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Studies of conflicts of interest in clinical research have focused on academic centers, but most clinical research takes place in nonacademic settings.
To compare oversight and management of investigators’ financial relationships in academic and nonacademic research settings.
Survey of officials at 199 sites that contributed participants to commercially sponsored phase 3 clinical trials published in JAMA or the New England Journal of Medicine in 2006 and 2007.
Response rates were 66% for academic medical centers, 37% for nonacademic medical centers (inpatient), and 27% for outpatient nonacademic sites. Almost all academic medical centers (97%) and most nonacademic medical centers (87%) followed written conflict-of-interest policies, whereas 44% of outpatient nonacademic sites had written policies (P<0.001). Academic and nonacademic medical centers relied mainly on internal institutional review boards (69% and 71%, respectively); outpatient nonacademic sites relied primarily on independent institutional review boards (59%; P<0.001).
Nonacademic sites have substantially different approaches to the oversight and management of financial relationships in commercially sponsored clinical research than academic medical centers. These differences warrant more attention to how financial relationships are monitored in community research settings.
The Institute of Medicine’s Conflict of Interest in Medical Research, Education, and Practice1 is the latest of numerous reports about financial relationships in clinical research.2–14 Out of concern that conflicts of interest will bias investigators, increase risks to participants, or undermine public trust, government agencies and influential private groups have recommended or required that research organizations limit, manage, and disclose investigators’ financial relationships.1–3
Most of this work has focused on policies and practices of academic medical centers. Little is known about how financial relationships are managed at nonacademic research sites. Yet, the majority of clinical research takes place in nonacademic settings,15 especially commercially funded research, the type most likely to entail financial relationships such as recruitment incentives, consulting, or stock ownership. Guidance for academic institutions may not adequately address the nature of conflicts of interest in community hospitals or physician offices, and the mechanisms available in such settings to detect and manage investigators’ financial relationships might be substantially different. Therefore, we compared the oversight and management of investigators’ financial relationships in academic and nonacademic clinical research settings.
We identified sites that contributed research participants to phase 3 clinical trials meeting the following criteria: sponsored completely or partially by a commercial sponsor; trial results were published in JAMA or the New England Journal of Medicine between January 1, 2006, and December 31, 2007; registered in ClinicalTrials.gov; and included sites in the United States. Of the 190 trials identified, 30 met the inclusion criteria. Of these, we excluded 18 because we could not determine the sites’ locations using information in ClinicalTrials.gov.
We then compiled a list of clinical trial sites that contributed research participants to the 12 qualifying clinical trials published during the study period (Appendix A, available from the corresponding author by request). Removing redundant sites and those that had closed or no longer performed clinical research resulted in a final sample of 717 sites. Using Internet searches and the responses to the survey described herein, we categorized each site into 1 of 3 categories: academic medical center (n=107 [15%]); nonacademic medical center (n=272 [38%]), which included nonacademic institutions with inpatient facilities; or outpatient nonacademic setting (n=338 [47%]), which included multispecialty group practices, private physician offices, and freestanding clinical research centers. These sites constituted the population of sites from which we drew a random sample of 572 sites to achieve the desired sample size.
We sought to recruit 67 sites of each type (academic medical center, nonacademic medical center, and outpatient nonacademic setting). We calculated a sample size that would provide greater than 80% statistical power to detect differences as small as 15% in dichotomous item responses among the three types of sites. To increase the likelihood that the sites were actively conducting research, we sampled sites at random from trials published in 2007. Because of the small number of academic medical centers, we drew an additional random sample of academic medical centers from 2006. Sites were ineligible if they indicated that they no longer conducted clinical research.
Sites were recruited and the surveys administered from May through September 2008 by Huron Consulting Group (Chicago, Illinois) according to a protocol developed by the study team and approved or deemed exempt from formal review by the institutional review boards of the Duke University Health System, Johns Hopkins Medical Institutions, and Wake Forest University Health Sciences. Once the appropriate individuals were identified at each site, the interviewers made at least four contact attempts. Multiple individuals at each site could assist in the completion of the survey. Survey content was informed by previous interviews with officials at nonacademic research sites.16 All questions were pretested in cognitive interviews of six respondents (Appendix B, available from the corresponding author by request). No compensation was provided for participation.
We report standard descriptive statistics for all questions and used chi-square tests to compare frequencies across sites. We conducted all analyses using SAS version 9.1 (SAS Institute Inc, Cary, North Carolina).
Figure 1 shows the disposition of the sites identified and recruited. Participation was greatest for academic medical centers (61/[94–2]=66%), followed by nonacademic medical centers (77/[223–11]=36%) and outpatient nonacademic sites (61/[255–16]=25%). Table 1 shows the characteristics of the sites by type of setting.
There were large differences among sites in whether they followed a written policy on investigators’ financial relationships (P<0.001). Almost all academic medical centers (97%) and most nonacademic medical centers (87%) followed such a policy, whereas 44% of outpatient nonacademic sites reported having a written policy. The sites also differed in terms of transparency; most academic medical centers (81%) agreed to share their policies, compared with 39% of nonacademic medical centers and 26% of outpatient nonacademic sites (P<0.001).
Institutional review boards played a role in reviewing investigators’ financial relationships at over 70% of sites. Academic and nonacademic medical centers relied mainly on internal institutional review boards (69% and 71%, respectively), whereas outpatient nonacademic sites relied primarily on independent institutional review boards (59%; P<0.001).
Less than half of the sites, regardless of type, reported that they reviewed whether per capita payments for conducting research exceeded the reasonable costs of conducting the research.
Sites differed (P<0.001) with regard to whether all investigators were employees of the institution where the research was conducted. Nonemployee investigators were most common at nonacademic medical centers (77%), followed by academic medical centers (51%) and outpatient nonacademic sites (25%). For sites that reported having nonemployee investigators, most included review of their financial relationships in research (90% of academic medical centers, 83% of nonacademic medical centers, and 67% of outpatient nonacademic sites; P=0.35).
Previous research has focused on the oversight of financial conflicts of interest in academic settings. However, in our review of commercially sponsored phase 3 clinical trials published in two leading general medical journals, academic medical centers represented only 14% of the sites at which these trials were conducted. The more prevalent nonacademic research sites often do not follow formal written policies on investigators’ financial relationships in clinical research. These were also the sites where commercial entities were the main sponsors of the research. Previous work in academic settings has suggested that explicit policies encourage consistent management of conflicts of interest.14
Nonacademic sites may lack written policies for several reasons. First, much of the available policy guidance targets academic centers and may be inappropriate for other settings. For example, community hospitals that do not employ the physicians who conduct research with their patients have greater difficulty overseeing their financial relationships.16 More work is needed to understand concerns associated with importing policy guidance from academic to nonacademic settings. Second, nonacademic sites may conduct oversight and management of conflicts of interest without explicit written policies. Third, nonacademic sites, especially those outside medical centers, may be involved in little if any federally funded research, limiting the federal rules they are required to follow. For example, National Institutes of Health guidelines generally apply only to sites that conduct federally sponsored research.
Of the nonacademic sites that reported following written policies, approximately two thirds declined to share their policies with the study team. Although many policies and practices at research sites may understandably be considered proprietary, it would seem important for institutions to consider making policies on clinical research oversight, including those for conflicts of interest, widely available to help ensure that the clinical research enterprise is trustworthy.
One of the most basic financial relationships between sponsors, sites, and investigators is a per capita contract, whereby the institution or investigator is paid per recruited subject to cover the cost of conducting the research. Concerns have been raised that some per capita payments are inappropriately high.15–17 Our findings suggest that many sites do not review the reasonableness of per capita arrangements. Such reviews are undoubtedly challenging, but the absence of any review is likely to leave such arrangements susceptible to abuse. Additional work is needed to arrive at a consensus regarding appropriate per capita payments and to evaluate whether consistent review of these arrangements would help to protect human subjects and maintain the integrity of the research.
The results should be interpreted in light of several limitations. First, the selection criteria for trials and associated sites may have resulted in a sample that is not representative of the universe of clinical trial sites, especially since our study was limited to commercially sponsored research. Second, sites that declined to participate may have differed from sites that participated. For example, sites that refused may have had less developed policies for reviewing conflicts of interest in clinical research. Third, it was sometimes difficult to classify sites as academic or nonacademic. There is no apparent reason to believe these limitations would result in an overestimation of the differences between academic and nonacademic sites.
Among sites that participated in commercially sponsored clinical trials published recently in leading medical journals, the large majority were nonacademic. Oversight and management of conflicts of interest at these sites differed significantly from that of academic medical centers. These findings underscore the need, noted by others,1,16 for greater consideration of the environments in which clinical research occurs when developing guidance or regulations concerning financial conflicts of interest in clinical research.
Financial Disclosures None reported.
Funding/Support Supported by grant R01HL075538 from the National Heart, Lung, and Blood Institute.
Disclaimer The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health.
Additional Contributions We thank Nancy P. King, JD, Wake Forest University, for assistance with study design and for reviewing a draft of the manuscript; and Damon M. Seils, MA, Duke University, for assistance with manuscript preparation. Ms King and Mr Seils did not receive compensation for their assistance apart from their employment at the institutions where the study was conducted.
Financial Conflicts in Nonacademic Settings