- © 2004 Canadian Medical Association or its licensors
Physicians who participate in clinical trials can contribute to the evidentiary base for practice and can offer their patients a chance to receive cutting-edge therapies and the close follow-up that often accompanies a trial protocol. As well, trial participation can benefit physicians themselves, through research opportunities for those holding faculty appointments and, where trials are sponsored by industry, a flow of income outside the public health insurance system.
Clinical trials are clearly an important industry: in 2002, Health Canada reported 1287 new clinical trial applications.1 We estimate that hundreds, if not thousands, of physicians across Canada are involved in these trials and have signed contracts with industrial sponsors in recent years.
What provisions do these contracts normally include? The sponsor of a clinical trial to test an investigational drug or device enters into agreements with collaborating physicians about intellectual property issues, the trial protocol and the financial arrangements for the physicians' provision of services to the study patients and to the sponsor. Health Canada, the federal authority that regulates pharmaceutical agents, through its adoption of the International Conference on Harmonisation guidelines,2 states that the official documentation must include a clinical trial budget that is kept on record by the study sites and the sponsor. Current Canadian legislation3,4 does not specify the level of budgetary detail and does not provide guidance as to what constitutes a reimbursable service or what would be considered reasonable reimbursement levels. Health Canada considers the review of clinical trial agreements and any related financial agreements as outside the scope of their inspection strategy for clinical trials.5
The meaning of all this is simple: the information available to local administrators and research ethics boards (REBs) varies from one contract to the next, as do the arrangements for physician compensation. Even the agreements between individual physicians and the sponsor within the same clinical trial can be heterogeneous, since negotiated terms and conditions may vary by physician and by site.
Industry's role in innovation and research is important, but concern continues that investor-owned corporations must perforce tend to business interests, and these could adversely influence research and compromise its integrity.6,7,8,9 For individual physicians and sites, a partnership with industry may therefore create conflicts of interest, “a set of conditions in which professional judgment concerning a primary interest (e.g., a patient's welfare or the validity of research) tends to be unduly influenced by a secondary interest (e.g., financial gain).”10 Actual conflicts of interest raise serious ethical concerns.11,12 However, even absent direct conflicts of interest, the public's trust may be eroded by perceptions that industry's business interests are influencing or compromising clinical judgement and scientific integrity.13,14 Although we agree with the Kirby report that the “majority of industry works to high standards of ethics, fully consistent with the expectations of Canadians,”15 as do physicians, the stakes are high and some oversight is surely appropriate for clinical trial contracts. A first step is to address what is reasonable and just remuneration for physicians involved in clinical trials.
General principles for physician reimbursement
The Canadian Medical Association Policy on Physicians and the Pharmaceutical Industry16 has reinforced the principle of “reasonable” physician remuneration (Table 1). However, it does not specify which services should be included or how reasonable levels of compensation can be set. The policy stresses the importance of oversight of remuneration by an approved board, agency or body (which has the authority to approve the use of human subjects). Although all studies involving human subjects must undergo REB review, such groups have to date received no guidance in the matter of remuneration. For example, REBs are guided by the Tri-Council Policy Statement, which offers only that “REBs shall examine the budgets of clinical trials to assure that ethical duties concerning conflict of interest are respected.”19
One of the first needs, therefore, is for an informed debate to frame a consensus on parameters for reasonable remuneration for physicians participating in clinical trials. To start that debate, Table 2 shows a potential classification for physician remuneration in clinical trials and suggests possible standards for each group.
Standardizing clinical trial budgets
Agencies reviewing clinical trial applications at the institutional level (e.g., REBs) can assess potential conflicts of interest only if they see the clinical trial budgets — something that does not always happen today. Those budgets must be organized in a uniform manner that reflects the agreed categories of remunerable service. Absent access to a template budget for clinical trials, REBs may have difficulty evaluating what services are being remunerated and at what rate. We therefore suggest the use of a standardized budget template for classifying the categories of physician remuneration, regardless of the type of trial or location. It is premature to provide “best practice” parameters for these categories, but progress toward a common method of reporting categories of remuneration should lead to improved sector-wide communication and allow some basic standards for clinical trial budgets to emerge rapidly. Standardized clinical trial budgets would be based on categories, definitions and standards such as those in Table 2. At a minimum, the unit cost per patient for each service rendered should be easily identifiable in the budget, making it possible to determine what services are offered and for what cost. We recognize that flexibility in the template is needed to accommodate different study types (e.g., phase II versus phase III, or single versus multicentre trials), but greater standardization is still possible and, in our view, desirable.
Sharing of clinical trial budgets
The uncertainty about current practices arises not just from the lack of detail in current budgets, but also from the fact that they are rarely shared across institutions. Only with disclosure and discussion can “best practices” emerge with respect to physician remuneration. In addition to reducing potential financial conflicts of interest and conforming to broad principles of transparency and accountability, disclosure will promote equity in physicians' clinical trial remuneration. We believe that institutions and physician-researchers should reject any industry contract that prohibits appropriate disclosure of information about the financial arrangements or that allows only conditional disclosure. Disclosure also extends to patients. As such, physicians and site administrators should include a statement in the trial consent form about reimbursement for physicians and others involved in running the trial.
Although our focus here is on physician payment, institutional remuneration must also be considered in the near future. Some institutions receive funds from industry for actually running or administering a trial (e.g., overhead charges), for simply agreeing to participate in the trial (e.g., donations to the institution for that decision) or for other trial-associated activities, including related research programs and clinical services. “Sunshine rules” for all financial aspects of clinical study agreements, similar to those suggested above for physician remuneration, would mitigate potential institutional conflicts of interest.
Conclusions
Financial conflict of interest is subjective and may never be completely avoided. However, no one wants to see patterns of physician remuneration that could be interpreted as a threat to scientific integrity or good clinical judgement. Numerous editorials and empirical studies have examined conflict of interest,22,23 and there is a consensus that some physician payments should be banned (e.g., finders' fees and completion fees). However, there has been surprisingly little debate about clinical trial budgets in general and reasonable physician remuneration. In this brief commentary, we have urged standardization of categories of remunerable services, agreement on how physician payment levels should be set and transparency regarding the budgetary provisions in clinical trial agreements. These initial steps would help physicians and those who manage their practice sites to address perceived, potential or actual financial conflicts of interest in clinical research.
Footnotes
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Contributors: Lorraine Ferris and David Naylor conceptualized the content of the article and its direction. Lorraine Ferris wrote the initial draft of the paper and approved the final version. David Naylor revised the draft and approved the final version.
Competing interests: None declared.
Correspondence to: Dr. Lorraine E. Ferris, Department of Public Health Sciences, McMurrich Building, 12 Queen's Park Cres. W, 4th flr. Toronto ON M5S 1A8; fax 416 480-6048; lorraine.ferrisutoronto.ca