APPENDIX C

VA Human Research Protection Accreditation Program Draft Accreditation Standards

BACKGROUND

The Department of Veterans Affairs has contracted with NCQA to develop and implement an accreditation program for Veterans Affairs Medical Center (VAMC) Human Research Protection Programs (HRPPs). The purpose of the program is to strengthen the protections afforded human subjects of research at VAMCs through an ongoing program of independent, external review. The public must be assured that research is performed ethically and in the best interests of study volunteers to ensure its continued support for, and participation in, research studies. The VA has long held a set of policies governing the conduct of research, and in particular, the protection of human study participants. This program is the first to provide a routine, independent evaluation of VAMCs ' compliance with these policies.

These draft standards for the accreditation of Veterans Affairs Medical Center (VAMC) Human Research Protection Programs (HRPPs) are being published for public comment. In June 2001, program standards will be finalized after analysis of public comments and results of pilot tests to be conducted in April and May, 2001. The resultant standards will be revised annually to reflect changes in VA policy and other applicable federal regulation.

These standards apply to VAMCs that operate their own IRBs, those that operate an IRB jointly with an affiliated university, and those that delegate IRB functions to the affiliated university's IRB. Standards include requirements for the oversight of affiliated IRBs. The VAMC retains responsibility for protecting human subjects of research even when it delegates the performance of some functions (e.g., IRB) to the affiliated university. All the standards for the performance



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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs APPENDIX C VA Human Research Protection Accreditation Program Draft Accreditation Standards BACKGROUND The Department of Veterans Affairs has contracted with NCQA to develop and implement an accreditation program for Veterans Affairs Medical Center (VAMC) Human Research Protection Programs (HRPPs). The purpose of the program is to strengthen the protections afforded human subjects of research at VAMCs through an ongoing program of independent, external review. The public must be assured that research is performed ethically and in the best interests of study volunteers to ensure its continued support for, and participation in, research studies. The VA has long held a set of policies governing the conduct of research, and in particular, the protection of human study participants. This program is the first to provide a routine, independent evaluation of VAMCs ' compliance with these policies. These draft standards for the accreditation of Veterans Affairs Medical Center (VAMC) Human Research Protection Programs (HRPPs) are being published for public comment. In June 2001, program standards will be finalized after analysis of public comments and results of pilot tests to be conducted in April and May, 2001. The resultant standards will be revised annually to reflect changes in VA policy and other applicable federal regulation. These standards apply to VAMCs that operate their own IRBs, those that operate an IRB jointly with an affiliated university, and those that delegate IRB functions to the affiliated university's IRB. Standards include requirements for the oversight of affiliated IRBs. The VAMC retains responsibility for protecting human subjects of research even when it delegates the performance of some functions (e.g., IRB) to the affiliated university. All the standards for the performance

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs of the IRB apply to the IRB, whether operated by the VAMC, the affiliated university, or jointly. SOURCE OF STANDARDS These draft standards were compiled from regulations and other applicable policies that apply to research conducted at VA medical facilities and by VA employees. The principal sources were: VA regulations at 38 CFR 16-17; DHHS regulations at 45 CFR 46; FDA regulations at 21 CFR 50, 56, 312, and 812; VA policy as documented in Chapter 9 of the M-3 manual; FDA Information Sheets; International Conference on Harmonisation Good Clinical Practice Guideline; and OHRP Compliance Activities: Common Findings and Guidance. Accreditation standards may not necessarily match a specific regulation word-for-word. In general, if a regulation specifies an activity that must occur the standard reflects this fact, and focuses on measurable evidence that it occurred. Where allowed by a regulation, standards are flexible, for example, with respect to methods to be used to achieve a specified process or outcome. If a regulation has a specified intent, but does not specify how such intent shall be achieved, the required level of achievement, or other relevant details, standards were developed that are consistent with the expressed regulatory intent. Because these standards focus on VA research, they do not cover all regulations and policies pertaining to the conduct of international research, research involving children, fetuses, and prisoners, or genetic research. ORGANIZATION OF THE STANDARDS In this document unless otherwise specified, the term “standards” encompasses the rationale, standards, requirements, and elements, inclusively. The standards are organized into the following six domains: Institutional Responsibilities; IRB Structure and Operation; Consideration of Risks and Benefits; Subject Recruitment and Selection; Privacy and Confidentiality; and Informed Consent. Each of the six domains of standards includes a statement of rationale. Following in hierarchical fashion, are standards, requirements, and elements that

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs detail the performance expectations of the VAMC HRPP. The standards are organized to indicate a chain of activity, from policy and procedure (suggesting intent), through results (documented demonstration that the intent is being met and the desired outcome achieved). Each standard may be composed of one or several requirements. Each requirement contains many specific elements that provide detail and dimension to the requirement. Standards pertain to the following areas: Policies and procedures; Implementation of required activities; Performance of activities to demonstrate the HRPP is achieving required results (quality assurance and improvement); and Required results. Standards identify the allowable sources of evidence, and methods for the evaluation of evidence, to determine whether or not a particular standard has been met. While many data sources may be listed for a requirement, they are generally listed as alternative sources. That is, a VAMC need not demonstrate compliance with a requirement in each and every data source listed; rather, it must demonstrate compliance in at least one data source (and not contradict the finding in others). Interviews are the exception and will be used only to clarify and confirm information from other sources. Data sources listed are intended to provide information about different aspects of performance (generally reflected in the different elements). For example, a requirement may include data sources such as policies and procedures, as well as IRB protocol files. In this instance, the surveyor will look for evidence that the HRPP has a policy or procedure governing an issue, and will look in a sample of protocol files to assess whether the policy has been implemented effectively. The accreditation survey will result in one of four outcomes, as documented in the draft Accreditation Outcome Table below. Depending on their performance, Human Research Protection Programs can achieve Full Accreditation, Conditional Accreditation, Probational Accreditation, or No Accreditation. Each accreditation outcome brings with it a set of actions by NCQA as well as VA offices. These actions include, for example, follow-up oversight by NCQA, VA Office of Research and Development requirements for, and restrictions on, starting new research or continuing research, and VA Office of Research Compliance and Assurance follow-up, remedial action, and training. Please note that NCQA can only address its own actions and policies related to each outcome.

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs TABLE C-1 Draft Accreditation Outcomes and Remedial Action Outcome Description Criteria Programmatic Outcome Actions by ORCA Actions by ORD Actions by Accreditor Full Meets all standards at acceptable level. Score above xx points on 100-point scale; performance meets all threshold standards. Research continues. Resurvey in 3 years. Reviews accreditation report. [Note: May independently comment or request additional information from the VAMC.] Reviews accreditation report. [Note: May independently comment or request additional information from the VAMC.] Resurvey in 3 years. Conditional Meets most standards at acceptable level. Score between yy and xx points on 100-point scale; performance meets all threshold standards. Research may proceed. Submit Remediation Action Plan (RAP) to accreditor, ORCA, and ORD within 30 days. Reviews accreditation report. [Note: May independently comment or request additional information from the VAMC. Monitors performance against RAP via periodic VAMC reporting at least until Full Accreditation is achieved. May require education and development (TED) program.] Reviews accreditation report. [Note: May independently comment or request additional information from the VAMC. Monitors performance against RAP via periodic VAMC reporting at least until Full Accreditation is achieved.] Monitors performance against periodic VAMC reporting at least until Full Accreditation is achieved. Followup survey may advance to Full Accreditation when RAP is fully implemented. Resurvey in 3 years (from date of original accreditation determination).

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs Probational Meets some standards at acceptable level, but inadequate performance on many others. Score between zz and yy points on 100-point scale; performance meets all threshold standards. No new projects may be initiated until all deficiencies are corrected. Submit RAP to accreditor, ORCA, and ORD within 30 days. Reviews accreditation report [Note: May independently comment or request additional information from the VAMC. Monitors performance against RAP via periodic VAMC reporting at least until Full Accreditation is achieved. May require TED program. Consider ORCA site visit.] Reviews accreditation report. [Note: May independently comment or request additional information from the VAMC. Monitors performance against RAP via periodic VAMC reporting at least until Full Accreditation is achieved. In addition, withhold funding for new projects and may withdraw funding for current projects until at least Conditional Accreditation is achieved.] Follow-up survey required to advance to Conditional Accreditation. Resurvey in 1 year (from date of Accreditation upgrade to Conditional).

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs Outcome Description Criteria Programmatic Outcome Actions by ORCA Actions by ORD Actions by Accreditor Not Accredited Fails to meet basic accreditation standards. Score below zz points on 100-point scale; OR unacceptable performance on one or more threshold standards. All research must cease until corrections are made. A patient already enrolled in studies may continue only if that is in the subject' s best interest. No new subjects may be enrolled and no new projects may be started. Submit RAP to accreditor, ORCA, and ORD within 30 days. Reviews accreditation report [Note: May independently add comments or request additional information from VAMC. Monitors performance against RAP via periodic VAMC reporting at least until Full Accreditation is achieved. May require TED program. Consider ORCA site visit.] Reviews accreditation report. [Note: May independently add comments or request additional information from the VAMC. Monitors performance against RAP periodic VAMC reporting at least until Full Accreditation is achieved. Withdraw funding for all research (except amounts required to assure patient safety) until at least Probational Accreditation is achieved.] Decides when to determine if site can advance to Probational Accreditation. Resurvey in 1 (one) year (from date of Accreditation upgrade to Probational). NOTE: At the accreditor's discretion, a site may not need to have a follow-up survey to move out of Conditional status to Full Accreditation. Rev. 12/21/00

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs OPERATION OF ACCREDITATION PROGRAM VAMCs to be accredited will submit documents to demonstrate their compliance with accreditation program standards. A team of certified surveyors will visit each VAMC to be accredited. Surveyors will verify the VAMC's compliance with each standard and record their assessments in a structured report. The VAMC will be allowed to comment on the report's accuracy. The Program Accreditation Committee will review the surveyors' report and any VAMC comments, and issue an accreditation decision. PROGRAM COMPONENTS UNDER DEVELOPMENT Work is still underway to finalize data collection methods and protocol sampling strategies. These will be formalized in guidelines for surveyors. Sampling issues under consideration include how many protocols to sample and how to stratify samples to provide meaningful information about issues that present infrequently in some institutions. In addition to work on the sampling strategies, work is underway to determine the scoring of elements and requirements, including those that are applicable only in some instances (e.g., requirements relating to planned emergency research). First-year scoring will be more lenient than scoring in future years, when it will be possible to provide more advance notice of standards. Finally, the threshold scores required to achieve each accreditation outcome will be determined after each element's and requirement's relative weight has been determined. Comments on sampling and scoring are invited along with comments on the standards, requirements, elements, data sources, and review methods presented. DEFINITIONS ADVERSE EVENT (AE) Any untoward medical occurrence that does not necessarily have a causal relationship with treatment. An AE can be any unfavorable and unintended sign, symptom, or disease. AFFILIATE'S HUMAN RESEARCH PROTECTION PROGRAM The HRPP of a VAMC's academic affiliate. See HRPP. CERTIFICATE OF CONFIDENTIALITY Where data are being collected from subjects about sensitive issues (such as illegal behavior, alcohol or drug use, or sexual practices or preferences), researchers can obtain an advance grant of confidentiality from the Public Health Service that will provide protection even against a subpoena for research data. FDA FORM 3454 The financial disclosure form required by the FDA to reveal/identify any potential financial conflict of interest that an investigator(s), sub-investigator(s), or their spouse and children may have that is applicable to the submission of marketing applications for human drug, biological product, or device for each covered study.

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs FEDERAL WIDE ASSURANCE (FWA) An agreement or contract between the institution and OHRP, on behalf of the Secretary, HHS, stipulating the method(s) by which the organization will protect the welfare of research subjects in accordance with the regulations. The Assurance, approval of which is a condition of receipt of DHHS support for research involving human subjects, spells out the organization's responsibilities for meeting the requirements of 45 CFR 46. The FWA replaces all other previous forms of assurance (i.e., MPA, SPA, etc.). FOOD AND DRUG ADMINISTRATION (FDA) The federal agency responsible for the regulation of food, drugs, and cosmetics, including the human subject research performed for FDA-regulated articles. HUMAN RESEARCH PROTECTION PROGRAM (HRPP) The systematic and comprehensive approach by an organization to ensure human subject protection in all research. The implementation of any part of the program may be delegated to specific committees, individuals, or entities (i.e., academic affiliate or another VAMC) by the organization. HUMAN SUBJECT A living individual about whom a research investigator (whether professional or student conducting research) obtains data through intervention or interaction with the individual or identifiable information. INSTITUTION The individual VAMC. The institution retains ultimate responsibility for human subject protection in research conducted at their facility and/or by their staff. INSTITUTIONAL REVIEW BOARD (IRB) An independent committee comprised of scientific and non-scientific members established according to the requirements outlined in Title 38, part 16 (same as Title 45, part 46 and Title 21, part 56) of the U. S. Code of Federal Regulations. INVESTIGATIONAL DEVICE EXEMPTION (IDE) The process by which the FDA permits a device that otherwise would be required to comply with a performance standard or to have premarket approval to be shipped lawfully for the purpose of conducting investigations of that device. INVESTIGATIONAL NEW DRUG APPLICATION (IND) The process by which new drugs or biologies, including the new use of an approved drug, are registered with the FDA for administration to human subjects. An IND number is assigned by the FDA to the drug or biologic for use in tracking. INVESTIGATOR (Principal investigator) An individual who conducts an investigation, that is, under whose immediate direction research is conducted, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team. INVESTIGATOR/SPONSOR A term defined in the FDA regulations as an individual with responsibility for initiating and conducting a research study. LEGALLY AUTHORIZED REPRESENTATIVE An individual, judicial, or other body authorized under applicable law to consent on behalf of a

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs prospective subject to the subject's participation in the procedure(s) involved in research. MEDWATCH The FDA Medical Products Reporting Program, is an initiative designed both to educate all health professionals about the critical importance of being aware of, monitoring for, and reporting adverse events and problems to FDA and/or the manufacturer and to ensure that new safety information is rapidly communicated to the medical community, thereby improving patient care. The purpose of the MedWatch program is to enhance the effectiveness of postmarketing surveillance of medical products as they are used in clinical practice and to rapidly identify significant health hazards associated with these products. MEMORANDUM OF UNDERSTANDING (MOU) A legal agreement outlining the details of the relationship between organizations, including the responsibilities of each. Such an agreement is used by the VAMC to delineate the terms and conditions under which it may utilize another entity's IRB. MINIMAL RISK The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. MULTIPLE PROJECT ASSURANCE (MPA) An agreement or contract between the institution and OPRR, on behalf of the Secretary, HHS, stipulating the method(s) by which the organization will protect the welfare of research subjects in accordance with the regulations. The Assurance, approval of which is a condition of receipt of DHHS support for research involving human subjects, spells out the organization's responsibilities for meeting the requirements of 45 CFR 46. MPAs will be replaced by FWAs. POLICY A principle or course of action to guide decision-making. PROCEDURE See Standard Operating Procedure (SOP). PROTOCOL A plan that includes, at minimum, the objectives, rationale, design, methods, and other conditions for the conduct of a research study. PROTOCOL FILE The documents maintained by the IRB administration containing the protocol, investigator's brochure, IRB/investigator communications, and all other supporting materials. QUALITY IMPROVEMENT (QI) The effort to assess and improve the level of performance of a program or institution. QI includes quality assessment and implementation of corrective actions to address any deficiencies identified. RESEARCH A systematic investigation, including development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. SAFETY REPORTS (IND/IDE) Written reports from sponsors notifying the FDA and all participating investigators of any adverse experience associated with the use of a drug that is both serious and unexpected. SERIOUS ADVERSE EVENT (SAE) Any event that results in death, a life-threatening situation, hospitalization or prolonged hospitalization, persistent

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs or significant disability/incapacity, or a congenital anomaly/birth defect. SAEs require reporting to the sponsor and the IRB. SPONSOR Any person or entity who takes responsibility for and initiates a clinical study. The sponsor may be an individual, pharmaceutical company, device manufacturer, governmental agency, academic institution, private organization, or other organization. STANDARD OPERATING PROCEDURE (SOP) A formalized established series of steps for the uniform performance of a function or activity. UNEXPECTED ADVERSE EVENT Any adverse event that has not previously been observed (e.g., included in the investigator brochure). VULNERABLE SUBJECTS Individuals whose willingness to volunteer in a research study may be unduly influenced or coerced and individuals with limited autonomy.

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs TABLE C-2 INSTITUTIONAL RESPONSIBILITIES Rationale Each institution engaged in research involving human subjects is responsible for ensuring the rights, safety, and well-being of those recruited to participate in research activities. It is also responsible for assuring that investigators and their staffs understand and comply with standards for the ethical conduct of research. These broad responsibilities can be met through three institutional actions: developing a Human Research Protections Program to monitor, evaluate, and improve the protection of human research subjects; establishing and/or designating an Institutional Review Board to review research following federal and institutional requirements; and educating staff involved in research about their ethical responsibility to protect research participants. This standard outlines the responsibilities of institutions that conduct human subjects research. KEY for Regulatory Guidance CFR = Code of Federal Regulations M-3, Part 1 = The Veterans Affairs Manual, Chapter 9 VA MPA = Veterans Affairs Multiple Project Assurance Contract IRB-GB = OPRR IRB Guidebook FDA-IS = FDA Information Sheets FDA-IS, (CL) = Appendix H: Self-Evaluation Checklist for IRBs FDA-IS, (FAQ) = Frequently Asked Question FDA-IS, (ICG) = The Guide to Informed Consent FDA-IS, (CR) = Continuing Review After Study Approval ICH-GCP = International Conference on Harmonization, Good Clinical Practice Guidelines OHRP CFG = OHRP Compliance Activities: Common Findings and Guidance for 9/1/2000

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs   1.B.4.The IRB requires all information concerning payment to subjects, including the amount and schedule of payments, to be included in the informed consent document. 1.B.5. The IRB requires the content of consent forms to be consistent with state laws regarding content (if applicable). 1.B.6. The IRB prohibits any informed consent, whether oral or written, from including any exculpatory language through which the subject or the legally authorized representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence. 1.B.7. The IRB conducts audits or self-assessments to determine that only approved consent forms are used and have the required content. 1.B.7.1. The IRB uses the results for QI purposes and takes action, as needed.   QI results show evidence of compliance in evaluating consents for VA, federal, local, and institutional requirements and that only approved consent forms are used by investigative staff. 1.C. The IRB has policies and procedures regarding documentation of informed consent and ensures that investigators and staff conform to these policies and procedures. 1.C.1. The IRB requires informed consent to be documented by the use of a written consent form, VA Form 10-1086, approved by the IRB and signed by the subject or the subject's legally authorized representative. Policies and procedures for documentation of informed consent IRB template consent Review of policies and procedures for evidence of requirements for consent documentation Review of template consent for required signature and date lines

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs Regulation/Source 38 CFR 16.117(c) M-3, Part 1, 9.11 45 CFR 46.117(c) 21CFR 50.23(a) 21 CFR 50.27(b)(2) IRB-GB, (III)(B) 1.C.1.1. Consent forms contain the required signature lines. 1.C.1.1.1. Subject signature and date of signature. 1.C.1.1.2. Signature of person conducting the informed consent process. 1.C.1.1.3. Witness to the signature. 1.C.1.1.4. Investigator, if an investigator did not conduct the consent process. 1.C.1.1.5. Witness signature on “short form.” 1.C.2. Policies describe situations where the signature of a witness is required. 1.C.3. Policies describe conditions under which a “short form” informed consent may be used. 1.C.4. The IRB conducts audits to determine that investigators have documented informed consent through the use of the approved consent form, dated and signed, with a copy given to the subject or legally authorized representative, and the original is kept in the medical record. 1.C.4.1. In conjunction with the use of an IRB-approved “short form,” the IRB-approved written summary of what was said to the subject or legally authorized representative, is signed by the witness. 1.C.4.2. The IRB uses the results for QI purposes and takes action, as needed. Sample of approved consents IRB minutes Sample of protocols where shortform consent is used IRB communications Sample of signed consent forms QI results Review of sample of IRB-approved consents for evidence of required signature lines Review of IRB minutes for documentation of evaluation for use of shortform consent Review of sample of protocols with short-form consents for evidence of requirements for appropriateness of use Review of communications to investigators regarding the requirements for documentation of consent Review of sample of signed consent forms for presence of required signatures Review of QI results for evidence of IRB evaluation of consents and compliance of investigators with requirements for documentation of consent.

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs 1.D. The IRB has policies and procedures for approving waiver or alteration of the informed consent form and complies with these policies and procedures. Regulation/Source 38 CFR 16.116 38 CFR 16.117 M-3, part 1, 9.11 45 CFR 46.116 45 CFR 46.117 21 CFR 50.109(c) IRB-GB, (III)(B) FDA-IS, (ICG) 1.D.1. The IRB defines the conditions under which it will permit waiver or alteration of any element of informed consent to include: 1.D.1.1. The research involves no more than minimal risk. 1.D.1.2. The waiver or alteration will not adversely affect the rights of the subjects. 1.D.1.3. The research could not be practically done without such waiver or alteration. 1.D.1.4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation. 1.D.1.5. The research or demonstration project is to be conducted by, or subject to the approval of, state or local government officials and is designed to study, evaluate, or otherwise examine public benefit of service programs, procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs, or possible changes in methods or levels of payment for benefits or services under those programs. 1.D.2. The IRB does not allow waiver or alteration of informed consent forms when FDA-regulated test articles are involved. Policies and procedures for waiving or altering consent Sample of protocols IRB minutes QI results Review of policies and procedures for conditions for waiving or altering consent, content Review of protocols where consent was waived or altered for assurance that conditions were met IRB minutes show evidence of evaluation of conditions for waiver or alterations of consent content consistent with policies and procedures QI results show evaluation of and compliance with conditions for waiving or altering consent, content

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs   1.D.3. In its approval of waiver or alteration, the IRB documents its specific findings that conditions permitting waiver or alteration are met. 1.D.4. In its decision to waive the requirement for the investigator to obtain a signed informed consent form for some or all subjects, the IRB documents the regulatory basis for such waiver, providing either that: 1.D.4.1. The only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from breach of confidentiality or 1.D.4.2. The research presents no more than minimal risk and involves no procedures for which written consent is normally required outside of the research context. 1.D.5. The IRB conducts audits to determine that waivers or alterations of informed consent are only made when permitted by regulation. 1.D.5.1. The IRB uses the results for QI purposes and takes action, as needed.  

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs IC 2 The IRB protects human subjects participating in research conducted with exceptions from the informed consent requirements. Requirement Element Data Source Method 2.A. The IRB has policies and procedures for exceptions from the general requirements for obtaining informed consent before the use of a test article and appropriately reviews such exceptions. Regulation/Source 21 CFR 50.23 IRB-GB, (III)(B) FDA-IS, (CL)(XIII) FDA-IS, (ICG) For each individual situation in which a test article is to be administered and informed consent may not feasibly be obtained: 2.A.1. The IRB requires that the investigator and a physician who is not otherwise participating in the clinical investigation must certify in writing all of the following: 2.A.1.1. The subject is confronted by a life-threatening situation necessitating the use of the test article. 2.A.1.2. Informed consent cannot be obtained from the subject because of an inability to communicate with, or obtain legally effective consent from, the subject. 2.A.1.3. Time is not sufficient to obtain consent from the subject 's legal representative. 2.A.1.4. There is no alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject. 2.A.2. The IRB requires that if the immediate use of the test article is, in the investigator's opinion, required to preserve the life of the subject, and time is not sufficient to obtain the independent determination by a physician not otherwise participating in the study, in advance, the use of the test article shall be reviewed and evaluated within 5 working days in writing by a physician not participating in the investigation. Policies and procedures for exceptions from the general requirements for obtaining informed consent before the use of a test article IRB minutes Sample of protocols IRB Chair interview QI results Review of policies and procedures for evidence of requirements for obtaining informed consent before the use of a test article IRB minutes document evaluation of each exception to the general requirements for obtaining informed consent Exceptions to the general requirements to informed consent met all required conditions Ask the IRB Chair to express conditions for exceptions to the general requirements for obtaining informed consent QI results show evidence that exceptions to general requirements for obtaining informed consent met required conditions

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs   2.A.3. The IRB requires documentation of emergency situations where exceptions to the general requirements to informed consent have occurred to be submitted to the IRB within 5 working days. 2.A.4. In its review of requests for exceptions, the IRB documents the regulatory basis for the exception and the timely receipt of written certification. 2.A.5. The IRB conducts audits to determine that exceptions from the general requirements for obtaining informed consent before use of a test article are made appropriately. 2.A.5.1. The IRB uses the results for QI purposes and takes action, as needed.   2.B. The IRB has policies and procedures for exceptions from informed consent requirements in planned emergency research and appropriately reviews such exceptions. 2.B.1. The IRB requires planned emergency research proposals include documentation of all of the following: 2.B.1.1. The human subjects are in a life-threatening situation, available treatments are unproven or unsatisfactory, and the collection of valid scientific evidence is necessary to determine the safety and effectiveness of particular interventions. Policies and Procedures IRB minutes Review of policies and procedures for requirements for emergency research exceptions from informed consent requirements IRB minutes reflect evaluation of exceptions from informed consent in planned emergency research

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs Regulation/Source 21 CFR 50.24 IRB-GB, (III)(B) FDA-IS, (CL)(XIII) FDA-IS, (ICG) 2.B.1.2. Obtaining informed consent is not feasible. 2.B.1.3. Participation in the research holds out the prospect of direct benefit to subjects. 2.B.1.4. The clinical investigation could not practically be carried out without the waiver. 2.B.1.5. The proposed investigational plan defines the length of the potential therapeutic window based on scientific evidence and the investigator has committed to attempting to contact a legally authorized representative within that window of time. 2.B.1.6. The IRB has reviewed and approved informed consent procedures and an informed consent document as set forth in VA and other federal regulations to be used in situations where the use of such procedures and documents is feasible. 2.B.1.7. Additional protections of the rights and welfare of the subjects will be provided through, at least, 2.B.1.7.1. Consultation with representatives of the community. Sample of protocols IRB communications QI results Review of protocols for planned emergency research shows evidence of meeting requirements (i.e., public disclosure, plan for subject and family notification, etc.) IRB communications provide evidence of meeting requirements (i.e., public disclosure, plan for subject and family notification, etc.) QI results show evidence of compliance in evaluating and implementing planned emergency research

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs   2.B.1.7.2. Public disclosure to the community prior to the study. 2.B.1.7.3. Public disclosure of the results of the investigation following completion. 2.B.1.7.4. Establishment of an independent data monitoring committee. 2.B.1.7.5. The investigator will summarize efforts made to contact family members and make this information available to the IRB at the time of continuing review. 2.B.1.8. Procedures are in place to inform, at the earliest feasible opportunity, each subject or legally authorized representative or family member, of the subject's inclusion in the clinical investigation. 2.B.1.9. There is a procedure to inform the subject, legally authorized representative, or family member that the subject's participation may be discontinued at any time without penalty or loss of benefits to which the subject is otherwise entitled. 2.B.1.10. There must be a separate IND or IDE for the study for any FDA-regulated product. 2.B.1.11. If the study does not involve an FDA-regulated product, there is concurrence by the Agency Secretary that the waiver is appropriate.  

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs   2.B.2. In its review of requests for exceptions in planned emergency research, the IRB documents its evaluation and the regulatory basis for approving the exception. 2.B.3. The IRB conducts audits that include a review of requests for exceptions from informed consent in planned emergence research. 2.B.3.1 The IRB uses the results for QI purposes and takes action, as needed.  

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Preserving Public Trust: Accreditation and Human Research Participant Protection Programs Process for Submitting Comments (due by May 15, 2001) Please address all comments to VAHRP: E-mail (preferred method) to vahrpap@ncqa.org. You will receive an e-mail confirmation of receipt. Mail to VAHRPAP, NCQA, 2000 L Street, N.W., Suite 500, Washington, D.C. 20036 Fax to 202-955-3599, Attention – VAHRPAP. Please provide the following information: Name Position Organization Please organize comments as described below. Word document (preferred method) formatted as below. Domain Issue* Comment Privacy and Confidentiality Requirement 1.B Data source/method Should the IRB minutes be included as a possible data source/method for evaluating IRB assessment of provisions to protect privacy in individual proposals? All Data Source/method Is a one-year look-back period an appropriate timeframe for adequate evaluation of an HRPP? * Issue may address a global comment, a specific requirement or element, the data sources or methods

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