u t C O M M E N TA R Y
Why Guidance Comes from the Research Community By Davi d E. Wri ghT
T
he mere fact that leaders in the research regulatory community thought it was necessary to develop guidance on how to reconcile two key sets of regulations—those protecting human research participants with those relating to investigations of alleged research misconduct—warrants some observations. Officials at institutions that receive U.S. federal research funding must administer a suite of regulations governing the conduct of that research—regulations on the use of laboratory animals; regulations on research with human participants; regulations assuring chemical, biological, and radiation safety in research; regulations for disclosing and managing financial conflicts of interest; regulations on investigating alleged misconduct in research; and regulations on select agents (revised from 2012 to 2013) and export controls. Proposals to conduct large and complex research projects may trigger several or even all of these regulations. Gaining the necessary approvals to conduct research in such projects can present a substantial task for investigators and impose a substantial regulatory burden on their institutions. When something goes seriously wrong in research governed by multiple regulations, what ensues is the even more daunting challenge of analyzing and rectifying the problems in a way that is consistent with the require-
David E. Wright, “Why Guidance Comes from the Research Community,” The Intersection of Research Fraud and Human Subjects Research: A Regulatory Review, special report, Hastings Center Report 45, no. 4 (2014): S27-S28. DOI: 10.1002/hast.337
ments of all the applicable regulations, which may be partially incompatible, both substantively and procedurally. This is a challenge that the federal government did not foresee or at least did not take effective steps to minimize. It is also a challenge that most research institutions have only recently begun to address. The thumbnail history of federal research regulation in the United States begins with World War Two and its aftermath. Thanks to a flood of federal money supporting research at that time, the National Institutes of Health began to grow from a public health agency to the biomedical research behemoth it is today, and the
The task of analyzing and rectifying problems in research governed by multiple regulations is daunting. National Science Foundation was created. With the new federal money came instances of waste, fraud, and abuse by a small but not insignificant number of investigators. Many in the research community responded to press reports and to eventual congressional hearings by minimizing the problem and asserting that science was effectively self-governing. Eventually, however, in each major regulated area, an event occurred that triggered the development of federal regulations. A uniquely American formula for research regulation emerged: application of the regulation through peer review at regulated institutions (by institutional animal care and use committees [IACUCs], institutional review boards, institutional biosafety committees, radiation safety committees, and research misconduct investigation committees) with oversight from federal offices and agencies. The good news is that this formula has worked well, on the whole, by placing the first-line administration of the regulations with peers in the institutions and by minimizing the size of the federal oversight agencies and generally limiting intrusive oversight to serious matters. The bad news has been lack of regulatory coordination,
SPECIAL REP ORT: T h e I nt er sec t io n o f Resea r ch Fra u d a n d H u ma n S u bj e c ts Re s e a rc h : A Re g u l a tory Re v i e w
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both in the federal government and at research institutions. The reasons for this lack of coordination are clear. Nearly fifty years has elapsed from the promulgation of the original laboratory animal care regulations in the mid-1960s to the present, when a revised regulation protecting human research participants is being negotiated. Each of the research regulations was developed against very different political and cultural backdrops to govern research that was itself rapidly evolving. The two regulations that are the subject of this discussion are both overseen by offices in the same part of the Department of Health and Human Services. The other regulations are overseen by a variety of agencies and offices from the Department of Agriculture to the Nuclear Regulatory Commission. Given this expanse of time and the complexity of the federal system, it is not surprising that regulatory harmonization—or even compatibility—was never considered. This is true even within a single regulatory area. For example, last year the Office of Research Integrity sponsored a series of discussions among the fifteen or more federal agencies that have research misconduct policies pursuant to the 2000 Office of Science and Technology Policy mandate. The policies and procedures among these agencies for handling allegations of research misconduct vary dramatically. Before the meetings, these agencies typically had not talked to their counterparts, let alone tried to harmonize their policies and procedures. In the regulated institutions, the situation has been much the same. As the federal regulations were promulgated, universities developed compliant policies and procedures, often just before the required deadline for implementation. They often placed the new institutional oversight offices and committees where the regulated research was conducted (for example, with animal care facilities and IACUCs in medical or veterinary schools) but without regard either to coordination with other committees administering other regulations or to prob-
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lems such as institutional conflicts of interest. Research institutions have evolved, often changing dramatically from the 1960s into the second decade of this century, but the offices and committees have tended to stay where they were originally placed, with the result that many institutions have a decentralized and uncoordinated regulatory system. Research misconduct cases that involved multiple regulated areas of research and were poorly handled, in part because of lack of regulatory coordination, spun out of control, costing their institutions dearly— in some cases tens of millions of dollars, disruption of research, and the replacement of senior administrators. These episodes have moved some institutions to develop integrated compliance models. Integrated research compliance structures at research institutions have tremendous advantages in meeting regulatory obligations while reducing the regulatory burden (through shared databases and reporting, for example). They can develop confidential internal systems of communication so that when research does not comply with one of the multiple regulations that apply to it, those who oversee the other applicable regulations are alerted. Within such integrated compliance programs, a senior official is often designated to handle the triage of complex cases—sorting out what should be done in what order to protect health and public safety and to assure that the requirements of each regulation can be met. This is exactly the problem addressed in the report by Barbara Bierer and Mark Barnes. Appropriately, this document was developed with the help of a large number of officials and investigators who are either involved in research involving human participants or are responsible for investigating allegations of misconduct in research, or both. The federal government is not likely, in this geological age, to undertake this kind of discussion to increase regulatory compatibility, if not harmonization. It is therefore entirely fitting that the research community take the lead, as they have done in this guidance document.
July-August 2014/ H AS TI N GS CE NTE R RE P O RT
Why Guidance Comes from the Research Community By Davi d E. Wri ghT
T
he mere fact that leaders in the research regulatory community thought it was necessary to develop guidance on how to reconcile two key sets of regulations—those protecting human research participants with those relating to investigations of alleged research misconduct—warrants some observations. Officials at institutions that receive U.S. federal research funding must administer a suite of regulations governing the conduct of that research—regulations on the use of laboratory animals; regulations on research with human participants; regulations assuring chemical, biological, and radiation safety in research; regulations for disclosing and managing financial conflicts of interest; regulations on investigating alleged misconduct in research; and regulations on select agents (revised from 2012 to 2013) and export controls. Proposals to conduct large and complex research projects may trigger several or even all of these regulations. Gaining the necessary approvals to conduct research in such projects can present a substantial task for investigators and impose a substantial regulatory burden on their institutions. When something goes seriously wrong in research governed by multiple regulations, what ensues is the even more daunting challenge of analyzing and rectifying the problems in a way that is consistent with the require-
David E. Wright, “Why Guidance Comes from the Research Community,” The Intersection of Research Fraud and Human Subjects Research: A Regulatory Review, special report, Hastings Center Report 45, no. 4 (2014): S27-S28. DOI: 10.1002/hast.337
ments of all the applicable regulations, which may be partially incompatible, both substantively and procedurally. This is a challenge that the federal government did not foresee or at least did not take effective steps to minimize. It is also a challenge that most research institutions have only recently begun to address. The thumbnail history of federal research regulation in the United States begins with World War Two and its aftermath. Thanks to a flood of federal money supporting research at that time, the National Institutes of Health began to grow from a public health agency to the biomedical research behemoth it is today, and the
The task of analyzing and rectifying problems in research governed by multiple regulations is daunting. National Science Foundation was created. With the new federal money came instances of waste, fraud, and abuse by a small but not insignificant number of investigators. Many in the research community responded to press reports and to eventual congressional hearings by minimizing the problem and asserting that science was effectively self-governing. Eventually, however, in each major regulated area, an event occurred that triggered the development of federal regulations. A uniquely American formula for research regulation emerged: application of the regulation through peer review at regulated institutions (by institutional animal care and use committees [IACUCs], institutional review boards, institutional biosafety committees, radiation safety committees, and research misconduct investigation committees) with oversight from federal offices and agencies. The good news is that this formula has worked well, on the whole, by placing the first-line administration of the regulations with peers in the institutions and by minimizing the size of the federal oversight agencies and generally limiting intrusive oversight to serious matters. The bad news has been lack of regulatory coordination,
SPECIAL REP ORT: T h e I nt er sec t io n o f Resea r ch Fra u d a n d H u ma n S u bj e c ts Re s e a rc h : A Re g u l a tory Re v i e w
S27
both in the federal government and at research institutions. The reasons for this lack of coordination are clear. Nearly fifty years has elapsed from the promulgation of the original laboratory animal care regulations in the mid-1960s to the present, when a revised regulation protecting human research participants is being negotiated. Each of the research regulations was developed against very different political and cultural backdrops to govern research that was itself rapidly evolving. The two regulations that are the subject of this discussion are both overseen by offices in the same part of the Department of Health and Human Services. The other regulations are overseen by a variety of agencies and offices from the Department of Agriculture to the Nuclear Regulatory Commission. Given this expanse of time and the complexity of the federal system, it is not surprising that regulatory harmonization—or even compatibility—was never considered. This is true even within a single regulatory area. For example, last year the Office of Research Integrity sponsored a series of discussions among the fifteen or more federal agencies that have research misconduct policies pursuant to the 2000 Office of Science and Technology Policy mandate. The policies and procedures among these agencies for handling allegations of research misconduct vary dramatically. Before the meetings, these agencies typically had not talked to their counterparts, let alone tried to harmonize their policies and procedures. In the regulated institutions, the situation has been much the same. As the federal regulations were promulgated, universities developed compliant policies and procedures, often just before the required deadline for implementation. They often placed the new institutional oversight offices and committees where the regulated research was conducted (for example, with animal care facilities and IACUCs in medical or veterinary schools) but without regard either to coordination with other committees administering other regulations or to prob-
S28
lems such as institutional conflicts of interest. Research institutions have evolved, often changing dramatically from the 1960s into the second decade of this century, but the offices and committees have tended to stay where they were originally placed, with the result that many institutions have a decentralized and uncoordinated regulatory system. Research misconduct cases that involved multiple regulated areas of research and were poorly handled, in part because of lack of regulatory coordination, spun out of control, costing their institutions dearly— in some cases tens of millions of dollars, disruption of research, and the replacement of senior administrators. These episodes have moved some institutions to develop integrated compliance models. Integrated research compliance structures at research institutions have tremendous advantages in meeting regulatory obligations while reducing the regulatory burden (through shared databases and reporting, for example). They can develop confidential internal systems of communication so that when research does not comply with one of the multiple regulations that apply to it, those who oversee the other applicable regulations are alerted. Within such integrated compliance programs, a senior official is often designated to handle the triage of complex cases—sorting out what should be done in what order to protect health and public safety and to assure that the requirements of each regulation can be met. This is exactly the problem addressed in the report by Barbara Bierer and Mark Barnes. Appropriately, this document was developed with the help of a large number of officials and investigators who are either involved in research involving human participants or are responsible for investigating allegations of misconduct in research, or both. The federal government is not likely, in this geological age, to undertake this kind of discussion to increase regulatory compatibility, if not harmonization. It is therefore entirely fitting that the research community take the lead, as they have done in this guidance document.
July-August 2014/ H AS TI N GS CE NTE R RE P O RT
