Human Research Protection Program Guidance for Human Research Determination

Transcription

1 Human Research Protection Program Guidance for Human Research Determination I.1.A The sole purpose of the Institutional Review Board (IRB), as defined in federal statutes, is the protection of human subjects during the course of activities defined as research. (Code of Federal Regulations, Title 45 Public Welfare, Department of Health and Human Services, Part 46, Protection of Human Subjects). Any project that is collecting or reviewing data from human subjects could qualify as research under federal definitions and thus require review by the IRB. Identifying a project as research is often clear cut, for example when an experimental drug or device is administered, a study involves randomization of subjects to different treatment arms, or a protocol is used that limits treatment options or utilizes options that differ from current practice. On occasion, however, differentiating research from other activities, such as those designed to assess and improve quality of care is challenging. This document provides definitions, guidelines and examples to assist investigators and staff at Maine Medical Center in understanding which activities involving human subjects fall under the category of research and require IRB review. If you determine that your project is research, please proceed to the HRPP website for guidance documents, forms and templates. The Research Compliance Office at will assist you in determining whether your project constitutes research and whether it needs to be reviewed by the IRB. In all cases the authority to determine whether a study constitutes research and whether it is exempt from IRB review or entails only minimal risk lies with the IRB itself Research means 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 Federal Food, Drug, and Cosmetic Act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the Federal Food, Drug and Cosmetic 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 terms research, clinical research, clinical study, study, and clinical investigation are synonymous for purposes of FDA regulations. (21 CFR 50.3(c), 21 CFR (c)) Human subject means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject might be either a healthy individual or a patient. For research involving medical devices a human subject is also an individual on whose specimen an investigational device is used. When medical device research involves in vitro diagnostics and unidentified tissue specimens, the FDA defines the unidentified tissue specimens as The two key elements of the federal definition of research, namely that it is a systematic investigation and that it is designed to contribute to generalizable knowledge, are not further defined in the regulations. This lack of clarity may lead to uncertainty in determining whether an individual study qualifies as research. As a general guide, the IRB at MMC defines a systematic investigation as one that uses specific pre-planned procedures as part of the study process, whereas contributing to generalizable knowledge is assumed if the study is conducted to provide data about a method, treatment or program that can be replicated or implemented at other sites. The mere decision to disseminate or publish the results of a study, does not necessarily imply that research, as defined above, has been conducted, and that IRB review is required. Thus, studies focusing Page 1 of 6 SOP # FO 301-D Effective Date: Supersedes N/A

2 on educational initiatives or quality assessment that do not meet the above definition of research, or are specified within federal statures as being exempt from IRB review, may be conducted, published and presented at meetings without IRB approval. However, the implications of engaging in a qualifying research activity, as defined above, that has not been reviewed and approved by the IRB are significant. Of paramount importance are concerns regarding subject and patient safety and the potential liabilities incurred by the institution and the investigators should an incident occur or the study undergo audit. In addition, the results from qualifying research studies that have not been approved by the IRB prior to data collection may not be presented or published. To do so is in violation of federal and Institutional policies regulating the conduct of research and in some cases may violate the Institutional Policy regarding the Uses and Disclosure of Private Health Information. It is also against Institutional policy to use data from a non-irb-approved qualifying study to satisfy thesis or dissertation requirements. Thus, the classification of a study as research and as being subject to IRB review should be determined prospectively prior to the enrollment of subjects or the collection of data. Federal regulations define certain types of research as being exempt from IRB review. Please review the exempt review categories. If your project is research and meets one of the exempt review categories, please submit a request for exemption from IRB review form. Federal regulations also define a category of research studies that while not being exempt from IRB review, do allow the IRB to conduct an expedited review. These include studies that are judged by the IRB to involve minimal risk, which means that 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. (45, CFR (i)) The information below includes a list of factors, examples and questions that have been developed by the MMC IRB to aid investigators and staff in understanding the classification of a study as research or not, and whether the study may be exempt from IRB review or judged to be minimal risk and thus qualify for a expedited IRB review. The following table lists common attributes of studies gauged to be research or not research. single feature, however, can be used to make a definitive determination. Furthermore, it is expected that any study deemed not to be research will involve no more than minimal risk as defined above. MMC policy states that any study that puts subjects or patients at greater than minimal risk, including issues related to individual privacy, must be reviewed by the IRB. Topic Research t Research 1 Purpose To generate new, scientific generalizable knowledge To improve internal processes, practices, costs, or productivity 2 Goal To test a hypothesis or describe a phenomenon To implement evidence-based practice and/or measure an existing practice 3 Patient Expectations t a part of routine care Part of routine clinical practice 4 Consent Almost always, occasionally waived t required 5 Risks Often some risk (eg. extra blood draw, experimental care or drug) risk beyond usual care Page 2 of 6 SOP # FO 301-D Effective Date: Supersedes N/A

3 6 Voluntary participation Always 7 Extraneous variables Usually measured or controlled in study design Rarely t manipulated or tracked Page 3 of 6 SOP # FO 301-D Effective Date: Supersedes N/A

4 The following examples are provided to illustrate some of the concepts cited above: 1. After several randomized trials confirmed improved outcomes when cardiac arrest survivors were cooled for 24 hours, a clinical protocol was developed and initiated. Patients treated with what was considered to be a new standard of care were monitored to access the impact the change on the unit. This activity was judged not to qualify as research as there was no intent to generalize the knowledge. 2. After 15 patients had been treated, the clinical team decided to begin entering data into an international registry that serves as a data repository for future investigations. This systematic collection of data, designed to be used to investigate questions and generate generalizable results was at that point considered to be research. A protocol was thus submitted to the IRB and an expedited review undertaken based on the provision of research involving minimal risk according to 45 CFR (b)(1). 3. After using surface cooling technology for these patients for 4 years, the clinicians wished to use another technique involving an intravascular catheter, which was in use as the standard of care at some other institutions. Two approaches to introducing this alternative technique were considered. Approach A involved randomizing patients to receive the new or old method, with a comparison of adverse events and outcomes between the two methods. This approach was judged to qualify as research as the randomization process and comparison of the outcomes between the two groups was considered a systemic investigation with the likelihood of generating generalizable results. Approach B allowed the clinicians managing the patients to simply pick one technique or the other, and similar data would have been monitored as a process improvement effort. This would not have been considered research. 4. A health care provider wished to introduce culturally appropriate clinical treatment algorithms designed for patients and providers into a clinical practice and simply gauge the degree to which these educational materials were adopted. This intervention would not be considered research, as there was no intent to generate generalizable results. However, if outcomes were defined and measured to evaluate changes in practice generated by this intervention with the intent to disseminate the findings, then the activity does constitute research and does require IRB review and approval. Such a research project would likely be classified as minimal risk and receive an expedited review. 5. A scientist has discovered a circulating protein that affects heart muscle function. S/he proposes a study to define the range of blood levels of this protein in healthy normal individuals and patients with known cardiac disease. Volunteers will be subjected to phlebotomy of 5 cc of blood and the level of the protein in her/his blood determined. Subjects will not be told the results of the findings. This project is considered research since it involves a systematic investigation to generate generalizable knowledge. The federal regulations consider a small volume phlebotomy to represent a minimal risk based on the definition above and so this protocol was granted an expedited review. 6. Quality and patient safety experts at the Johns Hopkins Hospital and the Michigan Health and Hospital Association undertook a project designed to determine if they could reduce the rate of central line infections in 103 intensive care units in Michigan. The initiative included an ICU based safety program and use of a checklist to ensure that five evidence-based procedures previously demonstrated to improve central line infection rates were followed. There was no stratification of patients into groups, no randomization and no control group. Page 4 of 6 SOP # FO 301-D Effective Date: Supersedes N/A

5 Most, but not all, participating hospitals were already collecting data on these procedures, and instituting the project ensured that all hospitals collected the same data and used the CDC standard definition of central line associated bloodstream infections. The study documented that implementing the procedures was associated with a dramatic reduction in the rate of infections and the results were published. This project, while clearly research in that it involved a systematic investigation to produce generalizable results, was initially exempted from IRB review by the Johns Hopkins Hospital under provision 45 CFR (b)(4) (see above collection of existing data in such a manner that subjects cannot be identified). However the NIH Office of Human Research Protection determined that this classification was incorrect, and that the study could not be judged as exempt research since it involved the analysis of prospectively collected data and biological specimens. The correct classification of this study was minimal risk research, since only usual data were being collected and the intervention, which was based on strong evidence-based guidelines, could thus be considered standard of care. Thus, IRB review and approval was required for this study. 7. A practictioner wishes to collect specific data on all patients who have previously undergone an ERCP in the past year. The project is being conducted to determine whether these patients, who received a new technique to prevent post-operative pancreatic duct leaks using pre-operative ERCP pancreatic duct stenting, had fewer post-operative complications. This project was determined to be research in that it represented a systematic investigation (i.e. a retrospective chart review) with the potential to generate generalizable results. However, since it involved the collection of existing data in a manner that but as it involved the collecting of existing data in a manner such that individual patients were not to be identified or tracked, it received an exemption from IRB review according to 45 CFR (b)(4). Page 5 of 6 SOP # FO 301-D Effective Date: Supersedes N/A

6 The following questions maybe helpful to you and the IRB to determine the most appropriate classification of your project: 1. Does this project involve a prospective intervention or interaction with living individuals (e.g. the administration of drugs or devices, the employment of other types of interventions such as counseling, the administration of oral or written questionnaires, the use of assessment tools that are not part of standard of care )? 2. Is this project intended to develop or test the efficacy of an intervention or to test a hypothesis that is beyond the current state of knowledge? 3. Does the project involve assigning subjects, through randomization or by other means, to different groups? 4. Is the intent of the project to achieve results that will be disseminated outside of the immediate site where the study is being performed? 5. Is the risk to subjects in your project greater than what is encountered in every day life or what is considered standard of care? 6. Will this project alter or influence the care of subjects participating in the study (outside standard of care)? 7. Does the project involve the prospective collection of data on human subjects? 8. Will subjects be identified and/or tracked during the course of the study? If the answer to ANY of these questions is YES then the activity may be research and thus subject to IRB review. Page 6 of 6 SOP # FO 301-D Effective Date: Supersedes N/A