Approved For Release 2000/08/08 : CIA-RDP96-007%8RO,?,,1t5OOI -0 1 11 A09Y2 Army egu a ion - Research and Deveiopment Use of Volunteers as Subjects of Research Headquarters Department of the Army Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 71fCKA111GE AR 70-25 Use of Volunteers as Subjects of Research This change is published to correct a serious error that occurred during the final editing of the current revision. In attempting to respond to guidance from the Office of The Judge Advocate General that a subparagraph be moved from the text of the regulation to appendix F, the wrong sub- paragraph was moved. Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 Headquarters *Army Regulation 70-25 Depaftment of tii~r pirm -0 ~09W oPfRelease 2000/08/08 : CIA-RDP96-00788ROO1500140002 25 January 1990 Effective 24 February 1990 Research and Development Use of Volunteers as Subjects of Research This publication was last revised on 8 August 1988. Since that time, permanent Change 1 has been issued. As of 25 January 1990, that change remains in effect. This UPDATE print- ing incorporates that change into the text. This UPDATE printing publishes a Change 2. The portions being revised by this change are highlighted. By order of the Secretary of the Army: CARL E. VUONO General, United States Aray Chief of Staff Official: MILTON H. HAMILTON Administrative Assistant to the Secretary of the ArrW Summary. This revision implements De- partment of Defense (DOD) Directive (DODD) ~216.2. It reflects the present legal requirements pertaining to the use of humans as research subjects funded by re- search, development, test, and evaluation appropriations. This revision provides gui- dance for establishing human use commit- tees (HUCs). Excluding limited situations, authority to approve research using human subjects can be delegated within the military chain of command. Applicability. This regulation applies to research, development, test, and evaluation (RDTE) programs conducted by the Active Army. It does not apply to the Army Na- tional Guard (ARNG) or the U.S. Army Reserve (USAR) unless there is involve- ment of Active Army personnel. Internal control systems. This regula- tion is subject to the requirements of AR 11-2. It contains internal control provisions but does not contain checklists for con- ducting internal control reviews. A checklist will be published at a later date. Supplementation. Supplementation of this regulation is prohibited unless prior ap- proval is obtained from HQDA (DASG-RDZ), 5109 Leesburg Pike, Falls Church, VA 22041-3258. Interim changes. Interim changes to this regulation are not official unless they are au- thenticated by the Administrative Assistant to the Secretary of the Army. Users will de- stroy interim changes on their expiration dates unless sooner superseded or rescinded. Suggested Improvements. The propo- nent of this regulation is the Office of The Surgeon General. Users are invited to send comments and suggested improvements on DA Form 2028 (Recommended Changes to Publications and Blank Forms) directly to Commander, U.S. Army Medical Research and Development Command, ATTN- SGRD-HR, Fort Detrick, Frederick, MD 21701-5012. Distribution. Distribution of this publica- tion is made in accordance with the require- ments on DA Form 12-09-E, block number 3724, intended for command level D for Active Army and None for the ARNG and USAR. Contents (Listed by paragraph number) Commander, Soldier Support Center-National Capital Region (SSC-NCR) * 2-6 Major Army commanders * 2-7 Commanders of RDTE organizations 9 2-8 Other responsibilities 9 2-9 F. Exemptions G. Legal Implications H. Volunteer Data Base Glossary Chapter I Introduction Purpose e 1-1 References # 1-2 Explanation of abbreviations and terms & 1-3 Limitations * 1-4 Chapter 2 Responsibilities The Under Secretary of Defense for Acquisition (USD (A)) * 2-1 Assistant Secretary of Defense (Health Affairs) (ASD (HA)) 9 2-2 Assistant Secretary of the Army (Research Development and Acquisition) (ASA(RDA)) - 2-3 The Deputy Chief of Staff for Personnel (DCSPER) e 2-4 The Surgeon General 9 2-5 Chapter 3 Research General guidance * 3-1 Procedural guidance * 3-2 Appendixes A. References B. Guidelines for Preparation of Research Protocol and/or Test Plan C. Human Use Committees D. Expedited Review Categories E. Instructions for the Completion of the Volunteer Agreement Affidavit *This regulation supersedes AR 70-25, 25 September 1989. AR 70-25 o UPDATE Approved For Release 2000108/08 : CIA-RDP96-00788ROO1500140002-0 Approved For-Release 2000/08/08 C IA-RDP96-00788 ROO 150014000.2-0. RESERVED t;napter 1 Introduction Approved For Release 2000/08/08 : CIA-RDP96-00788RO01 1-1. Purpose This regulation- a. Prescribes Army policy on the conduct and management of human subjects in testing, including- (1) Command responsibilities. (2) Review process requirements. (3) Approval authorities. (4) Reporting requirements. b. Allows a decentralized approval option for those elements that have established review committees and an internal review process. 1-2. References Required and related publications and prescribed and referenced forms are listed in appendix A. 1-3. Explanation of abbreviations and terms Abbreviations and special terms used in this regulation are ex- plained in the glossary. 1--C Limitations a. Nothing in this regulation is intended to supersede require- ments for health hazard or other safety review required by De- partment of the Army (DA) regulations. b. Nothing in this regulation limits the authority of a health care practitioner to provide emergency care under laws that apply in the jurisdiction in which care is provided. c. Protocols for the use of drugs or Schedule I controlled sub- stances for investigational purposes will be approved as per AR 40-7. d. The guidance in this regulation pertains to the following, re- gardless of whether conducted by DA, a contractor, grantee, or other agency utilizing Army funds: (1) Biomedical research and behavioral studies involving human subjects. (2) RDTE involving new drugs, vaccines, biologicals, or inves- tigational medical devices. (3) Inclusion of human subjects, whether as the direct object of research or as the indirect object of research involving more than minimal risk in the development and testing of military weapon systems, vehicles, aircraft, and other materiel. The determinati ion of whether a research protocol involves more than minimal risk will be made by review committees established in accordance with paragraph 3-2b of this regulation. (4) inclusion of hunian subjects as the inditect object of re- smich involving minimal risk or less in the development and t ing of military weapon systems, vehicles, aircraft, and o mateLial axe exempt from flie re4ttirernent fbi obtaining infon consent froin tire PaL tiCipantS. Vie dete, initiation of whethel a propo&-a is minimal risk o. less is made by a HUC- establishe accordance with VamrL.pl. 5-2b of this egufatiorrResearch in- volving deliberate exps~sure of human subjects to nuclear weapons effect, to chemical warfare agents, or to biological warfare agents. ,(5) Activities funded by non-Army resources in which the human subjects are DA military or civilian personnel. e. See appendix F for a listing of research exempt from the re- quirements of this regulation. Chapter 2 Responsibilities 2-1. The Under Secretary of Defense for Aquisition (USD (A)) In accordance with DOD Directive 3216.2, the USD (A) or desig- nee will be the approval authority for studies involving the actual exposure of human subjects to nuclear weapons effect, chemical warfare agents, or biological warfare a6ents. 500140 02-0 2-2. Assistant Secretary of Defense (Health Affairs) (ASD (HA)) In accordance with DOD Directive 32116.2, the ASD (HA) serves as the DOD representative on matters relating to implementation of Food and Drug Administr .ation (FDA)' regulatory requirements. 2-3. Assistant Secretary of the Army (Research, Development, and Aquisition) (ASA (RDA)) The ASA (RDA) will manage all DA RDTE activities, including those in which human use is planned. 2-4. The Deputy Chief of Staff for Personnel (DCSPER) The DCSPER will- a. Supervise and review RDTE activities under the Army Per- sonnel Performance and Training Program. b. Within established areas of responsibility, monitor RDTE in- volving human subjects to ensure implementation of policies con- tained in this regulation. c. Approve or disapprove those studies involving alcohol and drug abuse programs. 2-5 The Surgeon General The*Surgeon General (TSG) will- a. Prepare policies and regulations on research using human subjects. b. Establish and maintain the Human Subjects Research Re- view Board (HSRRB), chaired by the Assistant Surgeon General for Research and Development. c. Establish and maintain the Human Use Review and Regula- tory Affairs.Office (HURRAO) attached to the U.S. Army Medi- cal Research and Development Command (USAMRDC) and reporting to the Assistant Surgeon General for Research and Development. d Approve or disapprove research proposals from major Army Commands (MACOMs) that do not have a HUC or an internal review process. e. Provide an evaluation of protocols as described in paragraphs 2-1 and 2-4, above, and 2-6, below, to the following heads of of- fices or command: (1) The USD (A). (2) The DCSPER. (3) Upon request, the Commander, SSC-NCR. f. Be the approval authority for studies and research protocols involving human subjects using Schedule I controlled drug substances. g. Be the approval authority for research involving minors, or other vulnerable categories of human subjects, when subjects are wards of a State or other agency, institution, or entity, h. Be the approval authority for MACOM or agency requests to establish a HUC and a human use review process. ~ L Manage the Army's Health Hazard Assessment Program and assess health hazards of medical and nonmedical materiel. j. Direct medical followup, when appropriate, on research sub- jects to ensure that any long-range problems are detected and treated. - k- Report on a frequent basis, findings associated with classified investigational drug and device studies to the USD (A), the ASD (HA), and the FDA. L Be the approval authority for all in-house and contract re- search (other than that noted in paras 2-1, 2-2, 2-4, and 2--6) in- volving human subjects for which the Army has been designated the executive agent. Except for those categories of research noted above for which TSG is specifically designated as the approval au- thority, the authority to approve such research may be delegated by TSG within the military chain of command to the lowest level operating a human-subjects review process approved pursuant to paragraph 3-2b. AR 70-25 UPDATE Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 2-6. Commander, Soldier Support Center-National Capl~al Re9J ~?r Release 2000/08/08 p r'" TheComman r, l be the approval authority in ac- cordance with AR 600-46 for attitude and opinion surveys or Ar- my occupational surveys. 2-7. Major Army commanders These commanders will- a. Monitor RDTE involving personnel within their command to ensure effective implementation of the policies and procedures contained in this regulation. b. Provide assistance to volunteer recruiting teams. c. Ensure that only individuals who freely volunteer to partici- pate are enrolled in research protocols or studies. 2-8. Commanders of RDTE organizations These commanders will- a. Ensure the effective implementation of the policies and pro- cedures contained in this regulation. b. Use the established review process through TSG's HSRRB for all protocols and test plans or establish a HUC and implement review process consistent with the policies and procedures con- tained in this regulation. c. Ensure that research volunteers are adequately informed con- cerning the risks associated with their participation, and provide them with any newly acquired information that may affect their well-being when that information becomes available. d. Comply with AR 40-10, AR 70-10, AR 385-16, AR 602-1, and AR 602-2 in planning and conducting development and/or operational testing- 2-9. Other responsibilities a. Members of the HSRRB will- (1) Evaluate methods by which DA involves human subjects in research. (2) Recommend policy to TSG on the treatment of volunteers consistent with current moral, ethical, and legal standards. (See app G for legal implications.) (3) Evaluate research protocols and test plans submitted to TSG for approval. b. The Chief of the HURRAO will- (1) Provide, for TSG, administrative support for the HSRRB. (2) Conduct a compliance review of all protocols submitted to TSG for approval. (3) Submit DA-sponsored Notices of Claimed Investigational Exemption for a New Drug (INDs) and Investigational Device Exemptions (IDEs) directly to the FDA. (4) Submit DA-sponsored New Drug Applications (NDAs) di- rectly to the FDA. (5) Maintain DA record files for IND and NDA submissions to the FDA. (6) Conduct post-marketing surveillance for NDAs sponsored by DA. (7) Serve as the DA point of contact for policies and regula- tions on human use in RDTE programs. (8) Advise and assist MACOMs and DA staff agencies that conduct research or sponsor research by contracts and grants that involve the use of human volunteers. c. Investigators will- (1) Prepare a protocol following the policies and procedures in this regulation. (2) Prepare adequate records on- (a) Receipt, storage, use, and disposition of all investigational drugs, devices, controlled drug substances, and ethyl alcohol. (b) Case histories that record all observations and other data important to the study. (c) Volunteer informed consent documents (see app E). The principal investigator will fill in the information in parts A and B of DA Form 5303-R and inform the subject of each entry on the form. (3) Prepare progress reports, including annual reports, as deter- mined by the approving authority and regulatory agencies. (4) Promptly notify the approving authority, through the medi CtA-~ROP98407438ROO16004AM2c4sed by the research. (5) Report serious and/or unexpected adverse experiences in- volving the use of an investigational device or drug to the sponsor and the FDA in accordance with AR 40-7. (6) Ensure that the research has been approved by the proper review committee(s) before starting, changing, or extending the study. (7) Ensure that all subjects, including those used as controls, or their representatives are fully informed of the nature of the re- search to include potential risks to the subject. (8) Ensure that investigational drugs or devices are adminis- tered only to subjects under their personal supervision, or that of a previously approved associate investigator. (9) Ensure that a new principal investigator (PI) is appointed if the previously appointed PI cannot complete the research (for ex- ample, permanent change of station (PCS), retirement, etc.). (10) Apprise the HUC of any investigator's noncompliance with the research protocol. (11) Seek HUC approval for other investigators to participate in the research. (12) Ensure that research involving attitude or opinion surveys are approved in accordance with AR 600-46 (3-2c(5) below). d. Volunteer recruiting teams. Members will- (1) Establish volunteer requirements prior to recruitment. (2) Coordinate recruiting activities with unit commanders. (3) Undertake recruiting in a moral, ethical, and legal manner. e. Medical monitor. The medical monitor is responsible for serving as advocate for the medical safety of volunteers. The mon itor will have responsibilities as determined by the approving offi cial and the authority to suspend or terminate the effort consistent with the policies and procedures contained in this regulation. Chapter 3 Research 3-1. General guidance a. Only persons who are fully informed and volunteer in ad- vance to take part may be used as subjects in research; except, when the measures used are intended to be beneficial to the sub- ject, and informed consent is obtained in advance from a legal rep- resentative on the subject's behalf b. Nothing in this regulation is intended to limit the authority of a health care practitioner to provide emergency medical care under applicable law of the jurisdiction in which care is provided. c. Any human tissue or body fluid, obtained by autopsy, and used in research will be donated for such purpose. The donor will be the next of kin or legal representative of such person. Donation is made by written consent and relinquishes ownership and/or rights to the tissue or fluid. Consent to donate will not preclude payment for such donation. Organ donation intended for trans- plant will be accomplished in accordance with AR 40-3, chapter 18, d. Any tissue or body fluid linked by identifiers to a particular person, obtained by surgical or diagnostic procedure and intended for use in research will be donated for such purpose. The donor will be the person from whom the tissue or fluid is removed or, in the event of death or legal disability of that person, the next of kin or legal representative of such person. Donation is made by writ- ten consent and relinquishes ownership and/or rights to the tissue or fluid. Consent to donate does not preclude payment for such donation. e. The determination of level of risk in a research protocol will be made by a HUC established in accordance with this regulation. (See app G for a complete listing of legal implications.) f Moral, ethical, and legal concepts onthe use of human sub- jects will be followed as outlined in this regulation. Voluntary con- sent of the human subject is essential. Military personnel are not subject to punishment under the Uniform Code of Military Justice 4 AR 70-25 UPDATE Approved For Release 2000/08/08 CIA-RDP96-00788ROO1500140002-0 . g6s~uman su for chx 'a not lioaa,~ par VJigYdr0~Wr1Co minis rw s Wir aspi Mi&A-R[Ak personnel for choosing not to participate as human subjects. g. RDTE using human subjects is conducted in such a manner that risks to the subjects are minimized and reasonable in relation to anticipated benefits. h. The proposed number of subjects is the minimum needed to ensure a statistically valid conclusion. L The research is conducted in such a manner as to avoid un- necessary physical and mental suffering. Preparations are made and adequate facilities provided to protect the subject and investi- gators against all foreseeable injuries, disabilities or death. Such research is not to be conducted if any reason exists to believe that death or injury will result. j. Volunteers are given adequate time to review and understand all information before agreeing to take part in a study. k- Volunteers are authorized all necessary medical care for in- jury or disease that is a proximate result of their participation in research. (1) Medical care for civilian employees who volunteer and who perform duty as a volunteer during their regularly scheduled tour of duty will be providcd in accordance with AR 40-3. (2) Medical care costs for all other categories of personnel, who under the provisions of AR 40-3 are routinely authorized care in a military MTF will be waived for the volunteer while in the -hos- pital, if the volunteer would not normally enter the hospital for treatment but is requested to do so to facilitate the research. This also applies to a volunteer's extension of time in a hospital for re- search when the volunteer is already in the hospital. (3) Subsistence charges for all other categories of personnel, ex- cept for active duty and retired commissioned officers, may be waived in the circumstances noted in (2) above. The costs for sub- sistence charges for commissioned officers may be reimbursed to the officer by the research organization. (4) Costs of medical insurance coverage or direct charges for medical care for volunteers participating in research performed by a contract or grant may be negotiated between the DA contracting officer and the contractor or grantee. (See app G.) 1. Information obtained during, or as a result of, an epidenno logic-assessment interview with a human immunodeficiency virus rAA%6~o6 is so limited that (b) Procedure involved in the research holds out a prospect for direct benefit that is important to the health or well-being of the minor, and is available only in the context of research. p. The personnel responsible for the conduct of the research are the best qualified to recruit volunteers for a study and should be the primary recruiters whenever possible. q. Only persons judged qualified by the appropriate approving official will conduct research involving human subjects. r. A medical monitor is appointed by name if the HUC or ap- proving official determines that the risk is more than minimal. A medical monitor may be appointed to minimal risk or less than minimal risk studies if so determined by the HUC or approving authority. The principal investigator may function as medical monitor only in situations where no other physician is reasonably available and approval for the principal investigator to function as medical monitor is granted by TSG. Requests for the principal in- vestigator to function as the medical monitor will be sent to the Assistant Surgeon General for Research and Development, c/o Headquarters, U.S. Army Medical Research and Development Command, ATTN: SGRD-HR, Fort Detrick, Frederick, MD 21701-5012. s. Safeguards or special conditions imposed on a protocol by a HUC may not be reduced or waived by the approving official up- on approval of the protocol. The approving official may require additional safeguards, may disapprove the protocol, or may refer it to a higher review and approving authority. t. User testing, as defined in AR 71-3, which involves the use of volunteers, is reviewed and approved by a HUC established in accordance with this regulation. u. Research on medical devices is conducted in accordance with Part 812, Title 21, Code of Federal Regulations (21 CFR 812) v. Emergency one-time use of an investigational drug or medi- cal device is accomplished to the extent permitted under applica- ble law and in accordance with AR 40-7. w. Public Affairs guidelines on the release of information are in AR 360-5. k... ,I - .... ... V. k~.~ . VLV~a -ay nvv ., used to support any adverse personnel action against the member. (See glossary for definition of the terms "epidemiologic-assessment interview," "serum positive member of the Armed Forces," and "adverse personnel action.") rn. Research may be conducted outside the United States that involves non-U.S. citizens (for example, research on diseases of military interest, such as malaria, that are not endemic to the United States). However, in the conduct of such research, the laws, customs and practices of the country in which the research is conducted or those required by this regulation, whichever are more stringent, will take precedence. The research must meet the same standards of ethics and safety that apply to research con- ducted within the United States involving U.S. citizens, and will be conducted in accordance with applicable international agreements. n. The use of prisoners of war and detainees as human research subjects is prohibited. o. Minors may be enrolled as human research subjects when the following conditions are met: (1) The research is intended to benefit the subject, and any risk involved is justified by the expected benefit to the minor. (2) The expected benefits are at least as favorable to the minor as those presented by available alternatives. (3) A legally authorized representative has been fully informed and voluntarily consents, in advance, for the minor to participate in the research. (4) The minor, if capable, has assented in writing. In determin- ing whether the minor is capable of assenting, the HUC will con- sider the minor's age, maturity, and psychological state. The HUC may waive assent for some or all minors involved in the study if it determines that the- 3-2. Procedural guidance a. Duties. MACOM commanders and organization heads con- ducting RDTE research involving human subjects will- (1) Publish directives and regulations for- (a) Protocol and/or test plan preparation (see app, B). (b) The use of volunteers as subjects of research conducted or sponsored by the organization. (c) The procedures for reporting and responding to reports of improper use of volunteers as subjects of research conducted or sponsored by the organization. (d) The procedures to assure that the organization can accom- plish its "duty to warn" (see para 3-2h for a discussion of "duty to warn"). (2) Forward one copy of published regulations and directives (see (1) above) to the Assistant Surgeon General for Research and Development, c/o Headquarters, U.S. Army Medical Research and Development Command, ATTN: SGRD-HR, Fort Detrick, Frederick, MD 21701-5012, within 60 days of publication. (3) Establish a HUC, if appropriate (see b below). (4) Establish a system that permits the identification of volun- teers who have participated in research conducted or sponsored by that command or organization. Such a system will be established in accordance with AR 340-21. (App H describes data elements which could comprise such a system.) b. Establishing a HUC. As noted in paragraph 2-8b, com- manders or heads of RDTE organizations will either use TSG's HSRRB or implement their own HUC. (1) HUCs will be established for research conducted by DA in accordance with appendix C. (2) Institutional review boards will be established by contrac- tors or grantees in accordance with 45 CFR 46. Approved For Release 2000/08/0 :WA-i -00788RO01 500140002-0 (3) RDTE o An PTtQ)1seAi6P1sEWJJeW%t2W04QB408: AL4mRDR9S4W66RQ04oMt4( Ll whether rm WID LTO procesR will forward the items listed below to the Assistant Sur- geon General for Research and Development, c / o Head- quarters, U.S. Army Medical Research and Development Command, ATTN: SGRD-HR, Fort Detrick, Frederick, MD 21701-5012. (a) See a(2) above. (b) A listing of the membership of the HUC and the curricu- lum vitae for each member. (4) Newly established HUCs may not review research protocols until the items in (a) and (b) above are reviewed and approved by TSG. c. Protocol andlor test plan review before submission to a HUC. (1) A protocol or test plan will be prepared for all research re- quiring approval pursuant to this regulation. Certain studies may be exempt (see app F). The format in appendix B should be fol- lowed, but may be modified to meet local requirements. DA Pam 70-21 and DA Pam 71-3 provide guidance for preparation of test plans and equivalent documents. Protocols and test plans are ex- empt from management information requirements per AR 335-15, para 5-2b. An informed consent document will be pre- pared using DA Form 5303-R (Volunteer Agreement Affidavit), or functional equivalent, in accordance with appendix E (see d be- low). DA Form 5303-R will be reproduced locally on 8 ~6 - by I I - inch paper. A copy for reproduction is located at the back of this regulation. (2) If a study calls for the use of tissue or fluids obtained from a human, and is not an exempt study as defined by appendix F, par- agraph e, then a protocol is prepared. The following must be con- sidered in determining whether informed consent is required. (a) Fluid or tissue obtained at autopsy: informed consent is required. (b) Fluid or tissue obtained at surgery or as the result of a diag- nostic procedure and linked by identifiers directly or indirectly to a particular person intended for research: informed consent is required. (c) Fluid or tissue obtained at surgery or as the result of a diag- nostic procedure not intended for research and not linked by iden- tifiers: no informed consent is required. (d) Fluid or tissue obtained from a tissue or blood bank which is linked to a personal identifier and the research data is recorded in such a manner as to identify the donon informed consent is required. (e) Fluid or tissue obtained from a tissue or blood bank, which is linked to a personal identifier, but the research data is recorded in such a manner that the donor's identity is unknown: no in- formed consent is required. (0 Fluid or tissue obtained from a tissue or blood bank which is not linked to a personal identifier: no informed consent is required. (The informed consent document used in these cases may be the DA Form 5303-R, an overprinted consent for surgery or autopsy, or other form approved by the HUC and the forms management office at the organization.) (3) The protocol or test plan is submitted to a scientific review committee composed of individuals qualified by training and expe- rience, and appointed by the commander of the unit to evaluate the validity of the protocol. The purpose of this peer review is to assure that the protocol design will yield scientifically useful data which meets the objective(s) of the study. The committee recom- mendations and actions taken by the investigator in response to the recommendations are submitted with the protocol to the HUC. (4) When applicable, the protocol or test plan will be submitted to the radioisotope/radiation control committee, or equivalent, es- tablished in accordance with TB MED 525. The committee rec- ommendations and actions taken by the investigator in response to those recommendations are submitted with the protocol to the HUC. (5) When applicable, the protocol will be submitted to the SSC-NCR for research which calls for the use of an attitude or opinion survey, as defined by AR 600-46. If such studies are the survey requires approval of that Center. This information should accompany the proposal when it is submitted for review. Surveys that cross command lines or are sent to other Services re- quire approval. Inquiries should be directed to Commander, SSC- NCR, Attitude and Opinion Survey Division, ATTN: ATNC- MOA, 200 Stovall Street, Alexandria, VA 22332-0400 (AUTOVON 221-9680). d. Informed consent documentation. The subject's agreement to participate in the study will be documented using DA Form 5303-R, or functional equivalent, in accordance with appendix E. If additional pages are required, plain bond paper will be used and each page will be initialed by the volunteer and the witness. This form is not appropriate for research performed by contract. The volunteer agreement will be written in language that is easily un- derstood by the subject. In research conducted outside the United States involving non-U.S. citizens, a locally produced form in the subject's native language may be used. An English translation of the form will be provided to the HUC. e. Protocol andlor test plan review after submission to the local HUC (1) HUC actions. (a) The HUC determines the level of risk associated with the protocol or test plan. (b) The HUC may make the following recommendations to the approving authority: Approved, approved with modification, defer review to higher authority, disapproved, or exempt from further human use review. (c) The HUC requires that the information given to subjects as a part of the informed consent is in accordance with the applicable portions of appendix E. The committee may require that informa- tion, in addition to that specifically mentioned in appendix E, be given to the subject when, in the HUC's judgement, the informa- tion would meaningfully add to the protection of the rights and welfare of the subject. (d) The HUC reviews research involving minors. The commit- tee will determine if assent is required and establish the method documenting such assent. The committee may waive the require- ment for assent provided the HUC finds and documents that the research could not practicably be carried out without the waiver (see para 3-lo(4)). (e) The HUC reviews research involving wards of a State agen- cy, and other vulnerable categories of human subjects. The HUC determines if the use of such a category of subjects is warranted. If, in the opinion of the committee, the use of this category of sub- jects is appropriate, then the protocol is forwarded through com- mand channels to the Assistant Surgeon General for Research and Development, c/o Headquarters, U.S. Army Medical Research and Development Command, ATTN: SGRD-HR, Fort Detrick, Frederick, MD 21701-5012, for approval. (0 The HUC conducts a continuing review of the research ap- proved by the HUC at intervals appropriate to the level of risk, but at least annually, The format for the review (for example, pro- greSs report from the investigator) will be determined by the HUC. (g) A HUC reviews research involving medical devices. If, in the opinion of the HUC, the device does not pose a significant risk to the research subject, the organization will not be required to submit an IDE to the FDA. (h) Certain categories of research may be reviewed by the HUC using the expedited review procedures in g below. (i) Exempt categories of research are discussed in appendix F. (2) Approving official actions. Approving officials- (a) Will accept or reject the recommendations of the HUC. Safeguards or special restrictions imposed on a protocol by a HUC may not be reduced or waived by approving officials upon approv- al of the protocol or test plan. (b) May require additional safeguards, may disapprove the pro- tocol or test plan, or may refer it to a higher review committee and approving authority. (c) Appoint a medical monitor (see glossary) for all studies that are greater than minimal risk. 6 Approved For Release 2000Q&M&:- (DPA4RDP96-00788 ROO 1500140002-0 (d) Obtain a health hazard assessment(b) prior to approving a re- If research is conducted in-house, primary responsibility 4 br~_C&al investigator is search ~k"ftved IRO!bRIaled~Sea2OO6lOi8tWreCIA-R'M PV-ft7VfflkMisobp bb ation of military materiel. ass ign (e) Notify the investigator of their(c) decision to approve or disap- If research is not funded by a DOD or DA component and prove the research proposal, or of there modifications required to secure is no DOD or DA principal investigator, primary responsi- approval. bility rests with the component to which the prospective human (f) Ensure the continued evaluation subject of research programs by is assigned. the program or project manager or (3) equivalent official to assure Studies funded by the Uniformed Services University of the that the policies and procedures Health established by this regulation are Sciences (USUHS) or the Defense Nuclear Agency are re- being followed. viewed and approved in accordance with policies established by (g) Will, when higher approval authoritythe is required, forward funding activity, and DODD 3216.2. two copies of the research protocol j. or test plan, informed consent Records. Organizations or agencies conducting research in- documentation (DA Form 5303-R, or volving functional equivalent if ap- volunteers will maintain records in accordance with AR plicable), all minutes of committees25-400-2, reviewing the protocol, and which are pertinent to the research conducted. These the commander's recommendations throughrecords command channels will include, at a minimum- to the Assistant Surgeon General (1) for Research and Development, Documentation of approval to conduct the study. c/o Headquarters, U.S. Army Medical (2) Research and Develop- A copy of the approved protocol or test plan. ment Command, ATTN: SGRD-HR, Fort (3) Detrick, Frederick, The volunteer's signed informed consent (for example, DA MD 21701-5012. Form 5303-R). f Actions taken by an organization (4) without a local HUC. A summary of the results of the research, to include any un- (1) The investigator accomplishes toward the actions noted in c above. reactions or occurrences. (See app H for a discussion of (2) The commander or organizational the head accomplishes the composition of the Volunteer Data Base.) actions noted in e(2)(d) above, and k. forwards the protocol with his Contractors or grantees. Contractors or grantees holding an or her recommendations, through the approved military chain of command, Department of Health and Human Services (DHHS) to the next level of command having Form an approved HUC. HHS 596 (Protection of Human Subjects Assurance/Certifi- g. Expedited review procedures. Thesecation/Declaration) procedures are as follows: are considered in compliance with this regula- (1) Research activities involving tion. no more than minimal risk (See fig 3-1 for sample DHHS Form HHS 596.) In the and in which the only involvement absence of human subjects will be in of such an assurance, a special assurance will be negotiat- one or more of the categories listeded at appendix D may be re- by the contracting officer with the contractor or grantee. Orga- viewed by the HUC through the expeditednizations review procedure. can verify that a contractor has a valid DHHS Form (2) The HUC may also use the expeditedHHS review procedure to 596 by contacting the Assistant Surgeon General for Re- search and Development, c/o Headquarters, U.S. Army Medical review minor changes in previously Research approved research during the and Development Command, ATTN: SGRD-HR, Fort period for which approval is authorized.Detrick, Under an expedited re- Frederick, MD 21701-5012. Even though a contractor view procedure, the HUC chairman has or one or more HUC review- a review process which is consistent with Federal law (that is, ers designated by the chairman may 45 carry out the review. The CFR 46), it is incumbent upon the approving official to admin- reviewers may exercise all of the istratively authorities of the HUC except review the protocol to assure that it complies with the that of disapproval. Research may policies be disapproved only after re- established in this regulation. view according to the nonexpedited 1. procedure in e above. Technical reports and publications. (3) Each HUC using an expedited review(1) procedure adopts a Technical reports will be prepared in accordance with AR method for keeping all members and 70-31 the commander advised of and follow the format established in MIL-STD 847B or its approved proposals. revisions. (4) The approving official may restrict,(2) suspend, or end a Publications regarding the results of DA conducted re- HUC's use of the expedited review search procedure when necessary to will be released by the approving official in accordance with protect the rights or welfare of the subjects. provisions of AR 360-5 and will contain the following state- h. Duty to warn. Commanders have ment: an obligation to ensure that "The investigators have adhered to the policies for protec- research volunteers are adequately tion informed concerning the risks of human subjects as prescribed in AR 70-25." involved,with their participation (3) in research, and to provide them Publications regarding the results of DA sponsored research with any newly acquired information conducted that may affect their well-be- by contract or grant will note adherence with 45 CFR ing when that information becomes 46, available, The duty to warn as amended. exists even after the individual m. volunteer has completed his or her Requests for exceptions to policy. Requests for exceptions to participation in research. To accomplishpolicy this, the MACOM or are submitted to the Assistant Surgeon General for Re- agency conducting or sponsoring researchsearch must establish a system and Development, c/o Headquarters, U.S. Army Medical which will permit the identificationResearch of volunteers who have partic- and Development Command, ATTN: SGRD-HR, Fort ipated in research conducted or sponsoredDetrick, by that command or Frederick, MD 21701-5012. Requests will then be sub- agency, and take actions to notify mitted volunteers of newly acquired in- to TSG's HSRRB for evaluation and recommendation to formation. (See a above.) TSG; and TSG's recommendation to the ASD (HA) or USD (A), L Determining responsibility for as review of protocols when more appropriate. than one DOD or DA component is involved. The commander will determine primary responsibility based upon consideration of whether the subjects are inpatients or outpatients of a DOD medi- cal treatment facility (MTF); whether the study is conducted in- house or by contract; or whether the prospective subjects are members of a DOD component. (1) When the research, regardless of in-house or contract sta- tus, involves use of patients in a DOD MTF, the component to which the MTF belongs organizationally will have primary re- sponsibility; except as provided in (3) below. (2) For research not involving the use of inpatients at a DOD MTF, primary responsibility rests as follows: (a) If the research is done on grant or contract, primary re- sponsibility rests with the component providing funds. AR 70-25 UPDATE Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 Approved For Release 2000/061WM IA-RDP96-00788 ROO 15OO14Q90.2aQ..,, DEPARTMENT OF HEALTH AND HUMAN SERVICES C3 GRANT Q CONTRACT C3 FELLOW 0 OTHER PROTECTION OF HUMAN SUBJECTS 0 Now 0 Competing 0 Noncompoting 13 Supplernomts! ASsURANCE/CERTIFICATION/DECLARATION continuation continuation ORIGINAL 0 FOLLOWUP C3 EXEMPTION APPLICATION IDENTIFICATION No. 0fknovM) Iprvviously undesignated) POLICY: A research activity involving human subiects that is not exempt from HNS regulations may not be funded union an Institu- tional Review Board (IRO) has reviewed and approved the activity in accordonce with Section 474 of the Public Health Solvice Act as implemented by ritle 45, Part 46 of the Code of Federal Regulations (45 CFft 46-as revised). The applicant institution must submit ctIrrificstion of IRS approval to HHS unless the applicant institution has designated a specific exemption under Section 46. 101 (b) which Mp/;m to the proposed research activity. Institutions with an anurance of compliance on file with HNS vAich cowrs the proposed activity should submit certification of IRS review and approval with each application. (in exceptional cam, certification may be ac. cdpted up to 60 days after the receipt date for which the application is submitted.) In the cam of institutions which do not have an assurance of compliance on file with HNS covering the proposed activity. certification of IRS review and approval must be submitted within 30 days of the receipt of a written request from HHS for certification. 1. TITLE OF APPLICATION OR ACTIVITY Evaluation of Mefloquine in the Treatment of P.falciparum malaria 2. PRINCIPAL INVESTIGATOR, PROGRAM DIRECTOR, OR FELLOW John Boslegb, MD 3. FOOD AND DRUG ADMINISTRATION REQUIRED INFORMATION Iwo reverse side) 4. HNS ASSURANCE STATUS This institution has an approved anurance of compliance on fife with HNS which covert this activity. M1369 - Assurance identification number - IRS identification number No assurance of compliance which applies to this activity hot been established with HNS but the applicant institution will provide written assurance of complience and certification of I RB review and approval in accordenca with 45 CFA 46 upon request. 5. CERTIFICATION OF IRS REVIEW OR DECLARATION OF EXEMPTION This octWity has been reviewed and approved by an IRS in accordance with the requirements of45 CFA 46, including in relevant Suboaru. This certifi- cation fulfills, whom applicvWo, requirements for certifying FDA status for each investigational now drug or device law reverse sido of this form). Jul 31.1987 Date of IRS review and approval. Of approval is pending. write "pending". Followupewtificationisrisquirvd.) (month1davIvead Full Board Review Expedited Review This activity contains multiple projects, sonu of which have not been reviewed. The IRS has granted approval on condition that oil projects covered by 45 CFA 46 will be roviso, and approved before they am initiated and that appropriate further certification (forr" HNSSM) will be submitted. Human subjects or* involved but this activity quallifin for exemption under 40.101 lb) in accordance with perWN* - linswrpon*Wk nuny- bar of exemption in 46. 1011b), I through 6), but the institution did not designate that oxemation an the application. 6 Each official signing below certifies ftt do information provided on this form is correct and that each Institution assumes tesponsibility for sissuring required fuwre reviews, approvals, and submissions of certification. APPLICANT INSTITUTION COOPERATING INSTITUTION NAME, ADDRESS, AND TELEPHONE NO. NAME, AOORGS8, AND TELEPHONe NO. Wonderful University PO Box 7 Anywhere, State 65473 NAME AND TITLE OF OFFICIAL *ifit NAME AND TITLE OF OF PICIAL J~Pdnt Or CYPS) Of type) William D. Clyde, Jr Cl~ancellor for Health Affairs liOIGN41TUPIE OF OFFICIAL LOS ED SIGNATURE OF OFFICIAL LISTED A~OV9 A1110ye Ianddeto) (SiOddaft) ace HHS Be$ imew. 1/821 11foalkilitional~ isnestollod. pAssetuarmerso sidounaills, *Won&-j Figure 3-1. Sample DHHS Form HHS 596 8 Approved For Release 2000/o'9/6W~'61W-W'ffP96-00788RO01 500140002-0 Approved For Release 2000/O8/O8sA0Ar,-RDP96 -00788 Roo 1500140002-0 3. FOOD AND DRUG ADMINISTRATION REQUIRED INFORMATION Ifforn front side) According to 45 CFR 40.121. if an application is made W "HS requiring ce"ification and involving use of an invatiolional flow drug or device. 6"- tional information is required. In addition, according to 21 CFA 312AN112), 30 days must sispee between date Of receipt by FDA of Form FO-1571 and use of the druo. unless the 30 day delay period is waived by FDA. 3s. INVESTIGATIONAL NEW DRUG EXEMPTION fit MOAP 1010" One it lftvofvad~ list Others below under florft): SPONSOR NAME Hoffman LaRoche, Inc DRUG NAME 14efloquine, 250'mg tablet EXPIRATION OR WAIVER I NUMBER ISSUED 1 Apr 85 IND 1423 3b. INVESTIGATIONAL DEVICE EXEMPTION: SPONSOR NAME DEVICE NAME. Unless notified otherwise by FDA, under 21 CFR 812.2(b) Yll a sponsor is deemed to have an approved IDE if: (1) the I RS has agreed with the sponsor that the device is a nonsignificant risk dilvice; and (2) the IRS has approved the study. faaclrappliGable box.) 0 The IRS agrees with the sponsor that this device is a nonsignificant risk device. OR 0 The IDE application was submitted to FDA on (date) Number ismied NOTES, HMO GM (Rev. 1/621 BACK Figure 3-1. Sample DHHS Form HHS 596-Continued Approved For Release 2000/08/08AP CM§R dF"N'E-O0788 ROO 1500140002-0 AppendiAPproved For Release 2000/08/08 : ClA9RDP%u047WRN1180~9P40W2aQnd Standards ReferencLas Requisition).) Section I Required Publications AR 25-400-2 The Modern Army Recordkeeping System (MARKS). (Cited in paras 3-2j and C-6b.) AR 40-3 Medical, Dental, and Veterinary Care. (Cited in para 3-1c and k-) TB MED 525 Occupational and Environmental Health Control of Hazards to Health from Ionizing Radiation Used by the Army Medical De- partment. (Cited in para 3-2c(4).) Section 11 Related Publications A related publication is merely a source of additional information. The user does not have to read it to understand this regulation. AR 40-7 Use of Investigational Drugs in Humans and the Use of Schedule I Controlled Drug Substances. (Cited in paras 1-4c, 2-9c(5), and 3-lv.) AR 40-10 Health Hazard Assessment Program in Support of the Materiel Acquisition Decision Process. (Cited in para 2-8d.) AR 70-10 Test and Evaluation During Development and Acquisition of Ma- teriel. (Cited in para 2-8d and the glossary.) AR 70-31 Standards for Technical Reporting. (Cited in para 3-21(l).) AR 71-3 User Testing. (Cited in para 3-1t.) AR 335-15 Management Information Control System. (Cited in para 3-2c(l).) AR 340-21 The Army Privacy Program. (Cited in paras 3-2a(4) and H-1.) AR 360-5 Army Public Affairs, Public Information (Cited in paras 3-1w and 3-21(2).) AR 385-16 System Safety Engineering and Management. (Cited in para 2-8d) AR 600-46 Attitude and Opinion Survey Program. (Cited in paras 2-6, 2-9c(12), and 3-2c(5).) AR 602-1 Human Factors Engineering Pr Iogram. (Cited in para 2-8d.) AR 602-2 Manpower and Personnel Integration (MANPRINT) in Materiel Acquisition Process. (Cited in para 2-8d.) DA Pam 70-21 The Coordinated Test Program. (Cited in para 3-2c(l).) DA Pam 71-3 Operational Testing and Evaluation Methodology and Procedures Guide. (Cited in para 3-2c(l).) AR 11-2 Internal Control Systems AR 40-38 Clinical Investigation Program AR 40-66 Medical Record and Quality Assurance Administration AR 70-14 Publication and Reprints of Articles in Professional Journals AR 70-65 Management of Controlled Substances, Ethyl Alcohol, and Haz- ardous Biological Substances in Army Research, Development, Test, and Evaluation Facilities AR 600-50 Standards of Conduct for Department of the Army Personnel AR 611-3 Army Occupational Survey Program (AOSP) DODD 3216.2 Protection of Human Subjects in DOD-Supported Research. (To obtain this publication, see MIL-STD 847B, see 1, above.) DODD 6465.2 Organ Disposition After Autopsy. (To obtain this publication, see MIL-STD 847B see 1, above.) FM 3-9/AFR 355-7 Military Chemistry and Chemical Compounds DHHS Regulation, 45 CFR 46 Protection of Human Subjects. (This publication is available from Commander, USAMRDC, ATTN: SGRD-HR, Fort Detrick, Frederick, MD 21701-5012.) FDA Regulation 21 CFR subchapters A, D, and H Food and Drugs. (This publication is available for reference at the local installation staff judge advocate office.) Memorandum of Understanding between the FDA and DOD Investigational Use of Drugs by Department of Defense, May 21, 1987. (This publication is available from the Commander, USAMRDC, ATTN: SGRD-HR, Fort Detrick, Frederick, MD 21701-5012.) MIL-STD 847B Format Requirements f6r Scientific and Technical Reports Pre- 10 USC 980 pared by or for the Department of Defense. (Cited in para Limitation on the Use of Humans as Experimental Subjects. (This 3-21(l).) (This publication is available from the Naval Publica- publication is available for reference at the local installation staff tions and Forms Center, 5801 Tabor Avenue, Philadelphia, PA judge advocate office.) 10 Approved For Release 2000/08MV-01ALMM16-00788 ROO 1500140002-0 w1or Published in the 10 us6pffoved For Release 2000/08/08: ClA-RDP964*74NW?&=c4eMt Restriction on the Use of Information Obtained During Certain proposed area of study. the way in ch the project will Epidemiologic-Assessment Interviews. (This publication is availa- relate to, or differ from, that which has been accomplished. ble for reference at the local installation staff judge advocate e. Bibliography. List all references used in preparing the office.) protocol. Unnumbered Publication Convention on the Prohibition of the Development, Production, and Stockpile of Bacteriological (Biological) and Toxin Weapons and on their Destruction, Article 1. (This article is printed as a part of the publication entitled "Arms Control and Disarmament Agreements: Text and Histories of Negotiations", and is available from the U.S. Arms Control and Disarmament Agency, Washing- ton, D.C. 20451.) Section III Prescribed Form DA Form 5303-R Volunteer Agreement Affidavit. (Prescribed in para 3-2c(l).) Section IV Referenced Forms DD Form 1425 Specifications and Standards Requisition DHHS Form HHS 5% Protection of Human Subjects Assurance/.Certification/Declara- tion. (Only the contractor or grantee will obtain and use this form. This form after approval, however, is shown to the contracting of- ficer as proof of the contractor's or grantee's compliance with this regulation. See para 3-2k, fig 3-1, and the glossary.) Appendix B Guidelines for Preparation of Research Protocol and/or Test Plan 0-1. Project title Enter complete project title. (If an amendment, the words "Amendment to. . must precede the project title.) B-2. Investigators a. Principal investigator. b. Associate investigators. 0-3. Location of study List of facilities to be used. 0-4. Time required to complete Give month and year of expected start and completion dates. B-5. Introduction a. Synopsis. (1) One-page summary of proposed study similar to the ab- stract of a scientific paper. (2) Major safety concerns for human subjects briefly 8-6. Plan Outline expected accomplishments in enough detail to show a clear course of action. Include technological validity of procedures and chronological steps to be taken. The plan should include, as a minimum, the information shown below on the study subjects. a. Number of subjects. Give the total number of subjects ex- pected to complete the study. b. Age range. c. Sex. d. Inclusion criteria. Specific and detailed reasons for inclusion should be presented. e. Diagnostic criteria for entry. f Evaluations before entry. Entries should include x ray, physi- cal examinations, medical history, hematology, chemistry, and urinalysis as deemed appropriate. g. Exclusion criteria. Include a complete list detailing the sub jects, diseases, and medications that are excluded from the study. h. Source of subjects. Describe briefly where the subjects will be obtained. i. Subject identification. Describe the code system used. j. Analysis of risks and benefits to subjects; risks to those con- ducting research. k. Precautions to be taken to minimize or eliminate risks to subjects and those conducting the research. L Corrective action necessary. m. Special medical care or equipment needed for subjects ad- mitted to the project. B-7. Evaluations made during and following the project An evaluation may also be represented by using a project schemat- ic. It is very important to identify in the protocol the person who will perform the evaluations below. a. Specimens to be collected. (1) Amount and schedule of collections. (2) Evaluations to be made on specimens. (3) Storage. State where and if special conditions are required. (4) Labeling and disposition. (5) Laboratories performing evaluations. (6) Special precautions for subject and investigators'. b. Clinical assessments. Include how adverse effects are to be recorded. c. Vital signs. When desired and frequency. d. Follow up procedures. e. Disposition.of data. State location and duration of storage. f. Methods used for data collection. State critical measurements used as end points to characterize safety, efficacy, or equivalency. D-8. Departure from protocol for Individual patients a. "en allowed. Use flexible but definite criteria. b. Who will be notified. (For example, patient, HUC, approving official.) 0-9. Incidents highlighted. a. Definition of incidents. b. Military relevancy. Explain briefly the medical importance b. Immediate reporting. and possible usefulness of the project. c. Routine reporting. c. Objective& State briefly, but specifically, the objectives of the project. Include items below when applicable. 0-10. Modification of protocol (1) Study design. Describe the procedure to be followed if the protocol is to be mod- (2) Type of subject population observed. ified, terminated, or extended. Approved For Release 2000/08/08 ~Iaqk2RDM40788 ROO 1.500140002-0 B-11. Exam0MQv"Fswt9Qhe8rvah2QW108/08 I I B-12. Use of Information and publications arising from the study B-13. Special or unusual funding Implications B-14. Name and telephone number of the medical monitor, when applicable B-15. Human use committee Brief explanation of which HUC will provide. initial, continued, and annual review. B-16. Signature of appropriate approving official and date B-17. Documentation a. Completed DA Form 5303-R. b. Institutional review of scientific and human use issues. c. HUC review with commander's approval. d. Biographical sketch of principal and associate investigators. Appendix C Human Use Committees C-1. Membership a. Membership will include only full-time Federally employed persons. b. Each HUC will have at least five members. Members will have diverse backgrounds to ensure thorough review of research studies involving human volunteers as research subjects. Members should. be sufficiently qualified through experience and expertise. The racial and cultural backgrounds of members and their sensi- tivity to such issues as community attitudes should ensure respect for their advice and counsel in safeguarding the rights and welfare of human subjects. C. Besides having the professional competency to review re- search studies, the HUC will be able to determine if the proposed research is acceptable. Acceptability will be in terms of Army Medical Department (AMEDD) commitments and regulations, applicable law, and standards of conduct and practice. A HUC may review research periodically that involves vulnerable catego- ries of human subjects (for example, those individuals with acute or severe physical or mental illness; or those who are economically or educationally disadvantaged). Therefore, it will include one or more persons concerned primarily with the welfare of these subjects. d. Normally, no HUC may consist entirely of men or women, or members of one profession. However, the approving official may waive this requirement in those cases in which compliance is impractical. e. Each HUC will include at least one member whose primary concerns are nonscientific; for example, lawyers, ethicists, and members of the clergy. Should a given proposal include more than minimal risk, a physician will be included as an ad hoc member of the committee. f Each HUC will include at least one member who is not oth- erwise affiliated with the institution and who is not part of the im- mediate family of a person affiliated with the institution. This requirement may be met by appointing a member of an institution or organizational unit not subject to the immediate authority of the approving official. g. Except to provide information requested by the HUC, no HUC member may take part in a review of any project in which the member serves as the principal investigator or associate investigator. 12 Approved For Release 2000/08M8oz-26 CIA-RIDIP96407184"' ce to assist 4P'VA!pR1Ve% in the review of complex issues tha re eyond that available on the HUC. These persons may not vote with the HUC. L The approving official may not be a member. The approving official may not approve research for whibli he or she is also a principal or associate investigator. A higher echelon of command must review and approve such research projects. C-2. Functionsand operations Each HUC- a. Will observe written procedures for the following: (1) Conducting the initial and continuing review of the re- search. Included are reporting findings and actions to the investi- gator and the approving official. (2) Determining those projects that must be-- (a) Reviewed more often than yearly. (b) Verified from sources other than the investigators, that no material changes have occurred since the previous HUC review. (3) Ensuring prompt reporting to the HUC of proposed changes in the research. Each HUC will ensure that changes in approved projects (during the period for which approval has al- ready been given) are not initiated without HUC review except to eliminate immediate hazards to the subject. (4) Ensuring prompt reporting to the HUC and approving offi- cial of unexpected problems involving risks to the subjects or others. b. Will review proposed protocols at meetings attended by a majority of members except when an expedited review is used (see C-3 below). For the protocol to be approved, it will receive the approval of a majority of those members present. . c. Will report to the approving official any serious or continu- ing noncompliance with HUC requirements and determinations found by investigators. d -Will conduct continuing review of research studies at inter vals proper to the degree of risk, but not less than once per year, e. Will have the authority to observe or have a third party ob serve the consent process and the investigation. f Will maintain a current list of HUC members. Members will be identified by name, earned degrees, representative capacity and, experience such as board certificates and licenses. The information will be complete enough to describe each member's chief expected contributions to HUC reviews. Any employment or other relation- ship between members and the institution will be noted. g. May recommend safeguards or special conditions to a proto- col. If the HUC does so, the approving official may take the fol- lowing action. (1) Not reduce the safeguards or conditions if he or she ap- proves the protocol. (2) Require additional safeguards. (3) Disapprove the protocol. (4) Refer the protocol to a higher echelon approving authority and review committee. C-3. Expedited review procedures a. See appendix D for a list of categories of investigations that the HUC may review in an expedited review procedure. b. See paragraph 3-2g for the expedited review procedure that the HUC will follow. C-4. Criteria for HUC approval of activities/investigations requiring volunteers a. In evaluating risks and benefits for research investigations, the HUC should consider only those that may result from the investigation. b. To approve investigations covered by this regulation, the HUC will determine that all of the requirements below are met. (1) Risks to subjects are minimized by using procedures that are- (a) Consistent with sound investigation design and do not un- necessarily expose subjects to risk. (b) Already being used on the subjects for diagnosis or treat- ment, when appropriate. WIW96-00788 ROO 1,500140002-0 (2) R~P benefits to s 1!Jects. (3) In making an assessment for the selection of subjects, the HUC should take into account the- (a) Purpose of the investigation. (b) Setting in which the research investigation will be conducted. (4) Informed consent will be sought from each prospective sub- ject or the subject's legally authorized representative. (5) Informed consent will be properly documented. (6) The plan makes adequate provision for monitoring the data collected to ensure the safety of subjects when appropriate. (7) Adequate provisions exist to protect the privacy of subjects and to maintain the confidentiality of data when appropriate. c. Some or all of the subjects may be vulnerable to coercion or undue influence such as persons with acute or severe physical or mental illness, or those who are economically or educationally dis- advantaged. If so, proper additional safeguards will be included in the study to protect the rights and welfare of these subjects. C-5. Suspension or termination of approved research Investigation a. A HUC will have the authority to suspend or end an ap- proved investigation that- (1) Is not being conducted according to the HUC's requirements. (2) Has been associated with unexpected serious harm to subjects. b. Suspensions or terminations of research will include a state- ment of the reasons for the HUC's action. They will be reported promptly to the principal investigator and approval official. C-6. HUC records a. A HUC will prepare and maintain adequate documents on HUC activities, including- (1) Copies of all protocols reviewed, scientific evaluations that accompany the proposals, approved sample consent documents, progress reports submitted by investigators and reports of injuries and adverse reactions. (2) Minutes of HUC meetings showing attendance; actions tak- en by the HUC; the vote on these actions, including the number of members voting for, against, and abstaining on a decision; the ba- sis for requiring changes or disapproving the investigation; and a written summary of the discussion of controverted issues and their resolution. (3) Records of continuing review activities. (4) Copies of all correspondence between the HUC and the investigators. (5) A list of HUC members. (6) Written procedures for the HUC. (7) Statements of significant new findings. b. The records required by this regulation will be retained per- manently (see AR 25-400-2). Such records will be reasonably ac- cessible for inspection and copying by authorized DA personnel and representatives of the FDA. C-7. Conflict of Interest a. It is essential that the members of the HUC continue to be perceived and, in fact, are free from conflict of interest in their daily duties and especially in regards to the protocols they review. b. The issue of conflict of interest has been addressed by public law, DOD directive, and Army regulation. The situations dis- cussed below are merely examples of the types of activities and re- lationships which may result in conflict or the appearance of conflicts of interest. They are by no means the only ways that con- flicts arise. (I The potential for personal or financial gain. A committee member who is deliberating a protocol which is to be performed by a contractor, in which the member or a member of his or her immediate family is a corporate officer, stockholder, consultant or could be accused of conflict of interest if he or she vot member (2) The potential for personal reward. A committee who is affiliated with a protocol in the capacity of principal, asso- ciate or co-investigator, could be accused of conflict of interest if he or she voted on the protocol, regardless of his or her vote. (3) Command influence. The mission (for example, the purpose of the research) should not override or obscure its methods. It is imperative that the committee, through its members, continue to be recognized as a reasonable, deliberative body, whose bias is the safety and welfare of the research subject. It is incumbent upon each committee member to assure his or her concerns regarding the moral, ethical, and legal issues of each protocol are answered to his or her satisfaction before voting according to his or her conscience. c. Commanders and organizational heads will establish a method to ensure that each committee member is familiar with the pertinent laws and regulatory guidance regarding conflict of interest. C-8. Legal review Prior to establishing a HUC, the commander or organizational head will obtain legal counsel from the staff judge advocate. Appendix D Expedited Review Categories D-1. Hair, nails, teeth Collection of- a. Hair and nail clippings in a nondisfiguring way. b. Deciduous teeth. c. Permanent teeth if patient care indicates a need for extraction. D-2. Excreta and secretions Collection of- a. Excreta and external secretions including sweat and uncan- nulated saliva. b. Placenta at delivery. c. Amniotic fluid at the time of rupture of the membrane before or during labor. D-3. Physical data Recording of data from subjects who are 18 years of age or older, using noninvasive procedures routinely employed in clinical prac- tice. This category- a. Includes the use of physical sensors that are applied either to the surface of the body or at a distance and do not involve input of matter or significant amounts of energy into the subject or an in- vasion of the subject's privacy. b. Includes such procedures as- (1) Weighing. (2) Electrocardiography. (3) Electroencephalography. (4) Thermography. (5) Detection of naturally occurring radioactivity. (6) Diagnostic echography. (7) Electroretinography. c. Does not include exposure to electromagnetic radiation outside the visible range (for example, x rays or microwaves). D-4. Blood Collection of blood samples by venipuncture, in amounts not ex- ceeding 450 milliliters in an 8-week period and no more often than two times per week. Subjects will be 18 years of age or older, in good health, and not pregnant. AR 70-25 UPDATE 13 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 0-5. DentaA"apmoRdEaruRe lease 2000/08/08 Collection of both supragingival and subgingival dental plaque and calculus. The procedure must not be more invasive than rou- tine prophylactic scaling of the teeth. The process must be accom- plished according to accepted prophylactic techniques. D-6. Voice records Voice recordings made for research purposes such as investiga- tions of speech defects. D-7. Exercise Moderate exercise by healthy volunteers. D-8. Existing data Study of existing data, documents, records, or pathological or di- agnostic specimens. D-9. Behavior Research on individual or group behavior or characteristics of in- dividuals, such as studies of perception, cognition, game theory, or test development, where the investigator does not manipulate the subject's behavior and research will not involve stress to subjects. Appendix E Instructions for the Completion of the Volunteer Agreement Affidavit E-1. Title and location The title of the study and place where it is to be conducted. E-2. Principal Investigator The name of the principal investigator conducting the study. E-3. Description of the study A statement that the study involves research. An explanation of the purpose of the study and the expected duration of the subject's participation. A description of the procedures to be followed. An identification of any experimental procedures. A statement giving information about prior, similar, or related studies that provide the rationale for this study. E-4. Risks A description of any reasonably foreseeable risks or discomforts to the subject. E-5. Benef Its A description of the benefits, if any, to the subject or to others that may reasonably be expected from the study. If there is no benefit to the subject, it should be so stated. E-6. Alternative treatment When applicable, a disclosure of proper alternative procedures or courses of treatment, if any, that might be advantageous to the subject. E-7. Confidentiality A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained. Also, in the case of an investigational drug or medical device protocol, a state- ment noting that the FDA may inspect the records. If the study is being performed by a contractor, a statement noting that represen- tatives of the DOD may inspect the records. E-8. Points of contact An explanation of whom to contact for answers to pertinent ques- tions about the study and the study subject's rights, and whom to contact in the event of a study-related injury to the subject. This should include a name or office and the commercial and AUTOVON telephone numbers. ChkoROW90SY68ROO1500140002-0 A statement that- a. Participation is voluntary. b. Refusal to participate will involve no penalty or loss of bene- fits to which the subject is otherwise entitled. c. The subject may discontinue participation at any time with- out penalty or loss of benefits to which the subject is otherwise entitled. E-10. Compensation For a study involving more than minimal risk, an explanation as to whether any compensation and medical treatment are available if injury occurs and, if so, what they consist of, or where further information may be obtained. E-1 1. Cautions When appropriate, one or more of the elements of information be- low will also be given to each subject. a. A statement that a certain treatment or procedure may in- volve risks to the subject (or to the embryo or fetus if the subject is or may become pregnant) that are currently unforeseeable. (Possi- ble genetic effects to the offspring of males should be addressed when applicable.) b. The anticipated circumstances under which the subject's par- ticipation may be terminated by the investigator without regard to the subject's consent. . c. Any additional costs to the subject that may result from par- ticipation in the study. d. The consequences of a subject's decision to withdraw from the study and procedures for the orderly end of the subject's participation. e. A statement that new findings developed during the course of the study which could affect the subject's willingness. to continue will be given to the subject. f. The approximate number of subjects involved in the study. g. The precautions to be observed by the subject before and af- ter the study. h. If photographs are to be taken, the degree to which actions will be taken to protect the identity of the subject. L A statement as to whether the results of the research will be made known to the subject. E-12. Disposition of the Informed consent The principal investigator will retain the original signed informed consent. A copy will be provided to the volunteer. If the volunteer consents, the investigator will provide a copy of the signed DA Form 5303-R to the medical records custodian for inclusion in the volunteer's medical treatment record (AR 40-66, para 6-2f.) Appendix F Exemptions Activities in which human subjects are involved in one or more of the categories below are exempt from this regulation. a. Routine epidemiological surveys that are of no more than minimal risk as set forth in the human protection regulations is- sued by the DHHS (45 CFR 46). (See the glossary for the defini- tion of epidemiological survey.) b. Research in educational settings which involves normal edu- cational practices such as- (1) Regular and special education strategies. (2) The effectiveness of, or the comparison among, techniques of instruction, curricula, or classroom management methods. c. Research that involves the use of educational tests when the data is recorded in such a way that subjects cannot be identified directly or indirectly. d. Research that involves survey, interview procedures, or the observation of public behavior (including observation by partici- pants) except where all the following exist: 14 Approved For Release 2000/OWG-2C4APR0P96 -00788 ROO 1500140002-0 (1) r4mmdbFoviRehmsw"OkD~M043y:tCa4A-RGFM&007)88RW5DQI ~kpp 4WO&O should be accom- subjectsbe identified directly or indirectly.panied by a statement to the effect can that the individual will not re- (2) ceive or become entitled to any compensation The other than that subject's responses or recorded observations, if they be- come stated in the contract for these known services. outside the research, could reasonably place the sub- ject at risk of criminal or civil liability, or would damage the subject's G-4. Use of appropriated funds for financial the purchase of standing or employability. (3) Insurance The research deals with sensitive aspects of the subject's be- havior, Since the payment of insurance premiums such on the life of an officer as illegal conduct, drug use, sexual behavior, or use of alcohol. or employee of the United States e. Research is a form of compensation which involving the collection or study of existing data , is not currently authorized, payment documents, of those premiums is records, prohibited. or pathological or diagnostic specimens, if these sources are publicly available or if the information is record- ed in G-5. Contractor's employees such a. way that subjects cannot be identified directly or indirectly. f Individual There appears to be no legal objection or to the use of employees of group training of military personnel such as combat contractors in research and development readiness, experiments. It is the re- effectiveness, proficiency, or fitness exercise (for example, sponsibility of the contracting officer Army to determine whether the Training and Evaluation Program (ARTEP), Skill Qualification terms of the contract are sufficiently Test broad to permit the participa- (SQT)). Evaluation of the training's effect on the tion of these employees. Generally, individual benefits to which contract em- participants may or may not be exempt depending on how ployees may become entitled by reason the of death or disability evaluation is made (for example, drawing of blood is not resulting from their employment are exempt). payable under State Work- g. Job men's Compensation law, except persons related covered by the survivor's tasks of military or civilian personnel who are qualified insurance provisions of the Social to Security Act (42 USC 402). Re- test by duty assignments that call specifically for such qualifications. imbursement of the employer for additional costs by reason of this h. Research liability for his or her employees involving will depend upon the terms of deliberate exposure of human subjects to nuclear each contract. These employees are weapons not disqualified from prosecut- e&ct, to chemical warfare agents ot to bi , ing claims against the government cal under the Federal Torts Claim warfare agents-.Inclusion of human subjects as the indirect ob- ject Act (28 USC 2671 et seq.), if such of a claim exists. research in,~o_lving minimal risk or less in the develoviiieRt er matenai are exempt trom the requirement for obtaining in- formed consent from the t)articinants. The determinationW wrietner a proposai is minimai risic or iess is made bv a HUC es- DHHS regulations, and which is consistent with this and DOD Directive 3216.2. Appendix G Legal Implications to G-6. Irregular or fee-basis employees Intermittent services of such employees are authorized. (Experts and consultants, 5 USC 3109(b) and See. 710 Defense Production Act of 1960 (64 Stat. 819, 50 USC App 2160); and for architects, engineers, and other technical and professional personnel on a fee- basis, 10 USC 4540.) Whether these employees can be detailed or assigned to the proposed experiments will depend upon the statu- tory authority for employment and the provisions of their employ- ment agreement in each case. The Federal Employees Compensation Act, supra, in all probability applies with respect to these irregular and fee-basis employees for any injury or disease resulting from their employment, although a final determination in such cases will have to be made by the Federal agency responsi- ble for deciding claims. Subject to such restrictions and limitations as may appear in the statutory authority under which he or she is employed, it would appear that the Government may legally bear the expense of premiums upon the life of an irregular or fee-basis employee whose rate of compensation is not fixed by law or regu- lations. In this regard, it may be advisable for the government to provide an additional allowance to the employee for financing such private insurance arrangements as he or she may wish to make rather than to undertake direct negotiations with insurance carriers for the desired coverage. G-1. Authority The Secretary of the Army is authorized to conduct research and development programs including the procurement of services that are needed for these programs (10 USC 4503). The Secretary has the authority to "assign, detail and prescribe the duties" of the members of the Army and civilian personnel (10 USC 3013). G-2. Military personnel and Department of the Army civilian employees Compensation for the disability or death of a civilian employee re- sulting from personal injury or disease proximately caused by em- ployment is payable under the Federal Employees Compensation Act (5 USC 8100 et seq.), regardless of whether employment was of a hazardous nature. The amount and type of disability compen- sation or other benefits payable by reason of the death or disability of a member of the Army resulting from injury or disease incident to service depends upon the individual status of each member, and is covered by various provisions of law. It may be stated generally that under present laws no additional rights against the govern- ment will result from the death or disability of military and civil- ian personnel participating in experiments by reason of the hazardous nature of the operations. Appendix H Volunteer Data Base H-1. General The intent of the data base is twofold: first, to readily answer ques- tions concerning an individual's participation in research conduct- ed or sponsored by the command; and second, to ensure that the command can exercise its "duty to warn." The data base must contain items of personal information, for example, name, social G-3. Private citizens It is the policy of the United States to prohibit the acceptance of voluntary services (31 USC 1342). Individuals may, however, enter into an independent contractual relationship and participate for compensation as authorized by applicable directives (for exam- ple, volume 45 Decision of the Comptroller General, 1966, p. 649 security number (SSN), etc., which subjects it to the provisions of The Privacy Act of 1974. AR 340-21 addresses the requirements for establishing such a system of records. For assistance in devel- oping the systems notice for publication in the Federal Register, contact Commander, U.S. Army Medical Research and Develop- ment Command, ATTN: SGRD-HR, Fort Detrick, Frederick, MD 21701-5012, AUTOVON 343-2165. Approved For Release 2000/08/N 70OVk-ROM-00788RO01 500140002-0 15 ROOSVOQT~.~f..Z 400 11 7 H4.'Dataie PIM edfg Reljasq V981P 009le ap CIA ~ A s 3 t y T , a ive.~o ;, ose I , 6 element are. re resen , The found in such, A database. It is ~ not ~meant to be all inclu- could be , , sive, and can be modified to meet individdal commandneeds. a. Records of the study. A copy of the- (1) Approvo tpst.~Plan 9F PTgtocol. (2) Letter or other document approving the c6nduct of thetest or protocol. d ~Q) 7i ' R p0 t gon protocol. r r D a e emen on. at I b (1) Name. (2) Rank (if applicable). (3) SSN. (4)Sex. (5), Date of birtho (6) ~ MOS orAOC.'(if applicable) 1bcAl add 'and telephone number. ress '(S)i-Permanent-address and telephone number. (9) Unif(if applicable). C. 'DaU:elements-test plan orprotocol;information. (1), Test br protocol title. 'Q). Principal inves4gator's name. (3) Laboratory;, unit, or facility conducting -the 'test protocol. (4) Location of the test. (5) Test period. Challenge material data (if applicable). (a) Name of the material used (both active and inert material). (b) Mapufacturer. (c) _"5, Lot number. j_f4), Expiratiqn,"date. volpnteer, completed, or withdrew from the -study. ,the ) Date J7 . . , ,~if -applicable). ~vithdra~al Reason, ior , , experien Desed -reactions ~by. the vol OY pftqfi~,qfuAtoward ced .1 Ajpdiptlrwg r1shible' data ~Pe ~$eleqtedjtc* I)f~peTson4linfprmrAtion!ar~o.perishable~,foi.,~x#mple, kd ~,elephono An Id be otab- local ~ad4ress. ar, mber., A, method-shom term v~hich is c6nsistent,mth the potential for-long- risk&of jlis~ed; , r -.protocol,jo,xpdate this, information.fVr example,- the .the-test o ' .risks gs"Q.with testing,,a. new r pgrachute,,will bg~regdily.#p- teO.with.-the testing. of- new,~ ob- associa parent;.whexw tbp~riqks , known.,for- some time to:come, smokemay -not be -scurept , , AOC NDA area of concentration New Drug Application ARNG OTSG Army National duard Offic~ of the Surgeon General aloe M4W]02iiGy in ii'pe'isonnel o ease 260/,98/08 -, CIA-RDP96-00788ROO*6 Mp 'roved, F r Rel I institu ional review board record. g. A bar to r istme'tif section I MACOM h. Any other action considered by the Abbreviation .9 major Army command DA'to be an adverse personnel action, AIDS MOS Approving official ,quired imm. mil itary occupation specialty. A military commander or civilian director Ac une deficiency pyndrome of an organizational element of a DA 06m AMEDD ponent who has been delegated authority to Army Medical Department medical treatment facility approve the use of. human subjects in research. ARTEP Army Training and Ev aluatio.n Program ASA (RDA) Assistant Secretary of the Army (Research, Development, and Acquisition) ' ;- ASD (HA) Assistant Secretary of Defetige (Health Affairs) CFR1 Code of Federal Regulations DA Department of the Andy DCSPER'- Deputy Chief of Staff tbr~Personnel FDA Food and,Drug Adridnistration, human immunodeficiency v~us PCs permanent change of station PI principal investigator RDTE research, development, test, and evaluation SI skill identifier SSC-NCR Soldier Support -Centier7---National Capital Region SSN social security.number SQT - skill -qualification test TSG. The Surgeon Qeneral USAMRDC U.S.. Army Medical Research and Develop- ment Command USAR U.S. Army Reserve USD (A) Under.Sec~etary of. Defense for Acquisition USUHS HSRRB the Uniformed Services University of HumanS IuIbjects.Research . Review. Board Health Sciences HUC Section W human use committee E[URRA0 Advern pei~ann Ia "on- Human Use Review and Regulatory, Affairs For-the purposes ot'pa ragraph .3; 11, this Office . tet-th included 11. 1, a A 6044t martial. 1. EDE b. ' Non-judicial punishment. ' Investigational Device Exemptionthan for c Involuntary separation (other . medical Ad7inmistrative IND Notice of Claimed Investigational Exemp- tion for a New Drug d. or punitive reduction in grade': e. Denial of vromotion. Anent A child's affirmative agreement to,partici- pate in research. -Mere failure to object should not, absent affirmative agreement,- be construed as assent. Associate Investigator A person who may be involved in the execu- tion of research, but does not have overall primary responsibility. The.FDA refers to such an individual as a subinvestigator. Certificate of Assurance See Protection of Human Subjects Assur- ance/Certification/Declaration. Chemical warfare agent (FM 3-9) A chemical compound.which, through its chemical properties, produces lethal or damaging effects on man. Excluded from considerad are riot coutrot agents, anti- plant agents,., and;~smpke. and flame materials. a. Chemical agents may..,be,,.grouped - ac- cording4g, use: (1) Toik chemical-, agents. ~Ageuts,cal~a- ble of producing incapacita .tion, serious in- jury, or, death, wbpn used. ip. (~elo Soncentrations., (2) Incapacitatint agent&'Agents th at produce physiological,or mentai effecis or both that may persist for hours or days after exposure, rendering individuals'incapable of concerted efforts in the performance of their assigned duties. Complete recovery of inca- pacitating agent casualties. is expected ~wlth_ out medical treatment b. Nonchemical wariare agents may be P4 acc6rding to use as follows:,,, grou I "Compounds (1), Riot, contro agents. 4 widely'used. by governments fbr'domestic law.purposes, and which piodude.transieiit effects on man that disappear minuies aftr removal from exposure. (2) Training agents and compounds. .(3) Screening and signaling sinoke~.:- (4) Anii-plant agents. c. It should be noted thai ih6 Convention on the Prohibition oft'he &4elopmeik K6; duction, and Stockpile of Bacteriological (Biological) and Toxin Weapons 1~ and on Their Destruction, Article 1, dated 26 March 1975, stipulates that- "Each State Party to this Convention un- dertakes never in any circumstance to devel- op, produce, stockpile, -or otherwise I acquire or retain: Ak 7M5 - Wii)Alt 17 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 An wmA Fnr 0-leaAp. ~QgWQN(Qt8 : CIA-RDP96-0(Wfgg8QAJW01 40002-0 kl) :Microbial a." h gicM ajaFl or toxins whatever their origin or method of See Human subject. The legally effective agreement of the sub- production, of types or in quantities that ject or subject's legally authorized represen- have no justification for prophylactic, pro- Health care personnel tative for the subject to participate in tective or other peaceful purposes; research covered by this regulation. In- (2) Weapons, equipment, or means of de- livery designed to use such agents or tox* t.,iIns for hostile purposes or in armed conflic Accordingly, chemical materials obtained from such sources or processes are consid- ered biological, not chemical, weapon's. Clinical investigation An organized inquiry into health problems for all conditions that are of concern in pro- viding health care to beneficiaries of the mil- itary health care system, including active duty personnel, dependents, and retired per- sonnel. The clinical investigation program is described in AR 40-38. Consent See informed consent. Development Systematic use of scientific knowledge, di- rected toward- a. Significant improvements in or crea- tion of useful products to meet specific per- formance requirements. b. Development of components for incor- poration in end items to meet specific per- formance requirements. c. Construction of hardware for test pur- poses to determine feasibility of technical approaches. d. Formulation and refinement of tech- niques and procedures which improve Ar- my capabilities in nonmateriel areas. Epidemiologic-assessment interview For the purpose of paragraph 3-11, this term means questioning of a serum positive member of the Armed Forces for the pur- poses of medical treatment or counseling, or for epidemiologic or statistical purposes. Epidemiological surveys For the purpose of this regulation, the term means studies of the distribution and deter- minants of disease frequency in humans, in- volving no more that minimal risk in which research data is not linked to personal iden- tifiers. Epidemiological surveys focus on "ills" of a population rather than on Military personnel, civilian employees, or contract personnel (including military and civilian staff members, assigned to, em- ployed by, or appointed to the USUHS) who provide patient care or patient care support services in military MTFs and den- tal treatment facilities (DTFs). formed consent includes, when appropriate, those elements listed in appendix E of this regulation. a. Permission. The agreement of parent(s) or guardian to the participation of their child or ward in research. b. Guardian. An individual who is au- thorized under applicable State or local law Health care delivery study Application of scientific methods to the study of availability, organization, adminis- tration, and management of health services. The efficiency and effectiveness with which such services are delivered are included. to consent on behalf of a minor (child) to general medical care. c. Assent. A minor's (child's) affirmative agreement to participate in research. Mere failure to object should not, absent affirma- tive agreement, be construed as assent. Health and Human Services Certificate of Assurance See Protection of Human Subjects Assur- ance/Certification/Declaration. Institution Any public or private entity or agency (in- cluding Federal, State, or other agencies). Human subject a. A living individual about whom an in- vestigator conducting research obtains data through interaction with the individual, in- cluding both physical procedures and ma- nipulations of the subject or the subject's environment. The term does not include military or civilian personnel who are quali- fied to test by assignment to duties that call specifically for qualifications such as test pi- lots or test engineers. b. Minor (child). A person who has not attained the legal age for consent to treat- ments or procedures involved in research, under the applicable laws and jurisdiction in which the research will be conducted. c. Human subjects may be thought of as direct objects when the research is to deter- mine the effects of a new system on humans (for example. the effects of a weapon's blast on hearing) as indirect objects when a test is conducted to determine how humans affect the ultimate performance of a system (doc- trine concepts, training programs). Human Subjects Research Review Board The principal body of the Office of The Sur- geon General (OTSG) for review of clinical investigation and research activities. Investigational drug A drug may be considered investigational when the composition is such that- a. Its proposed use is not recognized for the use under the conditions prescribed; or its proposed use is not recommended or suggested in its approved labeling. Experts qualified by scientific training and experi- ence evaluate the safety and effectiveness of drugs to make this determination. b. Its use has become recognized as in- vestigational, as a result of studies to d'eter- mine its safety and effectiveness for use under such conditions. Investigational medical device a. A device that is not generally used in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans, and rec- ognized as safe and effective. b. Research is usually, but not necessari- ly, initiated to determine if the device is safe or effective. Legally authorized representative A person or judicial or other body author- ized under applicable law to consent on be- half of a prospective subject to the subject's taking apart in the procedures involved in the research. persons. Human use committee Medical monitor A body set up to provide This person is a military initial and contin- or DA civilian Evaluation uing review of research physician qualified by involving the use of the training and/or The subjective determinationhuman subjects. A HUC experience required to of the military is fundamentally provide care to re- value of a hardware itemsimilar to an institutionalsearch subjects for conditions or system, real or review board that may arise conceptual, to the user.(IRB) (45 CFR 46), but during the conduct of There are three has somewhat dif- the research, and who types of evaluation: ferent authority as comparedmonitors human subjects Developer, technical, to an IRD. during the con- and operational. See Within DOD, authority duct of research. For 70-10 for more detail. to approve use of the purpose of this human subjects in researchregulation, the principal is vested in com- investigator may Expedited review proceduresmanders. Commanders act function as the medical on the recom- monitor only in sit- Those procedures used mendations of validly uations in which no other in research involving constituted HUCs. physician is avail- no more than minimal Outside DOD, IRBs tend able and approval for risk and those used to be vested with the principal for minor changes in this authority. Appendix investigator to function approved investiga- C describes the as medical monitor tions (see app D). Thesemembership, functions, is granted by TSG. Requests procedures mini- and operations of a for the princi- mize time req ' ed for revie HUC. pal investigator to function as the medical 18 X pprovea'For Release 200WRqo . 9AMDP96-00788RO01 500140002-0 monitor will be sent to the Assistant Sur- geon G J19W ea qXf cg~" ment, Vc rmy Medical Research and Development Com- mand, ATTN: SGRD-HR, Fort Detrick, Frederick, MD 21701-5012. In contractor accordance wiih the requirements specified 2"YOMT 6f 0ke-,"PAW.J0b?08 ROO 1500140002-0 mmission ibense an radioactive in material authorization and appropriate Fed- eral directives. performed research, a military or DA civil- ian physician may be the medical monitor, however, this is usually a contractor provid- ed resource. Minimal risk The proposed risks are not considered greater than these encountered in the sub- ject's daily life or during routine physical or psychological examinations. Non-U.S. citizens Foreign nationals, excluding personnel on active, duty. Personal identifier A method or system which links data to the individual from whom or about whom it pertains. Principal investigator A person, regardless of title, who is priman- ly responsible for the actual execution of the Yesearch. Prisoner Any person, (adult or minor) involuntarily confined or detained in a penal or coffee- tional institution (for example, jail, work- house~ house of detention, prison, military stockade, or brig). The term is intended to encompass individuals detained pending ar- raignment, trial, or sentencing; and prison- ers of war including detained personnel). The term does not include individuals vol- untarily confined nor those persons subject to civil commitment procedures that are not alternatives to criminal prosecution. Protection of Human Subjects Assurance/ Certification/Declaration. A document issued by them Office for Protec- tion from Research risk, DHHS, in which that office acknowledges that a research in- stitution has established policies and proce- dures consistent with 45 CFR 46. Protocol The written, detailed plan by Iwhich re- search is to be conducted. (See app B for an example of research protocol.) The plan contains, as a minimum- ii. The objectives of the project. b. The information to be collected. c. The means by whichit will be collect- ed and. evaluated, an assessment of potential risk and benefits to subjects; safety mea- sures, and other means to be used to reduce any risk to subjects. Radiolsot6pe/radiation control committee A committee appointed by the commander to ensure that individual users of radioac- tive materiels within the medical facility and each radionuclide will be approved and controlled. The approval and control is in Research A systematic investigation that is designed to.develop or contribute to generalizable knowledge. The term does not include indi- vidual or group training of military person- nel such as combat readiness, effectiveness, proficiency, or fitness exercises (DODD 3216.2) Research, development, test, and evaluation Includes those categories of research and development included in Program 6, Re- search and Development, and operational systems development contained in the Five- Year Defense Program. Schedule I controlled drug substances Any drug or substance by whatever official name, common or usual name, chemical name or brand name listed in 21 CFR 1308, for example, heroin Serum positive member of the Armed Forces For the purposes of paragraph 3-11, this term means a member of the Armed Forces who has been identified as having been ex- posed to a. virus. associated with the ac- quired immin'le 'd"60ft'c"i-ency syndrome (AIDS). Subinvestigator See associate investigator. Test A proem by which data are accumulated to serve as a basis for assessing the degree to which an item or system meets, exceeds or fails to meet the technical or operational properties required. AR 70-10 has a more detailed discussion of the RDTE type test. "AR,76-25 UPDATE 19 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 Approved For ~W-Wpqai 50014,0002-0 PRIVACY ACT OF 1974 Atillvoritin. 10 USC 3013. 44 USC 3101, and 10 USC 1071-1087. Principle Purpose: To document volu the Clinical Investigation and Research Program. SSN and home address will be used for identika=u Routine Uses: The SSN and home address will be used for Identification and locating purposes. Information derived from the study will be used to document the study; kniftmantation of medical programs; adjudication of claims; and for the mandatory reporting of medical conditions as required by low. Information may be furnished to Federal, State and local agencies. Disclosure: The furnishing of your SSN and home address Is mandatory and necessary to provide identification and to contact you if future information indicates that your health may be adversely affected. Failure to provide the information may preclude your voluntary partidpation In this investigational study PART A(1) - VOLUNTEER AFFIDAVIT Volunteer Sublem in Approved Department of Ow Army Re"arch Studin Volunteers under the provisions of AR 40-36 and AR 70-25 are authorized all necessary medical care for injury or disease which is the proximate result of their participation in Such studies. 1, SSN having full capacity to consent arid having attained my birthday, do hereby volunteer/give consent as legal representative for to participate in (Re"arch studyl under the direction of conducted at (Name of institution) The Implications of my voluntary participationtconsent as ftal representative; duration and purpose of the research study, the methods and means by which it W to be conducted; and the inconvenams and hazards that may reasonably be expected have been explained to me by I have boon given an opportunity to ask questions conceming this investigational study. Any such questions were answered to my full and complete satisfactm. Should any further questions anse concerning my rightsfthe tights of the person I represent on study- related injury, 1 may contact (14ame Address and Phom Nurobw of ftwilat tinclude Area cods)) I understand that I may at any time during the course of this A* mvoke my consent arid withdraw/have the person I represent withdrawn from the study without further penalty or loss of benefits, however, Who person I represent may be, required (mili vokin") or requested (divillan volunteer) to undergo certain examination if, in the op"on of the attending physician, s=uc examinations are necessary for myAhe person I represent's health and well-being. MyAhe person I represents refusal to participate will involve no penalty or loss of benefits to which I amilthe person I represent is otherwise entitlecl. PART A (2) - ASSENT VOLUNTEER AFFIDAVIT (MINOR CWLD) SSN having full capacity to assent and having attained my birthday, do hereby volunteer for to participle in 611emarch Study) under. die direction of conducted at awame of Insmution) (Continue an Reverse) DA FORM 5303-R, MAY 89 1 i,Tfl~EYPJkIkC11TlOf1S ARE OBSOLETE Approved For Release 2000/08/08 CIA-RDP96-00788ROO1500140002-0 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 dr PART A(2) - ASSENT VOLUNTEER AFFIDAVIT (AGNOR CHILD) (Conrd.) The implications of my voluntary participation; the nature, duration and purpose of the research study; the methods and mews by which it is to be conducted; and the inconveniences and hazards that may reasonably be expected have been explained to me by I have been given an opportunity to ask questions concerning this investigational study. Any such questions were answered to my full' and complete satisfaction. Should any further questions arise concerning my rights I may contact at (Name, Address, and Phone Number of Hospitel Onclude Area Cods)) I understand that I may at any time during the course of this study revoke my assent and withdraw from the study without further penalty or loss of benefits; however, I may be requested to undergo certain examination if, in the opinion of the attending physician, such examinations are necessary for my health and well-being. My refusal to participate will involve no penalty or loss of benefits to which I am otherwise entitled. PART 6 - TO BE COMPLETED BY INVESTIGATOR INSTRUCTIONS FOR ELEMENTS OF INFORMED CONSENT: (Provide a detailed explanation in accordance with Appendix C, AR 40-38 or AR 70-25.) I do[] do not C] (check one & inhial) consent to the inclusion of this form in my outpatient medical treatment record. SIGNATURE OF VOLUNTEER PERMANENT ADDRESS OF VOLUNTEER DATE SIGNATURE OF LEGAL GUARDIAN (ff volunteer is I a minor) TYPED NAME OF VATNESS SIGNATURE OF WITNESS DATE REVERSE OF DA FORM 5303-R, MA-61 OS, 0 -Release 2 '09/08': Apipr ved'For I &lk-R&09 6`266788 ROO 1500140002-0 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 H.5. USE OF HUMAN SUBJECTS: a. Defini ti ons I.. Subject at Risk - mneans any individual who may be exposed to the possibil.i.tv of injury, including physical, psychological or social injury, as a consE~O.U(7_~171r_e of participation as a subject in any research, development or- relat-ed ZActivity which departs from the application of those established 0~nd .accc~nted methods necessary to meet his needs, or which increases the I _: ror~dlinarv risk of daily life, including the recognized risks inherent in a -in or fi el d of servi ce. Investigational Drugs means those new drugs restricted by the 1clad. Drug and Cosmetic Act to be used by or under the supervision C)f a, 4 inlvest-ig.--Lor purSUant to a notice of Claimed Investigational Exemption h F -ru~ (IND) T J r Investigational Medical Devices - means those devices which are not s '~; aC-nd/or eff ctJ ve, e intended for use in the di.aqnosis, cure, mitigation, treatment, or prevention of disease in, or re.-n--earch on, humans where the research is usually (but not necessarily) for Lhe pLkrpDSe of determining whether or not the device is safe and/or e4: f j. ve. b Requi rements for the Use of Humans Safeguarding the rights and welfare of subjects at risk in activities supported by this contract is primarily the responsibility of the Contractor. Compliance with this contract will in no way render inapplicable pertinent federal, state, or local laws or regulations. In order to provide for the adequate discharge of this institutional responsibil i t -'L'= 'che pol i cy of the DIA that no activity involiVirig subJects under this contract shall be undertaken unless a Contractor Human Use Review Board (CRB) has reviewed and approved such activity. -n 4. The contractor shall provide to DIA a written assurance that it will abide by the policy for the protection of human subjects as contained in title 45, Part A6, of the Code of Federal Regulations (CFR), as amended. When the contractor has a Health and Human Services (HHS) approved assurance, evidence of CRB approval of this study shall have been accomplished by submission to DIA of an executed HHS form 596. For a contractor without an HHS approved assurance, an assurance concerning the protection of human subjects shall have been negotiated with the DIA COTR, and CRB approval. given. (Note: the CRB activity is referred to in the CFR as an Institutional Review Board (IRB) activity.) 3. In addition to the requirements of Title 45, Part 46 of the CFR, the following shall. arply to all DIA contracts supporting research, development, and related activities: a) Prisoners of war (POW) and detainees shall not be used under any circumstances. Page 6 of 8 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 b) Use of prisoners as research subjects shall have been specifically approved by the DIA Contracting Officer. c) A mentally disabled or institutionalized mentally infirm person shall not participate as a research subject unless the nature of. the research involved is such that it Would be impossible or meaningless if mentally infirm were restricted from participation, or other considerations are involved. Specific approval fnr- their use shall have been qranted by th(':-~ Coi-itractin(.-I 10'T'ficr::!r. The research must be concerned with. H tre-atment, prevention. or (-:~tioloqy of the 1:1-a-r4,-:[f_--.j_[J.a?` J_Flerit with which the =Vutbjert is: afflicted, or ii Piny other condition from which the SUbiect is suffering, providing 11-here is a direct potential. benefit to the SUbJect and adeqUate mp I -to give assurAr-ICE Ot s I:: , C) r en acca -;hed Ptable ri nriar j. J. The effects of institUtiori'al life upon the institutionalized mentally infirm subject, and involves no appreciable risk t 0 t 11 Q -F L. tb 4 C, C t , 0 1 - (j. V) Information which cannot be obtained from any other class of subject. d) Volunteers and/or research subjects, either contr:actor, consultant, u1- subcontractor, shall be the responsibility 0+ 'the con-tractor who shall provide all necessary medical care for injury or disease that is the proximate result of taking part in the contract research. e) New people entering this project for training purposes, or for participation as subjects of research, shall sign a statement that they will not use information attained during the course of participation to invade the privacy of US citizens. +) Studies conducted outside the United States, its territories or possessions, shall be conducted in compliance with all laws, customs and practices of the country in which the study is to be conducted. C. Requirements for -the Use of Investigational Drugs .;W Investigational drugs of any kind shall not be used for this contract. d. Requirements for Use of Investigational Medical Devices The Contractor shall comply with Title 21, Part 812, of the CFR, as amended, for the study and evaluation of those devices which are not generally recognized as safe and/or effective intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in, or research on, humans. The contractor shall have to provide with his proposal a copy of FDA approval of, or grant of waiver for, use of investigational device exemption. Page 7 of 8 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 e. Requirements for Reportinq and Documentation . .. .........- 1. Copies of all documents presented or required for initial and continuing review of the CRO, e.g., Board minutes pertaining only to the contract, record of subjects consent, transmittal an actions, instructions and conditions resulting from Board deliberations addressed to the activity director, are to be retained by the Contractor for at least three (3) years l?"'.ter cofi-(pletion of the research. All documents shall be accessible for -hir'--ig tlori-,,Ial working 11OUrs, bv the DrA COTR or aut'-rize-1 representat i ve. Exceint as ot!-iarwi~ie pro,,lided ov law, information in the records or- possElsslon of -the Contrator wihichl re-lcers to or can be identified wit-h Particular subjiect may not be d 4 S co-sed excep; - a -izp a, Wi~ -~he consecit of L o,~ his le, authot -d Ily re-pres.entative, or h As may be necessary -lor the DIA to carry out its legal. responsi bi'l i t i C-S'. 3. Upon expiration or termination of this contract, a list of all unused test material shall be provided to the DIA Contracting Officer. 4. The Contractor shall immediRtely notify the DIA Contracting Officer, by telephone, of inquiries outside the Department of Defense concerning the L, se of human subJects Linder this contract. In addition, the Contracting Officer shall be notified as soon as possible of inspections of the facility or contract protocols by the FDA. Page 0 of 8 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0 ease 2000/08/08 CIA-RDP96-00788ROO1500140002-0 46.114 Cooperative research. Cooperative research projects are those projects, normally supported through grants. contracts, or similar arrangements, which involve institutions in addition to the grantee or prime contractor (such as a contractor with the grantee, or a subcontractor with the prime contractor). fit such instances, the grantee or prime contractor remains responsible to the Department for sA'egtiarding the rights and welfare of human subjects. Also, when cooperaling institutions conduct some or all of (lie research involving, some or all of these subjects, cacti cooperating institution shall comply with these regulations as though it received funds for its participation in the project directly from the Department, except that in complying with these regulations institutions may rise joint review, reliance upon the review of another qualified IRB, or similar arrangements airned at avoidance of duplication of effort. § 46.115 IRB records. (a) An institution, or where appiopriate an IRB, shall prepare and maintain adequate documentation of IR13 activities, including the following: ( 1) Copies of all research proposals reviewed, scicatific evaluations, if any, that accompany the proposals, approved sample consent documents, progvess reports submitted by investigators, and reports of injuries to subjects. (") minutes of IRB meetings which shall be in sufficient detail to show attendance at the meetings; actions taken by the IRB: the vote on these actions including the number of members voting for, against, and abstaining; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controverted issues and their resolution. (3) Records of continuing review activities. (4) Copies of all correspondence between the IRB and the investigators. (5) A list of IRB members w; required bv § 46.103(h)(.I~. (6) Written procedure,,, for the IRB as required by § 46,103(h)(4). (7) Statements of significant new findings provided to subjects, as required by § 46.116(b)(5). (b) The records required by this regulation shall be retained for at least 3 years after Completion of the research, and the records shall be accessible for inspection and copyinp by authorized representatives of' the Department at reasonable times and in a reasonable manner. § 46.116 Cenerall requirements for informed consent. Except -.is provided elsewhere in this or other subparts, no investigator riav involve it human being Lis a su~iect in research covered by these regulations unless the investigator has obtained the legally effective informed consent of tire subject or the subject's legally authorized rept-cscatative. An investigator shall seek such consent only under circurilstances (hat provide"the prospective subject or the representative Suffiki .ent op oortunity -.to conside'r whether or not to participate and that mininnize the Possit5ility, of coercion or undue influnce. The information that is given to the subject or the representative shall be in language understandable to the Subject or the representative. No inforni'ed consent, whether oral or written, may include ally exculpatory language through vvhich the subject or the 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 front liability for negligence (a) Basic elements of inforined consent. E'xcept as provided in paragraph (c) or (d) of this section, in Page 9 5,eeking inlorl-ned consent the following information shall be provided to each subject: ( i) A'Itwrio j~#,Cjf& art explanation of' VO [lie I!i~rposes of the research and the cxp,.-cItcd Zration of the subject's participation, a description of the procedures to be followed, ;and identification of any procedures which are experimental; (2) A Sit"'EiTf Sdrjf any reasonably lo the I'll ),ect., ~(,`! - (3) A 4,0 .61CIIN any tM% to the sub 'ject or to others which may reasonably be expected from the iesearch, ~/O) A di~-closure of appropriate ~2IteffiItIVdIpTQcVVM or courses of treatment, Iffiffit, that might he advantageous to the subject; (5) A statement describing the extent. lVidy, to which conflidcntialify'orf~ ~C4,,J identifying the subject will be maintained; (6) -IW?ke _~Jpt, than,minirnal ri~.~, an explanation as to wht;ther ,my compensation and an explanation as to whether any medical treatments are available if inj.ury occurs and, if so, what they consist of, or where further information may he obtained; (7) Ali explanation of whorn to coatact for answers to pertinent questions about the research and rescaich subjects' rights, and whom to contact in the event of a research- related injury to the subject, and vl(8) A statement that participation is voluntary, refusal to participate will involve no penalty or loss of' benefits to which tl~e subject is otherwise entitled, and the subject may Jiscontinuc participation at any time withOLIt penalty or loss of benefits to which the subject is otherwise entitled. (b) Additional elements of' inforrbed consent. When appropriate, one or more of the following elements of' information shall also be provided to each subject: Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140002-0