All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- Tuesday, May 23, 2000 HHS Press Office (202) 690-6343 Federal policy has tried to preserve the benefits of medical research, while at the same time protecting against possible abuse or harm to research subjects. In particular, a regulation implemented by 17 federal agencies - known as the Common Rule - seeks to guarantee review of research. The Office for Protection from Research Risks in the Department of Health and Human Services is responsible for ensuring the safety of people who participate in HHS-sponsored research. The FDA must approve all clinical trials testing a new drug, biological product or medical device. The National Institutes of Health (NIH) has developed patient safety guidelines that must be followed in any research that agency funds. NIH also has a special panel - the Recombinant DNA Advisory Committee - that provides oversight and public discussion of gene transfer research. These agencies work with oversight committees, known as IRBs, or institutional review boards, which are responsible for ensuring that people who agree to participate in studies understand the nature of the research and willingly consent to participate. Research institutions such as academic health centers and universities have the ultimate responsibility to ensure that investigators properly apply the informed consent process. History 1) In the 1960s, amendments to the U.S. Food, Drug and Cosmetic Act established requirements that people must consent before participating in an experimental therapy. 2) A 1967 FDA policy added that informed consent must be obtained in writing. 3) In the 1970s, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research added IRBs, which are oversight committees that see to it that people who participate in studies understand the nature of the research and willingly consent to participate. 4) In 1972, the Office for Protection from Research Risks (OPRR) was created as part of NIH to ensure the safety of people who participate in research sponsored by HHS. 5) In 1981, the FDA revised its regulations to require written informed consent in all studies of products that the FDA regulates. Federal Oversight and IRBs OPRR has the primary responsibility in the federal government for putting in place policies, procedures, and regulations to protect humans involved in HHS-sponsored research. OPRR has formal agreements with more than 4,000 federally-funded universities, hospitals, medical and behavioral research institutions in the USA and abroad. These "assurances" outline each institution's responsibility to conduct its research projects in an ethically sound manner and to protect the people in those projects. Each institution sets up one or more IRBs, which should see to it that people who participate in studies fully understand the nature of the research and willingly consent to participate. Informed consent requires that potential participants be given: 1) an explanation of purposes of the research 2) the expected length of participation 3) a description of the procedures to be followed and their potential risks and benefits 4) identification of any procedures that are experimental. An institution's IRB usually includes doctors, scientists, patient representatives and others who monitor the design, development, and progress of research projects being done at that institution. Federal regulations require that a non-scientist and a person not affiliated with the institution be included on every IRB. OPRR guides IRB members on ethical issues relating to humans in medical or behavioral research. OPRR conducts national educational workshops and provides on-site technical assistance to institutions doing HHS-sponsored research. In addition to its educational activities, OPRR monitors and evaluates an institution's compliance with the rules governing research. If complaints arise about an institution's oversight practices, OPRR has the authority to investigate and require corrective action. OPRR can suspend human research until problems are resolved. Since 1993, OPRR has done about 30 site visits to review compliance. The FDA has oversight responsibility for all clinical trials testing a new drug, biological product or medical device, and their respective IRBs. This includes industry-sponsored trials. The FDA must review the design of all clinical trials testing a new medical product before those trials may begin. The FDA monitors adverse events during clinical trials and can suspend trials if problems arise. Its investigators inspect about 600 clinical investigators, as well as 250 to 300 IRBs, each year. Politics The Advisory Committee to the Director of NIH recommended that OPRR be relocated to the Office of the Secretary (of HHS) to raise its stature and effectiveness. The committee also recommended that an "independent" advisory council be established to provide scientific and ethical guidance to OPRR in its oversight role. Secretary Shalala accepted these recommendations and will soon be relocating OPRR to the Office of Public Health and Science within the Office of the Secretary. Gene Transfer Research Recent reports of gene transfer trials in which people were not adequately protected (and died), along with financial conflicts of interest have made better protection for human research subjects more urgent. As a result, in March of 2000, HHS announced 2 new initiatives: 1) gene transfer research sponsors are now required to routinely submit monitoring plans in advance to the FDA and related IRBs. 2) NIH and the FDA have initiated a series of public gene transfer safety discussions. The FDA also has increased the number of inspections they conduct. The NIH and FDA are working to strengthen and streamline their collaborative efforts to monitor gene transfer trials. Oversight Secretary Shalala announced on May 23, 2000, several new efforts designed to improve human research subject safety, to strengthen government oversight of medical research, and to reinforce researchers' responsibility to follow federal guidelines. 1) expand education and training for all clinical investigators and IRB (Institutional Review Boards) staff. Extra ethical training will be required for all investigators receiving NIH funds and will be a condition of getting an NIH grant. 2) enhance the informed consent process and require closer monitoring and oversight. For especially risky or complex trials, IRBs will have to take extra measures, including third-party observation of the informed consent process. Investigators will also have to re-confirm informed consent when trial-related events happen that may affect a subject's willingness to participate. 3) ensure that researchers comply with federal conflict of interest regulations. NIH will now require investigators conducting early smaller-scale trials (Phase I and Phase II) to submit clinical trial monitoring plans to the NIH when they apply for a grant. The NIH requires large scale (Phase III) trials to have Data and Safety Monitoring Boards (DSMBs). DSMBs will have new requirements to prevent financial conflicts of interest. Any researchers' financial interest in a clinical trial will have to be disclosed to potential participants. 4) give the FDA additional enforcement tools to enhance its oversight. HHS will pursue legislation to enable FDA to levy monetary penalties for violations of research practices - up to $250,000 per investigator and up to $1 million per research institution. The FDA can already issue warning letters or halt research until problems are corrected. HHS will hold public discussions this summer to find new ways to manage conflicts of interest to ensure that research results are analyzed and presented objectively.