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Release of records to government agencies in other countries

Hi, In the context of a particular study, the industrial sponsor has requested the addition of the quoted language to the list of enumerated entities that require access to the study-related records. To what extent have you seen this request before ? I presume it relates to the regulatory process in these other countries involved in the evaluation and approval of drugs for marketing. I am concerned about the propriety of the quoted language, and its conceivable implications with respect to a subject's privacy and confidentiality interests. I'd appreciate any thoughts from those who've encountered this kind of request before. Thanks, Howard

Anonymous 6/1/2000 5:20:00 PM

Telephone Consent

While telphone consent can be used for clinical emergencies I don't think that it should ever be appropriate for research projects. -----Original Message----- From: Workman, Don [mailto:Don.Workman@stjude.org] Sent: Wednesday, May 31, 2000 12:36 PM To: 'mcwirb@mcwirb.org' Subject: Telephone Consent I have an Investigator asking about procedures for obtaining informed consent via the telephone. Written guidelines for this would be advantageous in our Institution for two situations: One possible scenario would be the use of previously collected blood or tissue samples for a new research protocol. Another would involve obtaining the consent from the other parent for a study involving more than minimal risk with no likely benefit to the subject (many of our subjects travel here accompanied by only one parent). Would anyone be willing to share (on or off-line) written procedures or other guidelines for obtaining and witnessing informed consent over the telephone? Don E. Workman, Ph.D. IRB Administrator St. Jude Children's Research Hospital 332 N. Lauderdale Memphis, TN 38101 901-495-4359 _______________________________________________ MCWIRB maillist - MCWIRB@mcwirb.org http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb

John 6/1/2000 3:00:00 AM

Samples from tissue banks

There was a recent discussion of the ownership of samples from tissue banks. I have a related question. When an investigator proposes to use tissue from a tissue bank for a study, should the IRB require that the investigator obtain a copy of the approved protocol for the tissues contributed to the tissue bank? In other words, if a hospital or clinic is providing anonymous samples to one of our researchers, should we have a copy of the approval for the protocol used to collect those samples? Ruth Tallman Office of Research and Sponsored Programs Lehigh University 526 Brodhead Avenue Bethlehem, PA 18015 Phone: (610)758-3024 FAX: (610)758-5994 E-mail: rt01@lehigh.edu

Ruth Tallman 5/31/2000 3:52:00 AM

Federal oversight of non-federal research

Do we know how much IRB review of non-federal research will be the focus of future legal oversight? Half of our human subject research is non-federally funded, PI initiated. At a recent IRB conference I attended, the FDA representative stated that they only audit industry sponsored research seeking FDA approval. We use the same policies and procedures for all studies but are they not subject to any external review? Wendy Westling Mission St. Joseph's Health System Asheville, NC

Anonymous 5/31/2000 4:15:00 AM

Education Resources for Research Review and Compliance

Several messages have been posted recently asking for educational materials for use by IRBs and investigators, as well as a request for a calendar of educational events (e.g., see messages of 26 May 2000 by Richard Kelley and Craig Weiner). I am happy to say that the NIH (DHHS) has such a starting place entitled Bioethics Resources on the Web < http://www.nih.gov/sigs/bioethics >. This website contains a broad collage of annotated web links to make available educational and training opportunities offered by the NIH, other Federal agencies, as well as by many academic centers. Online courses are listed including online case studies and tutorials. Specific topics such as human subjects research, the responsible conduct of research, laboratory animal care and use, international research ethics and codes, genomics, gene therapy, human stem cell research, end-of-life care, health care policy, and more are listed. A particularly useful Research Resource is a comprehensive bibliography with over 4,600 citations on the Ethical Issues in Research Involving Human Participants. Easy research starting points include links to the National Library of Medicine's PubMed, Grateful Med, and MEDLINE as well as Georgetown University's BIOETHICSLINE. Many organizations and journals of interest are listed. Of particular help are easy links to important documents such as The Belmont Report and 45CFR46 (The Common Rule) and sources such as the Federal Register. A section on Upcoming Events in Bioethics will keep everyone's calendar up to date with the educational conferences and offerings that are forthcoming. While this resource is comprehensive, it is not totally inclusive and remains a work in progress. I therefore welcome any information about links that would be of use to our colleagues. In response to Richard Kelley's request to lighten the load, I would like to see this site offer an expanded generic set of educational materials for use by the IRBs and institutions as they develop programs to educate IRB members and administrators and research investigators. So, please, send me < rlfisch@nih.gov > any resources that you would like to share with colleagues and I will add them to the Bioethics Resources on the Web website. One additional resource to mention. The NIH has a Program Announcement (PA) that is currently available to support research on ethical issues that arise with research involving human participants. We want to encourage empirical studies to fill the many gaps in our knowledge and understanding of the challenging ethical issues that arise concomitantly with the rapid advances and complexities of our research enterprise. There are three receipt dates per year (June 1, October 1, and February 1), and applications are invited for the next two years. Please pass this information on to any colleague who might be interested in learning more about this opportunity. The PA is entitled Research on Ethical Issues in Human Studies and is found at this URL: < http://grants.nih.gov/guide/pa-files/PA-99-079.html > These are difficult times and I am grateful for mcwirb and the communication link it offers that provides answers to questions and useful resources that do help to lighten our load. Please contact me if there is any help that I can provide. Ruth Fischbach Ruth L. Fischbach, Ph.D., M.P.E. Senior Advisor for Biomedical Ethics National Institutes of Health Office of Extramural Research Building 1, Room 158 1 Center Drive, MSC 0152 Bethesda, MD 20892-0152 (301)496-1414 - Phone (301)402-7062 - FAX rlfisch@nih.gov

Ruth Od 5/31/2000 3:45:00 AM

Samples from tissue banks

Yes, I think it is prudent for the IRB to ensure that the tissue was collected in a proper fashion and is indeed residual or properly placed in a repository. In addition, you would want to ensure that the source individual had not placed any restrictions on the use of the material. The best way to do this is to view the protocol and consent forms under which it was collected. Dan Daniel L. Icenogle, MD, JD Icenogle & Associates 1858 Sand Ridge Ct. Verona, WI 53593-8814 608.832.0549 (voice and fax) Electronic mail from Daniel L. Icenogle, MD, c/o Icenogle & Associates at Dan_Icenogle@icenogle.net. This communication is intended for the use of the addressee. It may contain information which is privileged or confidential under applicable law. If you are not the intended recipient or the agent of the recipient, you are hereby notified that any dissemination, copy or disclosure of this communication is strictly prohibited. If you have received this communication in error, please notify Icenogle & Associates at (608) 832-0549 or via return Internet electronic mail at Dan_Icenogle@icenogle.net and expunge this communication without making any copies. Thank you for your cooperation. -----Original Message----- From: mcwirb-admin@mcwirb.org [mailto:mcwirb-admin@mcwirb.org]On Behalf Of Ruth Tallman Sent: Tuesday, May 30, 2000 12:50 PM To: mcwirb@mcwirb.org Subject: Samples from tissue banks There was a recent discussion of the ownership of samples from tissue banks. I have a related question. When an investigator proposes to use tissue from a tissue bank for a study, should the IRB require that the investigator obtain a copy of the approved protocol for the tissues contributed to the tissue bank? In other words, if a hospital or clinic is providing anonymous samples to one of our researchers, should we have a copy of the approval for the protocol used to collect those samples? Ruth Tallman Office of Research and Sponsored Programs Lehigh University 526 Brodhead Avenue Bethlehem, PA 18015 Phone: (610)758-3024 FAX: (610)758-5994 E-mail: rt01@lehigh.edu _______________________________________________ MCWIRB maillist - MCWIRB@mcwirb.org http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb

Daniel L . Icenogle 5/31/2000 3:46:00 AM

More on PRIM&R's Educational Offerings

Hello, I wanted to alert those on the listserv to one program I failed to mention when last I wrote about PRIM&R and ARENA's educational offerings: We will be offering a course entitled Responsible Conduct of Research 101 On the Road beginning in the fall of 2000. This effort will be spearheaded by Michael Kalichman, Ph.D. of UCSD and Frank Macrina, Ph.D. of VCU, two of the leading thinkers, lecturers, and writers in the field. Please stay tuned for more information on this new activity. I also wanted to pass along a note I received from Ruth Abramson, M.D., IRB Chair at Mt. Sinai Hospital in NYC, who writes as follows with respect to the PRIM&R IRB 101 courses held earlier this month: On two separate occasions we hosted an orientation program entitled IRB 101 On the Road hosted by Public Responsibility in Medicine and Research (PRIM&R) to educate our 100 IRB members and administrators from our own institution and affiliates and 400 investigators. The one full-day session (for members and administrators) and four half-day sessions (for investigators) proved to be extremely valuable. The sessions were very well received and the level of instruction was outstanding. Our newest IRB members and administrators gained essential knowledge about the IRB process. Our veteran members and investigators, in addition to receiving a refresher course on the federal guidelines, were also reminded of the history and foundation upon which the regulations they follow are based. These sessions helped educate our investigators and actually raised their levels of consciousness about how they conduct research involving human subjects. I have been getting superb feedback from lots of people. Investigators, who were initially very bitter about having to attend the mandatory session, actually thanked me for having arranging the sessions! Many seasoned clinical investigators were very impressed with the meeting and told me that they thought that it was extremely valuable. One investigator made it a point of telling me that he also thought it was great and very valuable, in part because it reminded the clinical investigators of THEIR responsibilities to all those involved in the research; subjects as well as staff. Thanks, Joan Rachlin

rachlinj@aol.com 5/31/2000 3:55:00 AM

Samples from tissue banks

I require our investigators to provide documentation that the existing anonymous specimens they acquired for their exempt study were initially obtained under an approved protocol belonging to the source of the tissue. I require that the PI append a copy of the protocol and IRB approval letter from the original source of the donated tissue. On two occasions this practice revealed that the original source either did not have approval or the approval had lapsed. It is interesting that the National Cooperative Human Tissue Network asks for a copy of the approved protocol of the tissue recipient as well.

Arthur O Col Usamriid 5/31/2000 3:52:00 AM

Education Resources for Research Review and Compliance

Education and training materials and opportunities for investigators and IRBs participating in industry-sponsored clinical research are widely available as well. I am extremely pleased to see our industry taking the May 23 and 24th communications from Shalala and this recent unpleasantness with NIH/FDA/DHHS seriously. It has been my experience that most IRBs take their responsibilities seriously, but few have had the support (in an all-volunteer environment anyway) from the institutions which they represent to obtain the type of training and education that the U.S. government is now calling for. My company trains thousands of investigators, CRAs and CRCs every year. In fact, we not only offer dozens of private seminars annually, but are the curriculum developer and key faculty for ACRP's public GCP courses. (By the way, the next course is June 23 and 24 in Indianapolis, and while it is geared toward the CRC and CRA, much of the information contained in the intermediate level offerings is quite germain to some of the issues that IRB members should be cognizant of). A few months ago we developed training materials especially for the IRB member as well as SOP templates for the IRB. Historically, we have had to conduct GCP training regarding human subject protection with the coordinator or investigator. We then had to rely upon the site to evaluate their IRB's responses to submissions to determine whether or not the IRB had GCP training. This was clearly not the most efficient method of disseminating information. I have discussed this with our training department and if there is enough interest, we can quickly assemble a customized IRB-focused training program and offer this at a special price to McWirb participants. I encourage you to ask colleagues in our industry about the quality of MedTrials training for I think you will find that it is indeed not only excellent, but presented by professional trainers who are in the thick of current research practice. Our trainers are involved in protocol design, monitoring, auditing, FDA interface, SOP writing, etc. It is through continuing to practice that we are able to stay abreast of not only regulatory, but climactic changes in our industry. In addition to MedTrials, there are many other excellent trainers and training options in the industry - some of which you have learned about in today's communications. No matter who you chose, I strongly encourage all interested parties to chose someone. If you have any questions or wish to get some feedback to decide what training option might be best for you, please contact me (rnewman@medtrials.com) or Lynn Palmer (lpalmer@medtrials.com). For a list of some of our most requested training modules, please visit our website at www.medtrials.com. Very best regards, Robin Zehr Newman Robin W. Newman, RN MSN CPNP Executive Vice President MedTrials, Inc. 2777 Stemmons Freeway #975 Dallas, Texas 75207 214-630-0288 fax: 214-630-0289 rnewman@medtrials.com www.medtrials.com >>> Fischbach, Ruth (OD) 05/29/00 07:30PM >>> Several messages have been posted recently asking for educational materials for use by IRBs and investigators, as well as a request for a calendar of educational events (e.g., see messages of 26 May 2000 by Richard Kelley and Craig Weiner). I am happy to say that the NIH (DHHS) has such a starting place entitled Bioethics Resources on the Web < http://www.nih.gov/sigs/bioethics >. This website contains a broad collage of annotated web links to make available educational and training opportunities offered by the NIH, other Federal agencies, as well as by many academic centers. Online courses are listed including online case studies and tutorials. Specific topics such as human subjects research, the responsible conduct of research, laboratory animal care and use, international research ethics and codes, genomics, gene therapy, human stem cell research, end-of-life care, health care policy, and more are listed. A particularly useful Research Resource is a comprehensive bibliography with over 4,600 citations on the Ethical Issues in Research Involving Human Participants. Easy research starting points include links to the National Library of Medicine's PubMed, Grateful Med, and MEDLINE as well as Georgetown University's BIOETHICSLINE. Many organizations and journals of interest are listed. Of particular help are easy links to important documents such as The Belmont Report and 45CFR46 (The Common Rule) and sources such as the Federal Register. A section on Upcoming Events in Bioethics will keep everyone's calendar up to date with the educational conferences and offerings that are forthcoming. While this resource is comprehensive, it is not totally inclusive and remains a work in progress. I therefore welcome any information about links that would be of use to our colleagues. In response to Richard Kelley's request to lighten the load, I would like to see this site offer an expanded generic set of educational materials for use by the IRBs and institutions as they develop programs to educate IRB members and administrators and research investigators. So, please, send me < rlfisch@nih.gov > any resources that you would like to share with colleagues and I will add them to the Bioethics Resources on the Web website. One additional resource to mention. The NIH has a Program Announcement (PA) that is currently available to support research on ethical issues that arise with research involving human participants. We want to encourage empirical studies to fill the many gaps in our knowledge and understanding of the challenging ethical issues that arise concomitantly with the rapid advances and complexities of our research enterprise. There are three receipt dates per year (June 1, October 1, and February 1), and applications are invited for the next two years. Please pass this information on to any colleague who might be interested in learning more about this opportunity. The PA is entitled Research on Ethical Issues in Human Studies and is found at this URL: < http://grants.nih.gov/guide/pa-files/PA-99-079.html > These are difficult times and I am grateful for mcwirb and the communication link it offers that provides answers to questions and useful resources that do help to lighten our load. Please contact me if there is any help that I can provide. Ruth Fischbach Ruth L. Fischbach, Ph.D., M.P.E. Senior Advisor for Biomedical Ethics National Institutes of Health Office of Extramural Research Building 1, Room 158 1 Center Drive, MSC 0152 Bethesda, MD 20892-0152 (301)496-1414 - Phone (301)402-7062 - FAX rlfisch@nih.gov _______________________________________________ MCWIRB maillist - MCWIRB@mcwirb.org http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb

Robin Newman 5/31/2000 3:45:00 AM

U.S. Agency Seeks Power to Fine Universities That ViolateRul es on Human Research Subjects

In responce to other comments: The amount of the fines may not seem significant to the average big organization (they do too me!) but the lawyers fees, the amount of time needed to be devoted to defending yourself, the total disruption in your professional and personal life, and the devastation to your reputation are all heavy factors. If anyone is innocent enough to believe that this is just a minor disruption has never been involved in an audit or law suit. Plus putting in these sanctions, the government gives more visibility to the problems and legitimacy to pursuing them. Margaret Ann Skelton The George Washington University icrmas@gwumc.edu 202 994 0844

Margaret Skelton 5/30/2000 6:31:00 AM

Ethics of adverstising - AMA

The AMA has a council on ethics, which includes some information on ethics in advertising. Their main website is http://www.ama=assn.org. One of the directives on ethics and advertising and HMOs can be found at: http://www.ama-assn.org/apps/pf_online/pf_online?f_n=browse&doc=policyfiles/CE JA/E-5.01.HTM&&s_t=&st_p=&nth=1&prev_pol=policyfiles/CEJA/E-4.07.HTM&nxt_pol=p olicyfiles/CEJA/E-5.01.HTM& Ginger French, Pharm.D.

Ginger French 5/30/2000 4:08:00 PM

Gary Ellis Reassigned....

Government to Reassign Head of Unit That Oversees Human-Subjects Research By JEFFREY BRAINARD/Chronicle of Higher Education/May 30, 2000 Washington The Department of Health and Human Services plans to reassign Gary B. Ellis, the director of the federal office that has aggressively clamped down on universities for violating regulations that protect human subjects in biomedical research. The move comes as the agency is planning to name a director to lead a new federal office that will replace Mr. Ellis's division, the Office for Protection from Research Risks. The department is reported to have chosen a candidate for that job -- E. Greg Koski, an administrator at Massachusetts General Hospital -- but as of Friday, the department had made no announcement. (See an article from The Chronicle, May 26.) Some observers have concluded that the department wants to scale back the tougher enforcement of the research-risks office under Mr. Ellis's leadership over the past 20 months. In that time, the office has suspended all clinical research at seven institutions for violations of federal regulations, forcing them to scramble to improve protections for research subjects in order to resume the research. That, in turn, has prompted criticism from some university officials, who have privately called Mr. Ellis's actions excessive and unwarranted. But even as critics questioned the department's commitment to protecting volunteers in medical research, Health and Human Services Secretary Donna E. Shalala announced new plans last week to increase enforcement efforts, as well as to educate university officials about the substance of the federal rules, and the need to comply with them. In an interview Friday, Mr. Ellis said that he had not learned where the department would assign him after he left the job directing the research-risks office. However, he said he was told it would involve different duties within the National Institutes of Health, of which the research-risks office is a part. He is covered by civil-service protections. A department official also told him in May that the agency had not selected him to lead the new office, to be called the Office of Human Research Protection, he said. Once a new director is named, the research-risks office will be replaced by that office, which will be part of a branch that is under Ms. Shalala's direct control. In announcing the move last year, Ms. Shalala said it would elevate the office's stature. Mr. Ellis would not comment about the future direction of the office. He said he was disappointed by his reassignment, but added: Obviously, attention is focused on protecting human-research subjects in a way that it never was before. That's a good thing for everyone. Some university officials have said that Mr. Ellis and his staff have gone overboard in interpreting the 18 pages of regulations that govern the protection of research volunteers at institutions that receive federal research financing. The research-risks office has enforced those regulations at institutions that receive financing from the National Institutes of Health, which is part of the Department of Health and Human Services. Mr. Ellis said that the rules were specific and detailed, and that it would be absolutely wrong for O.P.R.R. to go beyond them. As for the suspensions of research at universities, he said the office had acted in accordance with a directive from President Clinton. In 1994, in the wake of disclosures about decades of experiments that had exposed people to radiation unwittingly, Mr. Clinton ordered that research on human subjects that violated federal regulations cease immediately. Mr. Ellis added, There's not much wriggle room there. Mr. Ellis was named director of the research-risks office in January 1993 by Bernadine P. Healy, who was director of the N.I.H. at that time. When the Department of Health and Human Services announced the opening for the director of the

Anonymous 5/30/2000 4:45:00 AM

educational resources

As an educator, I use/rely on a great deal of the publications from the Center for Clinical Research Practice (CCRP...formally known as Research Nurse). Everything that I have ever read or used is excellent. I suspect that their education materials for IRBs upholds the very same high standards. I have no other connection to this group except admiration! Margaret Ann Skelton The George Washington University icrmas@gwumc.edu 202 994 0844

Margaret Skelton 5/30/2000 6:43:00 AM

Gary Ellis Reassigned: Part II

Chron Article Part II Mr. Ellis said that the rules were specific and detailed, and that it would be absolutely wrong for O.P.R.R. to go beyond them. As for the suspensions of research at universities, he said the office had acted in accordance with a directive from President Clinton. In 1994, in the wake of disclosures about decades of experiments that had exposed people to radiation unwittingly, Mr. Clinton ordered that research on human subjects that violated federal regulations cease immediately. Mr. Ellis added, There's not much wriggle room there. Mr. Ellis was named director of the research-risks office in January 1993 by Bernadine P. Healy, who was director of the N.I.H. at that time. When the Department of Health and Human Services announced the opening for the director of the Office of Human Research Protection in December, the job description appeared to have been written to exclude Mr. Ellis as the successful finalist. The department called for candidates with national reputations in scientific research, a background that Mr. Ellis does not have.

Anonymous 5/30/2000 4:47:00 AM

Educational resources

Does anyone have a good link or resource for educational opportunities for IRB members? Particularly when it comes to meetings and conferences, there doesn't appear to be any clearinghouse of information on upcoming meetings. Thanks for any help. Craig Weiner, MD Chair Mercy Healthcare Sacramento Regional IRB

Craig 5/30/2000 6:43:00 AM

Ethics of advertising

Dear colleagues: Does anyone know of any published materials discussing the ethics of physicians or other health care providers advertising their services to patients known to be in an existing doctor (healthcare provider) - patient relationship? Also, any materials on advertising via phone-calling, door to door, etc. re: targeting individuals to sign up for adult medical day care centers, medicare medigap policies, etc. Any help would be appreciated, Thanks, Henry Silverman, MD,MA University of Maryland School of Medicine 10 S. Pine St. Baltimore, MD 21201 Tel: 410-706-6250 Fax: 410-706-8162 Tel: 410-706-6250 Fax: 410-706-8162

Henry Silverman 5/30/2000 6:37:00 AM

PRIM&R/AAMC Workshop on Effective IRBs: The Fundamentals

The third and last scheduled PRIM&R/AAMC workshop on Effective IRBs: The Fundamentals will be held at the Westin O'Hare Hotel just outside Chicago on September 18, and there is still room to register. To learn more about the program, and to obtain the registration materials, you can connect to: . This event is for IRB staff and members, investigators, research administrators, and others who would like a solid grounding in the human subjects regulatory requirements. Our faculty for this event will include Dale Hammerschmidt, M.D. (University of Minnesota), Moira Keane (University of Minnesota), Gary Chadwick, Pharm.D., M.P.H. (University of Rochester), Jeffrey Cohen, Ph.D. (OPRR), and Ada Sue Selwitz (University of Kentucky). In addition to presentations on the history, ethics, and details of the regs, you will have ample opportunity to pose to this distinguished faculty questions concerning the special issues and challenges that you face. There will also be an interactive session involving small team discussions of specific cases. If after visiting the Web site, you still have questions on the program, contact Allan C. Shipp, AAMC, at (202) 828-0484. If you have other questions concerning registration matters, please contact Melissa Shaw, (202) 862-6103.

Allan Shipp 5/30/2000 11:37:00 AM

educational resources

Readers of MCWIRB seem to be most interested in what is available for investigator training and IRB member training. There also seems to be a great deal of confusion about the availability of suitable educational materials for all members of the clinical research enterprise. In addition to what has been discussed in this forum to date, I offer additional information. Over the past several years, The Center for Clinical Research Practice has conducted on-site training programs for site personnel, including investigators. In addition to these seminars, 2 texts have been published: Foundations of Clinical Research and Foundations of Human Subject Protection. The latter book was published just several months ago and is suitable for IRB members and investigators who need to understand the regulations, ethics, and other matters pertinent to conducting research with human beings. CEUs are available for each publication and, of potential interest to IRBs, a test has been constructed and is included with each book. In addition, a workbook accompanies the Foundations of Clinical Research book. For continuing education, CCRP has offered Research Nurse and the Journal of Clinical Research Practice. These have now merged into Research Practitioner. Readers of this bimonthly journal can receive either CEUs or CMEs as part of their subscription. More information on these and other educational materials is available at the CCRP web site: www.ccrp.com. Alan M. Sugar, M.D. Professor of Medicine, Boston University School of Medicine Medical Director, The Center for Clinical Research Practice Chairman, New England Institutional Review Board

Alan Sugar 5/30/2000 3:38:00 AM

educational resources

Alan Sugar 5/30/2000 3:41:00 AM

A rose by any other name?

Dan: Ah, yes, but Shakespeare was referring to what is consider to be a rose. With such the language and semantics matter not. Consider, however, that a vial of rose nectar also would presumably smell as sweet as the rose, but would lack essential ingredients required to be a rose. Our committee also lacks some essentials to be legitimately called an IRB. Your sense of smell has not let you down, however, because we do try to accomplish a mission similar to that of the IRB--protection of subjects. But as you know, if the IRB is functioning under the Department of Health and Human Services, 45 CFR 46 specifies particular requirements for IRBs. §46.102g states, IRB means an institutional review board, established in accord with and for the purposes expressed in this policy. § 46.103 provides requirements for certification, and reporting requirements which include, A list of IRB members identified by name; earned degrees; representative capacity; indications of experience such as board certifications, licenses, etc., sufficient to describe each member's chief anticipated contributions to IRB deliberations; and any employment or other relationship between each member and the institution (for example: full-time employee, part-time employee, member of governing panel or board, stockholder, paid or unpaid consultant). Changes in IRB membership shall be reported. . . Thus, we do not qualify as, or to call ourselves, an IRB--and we did not want to qualify. We chose not to go that route for several reasons. One was to avoid the administration of all the HHS requirements for an IRB. It can be expensive, and with tight budgets, we were concerned with being compromised because of insufficient resources to do the IRB job properly. We are a relatively small operation, with fairly high turnover of members on the committee, and the administration would have been challenging. Our committee's mission also includes more tasking than reviewing research proposals. We have the broader patient rights mission and the hospital ethics mission. So, if we had opted for our own IRB, we would have had to form a separate body as the IRB which would have then reported to us--just another layer of admin. This would have been required by HHS because we determined that the regulation would have required a change to the composition of our team, and being small, that would have increased the potential for conflicts of interests and obligations in the working environment. We would have had so many people reclusing themselves from decisions because of conflicts that we would have ended up without quorums. I have come to believe that there are some decided advantages of having research reviewed by IRB members who are disinterested people, completely separate from the institution in which the research is to be conducted. But there are also some disadvantages that need to be resolved, at least some of which can be resolved with the addition of a local review. Besides, there is an IRB at both our parent organization, and at the University where many staff members have joint hospital-faculty positions. Both of those IRBs are frequently required to be involved in the approval process for research that is done at our facility. Also, we function in an advisory capacity to administration, not regulatory (but I would not want to mislead here by minimizing the influence of our recommendations). We evolved from an advisory hospital ethics committee to a JCAHO patient rights and ethics team. We consider the law, but we are deliberately more attentive to ethical analysis of the proposed research, or any other ethical issue that is brought to our attention. We often find the law to be behind the power curve in terms of defining what is appropriate. I personally try to use 45CFR46 as a minimum baseline from which to start my consideration of what is required to adequately protect subjects. In support of the appropriateness of this approach, I will merely say that we have witnessed HHS Secretary Donna Shalala's Press Releases the past couple of days indicating more stringent requirements coming for researchers, and much more stringent sanctions for violators of human subjects protections. I continually stress with our committee that we should be trying to think ahead of the law, of what the law might say later in its evolution in terms of doing what is right to protect our patients/subjects. Laws passed and enforcement executed after publicity about research like the Tuskegee Syphilis Study and the hepatitis studies with retarded children at Willowbrook State Hospital come far too late for some. If the regulations are not stringent enough, we should be. For example, § 46.113 (Suspension or termination of IRB-approval of research), indicates: An IRB shall have authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements, or that has been associated with unexpected serious harm to subjects. Well, shall have the authority? That is not sufficient. An IRB should be required to terminate the research if there is unexpected serious harm to subjects. Further, I think it is appropriate to terminate even if the harm may not be serious. I question who we are to continue to inflict or allow any known harm to unknowing, or even knowing, subjects. I believe that many of the research problems that get reported in the press could have been avoided if additional thought had been given to the potential for harmful outcomes and the priority had been placed on protection of subjects. As I have been know to say frequently, that is why we exist. There are plenty of people to represent the interests of the rich and the powerful who will gain from the research outcomes, but not so of the poor and less empowered. Hope this has helped clarify, and thanks for your interest, Phillip At 06:40 PM 5/25/2000 -0400, Daniel Nelson wrote: >Phillip Michaels wrote: > > > At our hospital after much soul-searching and inquiries to JCAHO, we > opted to avoid having our own internal IRB, but we still have a committee > that reviews all research that PIs want to conduct at the hospital with > our patients and/or staff. We have found problems with IRB approved > research that in our opinion did not measure up to acceptable standards > of research subject protection--some even approved (we were told) by > NIH and then on-going in other hospitals. It seems to me that each > institution has ethical and legal responsibilities to protect its own > patients (and the institution)--responsibilities that are arguably not > avoided by placing one's complete reliance for physical and legal > protections on the review of an outside IRB.... I find it hard to believe > that a well-managed, risk-managed institution would rely solely on an > outside IRB for protection of the institution and its patients.>> > >You make a strong argument for local review, and identify many of the >issues that prevent institutions from feeling comfortable in >abdicating/deferring to external review. But given the strength and >clarity of your arguments, can you elaborate on your decision to avoid >having your own IRB? Your committee that reviews all research at your >hospital, making sure you want a given study to proceed at your >institution, fulfilling your ethical and legal obligations to protect >human subjects... sounds an awful lot like an IRB to me?? > >At the risk of abusing Shakespeare, That which we call a rose, by any >other name would smell as sweet. > >dan > >Daniel K. Nelson, Director, Human Research Studies >Research Associate Professor of Pediatrics and Social Medicine >University of North Carolina-Chapel Hill >Chapel Hill, NC 27599-7097 > >Phone: 919-966-1344 >fax: 919-966-7879 >e-mail: dnelson@med.unc.edu

Phillip Michaels 5/29/2000 3:10:00 PM

OPRR/FDA Town Meeting in North Carolina

Continuing the recent thread on educational offerings... We are pleased to be hosting a Town Meeting on June 16 at the Friday Center in Chapel Hill, North Carolina. This will be a single-day event, lasting from 8:30am to 3:30pm, structured to allow direct Q&A with federal regulatory authorities. Faculty will include representatives from the Office for Protection from Research Risks (OPRR), Food and Drug Administration (FDA), Veterans Administration (VA), and National Bioethics Advisory Commission (NBAC). Scheduled topics for discussion include adverse event reporting, compliance, genetics research, databases, confidentiality, educational programs, new DHHS initiatives... and many other topics which are on all of our minds these days. But the Town Meeting format is purposefully loose, and the audience will ultimately determine the flow of the discussion. Accordingly, there will be an emphasis on open-mike time with a minimum of didactic presentations. The target audience is anyone involved with the conduct, sponsorship or oversight of human subjects research, including IRB members, administrators, investigators, study coordinators, and institutional officials. The conference is jointly sponsored by the University of North Carolina-Chapel Hill, Duke University Medical Center and the National Institute of Environmental Health Sciences. These sponsors have kept registration fees low to promote attendance, and $25 covers lunch, breaks, materials and CME credit. Those interested in attending should NOT respond to this posting, but are invited to contact Continuing Medical Education at UNC-CH for further information (919-962-8887 or 2118). We look forward to seeing you in The Southern Part of Heaven!

Daniel Nelson 5/29/2000 11:28:00 AM

A rose by any other name?

Phillip Michaels wrote: > Your sense of smell has not let you down, however, because we do try to accomplish a mission similar to that of the IRB--protection of subjects.... But as you know, if the IRB is functioning under the Department of Health and Human Services, 45 CFR 46 specifies particular requirements... Thus, we do not qualify as, or to call ourselves, an IRB--and we did not want to qualify. We chose not to go that route for several reasons. One was to avoid the administration of all the HHS requirements for an IRB. It can be expensive, and with tight budgets, we were concerned with being compromised because of insufficient resources to do the IRB job properly.>> i'll admit that my first thought was that you're taking the easy way out. but as i kept reading, i concluded that you're probably just as effective as many IRBs that meet the letter of those requirements. indeed, you may be (dare i say?) more effective, because you're not diverted by the increasingly tangential elements that those requirements impose. you seem to have worked out a way to have your cake and eat it too, but in a positive way that allows you to attend to the truly important aspects of human subjects protection. would that all IRBs and other review bodies, whatever they are called, could do the same. i think others will have to be similarly flexible and imaginative, as our system enters (continues though?) this period of tremendous change. part of the problem is that we haven't evolved much since the regulations were drafted, while the clinical research we attempt to oversee has evolved a great deal. it's difficult to argue that 250 local IRBs reviewing a multicenter trial placed at 250 sites represents commensurate value added, particularly when the protocol is (for all intents and purposes) fixed by the time we see it. our current system results in 250 consent form versions, with little net gain in protection of subjects. yet you and i and our institutions all recognize the importance of local insight, and are not about to abdicate local responsibility and authority to a distant body. i predict we'll see more and more variations on the theme, whereby local review supplements, augments, complements, enhances (pick your term) that conducted by an external group that does meet those regulatory requirements. whether you choose to call your local board an IRB or not, you seem to have your subjects' interests firmly in mind, and that's what it's all about. > we have witnessed HHS Secretary Donna Shalala's Press Releases the past couple > of days indicating more stringent requirements coming for researchers, and > much more stringent sanctions for violators of human subjects protections...>> yes, and methinks there will be more opportunity for quoting shakespeare before the curtain falls on this act (from the same play... A plague on both your houses! comes to mind... unless donna and congress manage to consolidate regulatory oversight under one house??) >>Hope this has helped clarify, and thanks for your interest>> thanks for your thorough explanation, dan Daniel K. Nelson, Director, Human Research Studies Research Associate Professor of Pediatrics and Social Medicine University of North Carolina-Chapel Hill Chapel Hill, NC 27599-7097 Phone: 919-966-1344 fax: 919-966-7879 e-mail: dnelson@med.unc.edu

Daniel Nelson 5/29/2000 3:10:00 PM

U.S. Agency Seeks Power to Fine Universities That Violate Rul es on Human Research Subjects

> > Do we really want the > > federal government to have even more power to regulate IRBs > > It's not exactly as though IRBs emerged from a purely > grass-roots effort, > and the feds are suddenly trying to take them over. The IRB system is > arguably a creature of federal regulation, emerging from > federal mandates (not exactly unfunded, since overhead is built into > federal grants). Worrying about federal regulation of IRBs > is a bit like > worrying about federal regulation of the interstate highway system. I think that IRBs are more of a federal creature than almost anyone in the IRB world realizes. So far this has been hidden because there has been almost no litigation over IRB decisions, so no one has been forced to really explore the legal constraints on IRB action. There are a lot of things that could/will change this, with fines at the top of the list. IRBs are private groups enforcing federal regulations, with the feds backing up the IRBs by not funding grants that IRBs reject. So far, no one who has been turned down by an IRB has asked the obvious question: how do I appeal this? When they do, I am convinced that the courts will find a way, because they will not countenance the feds being able to prevent judicial review of a federal decision by relying on a private group's opinion. Fines by the feds will immediately increase the legal scrutiny of IRBs and big fines will make it worth fighting the fines, both for monetary and public relations reasons. If the feds do this, I think in 5 years we will look back and see this as what ended the chummy good old boy IRB review system, with its faults and its benefits. As someone who teaches federal agency law, it has always been amazing to me how little lawyers have been involved with the funding and oversight of medical research. For better or worse, I think research funding and regulation is about to be lawyerized, just as every other government agency function has been. Ed Edward P. Richards Executive Director - Center for Public Health Law Professor of Law University of Missouri Kansas City (816)235-2370 Fax (816)235-5276 richardse@umkc.edu http://plague.law.umkc.edu

Edward Richards 5/28/2000 10:58:00 AM

U.S. Agency Seeks Power to Fine Universities That Violate Rul es on Human Research Subjects

I think it is a great idea. Our job is to protect patients, not researchers or institutions. If we give appropriate guidance and it is ignored, there should be some penalty. -----Original Message----- From: Jeanette Stewart [SMTP:pharm@quik.com] Sent: Wednesday, May 24, 2000 1:30 PM To: mcwirb@mcwirb.org Subject: re: U.S. Agency Seeks Power to Fine Universities That Violate Rules on Human Research Subjects Does this strike anyone besides me as being scary? Do we really want the federal government to have even more power to regulate IRBs and the pharmaceutical industry? There may be some investigators who do not obtain adequate informed consent, but should all suffer more regulation for the sake of a few bad apples? And, aren't there enough systems already in place to find (and perhaps even fine) those bad apples? Comments, anyone? _______________________________________________ MCWIRB maillist - MCWIRB@mcwirb.org http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb

John 5/28/2000 10:58:00 AM

U.S. Agency Seeks Power to Fine Universities That Violate Rul es on Human Research Subjects

Edward Richards 5/28/2000 10:57:00 AM

Educational Resources from PRIM&R and ARENA!

Hello, There has been some discussion on the listserv recently about the need for, and availability of, programs, curriculum, and other tools to help educate IRB members, investigators, and administrators, and I wanted to share what PRIM&R and ARENA have to offer. As many of you know, Ada Sue Selwitz, in conjunction with Bob Levine and Charles McCarthy, developed an outstanding curriculum called IRB 101 three years ago, and they have taken it On the Road to over 16 institutions during the past year . More than two dozen other sessions of IRB 101 On the Road have already been scheduled, and we look forward to our second (and future years!) with gratitude for your support and warm reception. The 101 faculty includes two dozen of the most experienced, knowledgeable, and credible IRB chairs, administrators, bioethicists, and researchers in the country. It includes MCWIRB's own Dr. Robert (Skip) Nelson, and others who are well known to many of you. Each faculty member has augmented and enhanced Ada Sue Selwitz's original curriculum. If you would like a list of those who teach these courses for PRIM&R and ARENA, please contact Brenna Duncan in our office (brenna.duncan@primr.org). There is one version of the 101 On the Road course for members, and another for investigators. The latter was recently put on five separate times at Mt. Sinai Hospital in NYC for a total of over 400 clinical investigators, and drew rave reviews. An excerpted version of our flyer is included below, and I would be happy, as would Brenna Duncan in our office, to speak with anyone who is interested in IRB 101 On the Road. I would also be happy to discuss PRIM&R and ARENA's referral system for IRB auditors, as we have successfully been providing names of seasoned and highly respected individuals to audit IRBs and research protection programs for over twenty years. In additon to these offerings, PRIM&R/ARENA's annual IRB meetings will be held on October 29-31, 2000 in San Diego, and IRB 101 will be given in advance of the meetings on October 28. And, on September 18, the AAMC and PRIM&R will be holding the third of its IRB Fundamentals meetings at the Westin-O'Hare Hotel in Chicago. PRIM&R has also initiated the development of a CD-Rom course for clinical investigators, and will be pursuing other electronic and remote learning opportunities in the coming months. Finally, many of you have been calling and/or emailing me to inquire about the status of AAHRPP, PRIM&R's accreditation project. I am pleased to report that AAHRPP is going very well, and we are working hard, among other things, to develop the performance standards that will underlie the process. We have also begun work on the self-study/self-asssessment instrument. Once developed and vetted, we will then begin pilot testing both the standards and self-assessment instrument. Our plan is to hold our first site visits in the early winter of 2001. After we finish drafting the reports and debriefing from the first few pilot sites, we expect to be officially open for business by March of 2001. We hope to have additional AAHRPP staff hired by late summer, and they will work intensively through the fall to finalize the standards, distribute the self-assessment instrument and manual to applicate research institutions, set up the sites for 2001, and generally build the infrastructure. ARENA's certification plans and the development of CCIP, the Council for Certification of IRB Professionals, is also on the fast track, and will be administering its first certification exam on October 28 in San Diego. Things are going VERY well for CCIP, and you can read more about both accreditation and certification in the forthcoming (it's at the printer) issue of the ARENA newsletter. So as you can see, things are hopping! Thank you for allowing me an opportunity to give a PRIM&R/ARENA update. I would be happy to answer further questions via email or phone (617/423-4112), but please forgive my often slow e-mail response time. As noted, these are bustling times for IRBs, and thus bustling times for PRIM&R and ARENA. I wish all of you a wonderful long weekend, and look forward to being of help in any way we can. Joan Rachlin IRB 101 On the Road... After almost a quarter century of hosting national conferences on a range of research ethics issues, and over ten years of presenting capsulized educational programs for the IRB community, PRIM&R and ARENA are now proud to announce a traveling version of IRB 101. This course was first offered in late 1998 by PRIM&R and ARENA, and it is now being offered at individual institutions upon request. IRB 101 is designed to provide Institutional Review Board (IRB) members and clinical investigators with a basic knowledge of both the procedures for reviewing research involving protection of human subjects and the regulations governing IRB operations. THE DESIGN: IRB 101 was designed by Ada Sue Selwitz, Charles McCarthy, and Robert Levine as a one-day training course on the fundamentals of Institutional Review Board review and regulations. There is one version of the course for IRB members and another for researchers. Both of these are appropriate for, and of help to, IRB professionals. The courses features discussion of the history of the development of the IRB system, participatory discussions on ethical principles underlying the conduct of research involving human subjects and an overview of the federal regulations governing IRB operations, including specific case studies. Case studies are an integral part of the curriculum, and PRIM&R/ARENA has developed an impressive and responsive bank of relevant cases that are all wonderful teaching tools. They were developed by experienced IRB chairs and IRB professionals, including Susan Kornetsky, ARENA President. Between two and four faculty persons are available to come to your institution and present a streamlined, expanded, or identical version (depending on individual needs) of this highly successful and popular orientation program. YOU WILL RECEIVE: - Informative Reading Materials - History of the Development of Federal Regulations - In-depth Review of Ethical Principles - Comprehensive Overview of HHS and FDA Regulations - Provocative Case Studies THE COST OF PROGRAM DEPENDS ONâ€¦ - How many attendees are expected? - How many faculty persons are required? - How much educational material is needed? - What level of curricular customization is needed? - How many days you would like the course to last? - Base Rates: - $5,500 per day (based on three instructors) - Travel expenses for each faculty person THE HOST INSTITUTION PROVIDESâ€¦ - The meeting space - Any catering or audio-visual needs - Hotel and ground transportation arrangements for faculty - Photocopying of materials (PRIM&R will copy materials for additional cost if desired) Any other out-of-pocket costs associated with the production of this program. We are presently booked through December 2000, but we are accepting applications for sessions in the year 2001! If you would like to learn more about bringing IRB 101 On the Road to your institution, please contact Brenna Duncan at brenna.duncan@primr.org. We are also happy to provide a list of our references upon request, and have included just a few comments from those who hosted recent 101s: Bringing IRB 101 to your community is a time-efficient and effective way to provide training to IRB members and researchers. PRIM&R did an outstanding job. Nancy Buderer,Manager/Biostatistician The facultyâ€™s interaction with the audience was extremely valuable. Case studies were not simply presented. Instead attendees were asked for feedback, and a question and answer period followed each lecture. Ruth Abramson, IRB Chair/Professor of Medicine Overall, the program was wonderful! Diane Austin, Manager, Research Review/Regulatory Affairs

rachlinj@aol.com 5/26/2000 12:34:00 PM

U.S. Agency Seeks Power to Fine Universities That Violate Rules on Human Research Subjects

Wednesday, May 24, 2000 U.S. Agency Seeks Power to Fine Universities That Violate Rules on Human Research Subjects By JEFFREY BRAINARD Washington The U.S. Department of Health and Human Services proposed several new steps on Tuesday to strengthen oversight of research involving human volunteers, including imposing fines of up to $1-million on institutions for violations of federal rules. The department has been under fire from its own inspector general and from Congress for failing to correct widespread deficiencies in the protection of human subjects in research it sponsors. The secretary of health and human services, Donna E. Shalala, also announced that her department would: Require universities, as a condition of the grants they receive from the department for health research, to adequately educate scientists and campus officials about federal regulations governing research with human subjects. Prod universities to audit their researchers' records regularly to ensure that participants in experiments have given informed consent. Clarify its policy on conflicts of interest on researchers conducting studies with human>volunteers. The department may direct scientists to disclose all financial interests in a clinical experiment to participants. The steps follow a report by the department's inspector general, released in April, saying that the agency had made minimal progress in improving oversight of experiments involving human volunteers since a previous review by the inspector general in June 1998. President Clinton asked Ms. Shalala in February to reconsider the department's oversight of such research, following the death of 18-year-old Jesse Gelsinger during a gene-therapy experiment at the University of Pennsylvania in September. In releasing the measures, Ms. Shalala urged university officials to take a hard look at the adequacy of their own efforts to monitor biomedical research at their institutions. Public confidence in clinical trials is essential to the continued advances in medicine we all hope to see in the next century, she said in a statement. Research involving human volunteers also includes psychological studies. Her proposal for fines would add a new weapon to the government's arsenal for enforcing its regulations governing university research. Under the plan, individual researchers could be fined up to $250,000 each, in addition to the $1-million fines that could be imposed on universities. Ms. Shalala did not describe the specific circumstances under which universities would be fined, but she said institutions could be penalized for violating federal rules on informed consent and other important research practices. The department is drafting legislation that would authorize the fines, and officials hope a member of Congress will introduce it this summer, said William F. Raub, deputy assistant secretary for science policy. Department officials have said that fines would give the agency a less-draconian alternative to its only other existing sanction, which is to suspend federal research grants temporarily. For the most research-intensive university medical centers, such a suspension could cost several million dollars. Over the past 19 months, the National Institutes of Health has suspended studies at seven institutions for failing to follow federal procedures. Some university officials have called the punishments disproportionate to the violations. The other steps announced by Ms. Shalala will not require new legislation, but will be spelled out by the department this summer in clarifications of existing regulations. For example, although existing regulations require scientists to document that research participants have given informed consent, there is no current requirement that anyone else review this paperwork. Problems have been uncovered only after spot audits by the Food and Drug Administration, or after complaints were filed with the Office for Protection from Research Risks, which is part of the National Institutes of Health. The proposed clarification would encourage university institutional review boards, or I.R.B.'s -- which are responsible for reviewing research involving human volunteers -- to order that monitors observe the process by which people in especially risky or complex medical experiments give consent. I.R.B.'s have been faulted for not paying enough attention to whether investigators adequately inform volunteers about the risks of research. But some university scientists view the idea of independent monitors as cumbersome and objectionable. Meanwhile, the National Institutes of Health will hold a conference at its Bethesda, Md., headquarters in mid-August to gather public comments about the proposed clarification of its conflict-of-interest policy. Nils Hasselmo, president of the Association of American Universities, said the organization applauds the department's proposals. Our association and other, similar organizations are working to strengthen the protection of human research subjects on our campuses, and more vigorous, coordinated federal oversight and enforcement will assist that effort, he said. In related news, the Department of Health and Human Services plans to appoint by this summer a director for the Office of Human Research Protection, said Bill Hall, a spokesman for the department. E. Greg Koski, director of human-research affairs at Massachusetts General Hospital, is reported to be the agency's top candidate to lead the office, which will replace the Office for Protection from Research Risks. The research-risks office is part of the National Institutes of Health. When a new director is appointed, the renamed office will be relocated to the group of offices under Ms. Shalala's direct control.

Anonymous 5/26/2000 7:31:00 AM

Research Review and Compliance

Several thousands of IRBs are currently struggling to generate appropriate programs to educate IRB members and research investigators in the various aspects of the proper review and carrying out of research studies. The personnel involved in these efforts have varying degrees of experience and expertise. The efforts are almost uniformly understaffed. One of the most helpful measures that the DHHS could take is to assign properly chosen, qualified personnel to the task of generating a generic set of educational materials for use by the IRBs. Let's minimize the duplication. Lighten our load, please!! Dick Kelley, Member IRB, Newark Beth Israel Medical Center Mailto:rakelley@ieee.org

Richard A Kelley 5/26/2000 9:42:00 AM

A rose by any other name?

Phillip Michaels wrote: > At our hospital after much soul-searching and inquiries to JCAHO, we opted to avoid having our own internal IRB, but we still have a committee that reviews all research that PIs want to conduct at the hospital with our patients and/or staff. We have found problems with IRB approved research that in our opinion did not measure up to acceptable standards of research subject protection--some even approved (we were told) by NIH and then on-going in other hospitals. It seems to me that each institution has ethical and legal responsibilities to protect its own patients (and the institution)--responsibilities that are arguably not avoided by placing one's complete reliance for physical and legal protections on the review of an outside IRB.... I find it hard to believe that a well-managed, risk-managed institution would rely solely on an outside IRB for protection of the institution and its patients.>> You make a strong argument for local review, and identify many of the issues that prevent institutions from feeling comfortable in abdicating/deferring to external review. But given the strength and clarity of your arguments, can you elaborate on your decision to avoid having your own IRB? Your committee that reviews all research at your hospital, making sure you want a given study to proceed at your institution, fulfilling your ethical and legal obligations to protect human subjects... sounds an awful lot like an IRB to me?? At the risk of abusing Shakespeare, That which we call a rose, by any other name would smell as sweet. dan Daniel K. Nelson, Director, Human Research Studies Research Associate Professor of Pediatrics and Social Medicine University of North Carolina-Chapel Hill Chapel Hill, NC 27599-7097 Phone: 919-966-1344 fax: 919-966-7879 e-mail: dnelson@med.unc.edu

Daniel Nelson 5/26/2000 2:38:00 AM

U.S. Agency Seeks Power to Fine Universities That Violate Rul es on Human Research Subjects

John was brief in his comments, but given what he said, I decidedly lean in the same direction. No, I am generally not in favor of even more government regulation. But the reason we need government regulation at all in anything is that individuals and groups and organizations and entire societies fail to do what they should. When there are power imbalances in relationships, as there inevitably are in clinician-patient and researcher-subject relationships, there need to be sanctions. Strong sanctions are quite definitely required because only strong sanctions get sufficient attention to get leaders thinking, Gee, I guess we'll have to really pay attention here, or somebody is going to be on my butt big time! Many, and particularly at the sociological level of the organization, are driven by economics. As the hundred dollar fines for speeding obviously do little to limit speeding, I would question whether $250,000 individual fines, and $1,000,000 institutional fines are sufficient when there are $1,000,000,000s of dollars to be made. There are many out there who would risk a million dollar fine to get a return of one thousand times that for years, even decades. For an example, consider tobacco. Not all in the health research field are more pure. In fact, as I indicated to one person in this forum recently, Drummond Rennie, Deputy Editor (West) of the Journal of the American Medical Association and Professor of Medicine at UCSF, . . . tells of appallingly common abuses--utterly disgusting behavior of people who want to get ahead, who want to get something published. There is a huge history of research abuse. How, for example, could multitudes of U.S. Public Health Service researchers have perpetuated--over decades--the Tuskeegee Syphilis experiments? The UN Foundation also just today announced the following at it's web site (http://www.unfoundation.org/unwire/unwire.cfm) in it's #3 article, DRUGS: Poor Countries Suffer From Drug Makers' Profit-Seeking -- NYT The resurgence of sleeping sickness in Africa, despite its near eradication 50 years ago, is a vivid example of the gap between priorities of the world's pharmaceutical companies and the need for drugs to minimize fatal or debilitating diseases in poor countries, the New York Times reports. While 300,000 people are infected with sleeping sickness annually, the only medicine available to treat the advanced stage of the disease kills 5% of patients who take it. An alternative drug ran out in July when the manufacturer abandoned its production because it was unprofitable. The poor have no consumer power, so the market has failed them, said James Orbinski, international president of Medecins sans Frontieres. According to US-based market research company IMS Health, Africa accounts for 1% of world drug sales while North America, Japan and Western Europe account for 80% (Donald McNeil, New York Times, 21 May). Yet Africa bears 80% of the world's disease burden, according to the World Health Organization's Regional Director for Africa, Ebrahim Samba (UN Wire, 28 Apr). Each year, $27 billion is invested by pharmaceutical research, mostly focused on finding drugs that lengthen the lives of consumers who are already relatively healthy. A blockbuster drug makes [pharmaceutical companies] $1 billion to $1.5 billion a year, said a senior WHO official. If you're running the [research and development] department of one of these companies, you're under a lot of pressure, and they're going to invest in things they see a market for. Their behavior is perfectly predictable. Many health policy-makers say governments should force drug makers to focus on diseases like sleeping sickness, malaria, tuberculosis, leishmaniasis and the various burrowing worms that kill or cripple millions each year in Africa, Asia and South America. That would require wealthy nations to pay drug makers directly, offer them tax incentives or longer patents on their drugs, or allow poor nations to ignore Western patent law and create their own generic versions of medicines (McNeil, New York Times). As this example indicates, most--not even nations, certainly not drug companies, nor their researchers--will put money or effort into things that do not benefit them. Another example comes to mind of another recent announcement--that AIDS vaccine(s) has/have been approved for testing--in Uganda! What IRB approved that? Do we think approval could have been attained for testing in the good ole USA? And even if an IRB could have been found that would have approved it, how many more IRB would not have? That potential for divergence is also something that needs to be addressed, and as long as organizations fail to address it, government will discover the need to at some point--hopefully sooner rather than after more have been harmed. I think that all patients should be equally well-served and protected by IRBs, not just those who have more diligent or demanding IRBs watching over their interests. Regrettably, we need more government intervention, sanctions, motivators to help us do the right thing in the research arena. At 03:51 PM 5/24/2000 -0500, Burke, John wrote: >I think it is a great idea. Our job is to protect patients, not >researchers or institutions. If we give appropriate guidance and it is >ignored, there should be some penalty. > > -----Original Message----- > From: Jeanette Stewart [SMTP:pharm@quik.com] > Sent: Wednesday, May 24, 2000 1:30 PM > To: mcwirb@mcwirb.org > Subject: re: U.S. Agency Seeks Power to Fine Universities >That Violate Rules on Human Research Subjects > > Does this strike anyone besides me as being scary? Do we really >want the > federal government to have even more power to regulate IRBs and the > pharmaceutical industry? There may be some investigators who do not >obtain > adequate informed consent, but should all suffer more regulation for >the sake > of a few bad apples? And, aren't there enough systems already in >place to > find (and perhaps even fine) those bad apples? Comments, anyone? > > > _______________________________________________ > MCWIRB maillist - MCWIRB@mcwirb.org > http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb > > >_______________________________________________ >MCWIRB maillist - MCWIRB@mcwirb.org >http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb

Phillip Michaels 5/26/2000 2:38:00 AM

Informed Consent of Cognitively Impaired

Bill Hirschhorn wrote : I would like to offer for your consideration a textbook written by Thomas Grisso and Paul Appelbaum titled, Assessing Competence to Consent to Treatment, 1998, Oxford University Press. This book clearly addresses the clinical, legal and scientific issues of informed consent of the incompetent patient. Chapter 6, in particular, discusses the use of the MacArthur Competence Assessment Tool - Treatment (MacCAT-T) which enables the clinician to assess the patient's decision-making abilities in the context of the informed consent process. ......................................................................................................................................................... Hi, Thanks for the reference. In return, I offer these two references: 1. The report of the NBAC : http://bioethics.gov/pubs.html Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity, December 1998 2. The companion volume of commissioned papers : Volume II: Commissioned Papers (Adobe Acrobat® format, 700 kb) This has an article on the assessment tool you describe : Competency to Decide on Treatment and Research: The MacArthur Capacity Instruments by Elyn R. Saks Regards, Howard

Howard Mann 5/26/2000 2:38:00 AM

Use of international cDNA library

Dear All, I don't know the answer to Italy and Switzerland, but I suggest you contact the European Forum for Good Clinical Practice at www.efgcp.org This is a European association for Ethics Committees located in Belgium, email pth@eortc.be. Dr Nancy J Stark Clinical Design Group ----- Original Message ----- From: Bree Klotter To: Sent: Tuesday, May 23, 2000 12:36 PM Subject: Use of international cDNA library > A researcher at my site has been offered use of a fetal tissue cDNA library > created by researchers in Italy. Our researcher has been told the library was > created with completely anonymous/unidentified samples and that the women were > informed that samples might be used for research, but no consent form was > required (per Italian law). No Italian IRB was involved in this process. > Anyone familiar with Italian IRBs/ethical review boards? Would you consider > research uses of this library to be exempt from human subjects regulations? > Any feedback would be appreciated. > > Bree Klotter, IRB Administrator, Lawrence Livermore National Lab > klotter1@llnl.gov, 925-422-9782 > > > _______________________________________________ > MCWIRB maillist - MCWIRB@mcwirb.org > http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb

Nancy J Stark 5/26/2000 3:47:00 AM

Request for information on Price Waterhouse

Folks, Could someone give me a contact person at Price Waterhouse for the sort of training they provide on the Common Rule and IRB activities etc. etc. Has anyone else used them for training besides the U. of Arizona? Thank you.

M . D . Orca 5/26/2000 6:23:00 AM

Educational resources

The AAMC has some material on it's Website, and we are looking to add more. Connect to . Also, we are doing a third workshop on Effective IRBs: The Fundamentals and you can learn more about that at . >>> Craig 05/26/00 02:48pm >>> Does anyone have a good link or resource for educational opportunities for IRB members? Particularly when it comes to meetings and conferences, there doesn't appear to be any clearinghouse of information on upcoming meetings. Thanks for any help. Craig Weiner, MD Chair Mercy Healthcare Sacramento Regional IRB _______________________________________________ MCWIRB maillist - MCWIRB@mcwirb.org http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb

Allan Shipp 5/26/2000 12:10:00 PM

U.S. Agency Seeks Power to Fine Universities That Violate Rules on Human Research Subjects

On Wed, 24 May 2000, Jeanette Stewart wrote: > Does this strike anyone besides me as being scary? Not as such. > Do we really want the > federal government to have even more power to regulate IRBs It's not exactly as though IRBs emerged from a purely grass-roots effort, and the feds are suddenly trying to take them over. The IRB system is arguably a creature of federal regulation, emerging from federal mandates (not exactly unfunded, since overhead is built into federal grants). Worrying about federal regulation of IRBs is a bit like worrying about federal regulation of the interstate highway system. > There may be some investigators who do not obtain > adequate informed consent, but should all suffer more regulation for the sake > of a few bad apples? The full proverb is one bad apple can spoil a barrel, so if the situation is that one wants to keep one's barrel of apples from being spoiled, one probably wants to be able to catch the process early and decisively. > And, aren't there enough systems already in place to > find (and perhaps even fine) those bad apples? Comments, anyone? The current federal response to bad apples has been to shut down entire instutional research programs. The point of the new regulations seems to be to allow a more limited response, aimed at individuals and projects within an institution. While in one sense this involves more power for the regulators, it also allows them to act more moderately. When hanging was the penalty even for small crimes, juries would sometimes refuse to convict. Introducing lesser penalties for small crimes meant that convictions were more likely. It also mean that the people who were convicted weren't executed. This gave more power to the court system, at the same time that it put greater limits on the power of the court system to impose the death penalty. -- I'm sure that people with legal training would be able to come up with a more accurate account of the transition, but I think the point of the example would still be intact. Richard Brzustowicz (brz@u.washington.edu) (206) 543-4464 Human Subjects Division Box 355752 University of Washington Seattle, WA 98195 http://depts.washington.edu/hsd

R . Brzustowicz 5/26/2000 7:31:00 AM

Request for information on Price Waterhouse

Dear Colleagues: PricewaterhouseCoopers has several individuals who can be contacted regarding our various IRB services (assessment, training, development of policies and procedures, database development, etc). Tony Boccanfuso 704.350.7944 Rick Rohrbach 215.963.3028 Vikki Jenkins 213.236.3004 We have conducted IRB training at a number of institutions and can provide more information upon request. Thank you. Tony Anthony M. Boccanfuso, Ph.D. Manager PwC - Regulatory Consulting Practice 100 N. Tryon Street Charlotte, NC 28202 ---------------------- Forwarded by Anthony Boccanfuso/ABS/Price Waterhouse on 05/26/2000 10:31 AM --------------------------- Mather, John H, M.D. (ORCA) on 05/26/2000 09:51:23 AM To: 'mcwirb@mcwirb.org' cc: Subject: Request for information on Price Waterhouse Folks, Could someone give me a contact person at Price Waterhouse for the sort of training they provide on the Common Rule and IRB activities etc. etc. Has anyone else used them for training besides the U. of Arizona? Thank you. ---------------------------------------------------------------- The information transmitted is intended only for the person or entity to which it is addressed and may contain confidential and/or privileged material. Any review, retransmission, dissemination or other use of, or taking of any action in reliance upon, this information by persons or entities other than the intended recipient is prohibited. If you received this in error, please contact the sender and delete the material from any computer. _______________________________________________ MCWIRB maillist - MCWIRB@mcwirb.org http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb

Anthony Boccanfuso 5/26/2000 6:23:00 AM

Use of international cDNA library

A researcher at my site has been offered use of a fetal tissue cDNA library created by researchers in Italy. Our researcher has been told the library was created with completely anonymous/unidentified samples and that the women were informed that samples might be used for research, but no consent form was required (per Italian law). No Italian IRB was involved in this process. Anyone familiar with Italian IRBs/ethical review boards? Would you consider research uses of this library to be exempt from human subjects regulations? Any feedback would be appreciated. Bree Klotter, IRB Administrator, Lawrence Livermore National Lab klotter1@llnl.gov, 925-422-9782

Anonymous 5/26/2000 3:47:00 AM

Informed Consent of Cognitively Impaired

Bill and Howard: I would like to offer for your consideration a textbook written by Thomas Grisso and Paul Appelbaum titled, Assessing Competence to Consent to Treatment, 1998, Oxford University Press. This book clearly addresses the clinical, legal and scientific issues of informed consent of the incompetent patient. Chapter 6, in particular, discusses the use of the MacArthur Competence Assessment Tool - Treatment (MacCAT-T) which enables the clinician to assess the patient's decision-making abilities in the context of the informed consent process. Bill Hirschhorn Adjunct Professor of Pharmaceutics Temple University School of Pharmacy Graduate Program - Quality Assurance & Regulatory Affairs Philadelphia, Pennsylvania

William Hirschhorn 5/26/2000 2:38:00 AM

Informed Consent of Cognitively Impaired

Howard Mann 5/26/2000 2:35:00 AM

Change at OPRR

MEMORANDUM TO ALL OPRR STAFF FROM GARY ELLIS: On May 24, 2000, I was informed by NIH's Director of Human Resource Management, Stephen C. Benowitz, that my responsibilities as Director, Office for Protection from Research Risks, end at close of business, Friday, June 2, 2000. I have been designated for reassignment elsewhere at the National Institutes of Health.

Tom Od 5/26/2000 6:31:00 AM

A rose by any other name?

Phillip Michaels 5/26/2000 2:38:00 AM

A washingtonpost.com article from sms@rxtrialsinc.com

You have been sent this message from sms@rxtrialsinc.com as a courtesy of the Washington Post (http://www.washingtonpost.com). To view the entire article, go to http://washingtonpost.com/wp-dyn/articles/A64453-2000May24.html Penn Ends Gene Trials On Humans The University of Pennsylvania announced yesterday that its gene therapy institute, which has been an international leader in the cutting-edge field of medical research, will no longer experiment on people. Responding to concerns raised by the death of a teenage volunteer last September and subsequent revelations of numerous lapses in patient protections, the university will confine research at the Institute for Human Gene Therapy--and by its high-profile director, James Wilson--to animal and laboratory experiments, officials said. He [Wilson] will not sponsor clinical trials. He will not participate, said Penn President Judith Rodin in making the surprise announcement. Any future gene therapy experiments on people at the university will be carried out by researchers outside the institute and only after vigorous scientific and ethical review, she said. Rodin's announcement immediately followed release of a report by an independent panel, commissioned by the university, that questioned the wisdom of vesting so much responsibility and power over gene research in a single center and individual and raised many questions about the way the university has run the institute. Wilson responded with an upbeat statement that said he would refocus our efforts in the preclinical area--with the goal of developing a foundation of science necessary to ensure the ultimate success of this field. Although numerous scientific obstacles exist, gene therapy has tremendous potential to someday prevent or cure life-threatening diseases. The university's action came after the Food and Drug Administration found that Wilson had not properly reported the deaths of experimental animals or serious side effects suffered by volunteers who preceded Jesse Gelsinger, the Tucson teenager who died Sept. 17 after undergoing an experimental therapy for a rare metabolic disorder. Gelsinger suffered a fatal reaction to the genetic material he received. The agency also found that the institute enrolled Gelsinger and others even though they didn't meet some of the minimal health standards required for participation. As a result, the agency in January suspended seven active or pending gene therapy experiments at Penn, which has played a major role in moving gene therapy research out of the lab and into people. The decision to diminish the size and status of the institute is sure to reverberate through the controversial, 10-year-old field, which in less than a year has experienced both the first death caused by the therapy--Gelsinger--and its first tentative success--research in France that appears to have cured at least two children with an inherited immune system disorder. In addition to Penn's problems, the field--which tries to cure disease by giving people new genes--has been rocked by revelations that researchers elsewhere weren't properly reporting the deaths and illnesses of hundreds of volunteers to the National Institutes of Health as required by federal regulations. (Unlike the Gelsinger case, the deaths were all deemed unrelated to treatment by the researchers involved but still had to be reported under federal rules.) Most recently, the FDA shut down four gene experiments by a prominent researcher at Tufts University and cited him for numerous safety lapses, including the failure to tell his own institution about the death of a volunteer and the inclusion of patients who did not qualify and may have been harmed by the experimental treatment. Those developments have prompted government and university officials to search for ways to improve oversight, accountability and patient safety in gene therapy experiments. On Tuesday, the Department of Health and Human Services recommended that legislators give the FDA authority to impose fines on researchers and universities for patient safety violations. Rodin announced several initiatives to bolster patient safety that, while responding to general concerns raised by the independent panel and an internal review, also appear to address specific aspects of the fatal experiment. For example, Rodin said, she would follow a recommendation that the university review its policies on conflicts of interest created by researchers and the university having financial interests in companies trying to commercialize research. The university, Wilson and a company he founded, Genovo Inc., all had financial stakes in research carried out at the institute--including the experiment in which Gelsinger died. Without mentioning their business relationship specifically, the report said equity positions by investigators or the university are ill advised. Rodin said the university's contract with Genovo, which gives Genovo rights to gene research discoveries at the institute in exchange for substantial financial support, expires in June. She said negotiations are underway, and she does not know yet whether it will be renewed and under what terms. Another change highlighted by Rodin would move Penn's Center for Bioethics out of the institute and make it a separate department. The report had questioned whether bioethicists should report to the very person who's overseeing the research they're judging. The report also expressed concern that ethical decisions were made informally on the basis of conversations with bioethicists rather than through the university's formal review process by the review board that has primary legal responsibility for protecting research volunteers. In the case of the fatal experiment, Wilson made the controversial decision to give a risky gene treatment for a rare liver disorder to relatively healthy adults with a mild form of the disease, based on conversations with Arthur Caplan, the bioethics center director.

Consultants to Review IRB Operations

Has anyone ever used external consultants to review IRB operations? Do you have any advice, experience for me? In particular, has anyone ever worked with Price Waterhouse Coopers or Arthur Anderson? Sent out an RFP to some ARENA member consultants but none of them were to respond. Any experience is appreciated, Gill B. Abernathy, M.S., R.Ph. Inova IRB Inova Fairfax Hospital Falls Church, Virgina (metro D.C.) (703) 698-3167

Anonymous 5/25/2000 5:51:00 AM

Institutionally designated legally-authorized representative

Hi, I solicit comments concerning the designation of a legally authorized representative for research purposes pursuant to declared institutional policy. In Utah, there is no state law addressing this concept in the context of research. The NBAC defined a LAR as follows : Currently, an LAR is an individual authorized by law (statutory or judicial) or previously published institutional rules to make medical decisions on behalf of another individual. ( http://bioethics.gov/capacity/Moving.htm#IRBs ; Recommendation 14 ) Do you agree with the latter half of this definition ? Do any of you operate in an institution that has defined a LAR for research purposes as mentioned above ? I would appreciate any thoughts on this concept. Regards, Howard

Anonymous 5/25/2000 4:38:00 AM

Washington Post Article about Gene Therapy

The link below is to this morning's Washington Post article on the U. Penn Gene Therapy Institute. Several issues that came up toward the end of the Washington Post article interested me. A statement about the ease of access of Gene Therapy PI's to ethicists for informal advice may have contributed to progression of the problems. I noticed that there are risks associated with such propinquity between the regulated and the regulator. We IRB chairs and administrators all have a responsibility to educate the staff at our institutions about the ethics of research involving human subjects and ways of protecting their rights and welfare. However, we should also recognize that calls for advice are often motivated by specific intentions, planned actions or events that might come before the committee. Therefore, the Washington Post article highlights the risk of giving ethical advice outside of the formal processes of IRB function. That is, if you do not determine its relationship to something unmentioned by the PI, your advice may affect his actions but not in the way you intended nor in the way regulations require. Therefore, it is always worthwhile to document in writing this kind of interaction and to ask enough questions so that you can determine if the question was rhetorical or related to some specific unmentioned event. http://washingtonpost.com/wp-dyn/articles/A64453-2000May24.html The Washington Post article also points out that propinquity between the PI and ethical advisor becomes more risky when the University puts both functions together in the same administrative package to enable both the research and the ethics to occur. It doesn't look good whether it works or not.

Anonymous 5/25/2000 8:34:00 AM

Consultants to Review IRB Operations

Alice and Gill You may want to contact Dr. Felix Gyi of Chesapeake Research Review. Among the services his company offers is consulting to IRBs. Dr. Gyi has many years of clinincal research experience including several as the IRB administrator in an academic setting. He can be reached at felix@irbinfo.com or by phone at 410-884-2900. Sandra M. Sanford, RN, MSN, CCRC Director, Regulatory Affairs Rx Trials, Inc. 301-565-6717 301-565-5912 Fax Alice C Langen wrote: > The University of Arizona Research Integrity Education Program hired Price > Waterhouse to present training for our IRB members, IRB staff and clinical > administrators just last month. We did this prior to arranging for an IRB > review. We were pleased with the quality of the presentation and I'd be > happy to talk to anyone who's interested about what they did and also what > else they offer. > > My effort to hire someone from the academic community to conduct an > assessment of our IRB operation has been unsuccessful to date. But, we're > still trying. > > Alice Langen > Coordinator, Research Services > U of Arizona > 601 Administration Bldg > Tucson, AZ 85721 > 520-621-5196 > langena@u.arizona.edu > > _______________________________________________ > MCWIRB maillist - MCWIRB@mcwirb.org > http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb -- _________________________

Sandy Sanford 5/25/2000 5:51:00 AM

whole board and expedited review

Phillip: The duty (ethical and legal) to protect subjects is on-going and continuing, and is not just the investigator's to fulfill as the research is conducted; it is the IRB's and the parent institution's. The regs, dear colleague letters, guidance documents, and the IRB guidebook make numerous references to the continuing nature of review, the auditing and self-auditing and self-correcting functions, the appropriateness of adjusting protections to meet changing perceptions of risk, and so forth. So reversal of an earlier decision is clearly appropriate, if warranted. Any adherence to a prior decision, just because it is already made, that may expose a subject to unacceptable risk, or result in harm, or is otherwise deserving of revision in the considered view of an IRB, has ethical, if not worrisome legal, implications. The beauty of the IRB system is that it affords an opportunity for collective thinking about the wisdom of these matters, including at any time the need to reverse or amend an earlier decision (with input, perhaps, from the affected researcher), whether that decision was made by the IRB or the Chair or a primary reviewer, or whoever. The legitimate need on the part of researchers for constancy and predictability could be met in part a) by their understanding of the role of an IRB (and the legal duty of its parent institution) in providing protection that is continuing in nature and therefore inherently subject to change, b) by accumulating over time an informative, brief, and redacted documentation of such decisions (an ethical common law?) that could be accessed by researchers seeking guidance, and c) by the very likely fact that such reversals of and amendments to prior decisions would be rare. Tom Dalglish, J.D., Ph.D. Community Member, Committee C University of Washington (206) 543-0098 (University) (206) 706-1000 (Office) From: mcwirb-admin@mcwirb.org [mailto:mcwirb-admin@mcwirb.org]On Behalf Of Phillip Michaels Sent: Monday, May 22, 2000 11:49 PM To: mcwirb@mcwirb.org Subject: Re: whole board and expeditited review I concur with Joan Sieber on the example provided. But I am also interested in your thoughts on reversals in general, not just those of an expedited review. It seems to me that even if a full board meets and approves a research proposal, and then later has misgivings, that there is an obligation for additional review, and if that additional review finds problems with the research that may have been overlooked, or not attended to with sufficient rigor/diligence for whatever reason, then approval should be retracted for the sake of the subjects--whether that is one week, one month, or one year after the original approval. There is, after all, an annual review obligation anyway which would seem to have been incorporated into the rules for the reason that reversals were anticipated as a possibility, and perhaps even as recognition of the need for on-going reconsideration of past events. As this field evolves, so do (and should) the rules governing its functioning. If there is not the possibility of recognizing that we have also erred in approving something and that we need to correct our own action--well that seems to me to be dangerous and a failure to fulfill the mission of IRBs--protection of the subjects. I have heard an argument that such an approach is not fair to the researchers because the researchers have an investment in the research, thus it would have to be something of really serious harm before a board should reverse itself. I find such an approach to be just too excessively conservative--both for the adequate protection of patients, and for an evolving field. Where would IRB members draw that line for serious harm to subjects? It would seem to me that IRBs do not have the right to assume that less than serious harm (or even risk) to subjects is ever okay, whether we recognized it before or after we approved it. Thoughts please. Phillip Michaels

thomas k. dalglish 5/24/2000 2:54:00 AM

Consultants to Review IRB Operations

The University of Arizona Research Integrity Education Program hired Price Waterhouse to present training for our IRB members, IRB staff and clinical administrators just last month. We did this prior to arranging for an IRB review. We were pleased with the quality of the presentation and I'd be happy to talk to anyone who's interested about what they did and also what else they offer. My effort to hire someone from the academic community to conduct an assessment of our IRB operation has been unsuccessful to date. But, we're still trying. Alice Langen Coordinator, Research Services U of Arizona 601 Administration Bldg Tucson, AZ 85721 520-621-5196 langena@u.arizona.edu

Alice C Langen 5/24/2000 11:06:00 AM

Use of international cDNA library

Bree, Howard: Howard's point -- is a human subject even involved in the research -- and his cited materials are both extremely helpful. But I have two prior concerns. First, the facts. What are the facts, and can they be documented for the IRB records, surrounding the acquisition of the biological materials in the first place? Bree says her researcher has been told etc. etc., which raises hearsay issues. I would think some documentation from the source (beyond or prior to the researcher, such as the Italian hospital or clinic) might be appropriate, some certification for example, a signed letter perhaps attesting to exactly what the women were informed, what the status is under Italian law of such biological materials, and so forth. I don't think Bree should have to hire an Italian lawyer, or fly to Italy (sorry Bree), or engage in any first hand investigation (unless something untoward surfaces), but I do believe the local IRB (Bree's) needs some adequate (non-hearsay) documentation in its records that the provenance of the biological materials is ethically and legally acceptable under Italian law (not to mention U.S. and local law). The same point can be made with respect to the Swiss path specimens. Second, compliance with local (i.e. foreign) law. The second concern has to do with the acceptability under applicable local law (e.g. Italian, Swiss) of the original acquisition of the materials, then, next, whether those foreign standards are adequate under our (U.S. and local state) law and ethical standards. I believe that local Italian or Swiss law would govern the initial transfer of the materials from the subject to the specimen or sample bank or repository, or the next custodian in line after the subject. The mere fact, if true, that the biological materials, as presented by an investigator to one of our local U.S. IRBs, are anonymous or are stripped of identifiers, or are incapable of being individually identifiable, does not alone legitimate their use in research (as not involving human subjects) if concerns surrounding their original acquisition cannot be answered and documented. To verbally cartoon the issue, to make the point, local IRBs should be wary of unintentionally permitting the use of laundered and acquisitionally impaired biological materials in research, or of unintentionally or inadvertently laundering such materials themselves. Regards, Tom Dalglish J.D., Ph.D. Community Member, Committee C University of Washington (206) 543-0098 (University) (206) 706-1000 (Office) -----Original Message----- From: mcwirb-admin@mcwirb.org [mailto:mcwirb-admin@mcwirb.org]On Behalf Of Howard Mann Sent: Tuesday, May 23, 2000 3:59 PM To: klotter1@llnl.gov; mcwirb@mcwirb.org Subject: Re: Use of international cDNA library Bree Klotter wrote : A researcher at my site has been offered use of a fetal tissue cDNA library created by researchers in Italy. Our researcher has been told the library was created with completely anonymous/unidentified samples and that the women were informed that samples might be used for research, but no consent form was required (per Italian law). No Italian IRB was involved in this process. Anyone familiar with Italian IRBs/ethical review boards? Would you consider research uses of this library to be exempt from human subjects regulations? Any feedback would be appreciated. ............................................................................ ............................................................................ ............. Bree, Here are two items that address your question: Is a human subject involved ? http://grants.nih.gov/grants/oprr/humansubjects/45cfr46.htm#46.102 (f) (2) Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects. (An unidentified sample is supplied to the researcher from a repository that has a collection of unidentified human specimens.Research using such material is typically exempt from the requirement for IRB review. For additional definitions, see : http://www.ihc.com/ldsh/irb/hbm/fedregs.html ) This is a summary you may find useful: http://www.ihc.com/ldsh/irb/hbm/research1.gif Regards, Howard _______________________________________________ MCWIRB maillist - MCWIRB@mcwirb.org http://www.mcwirb.org/mailman/listinfo.cgi/mcwirb

thomas k. dalglish 5/24/2000 6:51:00 AM

Removal from Phase 1 Trial

A question: It is not uncommon for a P1 cancer trial to select patients who have already (excuse the expression) failed standard treatment. Investigational drugs are administered to cohorts of these patients with the primary intention of identifying toxicity. It is common to remove patients from these trials if their tumors progress, increasing in size by some amount. Patients early in the trial will, presumably, receive doses that are, at least theoretically, sub-therapeutic. Later cohorts will receive larger doses if safety -- the absence of toxicity -- permits. My understanding is that the reason why patients are removed from the study if their tumors progress is because it is, by that time, clear that the treatment is not benefitting them and, accordingly, they should be on something else. But these patients were initially selected in part because there were no other effective options remaining. It seems disingenuous to say We have to take you off this experimental drug because, for your own sake, you should be on some more effective course of treatment if, in fact, those other treatments had already been tried and had failed, and especially since those failures were the reason they were allowed onto the P1 study in the first place. And since the early patients in a P1 trial receive, for obvious reasons, theoretically sub-therapeutic doses, it is not clear to me why these patients shouldn't be kept on the study and receive escalated doses, especially if toxicity had failed to appear at those higher levels. Finding toxic effects at high and therapeutic-level doses is, after all, the main point of a P1 study. Wouldn't that purpose be furthered by retention? Moreover it seems investigators would not be doing all they can do to provide subjects with treatment that is at least as good as the alternatives. They could, it seems, administer to patients with progressing tumors doses closer to theoretically efficacious ones provided that contraindicating adverse reactions have failed to appear at those higher levels and certainly provided that low levels have proved to be ineffective, as predicted. And certainly retention should occur if the higher level proves to be both safe *and effective.* This is not a rhetorical question. I am simply baffled by the presence of the requirement that patients with progressing tumors be removed from P1 trials. Is there something I am not noticing or do others agree that these provisions should be set aside? Ken Kipnis . . . +-----------------------------------------------------------------+ | Kenneth Kipnis, PhD ............... kkipnis@hawaii.edu | | Dept of Philosophy ............... | | 2530 Dole Street ........... dept fax 808 956-9228 | | Univ of Hawaii at Manoa ........... home/ans mach 808 732-0072 | | Honolulu, HI 96822 USA ........... ofc/voicemail 808 956-8954 | +-----------------------------------------------------------------+

Kenneth Kipnis 5/24/2000 4:03:00 PM

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