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IRB’s Training for Subject Protection
In the absence of a regulation requiring training and education for those involved with clinical study subjects, many IRBs and investigator sites are voluntarily putting their staffs through the paces to ensure patients are protected.
BY DENISE MYSHKO Protecting patients’ rights during the clinical study process is paramount to ensuring the safety and well-being of the participants as well as the integrity of the trial. Integral to human subject protection is making sure IRB staff members, investigators, and institutional officials are well-trained, at the very least, in the basic ethical principles governing the conduct of human subjects research. These ethical principles are set forth by the Office for Human Research Protections (OHRP) in what is commonly referred to as the Belmont Report. While many IRBs (institutional review boards) already provide training to their board members and staff, some do not. Furthermore, there are no standard training modules, metrics, or requirements for these voluntary courses, nor is there a clear-cut answer as to who is responsible for funding the training. In an effort to determine whether initial and continuing training should be overseen by additional guidance or regulation, an advisory committee to OHRP issued a Federal Register notice in July 2008 to solicit comments from the industry. Thus far, OHRP is considering comments from more than 90 individuals and organizations. As of now, OHRP has made no decisions regarding its next steps and has no projected timeline for further action. “Oversight is necessary,” says Bob Gordon, senior director of quality assurance at Omnicare Clinical Research. “In the past, I have found instances in which IRBs had policies that were in conflict with the general interpretation of the current guidelines. I don’t think there is malicious intent, rather, it is a situation that could benefit from increased awareness. Lately, in our audits of study sites, there has been a greater incidence of staff members who are not as familiar as they should be with good clinical practice and its implementation.” Dr. Gordon believes the OHRP, as well as the FDA, should develop a regulation that provides for required training. “While guidances should be treated as seriously as regulations, the reality is that’s not always the case,” he says,” he says. “The Federal Register notice identifies IRB members and institutional administration staff, but any regulation really needs to apply across the board, even to the level of study coordinator.” John Clark, compliance officer at Coast IRB, says if sites and IRBs were willing to invest more into training programs, there might be fewer negative findings during audits. “Anyone involved in research should be subject to an audit,” he says. “Proper training would lead to a better-run trial and better protection of subjects with fewer audit issues.” Peter Reichertz, partner and leader of the Food and Drug Law Group at Sheppard Mullin Richter & Hampton, says the lack of training for both investigators and IRBs is an ongoing concern. “I’ve witnessed situations where IRBs do not even operate according to their own standards,” he says. “If someone is involved in clinical research at a pharmaceutical company, he or she has to undergo regularly scheduled training on standard operating procedures. I don’t know why there should be a different standard applied to individuals who are conducting research on a day-to-day basis at an IRB or site.” Mr. Reichertz and other experts say it’s probable that some type of training requirement will be put in place. “Up until now, regulators have been relying on voluntary measures to encourage people to take part in training efforts,” he says. “Now, with a new administration in office, chances are that more regulations will be implemented.” Industry experts say there is little agreement, however, about what constitutes adequate training and who is responsible for funding such activities. Felix Gyi, Pharm.D., founder and CEO of Chesapeake Research Review, says many leaders in the IRB sector are wrestling with how to gauge what should be considered adequate training for investigators to conduct research. “It would be helpful for the field to have more definition regarding what types of training are acceptable, including relevant regulations, as well as an understanding of how and why human research protection regulations came about,” he says. Dr. Gyi says concerns around who should pay for training have hampered efforts to bring standardization to the table. “Asking the IRB to be responsible for training of investigators is a misguided and misplaced pressure point,” he says. “In today’s environment, IRBs are mandated to provide oversight. But there isn’t a mandate to fund the oversight activities of IRBs, even on federally funded studies.” Dr. Gyi says the business model for an IRB to be appropriately funded is an uphill battle for many institutions. “Funding for training of investigators and IRBs should be a shared responsibility,” he says. “If an institution wants to conduct good, ethical research, I think it should commit to the training and partially support the related activity. Sponsors should also contribute, since they are ultimately the beneficiary of well-trained investigators and well-functioning IRBs.” Current Training Efforts Lynn Meyer, president and founder of IntegReview Ethical Review Board, says like other independent IRBs, her company provides annual training, which allows her employees to stay well-informed on topics of interest. “The topics are driven by the needs and interests of the board members and our staff,” she says. “Almost always there is a component related to ethics. Other modules relate to handling subject complaints, pediatric research, and informed consent.” Other organizations, such as MDS Pharma Services, use the OHRP online training module. Company executives say all of MDS’ U.S.-based IRB members have completed the OHRP module, which is required for any organizations working on government-funded or government-sponsored research. “The safety of clinical research participants is our greatest concern,” says Gaetano Morelli, M.D., senior director of global medical affairs for early clinical research at MDS Pharma Services. “Our IRB members and principal investigators are just as committed to participant safety as we are, and we hope they embrace such training requirements as an opportunity to demonstrate that commitment. Protection of human research subjects is paramount.” Dr. Morelli adds that two possible outcomes from a regulation requiring training could be a larger pool of prequalified investigators and IRB members and greater standardization in the conduct of clinical research. Coast and Chesapeake both use a program called Collaborative IRB Training Initiative (CITI), which was founded in March 2000. CITI is a Web-based training program developed for human research subject protection in collaboration with the University of Miami and the Fred Hutchinson Cancer Research Center. The collaboration was expanded to include experts from 10 institutions who provided the content for the first 12 biomedical modules. In addition, the CITI model provides the opportunity for institutions to post additional instructional materials specific to them. As of October 2007, the CITI program has been used by more than 830 participating institutions and facilities from around the world. More than 600,000 people have registered and completed a CITI course. “CITI has gained a great deal of traction,” Dr. Gyi says. “Its editorial teams and boards are very well-known and experienced practitioners who have created programs that are easy to use. We make it a requirement that our IRB members and staff actively participate in the CITI program. This way, everybody has the same level of understanding on which we build a more robust and ongoing training program.” Mr. Clark says at Coast, all employees and board members are required to take and pass the CITI program with an 80% pass rate (CITI also requires an 80% pass rate). “We use the CITI program to familiarize new people with what an IRB does and how it works,” he says. “The curriculum covers regulations and protocols, as well as how a study is conducted and how subjects are protected.” Ms. Meyer believes that in addition to a solid training program, there needs to be documentation that educational activities occurred. “When clients inspect our processes, they always request to review our training records,” she says. “They want to be assured that individuals with proper training and education are performing the duties necessary to protect human subjects.”F PharmaVOICE welcomes comments about this article. E-mail us at email@example.com. Bob Gordon • Omnicare Clinical Research A regulation that requires training will ensure that better research is done; data will be more credible; and everybody can sleep better at night. Dr. Gaetano Morelli MDS Pharma Services We strongly support initiatives to enhance the protection of human research subjects. Although such training is currently not required, we strongly recommend that our Phase I principal investigators achieve PI certification by taking an online or in-person course and passing a qualifying exam. In addition to the existing guidelines, our experts for this article suggest other areas that should be considered as part of the training process. • Good clinical practices • Relevant regulations • Quality assurance processes • Informed Consent Forms (ICFs) — what an ICF should include, and when and how to present an ICF • The Declaration of Helsinki • The Nuremberg Code • The Belmont Report • Subject complaints • Pediatric trials • Social and behavioral sciences • Biomedical research the belmont report The three basic ethical principles for the conduct of human subjects research: Respect for persons • Respect individual autonomy • Protect individuals with reduced autonomy Beneficence • Maximize benefits and minimize harm Justice • Equitable distribution of research burdens and benefits Application of the general ethical principles to the conduct of human subjects research leads to the following requirements: Respect for Persons • Informed consent • Protecting privacy and maintaining confidentiality • Additional safeguards for protection of subjects likely to be vulnerable to coercion or undue influence Beneficence • IRB assessment of risk/benefit analysis, including study design • Ensure that risks to subjects are minimized • Risk justified by benefits of the research Justice • Ensure that selection of subjects is equitable Source: Office for Human Research Protections. For more information, visit hhs.gov/ohrp/. John Clark • Coast IRB Advanced technologies that lead to new medical devices or drugs are great, but the bottom line is that we need to protect the human subjects who are involved in trials. This starts with prompt training and preparing investigators and IRBs. Experts on this topic John Clark. Compliance Officer, Coast IRB LLC, an independent institutional review board. For more information, visit coastirb.com. Bob Gordon. Senior Director, Clinical Quality Assurance, Americas, Omnicare Clinical Research, a Phase I to IV contract research organization serving the biopharmaceutical and medical-device industries. For more information, visit omnicarecr.com. Felix Gyi, Pharm.D., MBA, CIP, RAC. Founder and CEO, Chesapeake Research Review Inc., an independent IRB and ethics review business as well as a risk management partner operating in the global research arena to support human research subjects protections. For more information, visit chesapeakeirb.com. Lynn A. Meyer. President and Founder, IntegReview Ethical Review Board, an independent IRB accredited by the Association for the Accreditation of Human Research Protection Programs. For more information, visit integreview.com. Gaetano Morelli, M.D. Senior Director of Global Medical Affairs for Early Clinical Research, MDS Pharma Services, which offers a full spectrum of resources to meet the drug discovery and development needs of the pharmaceutical and biotechnology industries. For more information, visit mdsps.com. Peter Reichertz. Partner and Leader of the Food and Drug Law Group, Sheppard Mullin Richter & Hampton LLP, a law firm with more than 500 attorneys practicing in 11 offices. For more information, visit sheppardmullin.com. Enhancing Quality, Protection The Association for the Accreditation of Human Research Protection Programs Inc. (AAHRPP) promotes the highest quality research through an accreditation process that helps organizations worldwide strengthen their human research protection programs (HRPPs). An independent, nonprofit accrediting body, AAHRPP uses a voluntary, peer-driven, educational model to ensure that HRPPs meet rigorous standards for quality and protection. To earn accreditation, organizations must provide tangible evidence — through policies, procedures, and practices — of their commitment to scientifically and ethically sound research and to continuous improvement. A Gold Standard As the “gold seal,” AAHRPP accreditation offers assurances — to research participants, researchers, sponsors, government regulators, and the general public — that an HRPP is focused first and foremost on excellence. AAHRPP’s Mission AAHRPP accredits high-quality human research protection programs to promote excellent, ethically sound research. Through partnerships with research organizations, researchers, sponsors, and the public, AAHRPP encourages effective, efficient, and innovative systems of protection for human research participants. Education, Resources, Regulations, and Guidance AAHRPP takes a peer-reviewed, educational approach to accreditation and provides a variety of print, online, and training resources to help organizations interpret the accreditation standards and navigate the accreditation process. Workshops afford individuals conducting the self-assessment and preparing the accreditation application with a one-on-one experience with AAHRPP staff to learn about the accreditation process, as well as time for detailed questions, specific items related to their organization, and interpretation of regulations. Tip sheets aid organizational staff in writing policies, procedures, and other supporting documents for an organization’s human research protection program. Over a dozen topics are covered, such as financial conflicts of interest of investigators, reporting of unanticipated problems, and terminations, suspensions, and noncompliance. The quarterly newsletter, AAHRPP Advance, provides focused, practical, and topical information on accreditation and organizations that achieve it. For more information, e-mail AAHRPP at firstname.lastname@example.org with questions or visit aahrpp.org/www.aspx. Lynn Meyer • IntegReview It’s rare, but there have been occasions when we discovered that some principal investigators were unaware of federal regulations they are required to comply with when they are conducting research. Dr. Felix Gyi • Chesapeake Research Review Currently, under HHS requirements, there are no regulations governing investigator activities, unlike research regulated by the FDA where there are regulations and guidances for investigators and sponsors.