F.R. § 219.116(a)(1); AR 70-25,
> Appendix E-3; OTSG 15-2, Appendix B-1c.)
>
> 3\. Duration of Participation. Ensure that the duration of subject
> participation is clearly defined in the consent form. If the duration
> of a routine procedure will be prolonged as a result of participation,
> the subject should be informed how much extra time will be added.
> Estimated time taken to complete screening, questionnaires, tests,
> interviews, etc. should all be considered, as well as the number of
> visits required. (OTSG 15-2, Appendix B-1d.)
>
> 4\. Number of Subjects. The approximate number of subjects enrolled in
> the study and at each site should be present in the consent form. This
> is a requirement for IND/IDE studies, and a recommendation for some
> non-IND studies (for example, in studies that are high risk or have
> small numbers of subjects). (32 CFR § 219.116(b)(6); AR 70-25,
> Appendix E-11f.; OTSG 15-2 Appendix B-2f.)
>
> 5\. Procedures. The consent form must adequately describe what will be
> done during the course of the research project and indicate any
> procedures that are experimental. All tests and procedures must be
> described from initial screenings to subject follow-up. If the
> research is incorporated into standard care, research procedures must
> be clearly distinguished from standard care. The consent form should
> briefly explain the study design relative to what will be done to the
> subject (in blind or double-blind studies, subjects must be informed
> that they may receive either the experimental treatment or a placebo).
> If a placebo is used, its contents should be described. Specify what
> is required of the subject (hospital visits, blood donation, etc.). If
> blood is to be drawn, the amount(s) to be drawn should be expressed in
> lay terms. Although a subject may be familiar with the procedures,
> never assume that he or she comprehends everything. (OTSG 15-2,
> Appendix B-1e.)
>
> 6\. Inclusion and Exclusion Criteria. Criteria such as age, gender,
> ethnicity, health status and medical conditions that will be used as
> the basis for including or excluding study subjects should be
> explained in the consent form. (OTSG 15-2, Appendix B-1c.(5))
>
> 7\. Precautions. Any special precautions that should be observed by
> the subject before or after the study should be clearly stated in the
> consent form. If the possibility exists that participation in the
> study may have negative effects or is a risk for a developing embryo
> for any period of time during and/or after participation in the study
> if the subject becomes pregnant, the language from the HSRRB Clause on
> Pregnancy Prevention or the equivalent must be present in the consent
> form. (AR 70-25, Appendix E-11g.; OTSG 15-2, Appendix B-2g.)
>
> 8\. Similar Studies. If available, pertinent information from
> previous, similar or related studies should be provided in the consent
> form. (AR 70-25, Appendix E-3)
>
> B. Risks
>
> 1\. Risks. All reasonably foreseeable research risks must be clearly
> stated in the consent form. Ensure that the risks are not understated
> and appear prominently in the consent form. Ensure that all possible
> physical, psychological, emotional, social, legal, and economic risks
> are identified in the consent form. For studies of potential subject
> benefit, describe risks unique to the study; estimate their severity
> and likelihood; and/or compare these risks with risks that the subject
> might encounter in the course of his or her daily activities. If
> similar research has been conducted in the past, describe the
> incidence of adverse effects or injuries occurring in the past. For
> studies of no potential benefit to the subject, list all risks that
> are more than "minimal" (not greater, considering probability and
> magnitude, than those ordinarily encountered in daily life or during
> the performance of routine medical tests). (32 C.F.R. § 219.116(a)(2);
> AR-70-25, Appendix E-4; OTSG 15-2, Appendix B-1f.)
>
> 2\. Unknown Risks. When appropriate (e.g., investigational drug,
> device or procedure), the consent form should contain a statement that
> the treatment or procedure may cause risks to the subject (or embryo
> or fetus), which are currently unforeseeable. Both men and women need
> to understand the danger of taking a drug whose effects on the fetus
> are unknown. If measures to prevent pregnancy should be taken while in
> the study, this should be explained in the consent form. If there is
> no animal data on mutagenicity and teratogenicity available for an
> investigational agent, the subject should be informed in the consent
> form. Also, note that pregnant women or fetuses may be involved in
> research (where scientifically appropriate) only if preclinical
> studies, including studies on pregnant animals and clinical studies,
> including studies on non-pregnant women, have been conducted and
> provide data for assessing potential risks to pregnant women and
> fetuses. (Subpart B, 45 C.F.R. § 46.204(a); 32 C.F.R. § 219.116(b)(1);
> AR 70-25, Appendix E-11a.; OTSG 15-2, Appendix B-2a.)
>
> 3\. Genetic Effects to Male Offspring. Possible genetic effects to the
> offspring of males and the possibility of genetic mutations that may
> have an effect on male fertility should be addressed when applicable.
> There is a possibility of passing on a genetic defect in children
> sired by males with induced genetic mutations where either the male or
> female germ cells or gametes (egg or sperm) have been affected. This
> kind of damage, called a germ-cell mutation, could be inherited in the
> next generation. Therefore, if there are pre-clinical or clinical
> studies indicating the possibility of germ-cell mutations, this should
> be addressed in the consent form. Note that, among the children of the
> atomic-bomb survivors who have been examined thus far, no evidence of
> genetic effects has been observed, although ionizing radiation is
> known to cause DNA mutation. (AR 70-25, Appendix E-11a.)
>
> 4\. Investigational New Drug/Device. For any protocols involving the
> use of an investigational new drug or device, the language in the
> HSRRB Clause on IND/IDEs or the equivalent must be present in the
> consent form. (OTSG 15-2, Appendix B-1e.(3); HSRRB Clause 10.01,
> *Investigational New Drug*)
>
> C. Benefits
>
> 1\. General Benefits. Any benefits that can be reasonable expected to
> be derived by the subject or others from participation in the study
> must be clearly stated in the consent form. Ensure that the benefits
> are not overstated. If there is no direct benefit to the subject it
> must be stated in the consent form. Ensure that compensation is not
> identified as a benefit of participation. (32 C.F.R. § 219.116(a)(3);
> AR-70-25, Appendix E-5; OTSG 15-2, Appendix B-1g.)
>
> 2\. Disclosure of Research Results. The consent form should contain a
> statement informing the subject whether the results (individual and/or
> group results) of the research will be shared with them. For studies
> using non-validated testing methods (particularly genetic studies),
> test results may not be shared with the subject, as they will not have
> an effect on clinical care. When sensitive data may be revealed by the
> results, the subject should have the option of choosing whether or not
> to receive the results. (AR 70-25, Appendix E-11i.)
>
> D. Alternatives to Participation. Any appropriate alternative
> procedures or courses of treatment, which may be advantageous to the
> subject, must be stated in the consent form (for example, whether
> treatment is available outside the protocol). In some cases, the only
> alternative is not to participate in the study. (32 C.F.R. §
> 219.116(a)(4); AR 70-25, Appendix E-6; OTSG 15-2, Appendix B-1h.)

######### E. Payment/Costs

> 1\. Compensation. Where private citizens are enrolled, the consent
> form should specifically state any payment or compensation that the
> subject will receive as a result of participation in the study. The
> following statement or equivalent must also be included. "Other than
> medical care that may be provided and any other payment specifically
> stated in the consent form, there is no other compensation available
> for your participation in this research." This statement may be
> omitted if HSRRB Clause 3.01 is present in the consent form, because
> appropriate language is present in that clause. (OTSG 15-2, Appendix
> B-1j.)
>
> 2\. Costs. Any additional costs to the subject that may result from
> participation in the research must be stated in the consent form.
> Potential expenses could include travel, parking, meals, and
> procedures. (32 C.F.R. § 219.116(b)(3); AR 70-25, Appendix E-11c.;
> OTSG 15-2, Appendix B-2c.)

######### F. Possible Sample Donation/Commercial Products. If any samples donated in this study will be used in other studies, the language from HSRRB Clause 4.01 or the equivalent must appear in the consent form. If the study involves treatment in addition to sample donation, subjects should be given the option to participate in the study without donating their tissue. (AR 70-25, 3-1c.; AR 70-25 3-1d.; HSRRB Clause 4.01, *Sample Donation*)

######### G. Medical Care for Research Related Injury. The language found in HSRRB Clause 3.01 or the equivalent must be present in all consent forms for greater than minimal risk studies. For all studies, ensure that there is no conflicting language present in the consent form. (32 C.F.R. § 219.116(a)(6); AR 70-25, 3-1k.; OTSG 15-2, Appendix B-1j.; HSRRB Clause 3.01, *Medical Care for Research Related Injury*)

> H. Confidentiality.
>
> 1\. A section describing the extent to which confidentiality of
> records identifying the subject will be maintained must be included in
> the consent form. Procedures to maintain the subject's privacy and
> confidentiality must be described, including how identifying
> information will be stored and for how long, who will have access to
> the identifying data, disposition of the data, if specimens will be
> maintained and for how long. Active duty subjects cannot be guaranteed
> complete confidentiality. (32 C.F.R. § 219.116(a)(5); AR 70-25,
> Appendix E-7; OTSG 15-2, Appendix B-1i.)
>
> 2\. It should be noted in the consent form that representatives of the
> local IRB and the U.S. Army Medical Research and Materiel Command are
> eligible to review research records as a part of their responsibility
> to protect human subjects in research. For investigational drug or
> device studies, a statement that FDA and the sponsor (if applicable)
> may review the records should be included. (AR 70-25, Appendix E-7)
>
> 3\. For studies utilizing military personnel as subjects, the
> following wording may be substituted for the above: "All data and
> medical information obtained about you as an individual will be
> considered privileged and held in confidence; you will not be
> identified in any presentation of the results. Complete
> confidentiality cannot be promised, particularly to subjects who are
> military personnel, because information bearing on your health may be
> required to be reported to appropriate medical command authorities,
> and applicable regulation notes the possibility that representatives
> of the USAMRMC (and the FDA) may inspect the records of the research."
> (OTSG 15-2, Appendix B-1i.)
>
> 4\. If photographs are taken as part of the study, the degree to which
> actions will be taken to protect the identity of the subject must be
> described in the consent form. (AR 70-25, Appendix E-11h.)

######### I. Participation and Withdrawal 

> 1\. Voluntary Participation. The consent form must contain a statement
> that participation is voluntary, refusal to participate will involve
> no penalty or loss of benefits, and the subject may withdraw at any
> time without penalty or loss of benefits. (32 C.F.R. § 219.116(a)(8);
> AR 70-25, Appendix E-9; OTSG 15-2, Appendix B-1l.; HSRRB Clause 12.01,
> *Participation*)
>
> 2\. Assent. Assent should be obtained from minors, when applicable.
> Determining applicability should take into consideration the age,
> maturity, and psychological state of the minor. If assent will not be
> obtained, ensure conditions for waiver of assent are met. Assent forms
> should be provided for review. See policy on assent for further
> guidance on appropriate assent form content. (AR 70-25. 3-1o.)
>
> 3\. Subject Withdrawal. The consent form must describe the
> consequences of a subject\'s decision to withdraw and procedures for
> orderly end of subject\'s participation. Subjects must be allowed to
> withdraw at any time. If withdrawal results in any decrease in
> promised compensation this must be justified and described in the
> consent form. When withdrawal from the study may have deleterious
> effects on the subject's health or welfare, the consent form should
> explain any withdrawal procedures that are necessary for the subject's
> safety, and specifically state why they are important to the subject's
> welfare. The consent form should also state whether withdrawal of
> samples will be possible. (32 C.F.R. § 219.116(b)(4); AR-70-25,
> Appendix E-11d.; OTSG 15-2, Appendix B-2d.)
>
> 4\. Termination by Investigator. (32 C.F.R. § 219.116(b)(2); AR 70-25,
> Appendix E-11b.; OTSG 15-2, Appendix B-2b.) The consent form must
> inform the subject of any anticipated circumstances under which the
> subject\'s participation may be terminated by the investigator without
> regard to the subject's consent. Potential circumstances under which
> this might occur include:
>
> a\. Adverse reaction/condition occurs and it might be dangerous or
> detrimental to the subject's health to continue
>
> b\. The subject fails to keep study visits as explained, or does not
> follow the instructions given by the investigator
>
> c\. Limitations on the availability of the treatment
>
> d\. Other medical events
>
> e\. Protocol violation or early closure of the study.
>
> 5\. Significant New Findings. As appropriate, the consent form should
> state that any significant new findings developed during the course of
> research which may relate to the subject's willingness to continue
> participation will be provided. (32 C.F.R. § 219.116(b)(5); AR 70-25,
> Appendix E-11e.; OTSG 15-2, Appendix B-2e.)
>
> J. Contact Information. If multiple sites are involved, a local
> contact should be given as well as the contacts at the main study site
> whenever possible.
>
> 1\. Research Information. Ensure that the consent form indicates whom
> to contact with questions about the research, including name or office
> and telephone numbers. For studies enrolling subjects from a large
> geographic area at one site, a toll free number is recommended. An
> example of an appropriate individual is the Principal Investigator.
> (32 C.F.R. § 219.116(a)(7); AR 70-25, Appendix E-8)
>
> 2\. Subjects' Rights. Ensure that the consent form indicates whom to
> contact with questions about subjects\' rights including name or
> office and telephone numbers. Appropriate examples include the local
> IRB or Ethics Committee or a patient's advocate. (32 C.F.R. §
> 219.116(a)(7); AR 70-25, Appendix E-8; OTSG 15-2, Appendix B-1k.)
>
> 3\. Research Related Injury. Ensure that the consent form indicates
> whom to contact in the event of a research-related injury, including
> name or office and telephone numbers. Examples of appropriate
> individuals include the Medical Monitor and the legal office. (32
> C.F.R. § 219.116(a)(7); AR 70-25, Appendix E-8; OTSG 15-2, Appendix
> B-1k.)
>
> 4\. Principal Investigator. Ensure that the consent form contains
> contact information for the Principal Investigator (if not addressed
> above), including name and telephone number. (AR 70-25, Appendix E-2;
> OTSG 15-2, Appendix B-1b.)
>
> K. Volunteer Registry. For all \"greater than minimal risk\"
> intramural studies, the consent form must include the language from
> HSRRB Clause 2.01 or the equivalent describing the Volunteer Registry
> Database. (AR-70-25, Appendix H; HSRRB Clause 2.01, *Volunteer
> Registry Database Requirements*)

######### L. Documentation

> 1\. Signature of Subject. The consent form should contain spaces to
> record the printed or typed name and signature of the subject or the
> legally authorized representative and date. (21 C.F.R. § 50.27; AR
> 70-25, DA Form 5303-R; OTSG 15-2, Appendix B-1m.)
>
> 2\. Address of Subject. The consent form should contain a space to
> record the permanent address of the subject (or legally authorized
> representative). (AR 70-25, DA Form 5303-R; OTSG 15-2, Appendix B-1m.)
>
> 3\. Signature of Witness. When appropriate, the consent form should
> contain spaces to record the printed or typed name and signature of
> the witness to the consent process in accordance with 32 C.F.R. §
> 219.117(b)(2). (AR 70-25, DA Form 5303-R; OTSG 15-2, Appendix B-1m.;
> HSRRB Policy Memorandum, *Witness Requirement for Informed Consent
> Process and Form* (30 November 2001))
>
> 4\. Copy of Consent Form. The consent form must indicate that a copy
> of the form will be provided to the subject and, if applicable, the
> legally authorized representative. (OTSG 15-2, Appendix B-1c.(6))
>
> 5\. Consent must be provided for photos or audiotapes. (AR 70-25,
> Appendix E-11h.)
>
> 6\. Consent for Sample Donation. If any samples donated in the study
> will be used in other studies, consent must be obtained for sample
> donation. A donation form may be prepared for signature by the
> volunteer using language in HSRRB Clause 4.01 or the equivalent. If
> preferred, this can be an addition to the consent form rather than a
> separate form. (AR 70-25, 3-1c.; AR 70-25, 3-1d.; HSRRB Clause 4.01,
> *Sample Donation*)
>
> 7\. Consent for HIV testing. If the research will involve screening
> for HIV, separate consent must be given for the test. Documentation of
> consent for HIV antibody testing may be addressed in the body of the
> consent form or as a separate HIV test consent form in accordance with
> the State/jurisdiction in which the study is being conducted.

######### M. Presentation and Language

> 1\. Exculpatory/Coercive Language. Ensure that the document is free
> from any exculpatory language through which the subject or
> representative is made to waive or appear to waive any of the
> subject's legal rights, or releases or appears to release the
> investigator, the sponsor, the institution or its agents from
> liability for negligence. (32 C.F.R. § 219.116)
>
> 2\. Coercive Language. The consent form should avoid use of the term
> "I understand" and should not require subjects to certify completeness
> of disclosure, make claims of effectiveness that may unduly influence
> subjects, or include explicit statements that an IRB has approved
> solicitation of subjects to participate in research. (FDA Guide to
> Informed Consent (1998))
>
> 3\. Legibility/Readability. (32 C.F.R. § 219.116; AR 70-25, 3-2d.;
> OTSG 15-2, Appendix B-1c.) The consent form must meet the following
> requirements:
>
> a\. Be legible,
>
> b\. Use adequate font size (at least 12 point is generally
> recommended; 14 point is preferred for elderly or visually impaired
> subjects).
>
> c\. Be written at a reading level appropriate for the subjects (the
> eighth grade level is recommended for adults). Use of short sentences,
> non-scientific words with less than three syllables, and breaking up
> of text into short sections is generally recommended. If scientific or
> medical terminology is used an appropriate definition or explanation
> of the terms should be provided.
>
> d\. Be written in the second person. (It is acceptable to use the
> first person at the end of the form above the subject's signature with
> a statement such as "I have read the information above and been given
> an opportunity to ask questions.") (FDA Guide to Informed Consent
> (1998))
>
> e\. Provide translation as needed. In accordance with memorandum dated
> 21 February 1992, signed by the Deputy Commander, USAMRDC, subject:
> "Determination of Accuracy of the Translation of Foreign Consent
> Forms," subjects must be provided information about the study in a
> language that they can understand. When there is a probability of
> enrolling subjects that do not speak English, a copy of the consent
> form in the foreign language must be provided along with the English
> translation of the consent form. That documentation should include, on
> the English version, the statement \"I certify that this is an
> accurate and true translation\" as well as the signature, name,
> address, phone number and, if available, FAX number of the translator.
> If an approved version of an English consent form for the study is
> translated into a foreign language, the documentation may also be
> provided in the form of a letter from the translator, certifying that
> the foreign version of the consent form is an accurate and true
> translation of the English consent form and include signature, name,
> address, phone number and, if available, FAX number of the translator.
> (HSRRB Clause 5.01, *Certificate of Consent Form Translation*)
>
> N. Supportive Materials. Any materials used to supplement the consent
> form should be reviewed, which may include information sheets, videos,
> briefing slides, visit schematics and other materials.

# 

# IV. REFERENCES

> 10 United States Code (U.S.C.) 980, *Current Law for DOD Medical
> Research*.
>
> 21 Code of Federal Regulations (C.F.R.) § 50, *Protection of Human
> Subjects* (1980).
>
> 21 C.F.R. § 56, *Institutional Review Boards* (1981).
>
> 32 CFR § 219, *Protection of Human Subjects* (1999).
>
> Subparts B and C, 45 C.F.R. § 46, *Protection of Human Subjects*,
> (1996).
>
> Department of Defense (DOD) Directive 3216.2, *Protection of Human
> Subjects and Adherence to Ethical Standards in DoD Supported Research*
> (25 March 2002).
>
> Army Regulation (AR) 40-7, *Use of Investigational Drugs and Devices
> and the Use of Schedule I Controlled Drug Substances* (4 January
> 1991).
>
> AR 70-25, *Use of Volunteers as Subjects of Research* (25 January
> 1990).
>
> Office of The Surgeon General (OTSG) Regulation 15-2, *Human Subjects
> Research Review Board* (11 January 1989).
>
> International Conference on Harmonization of Technical Requirements
> for Registration of Pharmaceuticals for Human Use (ICH) *Guideline for
> Good Clinical Practise* (9 May 1997).
>
> FDA Guidance for Institutional Review Boards and Clinical
> Investigators, A Guide to Informed Consent (1998 Update).
>
> HSRRB Clauses:
>
> 1.02, *Reporting of Serious and Unexpected Adverse Events*.
>
> 2.01, *Volunteer Registry Data Base Requirements*.
>
> 3.01, *Medical Care for Research Related Injury.*
>
> 4.01, *Sample Donation.*
>
> 5.01, *Certification of Consent Form Translation.*
>
> 6.01, *10 United States Code (USC) 980.*
>
> 7.01, *Definition: Adverse Events.*
>
> 8.02, *Medical Monitor Requirement.*
>
> 9.01, *Pregnancy Prevention.*
>
> 10.01, *Investigational New Drug.*
>
> 11.01. *Review of Research Records.*
>
> 12.01, *Participation.*
>
> 13.01, *Responsibilities of Principal Investigator to the Surgeon
> General*.
>
> HSRRB Policy Memo, *Witness Requirement for Informed Consent Process
> and Form* (30 November 2001).