ࡱ> xzw#` Fbjbj\.\. .>D>D>.......B#####Bq.h$$$$$$$$-------$/hA2..)$$))...$$+.+++).$.$-+)-++..+$$ ۥ#*R+$,A.0q.+%4*%4+%4.+<$H&+''$$$..+ $$$q.))))BBB$fd BBBfBBB...... At the time of the Public Hearing held on October 11th I commented that we were in the process of analyzing data from two recent studies addressing our experience with the FDA rule for performing research using the exception from informed consent. Because we believe that this information will be useful to the FDA as you consider further guidance, we are providing some preliminary results from the two studies. One study was a mailed survey sent to the chairs of academic IRBs to determine their experience with reviewing studies proposing to use exception from consent. The other study reports our local experience with the community consultation process for the first of the Resuscitation Outcome Consortium (ROC) studies. In the Portland area our community consultation process included 2 random digit dialing surveys, community meetings and a web site. For each of these methods we used the same survey to gather respondents opinions about the research. The first of these studies is under review by a peer-reviewed journal and the second is in manuscript preparation. Although these data and interpretations should prove of value for the FDA, we ask that you do not disseminate the information outside of the FDA without our permission. Excerpts of the results are provided below. Institutional Review Board Experience with Exception from Informed Consent Nicole M. DeIorio, MD Katie B. McClure, MD Maria Nelson, BA K. John McConnell, PhD Terri A. Schmidt, MD (Abstract: DeIorio N, McClure K, Nelson M, et al: Institutional Review Board Members' Experiences with Exception from Informed Consent Protocols. Acad Emerg Med. 2006;13:S20-a) Methods: An anonymous survey was mailed to the chairs of IRBs at U.S. allopathic medical schools, excluding schools in Puerto Rico. A small qualitative phone survey of ten IRB members had been performed as a pilot study. The survey questions were developed based on this pilot study as well as modification of a previous survey used to assess public attitudes. Once the survey was refined, it was piloted again using IRB members at our institution. The study was designed to quantify IRB chairs experience using the regulations. In addition, the survey questions were developed to help identify IRB chairs attitudes about the rules. The instrument contained questions about demographics and about respondents knowledge of and experience with the federal regulations. In addition, there were 12 Likert scale questions assessing attitudes. Results: Of 126 schools,74 usable surveys were returned (59% response rate).Fifty-six respondents stated that they participate in review of research involving human subjects and had heard of the Rule;these weredeemed eligible for further analysis. Geographicdistribution of respondents was: East, 33%; Midwest, 26%; South, 22%; West, 20%. Forty-eight percent of respondents (25/52) had reviewed at least one protocol requesting exception from informed consent. Of those, 40% (10/25) had rejected at least one. Table 1 below reports the reasons for rejection. Respondents estimated that studies with exception from informed consent took longer to review, with a mean time of 8.8 hours versus 2.3 hours for studies not using exception to consent. This difference was statistically significant. (P < 0.001). Eighty-eight percent (45/51) of respondents stated that they are currently prepared to review these protocols. Though only 19% of respondents (10/52) were aware of their IRB offering formal training in the Rule, 49 of 52 respondents (94%) stated they can access the necessary information to apply the Rule. Thirty-eight percent (19/50) of those respondingagree thatthe regulations give sufficient direction. Fifty-six percent of subjects (29/52) agree that the difference between community notification and consultation is clear. Regarding the acceptability of the Rule, 72% of respondents (33/46) agree the Rule adequately protects human subjects, and 46% of those responding (21/46) do not believe that the Rule creates excessive barriers to resuscitation research. Sixty-nine percent of subjects (31/45) believe the Rule correctly balances protection of subjects with the need to do research and 24% (11/45) think it is overly weighted in favor of protecting subjects. Seven percent believe it is weighted too heavily in favor of the need to do research. Thirty percent of respondents (15/50) agree that community meetings are an effective means of community consultation. In the opinion of respondents, the best methods for community notification were listed to be (in order of descending preference with; more than one response possible to be selected): informing local politicians (68%), community meetings (55%), mailings (52%), tables in the hospitals (45%), radio announcements (29%), web sites (25%), newspaper advertisements (18%) and television advertisements (16%). Eight percent of respondents (4/51) agree with the statement, A national IRB should be formed to review studies that require emergency exception from informed consent for emergency situations. Forty-four percent (22/50) agree that every IRB reviewing resuscitation research should be required to have an emergency medicine researcher as a member. Table 1: Reasons for rejection of exception from informed consent protocols Reason for RejectionNumber Citing (Respondents could choose more than one)Did not meet guidelines for exception from informed consent4Problems with study design (e.g. improper control group, statistics, or randomization)3Concern that study may endanger subjects2Scientific problems (e.g. insufficient preliminary information, hypothesis not supported by information present, etc 2Adequate provisions for community consultation/notification not made1Fear of legal implications0Community input was unfavorable0 Table 2: Write in comments We briefly looked at being one of the sites for the Polyheme/blood substitute project. When we looked at the protocol (not as an IRB, just as a part of a group debating whether to participate or not) we felt it was not ethically designed and decided not to apply for the project. We investigated the community notification requirements.Need to use a combination of notification methods. One not adequate.[Re: the best methods of community notification:] This varies regionally e.g. web sites not helpful here nor community meetings (no one comes to either). No simple solution exists. This is a reason a natl IRB would be less effective. The IRB needs to be where the subjects live (in all cases) with comm. members from there.[Re: whether every IRB should contain a resuscitation researcher:] IRBs need the expertise to review a protocol appropriately-being a ED researcher may or may not provide that expertise. New requirements for IRB membership would be problematic.Its just that the regs are complicated and it is difficult to identify the target population so one is not sure what part of the community should be notified/ informed and how one would get the group together.We are currently limited by Missouri statute with respect to waiver (exception) of informed consent. We have made the interpretation that informed consent must be sought.A workshop on this would be helpful.The current regulations are too labor intensive and costly. Once investigators are fully informed, they give up and drop the protocol.2 of the 3 studies [rejected] never addressed stipulations or conducted the community sessions. Against NJ state lawNJ law forbidsState law specifically forbids use of the emergency exemption from informed consentWe have decided not to allow research without consent-we do have a proxy consent policy.The state of Florida doesnt allow this type of research and waiver of consent.We are in the process of developing detailed guidelines for 21CFR50.24. Comment: To our knowledge, our published qualitative study and this new survey are the only available data on the experience of IRB chairs with using the rules. Their experience is important because they are the ones that must interpret the rules and determine if the study can go forward. Of note, only about a third of respondents thought that the rules provide sufficient guidance. The majority of respondents believe that the rules adequately protect subjects. Forty-six percent believe the rules are not a significant barrier to resuscitation research. Interestingly, no IRB Chair reported rejecting a study because of unfavorable community input. Also of interest: many of the people who testified at the hearing supported a national advisory board or national IRB. In this survey, only 8% of IRB Chairs supported a national IRB for this research. A Comparison of the Responses to Different Methods of Community Consultation for a Study Proposing to be Conducted Using Exception to Informed Consent Maria Nelson, BA Terri A. Schmidt, MD Nicole M. DeIorio, MD Katie B. McClure, MD K. John McConnell, PhD Denise Griffiths METHODS: In preparation for the Portland area implementation of the Resuscitation Outcome Consortium (ROC) trial involving experimental IV fluid/saline, both random access dialing and community consultation meetings were conducted in accordance with Institutional Review Board (IRB)-approved community notification requirements. We did not design or conduct either the meetings or the phone calls, but rather analyzed (with permission) the results obtained from these public encounters. Four open forum meetings were conducted, one in each of the four counties participating in the Portland arm of the ROC trial. These meetings were publicized in local newspapers and by flyers posted at bus stops, grocery stores, hospitals, and public restrooms. These were open to anyone with an interest in the topic. A second type of community meeting was conducted, with presentations to organized community groups, especially minority groups or interested neighborhood groups and churches. After these presentations, attendees were given the opportunity to complete surveys, and a total of 54 were obtained. Efforts were made to present to multiple ethnic and community groups, but the full agendas by these organizations prevented many of the possible presentations. Two random digit dial phone surveys (including cell phone numbers) in the 4 counties were administered by personnel from an independent survey lab at Portland State University. The call recipients had to be 18 years of age or older and have a willingness to participate as a subject in the survey. Finally, a website was designed with information about the study. All published materials referenced the webpage, and viewers were invited to complete a survey containing the same questions that were asked during the second phone survey. See attached survey for the questions used. RESULTS There were a total of 361 useable surveys altogether, including 186 from phone survey #1, 86 from phone survey #2, 54 on paper, and 35 by website. We report here on the variation in responses to 4 questions asked as part of the community consultation. Question 1: If you were severely injured and had a one in three chance of not surviving with the standard treatment, would you want to have this experimental treatment given to you without consent? Overall, 77.5% (262/338) of the respondents answered yes. The two phone surveys (which used slightly different wordings of the same question) had statistically different answers to this question; 79.9% of the responders to the first phone survey said yes whereas only 66.2% of phone survey #2 respondents said yes. For the paper surveys completed at the community meetings, 93.6% responded yes to this question. This was the group with the highest level of agreement to the proposed scenario. Question 2: If there was less than 1 in 100,000 risk of an allergic reaction, would you still want the experimental treatment given to you? Overall, 83.6% (281/338) responded yes. Here again, the two phone surveys had significantly different responses; 87.0% of phone survey #1 responders said yes compared to 72.6% of phone survey #2, again suggesting that the exact wording of the question is influential in guiding public decision making. Furthermore, paper surveys indicate 95.6% agreement, the highest level of agreement with statistical significance. In both question 1 and question 2, phone survey #2 and the web survey had statistically equivalent responses (and used the exact same wording). Question 3: If you were in a severe accident and later learned that you were in this study (without consent), would you be upset? From all surveys combined, 82.% (271/327) responded no. Phone surveys #1 and #2 were not significantly different on this question, although they different from both paper and web surveys. On paper, 97.5% said no versus 83.0% and 81.7% from phone surveys 1 and 2, respectively. The web surveys were significantly different in that they indicated they would be upset more often, with only 59.1% answering no. Question 4: If one of your family members was severely injured and had a one in three change of not surviving with the standard treatment, would you want this experimental treatment given to them without written consent? Overall, 74.9% (245/327) responded yes. There was no statistical difference between phone survey #1 and #2 results. Paper results were again significantly different than phone surveys, with paper results showing 95.2% agreement versus 74.7% and 66.7% by phone. Comment: We are still in the process of analyzing this data but at this point a few things stand out. Despite efforts by the ROC investigators to advertise the community meetings held specifically to discuss the proposed trial, very few people attended those meetings. At the same time, the approval ratings for the study were the highest for the paper surveys returned at those meetings. This suggests to us that community meetings arranged to discuss a proposed study are not an effect means of community consultation. Similarly, web-based responses must be cautiously viewed due to restrictions in computer access and the self-selection for participation. We believe that random digit dialing surveys supplemented with discussion at already scheduled events such as church groups, community centers and gatherings of ethic minorities are a better approach. Thus, the random digit dialing can be used to provide a broad sample while the meetings can target special populations either because they are more likely to be enrolled in a particular study, are more likely to have concerns about are particular study or they may be under represented in the random digit dialing. Thank you again for the opportunity to comment on the proposed draft guidance. We think that as a group we have had the opportunity to study the rules from a number of different perspectives (see below) and that the two unpublished studies may be useful to you, as you develop the draft guidance. McClure KB, DeIorio NM, Schmidt TA, Chiodo G, Gorman P: A qualitative study of institutional review board members experience reviewing research proposals using emergency exception from informed consent Journal of Medical Ethics (in press) Mann NC, Schmidt TA, Richardson LD: Confronting the ethical conduct of resuscitation research: A consensus opinion Acad Emerg Med 2005; 12:1078-81. Mosesso VN, Brown LH, Greene LH, Schmidt TA, Aufderheide TP, Sayre MR, MD, Stephens SW, Travers A, Craven RA, Weisfeldt ML and The PAD Trial Investigators: Conducting research using the emergency exception from informed consent: The Public Access Defibrillation (PAD) Trial experience Resuscitation 2004; 61:29-36. 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