Research & Development Investigators Engaged in Research Involving Human Subjects Manual
New York Harbor Healthcare System
Research and Development
INVESTIGATOR’S MANUAL
Research Investigators Using Human Subjects
Investigator Name: ______
Protocol ID #: ______
Date: ______
Table of Contents
Introduction 2
Definitions 3
Human Subjects Research Determination 6
Request for Exemption 6
Requesting Expedited Review 6
Procedures for Activating a Study Involving Human Subjects 7
Protocol Application Materials 7
Submission to VA NYHHS IRB 9
Submission to VA Central IRB 9
Staff Credentialing and Training 10
IRB Review and Approval 11
Investigator Responsibilities for Reporting 12
Reporting Adverse Events and Unanticipated Problems Involving Risks to Participants or Others 12
Protocol Development 13
Continuing Review of Ongoing Research Studies Involving Human Subjects 16
Progress Reports: 16
Changes in Approved Research 18
Change of Investigators 18
Study Closure 19
Audit of Informed Consent 20
Documentation of Informed Consent 20
Issues in the Conduct of Research 21
Obtaining Informed Consent 21
Recruitment Incentives 21
Payment to Research Subjects 22
Use of Vulnerable Research Subjects 22
Privacy and Confidentiality 23
Use of Investigational Drugs 24
Use of Investigational Devices 24
Storing and Dispensing Drugs Used in Research Studies 25
Investigator Concerns/Complaints 25
Research Collaboration 26
Cooperative Studies of the Veterans Health Administration 26
Facilities and Affiliate Universities 26
Appendix A: Contact Information 28
Appendix B: Web Resources 29
Statements of Ethical Principles 29
Guidelines and Regulations 29
Protocol Forms 29
Appendix C: FWA 31
Appendix D: Research and Development Committee (R&D) Roster 32
Appendix E: Subcommittee for Human Studies (IRB) Roster 33
Appendix F: Subcommittee for Research Safety (Biosafety) Roster 34
Appendix G: Quality Assurance Quality Improvement Subcommittee for Research Roster 35
Appendix H: Calendar of Events 36
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Updated: December 3, 2009
Introduction
The VA New York Harbor Healthcare System (VA NYHHS) Research and Development Service is responsible for its Human Research Protection Program (HRPP) and is committed to conducting research with the highest regard for the welfare of human subjects. It upholds and adheres to the principles of The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects in Research by the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research (1979). These principles are:
· Respect for Persons, which is ensured by obtaining informed consent, consideration of privacy, confidentiality, and additional protections for vulnerable populations.
· Beneficence, which is assured by ensuring that possible benefits are maximized and possible risks are minimized to all human subjects.
· Justice, the equitable selection of subjects.
The NYHHS HRPP, in partnership with its research community, is responsible for ensuring the ethical and equitable treatment of all human subjects in research conducted under its auspices. Its mission is:
· To safeguard and promote the health and welfare of human research subjects by ensuring that their rights, safety and well-being are protected;
· To provide timely and high quality education, review and monitoring of human research projects; and
· To facilitate excellence in human subjects research.
The VA Research and Development Committee (RDC) has oversight responsibilities over all human subjects research conducted in this facility (VHA Handbook 1200.01). All human subjects research must receive approval by an Institutional Review Board or IRB prior to initiation of all research activities. The VA NYHHS has a Federal Wide Assurance (FWA 00001881) with the Office of Human Research Protection (OHRP) that includes two IRB of Record, namely: The VA NYHHS Subcommittee for Human Studies, and the VA Central IRB.
Complete details of the VA NYHHS HRPP are found in the VA New York Harbor Healthcare System Standard Operating Procedures – Human Research Protection Program.
The purpose of this manual is to serve as a guide for investigators conducting research involving human subjects regarding:
· The administrative procedures to be followed for establishing such a study
· The administrative procedures to be followed during the period that the study is active and upon terminating the study
· Special concerns regarding protection of human subjects involved in a research study
· The requirements for investigators and research team members
· Identifying and interpretation of applicable laws and regulations relevant to the research.
Definitions
Human Subject. A human subject is a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual or through identifiable private information (38 CFR 16.102(f)). The definition provided in the Common Rule includes investigators, technicians, and others assisting investigators, when they serve in a "subject” role by being observed, manipulated, or sampled. As required by 38 CFR 16.102(f) an intervention includes all physical procedures by which data are gathered and all physical, psychological, or environmental manipulations that are performed for research purposes.
For research covered by FDA regulations (21 CFR 50 and 56), human subject means an individual who is or becomes a participant in a clinical investigation (as defined below), either as a recipient of the test article or as a control. A subject may be in normal health or may have a medical condition or disease. In the case of a medical device, a human subject/participant is also means a human on whose specimen an investigational device is used.
Note: The terms “subject” and “participant” are used interchangeably in this document and have the same definition.
Research. Research is defined as the testing of concepts by the scientific method of formulating a hypothesis or research question, systematically collecting and recording relevant data, and interpreting the results in terms of the hypothesis or question. The Common Rule (38 CFR 16) defines research as a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalized knowledge.
Under FDA regulations, the terms research and clinical investigation are deemed to be synonymous. For the purposed of this document, the term research includes clinical investigations as defined below.
Clinical investigation. A clinical investigation is defined as any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that must meet the provisions of part 58, regarding nonclinical laboratory studies. An experiment is defined as any use of a drug or medical device, other than the use of a marketed (approved) drug or medical device in the course of medical practice.
Test Article. A test article is a drug, device, or other article including a biological product used in clinical investigations involving human subjects or their specimens.
Institutional Review Board (IRB). An IRB is a board established in accordance with and for the purposes expressed in the Common Rule (38 CFR 16.102(g).).
Institutional Official (IO). The IO is the Medical Center Director or Chief Executive Officer (CEO). The IO is the VA official responsible for ensuring that the HRPP at the facility has the resources and support necessary to comply with all federal regulations and guidelines that govern human subjects research. The IO is legally authorized to represent the institution, is the signatory official for all Assurances, and assumes the obligations of the institution’s Assurance. The IO is the point of contact for correspondence addressing human subjects research with OHRP, FDA, and VA Central Office, including the VA Office of Research Oversight (ORO).
Principal Investigator (PI). A PI is a qualified person [investigator is qualified through education, training, and experience to conduct the research] or persons designated by an applicant institution to direct a research project or program and who usually writes the grant application. The PI oversees scientific and technical aspects of a grant or protocol and the day-to-day management of the research. In the event of an investigation conducted by a team of individuals, the PI is the responsible leader of that team. The VA recognizes one PI for each VA-approved research project responsible for the conduct of the study at this facility. If the PI does not have a VA appointment, then a VA responsible individual must be identified in the proposal who must adhere to the PI responsibilities.
Investigator. An investigator is an individual under the direction of the PI who is involved in some or all aspects of the research project, including the: design of the study, conduct of the study, analysis and interpretation of the collected data, and writing of resulting manuscripts. A VA investigator is any individual who conducts research approved by the VA R&D committee while acting under a VA appointment, including full and part-time employees, without compensation (WOC) employees, and individuals appointed or detailed to VA under the IPA of 1970. In addition, a VA investigator must comply with all applicable VA and VHA regulations and policies.
Research Under the Auspices of the VA NYHHS. Research considered under the auspices of the VANHYHHS include all research involving human subjects that is conducted completely or partially in VANHYHHS facilities, conducted in approved off-site locations, facilities, and/or conducted by VANHYHHS researchers while on official VA duty time. The research may be VA funded, funded from extra-VA sources, or conducted without direct funding.
Research Protocol. The formal written plan for conducting a research investigation, including but not limited to biomedical, behavioral, social, health service, or educational research investigations, as well as clinical trials.
Serious Noncompliance. Failure to adhere to the laws, regulations, or policies governing VA research that:
– Results in substantive harm or damage (or risk of substantive harm or damage) to the safety, rights, or welfare of human subjects, research staff or others; or
– Results in substantive harm or damage (or risk of substantive harm or damage) to the safety or welfare of laboratory animals; or
– Substantively compromises the integrity or effectiveness of research protections, either systemically or relative to a particular protocol or project.
Serious AE (SAE) / Serious Problem. An AE or problem that involves or results in:
– Death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly, or birth defect; or
– Substantive harm or damage (or risk of substantive harm or damage) to the safety, rights, or welfare of research subjects, research staff; or
– Substantive harm or damage (or risk of substantive harm or damage) to the safety or welfare of laboratory animals; or
– The need for medical, surgical, behavioral, social, or other intervention to prevent any of the above.
Continuing Noncompliance. Persistent or repeated failure to satisfy VA or other federal research requirements either in the past or extending into the present.
Unanticipated Problem in Research. Any problem in research that is not expected in terms of nature, severity, or frequency of occurrence; as documented in the protocol or other materials approved by the R&DC, IRB, IACUC, etc. For human research, may include the informed consent document, clinical investigators’ brochure, product labeling, etc.
Human Subjects Research Determination
The responsibility for determining whether an activity constitutes human subjects research rests with the investigator. Since the VA will hold the PI responsible if the determination is not correct, investigators are urged to request a confirmation that an activity does not constitute human subjects research from the IRB Manager. If the request is verbal (by phone or in person) or by email, it is the investigator’s responsibility to maintain documentation of such a decision. If the investigator submits a formal submission, the request must include sufficient documentation of the activity to support the determination. Formal submissions will be responded to in writing and a copy of the submitted materials and determination letter/email will be kept on file.
Request for Exemption
Under certain circumstances, human subjects research may be exempt from IRB review. Investigator’s shall request for exemption by submitting a completed Certification of Exemption Form along with the initial review submission forms as applicable to the research. Contact the IRB Manager for guidance or information regarding exempt studies. (Refer to the VHA Handbook 1200.05 for additional information on criteria for exempt research studies.)
Exemption from the IRB requirements mean there is no requirement for continuing review by the IRB. The PI however must submit any changes to the protocol to the IRB prior to implementing the changes to ensure that the research continues to qualify as an IRB-exempt research. A Continuing Review Checklist should be completed at each anniversary of the protocol and submitted to the IRB Manager. At completion of the study a report of study closure must be submitted to the IRB.
Requesting Expedited Review
Expedited review may be conducted by the IRB Chair or a qualified member designated by the Chair. The categories of research activities that may be reviewed by an expedited review process are listed in Appendix B of VHA Handbook 1200.05.
The PI should initiate a request for expedited review by speaking with the IRB Manager. The completed Request for Expedited Review form indicating the applicable category along with the required materials for initial review application must be submitted to the IRB Chair or designee for review who either concurs or disapproves the request, in which case, the submission must be reviewed by the full IRB.
The full IRB must be informed of the approvals by expedited review. Since only the full IRB can disapprove a study, the expedited reviewer must refer studies that he/she thinks warrant disapproval to the full IRB.
Procedures for Activating a Study Involving Human Subjects
To apply, the Principal Investigator (PI) must submit a Request to Review Research Proposal and all initial review submission forms as applicable to the proposed research. All human subjects research conducted under the auspices of the VA NYHHS must obtain prior IRB approval. The PI is notified in writing by the ACOS for R&D of final approval to initiate research.
Forms may be obtained on-line from the Research and Development Program website.