A national survey of policies on disclosure of conflicts of interest in biomedical research

BACKGROUND: Conflicts of interest pose a threat to the integrity of scientific research. The current regulations of the U.S. Public Health Service and the National Science Foundation require that medical schools and other research institutions report the existence of conflicts of interest to the funding agency but allow the institutions to manage conflicts internally. The regulations do not specify how to do so. METHODS: We surveyed all medical schools (127) and other research institutions (170) that received more than $5 million in total grants annually from the National Institutes of Health or the National Science Foundation; 48 journals in basic science and clinical medicine; and 17 federal agencies in order to analyze their policies on conflicts of interest. RESULTS: Of the 297 institutions, 250 (84 percent) responded by March 2000, as did 47 of the 48 journals and 16 of the 17 federal agencies. Fifteen of the 250 institutions (6 percent)--5 medical schools and 10 other research institutions--reported that they had no policy on conflicts of interest. Among the institutions that had policies, there was marked variation in the definition and management of conflicts. Ninety-one percent had policies that adhered to the federal threshold for disclosure ($10,000 in annual income or equity in a relevant company or 5 percent ownership), and 9 percent had policies that exceeded the federal guidelines. Only 8 percent had policies requiring disclosure to funding agencies, only 7 percent had such policies regarding journals, and only 1 percent had policies requiring the disclosure of information to the relevant institutional review boards or to research subjects. Twenty journals (43 percent) reported that they had policies requiring disclosure of conflicts of interest. Only four federal agencies had policies that explicitly addressed conflicts of interest in extramural research, and all but one of the agencies relied primarily on institutional discretion. CONCLUSIONS: There is substantial variation among policies on conflicts of interest at medical schools and other research institutions. This variation, combined with the fact that many scientific journals and funding agencies do not require disclosure of conflicts of interest, suggests that the current standards may not be adequate to maintain a high level of scientific integrity.     

Rejuvenating a foundering institutional review board: one institution's story.

This report recounts one institution's experience in the fundamental reorganization of its institutional review board (IRB). With an appropriate approach, organizational structure, and ethos, the goals of research participant safety, regulatory compliance, and efficiency are not in conflict but, rather, mutually reinforcing. These important goals were realized because all aspects of the IRB reorganization were guided by and measured against five related principles: (1) expertise, (2) service, (3) credibility, (4) efficiency, and (5) accountability. This medium-sized academic IRB was successfully reorganized to increase the scrutiny of protection of human subjects and to promote efficiency and investigator services. On average, the office returned expedited submissions to investigators with approvals or queries within two working days of submission. On submissions requiring full committee review, letters and faxes were issued to investigators within 48 hours of committee meetings. This turnaround time (combined with a nine-day premeeting submission requirement) meant that investigators who had submitted new studies for full committee review received an approval, request for modifications, queries for more information, or disapproval within 11 days from the reorganized IRB. In contrast, an Office of the Inspector General study noted that IRBs in academic medical centers typically report decisions within an average of 37 days. The reforms included mechanical and operational changes within office procedure, a robust educational program for committee members, and a revamped IRB office staff that decreased the total number of office employees from five to four but that increased educational levels and skills of the staff members.     

Characteristics of medical school faculty members serving on institutional review boards: results of a national survey.

PURPOSE: To understand the characteristics of medical school faculty members who serve on institutional review boards (IRBs) in U.S. academic health centers. METHOD: Between October 2001 and March 2002, a questionnaire was mailed to a stratified random sample of 4,694 faculty members in 121 four-year medical schools in the United States (excluding Puerto Rico). The sample was drawn from the Association of American Medical College's faculty roster database for 1999. The primary independent variable was service on an IRB. Data were analyzed using standard statistical procedures. RESULTS: A total of 2,989 faculty members responded (66.5%). Eleven percent of respondents reported they had served on an IRB in the three years before the study. Of these, 73% were male, 81% were white (non-Hispanic). Virtually all faculty IRB members (94%) conducted some research in the three years before the study, and, among these, 71% reported conducting clinical research, and 47% served as industrial consultants to industry. Underrepresented minority faculty members were 3.2 times more likely than white faculty members to serve on the IRB. Clinical researchers were 1.64 times more likely to be on an IRB than were faculty members who conducted nonclinical research. No significant difference was found in the average number of articles published in the three years before the study comparing IRB faculty to non-IRB faculty. CONCLUSIONS: The faculty members who serve on IRBs tend to have research experience and knowledge that may be used to inform their IRB-related activities. However, the fact that almost half of all faculty IRB members serve as consultants to industry raises potential conflicts of interest.     

Institutional shared resources and translational cancer research

The development and maintenance of adequate shared infrastructures is considered a major goal for academic centers promoting translational research programs. Among infrastructures favoring translational research, centralized facilities characterized by shared, multidisciplinary use of expensive laboratory instrumentation, or by complex computer hardware and software and/or by high professional skills are necessary to maintain or improve institutional scientific competitiveness. The success or failure of a shared resource program also depends on the choice of appropriate institutional policies and requires an effective institutional governance regarding decisions on staffing, existence and composition of advisory committees, policies and of defined mechanisms of reporting, budgeting and financial support of each resource. Shared Resources represent a widely diffused model to sustain cancer research; in fact, web sites from an impressive number of research Institutes and Universities in the U.S. contain pages dedicated to the SR that have been established in each Center, making a complete view of the situation impossible. However, a nation-wide overview of how Cancer Centers develop SR programs is available on the web site for NCI-designated Cancer Centers in the U.S., while in Europe, information is available for individual Cancer centers. This article will briefly summarize the institutional policies, the organizational needs, the characteristics, scientific aims, and future developments of SRs necessary to develop effective translational research programs in oncology.     

An instrument for determining the amount of NIH support for clinical investigations at one academic health center.

PURPOSE: Although interest in supporting clinical investigators is increasing, information regarding the quantity, spectrum, and specific types of clinical research performed in academic health centers (AHCs) is generally not available. The authors report on an instrument to quantify the National Institutes of Health (NIH)-funded component of clinical research at one institution. METHOD: A systematic review of all NIH grants awarded to Massachusetts General Hospital (MGH) in fiscal year (FY) 1997-98 was performed using public information from two NIH Internet sources. Research abstracts from all 487 grants were reviewed and the percentage and type of clinical research activity within each was estimated and compared with estimates provided by a subset of principal investigators. RESULTS: During FY 1997-98, the MGH received $134 million in total NIH funding; $39.9 million (30%) supported the broadest definition of clinical research (that using human materials). When the definition of clinical research was narrowed to direct interaction between investigator and patient for investigative purposes (patient-oriented research), the total for clinical research was $18.2 million. These numbers significantly exceeded the institution's previous estimates of $.6 million for NIH-sponsored clinical trials and $2.2 million for population-based studies. CONCLUSIONS: Clinical investigation is an important component of AHCs' research portfolios from several perspectives, not the least of which is financial. Data on the clinical component of an institution's research effort should be collected prospectively and nationally to inform the optimal allocation of research resources and the alignment of the AHC's infrastructure.     

Trust us to make a difference: ensuring public confidence in the integrity of clinical research.

Investigator's and institutions' financial conflicts of interest in clinical research raise serious questions about the objectivity of such research, the safety of human subjects, and the threat to public trust in the integrity of clinical research. Yet the author makes clear that a conflict of interest is a state of affairs, not a behavior, and therefore not automatically a manifestation of improper actions. Indeed, conflicts of interest are quite common in complex settings such as those of academic medicine, and usually pose no problem, both because of the safeguards already in place and the integrity of most researchers. But it is clear that both non-financial conflicts of interest (e.g., career advancement, peer recognition, garnering grants and publications) and financial ones are double-edged: they can motivate individuals to do their best work but also can compromise judgment and undermine objectivity. In particular, conflicts of interest involving money, especially money from external sources, warrant special, targeted safeguards. And whether or not such conflicts of interest have actually created significant problems, academic medicine risks great peril if its leaders fail to respond to the growing perception that such problems exist. To foster public trust, the public needs to be better educated about how, with proper safeguards, limited financial incentives in the conduct of clinical research can benefit everyone. In addition, safeguards against the downsides of such financial incentives must be visibly strengthened. The author offers eight suggestions for what academic medicine's leaders might do in this regard (comply with existing full-disclosure requirements; establish principles governing institutional conflicts of interest; etc.). He closes by reiterating that the pursuit of clinical research depends entirely on the ability and willingness of the research community to merit public trust.     

Conflict-of-interest policies for investigators in clinical trials

BACKGROUND: There is substantial concern that financial conflicts of interest on the part of investigators conducting clinical trials may compromise the well-being of research subjects. METHODS: We analyzed policies governing conflicts of interest at the 10 medical schools in the United States that receive the largest amount of research funding from the National Institutes of Health. These institutions are Baylor College of Medicine, Columbia University College of Physicians and Surgeons, Harvard Medical School, Johns Hopkins University School of Medicine, the University of Pennsylvania School of Medicine, the University of California at Los Angeles School of Medicine, the University of California at San Francisco School of Medicine, the University of Washington School of Medicine, Washington University School of Medicine at St. Louis, and Yale University School of Medicine. RESULTS: All 10 universities required that faculty members disclose financial interests to university officials. Only four required disclosure by all members of the research staff. Five universities required disclosure of all financial interests, even though federal regulations specify a threshold for disclosure. Six universities required disclosure to the institutional review board as well as to a committee on conflicts of interest or a university official. Four universities had stricter requirements for investigators conducting clinical trials than required by federal regulations. One university prohibited investigators from having stock, stock options, consulting agreements, or decision-making positions involving a company that sponsored the research. A second university prohibited researchers from trading stock or stock options in a company that sponsored the research or sold the product or device under study. Two universities ordinarily did not allow faculty members to participate in clinical research if they had what federal regulations refer to as a "significant" financial interest in the company owning the product or device being studied, but exceptions were allowed. CONCLUSIONS: Policies governing conflicts of interest at leading medical schools in the United States vary widely. We suggest that university-based investigators and research staff be prohibited from holding stock, stock options, or decision-making positions in a company that may reasonably appear to be affected by the results of their clinical research. Of the 10 medical schools we studied, only 1 had a policy that was close to this standard.     

Three easy pieces

The author provides information about and analyzes three issues confronting academic medical centers in the realms of education, patient care, and research. (1) In the educational realm, he indicates why medical centers must play an expanded role in training primary care physicians, explains the dangers of not doing so, and describes ongoing and proposed approaches and reforms for achieving this goal. (2) In the arena of patient care, he explains why modifying physician reimbursement policies is essential for more physicians to develop careers as generalists. Other more controversial physician payment reform measures and their implications for health care and academic medical centers are discussed; the author urges that benefit to patients always be the first concern of such reforms, even at the expense of more narrowly based interests such as limits in faculty salaries or reduced overages to institutions. (3) Regarding research, he discusses various facets and implications of conflict of interest for biomedical scientists--both the reality of misconduct and the appearance of it--especially as they apply to the growing number and forms of university-industry relationships, and urges that such conflicts be managed within guidelines that clarify expectations and standards in an atmosphere of appropriate disclosure and oversight. He concludes by urging academic medical centers to rise to, rather than avoid, the three challenges he has described.     

Establishing procedures for institutional oversight of stem cell research.

Academic health centers (AHCs), which are at the forefront of stem cell research, need to establish institutional stem cell research oversight committees (SCROs) to comply with 2005 National Academy of Sciences (NAS) recommendations and to establish public trust in this sensitive research. Institutional review boards (IRBs) typically lack the expertise and time to adequately review the specific ethical issues raised by stem cell research. To assure careful, timely, and coordinated review of the science and ethics of stem cell protocols, AHCs need to address many practical procedural issues, such as SCRO membership, quorum, conflicts of interest, and procedures for protocol review. The SCRO committee at the University of California San Francisco (UCSF), established in 2003, has developed detailed policies and procedures on these issues. The UCSF SCRO has broad scientific expertise and uses ad hoc reviewers to strengthen the review process. Studies receiving full SCRO review have three lead reviewers: a scientist, a reviewer with ethics expertise, and a public representative. Studies introducing human stem cells into nonhuman blastocysts receive full review, even if the stem cells are anonymized. Some protocols are eligible for expedited review. The SCRO neither replaces nor duplicates review by the IRB and institutional animal care and use committees. Other AHCs can draw on the UCSF experience when developing their own policies and procedures for stem cell research oversight.     

Medical schools' attitudes and perceptions regarding the use of central institutional review boards.

PURPOSE: To investigate the current practices, attitudes, perceptions, and future plans of U.S. medical schools regarding the use of central institutional review boards (IRBs) to review research involving human participants. METHOD: In 2003, a survey instrument was distributed via fax and e-mail to the deans of research at the 125 accredited U.S. medical schools. Each dean was asked to have the instrument completed by the official at that school who decided on the use of a central versus local IRB. The survey instrument consisted primarily of a variety of closed-ended questions. RESULTS: Eighty-eight medical schools (69.8%) completed the instrument; 76% of these indicated that they had never used a central IRB and 24% had used a central IRB. Most of the respondents expressed no interest in using a central IRB in the future because they believed that their local IRB was working efficiently, and they were concerned about issues of institutional liability and the loss of local representation in the review process. Of the medical schools that had used a central IRB, most were pleased with the performance of the central IRB and would continue to use a central IRB in the future. Of interest, most of these respondents did not agree that a central IRB had helped them to attract industry-sponsored research. CONCLUSIONS: In spite of much discussion about the advantages of central IRBs in expediting overview of human subjects research, especially in multicenter trials, the majority of medical schools surveyed had never used a central IRB and expressed no interest in doing so.     

Medical informatics' promised land: are we there yet?

A decade ago, a "promised land" was envisioned in which the true potential of medical informatics would be realized. A decade later, it is time to assess academic medicine's progress in its journey into this medical informatics promised land. To that end, the author considers how our academic medical centers have been affected by changes in social, financial, and technical forces originating either "inside" or "outside" these institutions. He describes how the Internet and the World Wide Web have brought about an explosion in the availability of biomedical information, eased communication across the globe, made more information available at a lower cost, and changed the pace of everyday work. Although he argues that academic medical centers have not always kept pace with these changes, information systems are improving as the leaders in academic medicine come to appreciate the value of both information technology and the people who understand it. To reach the "promised land" envisioned a decade ago, academic medical centers must treat medical informatics as a central component of their academic mission.     

Consent documents, reproductive issues, and the inclusion of women in clinical trials.

PURPOSE: To describe language used in consent documents at one academic medical center to inform women participating in studies of potential reproductive and fetal risks. METHOD: The authors reviewed consent document language describing reproductive and fetal risks in 114 approved protocols. Protocols were identified as being of high, low, or unknown risk based upon FDA drug-risk and radiation-risk categories. RESULTS: Although most consent documents advised women against participating for one or more pregnancy-related reasons, specific information about reproductive or fetal risks was included in fewer consent documents: 8 (73%) of the high-risk studies, 12 (40%) of the low-to-moderate-risk studies, and 29 (40%) of the unknown-risk studies. CONCLUSIONS: Investigators often omit fetal risk information from consent documents. Full disclosure of reproductive and fetal risks in consent documents and discussions can be taught and modeled during the research training period. The authors present a template with language that can be used in consent documents and recommend ongoing discussion of reproductive and fetal risks with women subjects throughout the study period.     

Configuration challenges: implementing translational research policies in electronic medical records.

Prospective clinical trials are a key step in translating bench findings into bedside therapies. Electronic medical records (EMRs) are often cited as a significant new tool for advancing clinical trial capabilities into standard clinical practice. However, combining clinical research and clinical care activities into one unified electronic information system requires integrating a substantial body of regulatory requirements and institutional policies. Differing interpretations of external regulations and internal policies need to be reconciled so that the EMR configuration simultaneously conforms to all requirements.The authors describe how they used a detailed clinical vignette to help focus discussions about their institution's current research policies and how regulations and policies might be implemented in a commercial EMR. The vignette highlighted a number of inconsistencies in the institution's policies and in individual interpretations of regulatory intent.Attempts to implement potential policies in the EMR system also revealed a number of limitations and inconsistencies in the commercial system. The authors describe a set of compromises that will be implemented at The Children's Hospital until missing functionality is made available from the commercial vendor. Each institution that implements an EMR will need to resolve similar policy and configuration issues at its own facility. The authors highlight these configuration challenges by presenting a list of questions that must be answered unambiguously before implementing translational research capabilities into an operational EMR.     

Needs and challenges for health services research at academic health centers.

What are the institutional strategies used by academic health centers and other academic institutions to support and maintain the infrastructure that promotes health services research? Using the findings from interviews conducted in late 1998 with health services researchers at ten health services research centers of several types and from several geographic areas, and with the directors of ten health services research training centers, the authors address this key issue by examining four central infrastructure needs and challenges for health services research: (1) organizing core institutional resources (most centers received some level of core financial support from their parent organizations); (2) supporting career development of individual researchers (the more competitive health care system may diminish the ability of academic health centers and other institutions to give such support, but certain opportunities were noted); (3) supporting and enhancing training in health services research (such support comes from many different disciplines and organizations; the typical career path is in academic settings); and (4) establishing and supporting research partnerships (there are growing opportunities for such alliances). The authors reach a number of conclusions from their study, including the fact that there are a wide variety of models of successful health services research centers, with very different missions, organizational and interdisciplinary configurations, research and policy objectives, and collaborative relationships. Additional studies are needed to further specify those infrastructure elements that foster effective and productive health services research in academic health centers and other university settings.     

Current Levels of Conflict of Interest Disclosure in Medical Publications from Korea

Medical research should be fully transparent. The aims of this study were to determine the prevalence of author-related conflict of interest (COI) policies and evaluate the actual state of COI disclosure in Korean medical journals. To determine the prevalence of author-related COI policies, we examined the 198 medical journals listed in the KoreaMed database. To investigate the actual state of COI disclosures in published papers, we analyzed the publications in a representative medical journal, the Journal of the Korean Medical Science, from the perspective of the relevance of the ethics of COI disclosure. A total of 164 (82.8%) journals required an author''s statement of COI as a criterion for publication. Of these 164, most of them focused on financial COI, with 101 (61.6%) presenting the information related to COI disclosures as a separate paragraph with a clear title. We identified 114 articles published by the Journal of the Korean Medical Science over a seven-year period, from January, 2006 to December, 2012. Of these, 65 papers (57%) included an author''s statement of COI. We found that the policies of Korean medical journals regarding the disclosure of author COIs are still behind the internationally suggested level.     

The role of institutional support in protecting human research subjects.

Institutional review boards (IRBs) and the federal "assurance" procedures play critical roles in the current research and regulatory environments for clinical research in academic medical centers and other institutions. The author focuses on what institutions can and ought to do to create an infrastructure that assures the protection of human subjects. Specifically, an institution should (1) create an ethics infrastructure in which both IRBs and the function of protecting human subjects are respected; (2) assure that adequate resources (space, staff, equipment) are available; (3) support IRB members with appropriate recognition and time, since their IRB workloads can be heavy; and (4) provide adequate and appropriate education for IRB administrators, members, and staff, and for investigators and research staff. Academic medical centers should also use their expertise in analyzing the current system and developing means of improving it. Nevertheless, providing adequate resources for proper research conduct will be challenging, given the current financial limitations within academic medical centers.     

Disclosure of genetic information to family members: a systematic review of normative documents

PurposeFindings from genomic sequencing can have important implications for patients and family members. Yet, when a patient does not consent to the disclosure of genetic information to relatives, it is unclear how health-care professionals (HCPs) should balance their responsibilities toward patients and their family members and whether breaches in confidentiality are warranted.MethodsWe conducted a systematic review of normative documents to understand how HCPs should discuss and facilitate family disclosure, and what should be done in cases where the patient does not consent to disclosure.ResultsWe analyzed 35 documents from advisory committees at the national, European, and international level. We identified discrepancies regarding the recommended role of HCPs in disclosure. While almost all normative documents supported the disclosure of genetic information without patient consent in limited conditions, the conditions for disclosure were often not well defined. Documents provided varying degrees of information regarding what actions HCPs must take in such situations.ConclusionOur findings present concerns regarding the ability of these normative documents to guide HCPs’ decision making around the disclosure of genetic information to family members. Clearer guidance outlining the responsibilities and acceptability of disclosure is necessary to facilitate disclosure of genetic information to family members.     

IRB perspectives on the return of individual results from genomic research

PurposeReturn of individual research results from genomic studies is a hotly debated ethical issue in genomic research. However, the perspective of key stakeholders—institutional review board (IRB) professionals—has been missing from this dialogue. This study explores the positions and experiences of IRB members and staff regarding this issue.MethodsIn-depth interviews with 31 IRB professionals at six sites across the United States.ResultsIRB professionals agreed that research results should be returned to research participants when results are medically actionable but only if the participants want to know the results. Many respondents expected researchers to address the issue of return of results (ROR) in the IRB application and informed-consent document. Many respondents were not comfortable with their expertise in genomics research and only a few described actual experiences in addressing ROR. Although participants agreed that guidelines would be helpful, most were reticent to develop them in isolation. Even where IRB guidance exists (e.g., Clinical Laboratory Improvement Act (CLIA) lab certification required for return), in practice, the guidance has been overruled to allow ROR (e.g., no CLIA lab performs the assay).ConclusionAn IRB–researcher partnership is needed to help inform responsible and feasible institutional approaches to returning research results.Genet Med 2012:14(2):215–222     

Financial conflict-of-interest policies in clinical research: issues for clinical investigators.

As industry sponsorship of clinical research grows, investigators' personal financial relationships with those sponsors are under increasing scrutiny. The federal government, some states, and many universities have enacted conflict-of-interest policies to monitor and regulate investigators' financial relationships. Little is known, however, about investigators' awareness of or support for these policies or their attitudes toward regulatory efforts. To explore the possible implications of conflict-of-interest policies for clinical researchers, the authors interviewed active clinical investigators at two institutions where the conflict-of-interest policies differ. The most striking feature of the interviews was the range of perceptions and attitudes expressed by clinical investigators and their implications for administrators, professional societies, and policymakers concerned with conflicts of interest. Fewer than half of the interviewed investigators could accurately describe their campus' conflict-of-interest policy. Many investigators felt that professional societies, the public, and individual investigators were appropriate monitors of conflicts of interest. Many investigators recognized the general risks associated with conflicts of interest, but felt that they personally were not at risk. A fundamental challenge facing administrators and policymakers is to demonstrate to all investigators, both clinical and nonclinical, that the potential for bias, pressure and conflict is relevant to all investigators with industry relationships.