DISCLAIMER The following is a staff memorandum or other working document prepared for the members of the Advisory Committee on Human Radiation Experiments. It should not be construed as representing the final conclusions of fact or interpretation of the issues. All staff memoranda are subject to revision based on further information and analysis. For conclusions and recommendations of the Advisory Committee, readers are advised to consult the Final Report to be published in 1995. TAB E þþþDRAFTþ FOR DISCUSSION PURPOSESþþþ MEMORANDUM TO: Members of the Advisory Committee on Human Radiation Experiments FROM: Research Proposal Review Subcommittee DATE: September 2, 1994 RE: Status Report on Subcommittee Activities I. The Inclusion of a Journal Review Component to the Research Proposal Review Project The Subcommittee agrees that, on the basis of a pilot project conducted by Jay Katz, co-chair of the Subcommittee, it may be useful to go forward with a parallel journal article review project. The pilot review of journal articles reporting on contemporary human radiation research indicates that, with proper staffing, it may be worthwhile to examine journal articles for leads pointing to additional protocols and other materials to review. Reviewing journals in addition to going directly to the federal agencies for research protocol information will enhance the Advisory Committee's efforts to fully understand the current state of practices to adequately protect human subjects from research risks, inform subjects of what their participation entails, and the consent process by which they agree to participate. The criteria for selecting research studies reported in journal articles will be based on a judgement that the study involves more than minimal risk. To enhance the validity of the journal review project, the Subcommittee suggested retaining the denominator in reporting the results of the review (e.g., "x research protocols out of a total of y reviewed raised concerns and were therefore pursued"). It is unclear if the Protocol Review Subcommittee will need to restrict itself to selecting only journal articles reporting on federally funded research. II. Sampling Issues: Status of Agency searches for FY 1993 protocols Each agency has received a letter requesting details on databases that contain protocol information. The Protocol Review Subcommittee has asked staff to additionally request of each agency all abstracts of 1 human research approved in FY 1993 that involved ionizing radiation, to be submitted by September 7, 1994. Based on these abstracts, the Subcommittee will develop a principled mechanism by which to pare down and stratify the group of abstracts into a manageable sample. HHS Pilot Search of FY 1993 Protocols. The staff is conducting a pilot search of human research protocols approved and funded by DHHS in FY 1993. An extensive list of scientific search terms for the DHHS CRISP database was analyzed by staff to ensure the collection of ionizing radiation studies. The selected protocols were stratified according to whether the research involves ionizing radiation, and clinical vs. non-clinical research. The pilot yielded 184 human research protocols involving ionizing radiation, and 1554 other human research protocols (only 205 of which are identified as clinical). Staff is currently examining abstracts of ionizing radiation protocols, as well as sample of abstracts from the non-radiation protocols, to determine whether the CRISP clinical/non-clinical distinction is useful and to examine the quality of information contained in the abstracts. There may be a need to develop clearer criteria for what constitutes relevant human research, working within the limits of the HHS criteria for database search terms. Once a sample has been selected, abstracts will be distributed to members of the Protocol Review Subcommittee for review. Based on the Subcommittee's feedback, requests for the full protocols will be submitted to the institutions conducting the research. The Subcommittee has addressed the question of whether to include or exclude human tissue studies, as there may be some relevance to examining the ethics of asking patients for samples of tissue and body fluids. The Subcommittee decided to examine tissue studies included among the research protocols involving ionizing radiation because that subset offers a limited, and therefore manageable, number of such protocols. Tissue studies among non-radiation protocols will not be reviewed. The proportion of extramural and intramural protocols that will be reviewed for the DHHS pilot project will be based on the overall percentage of intramural vs. extramural research protocols approved by DHHS in FY 1993. IV. Basic Elements/Evaluation Criteria for Protocol Review The specific criteria to be used to evaluate the research proposals are currently under development. Although specific criteria for review have yet to be finalized, the general categories of review will include (1) informed consent, (2) risk-benefit analysis, and (3) subject selection recruitment. (See Attachment 1.) The benchmark criteria for the acceptability of a research study's provisions for protecting human subjects from research risk can be found in the current federal regulatory structure. The Subcommittee discussed the notion that proposals will range from ideal to grossly unacceptable, and will have to factor this into the establishment of criteria of "acceptable" proposals. 2 The extent of the paperwork necessary to conduct a meaningful review is not yet clear. Certain types of information not available on the research protocol may be found elsewhere in the documentation for that research project. At a minimum, three base documents will be sought for review: the grant application that was submitted to the appropriate federal agency, the IRB application, and consent form. Any deficiencies in this information will need to be augmented with additional requests to the IRB. The Subcommittee has yet to decide what types of supplementary information to request for IRBs (e.g., minutes, correspondence, etc.). In consideration of the logistical burden associated with each additional request, the Subcommittee will try to consolidate its requests of IRBs.