The pharmaceutical industry funds a substantial proportion of clinical drug trials conducted in the United States. This arrangement contains an inherent conflict of interest: that the investigator's dedication to the advancement of objective scientific knowledge may collide with the investigator's desire to produce results favorable to the company funding the project. Evidence from studies of the clinical drug trial process reveals that industry financing of clinical drug trials may be associated with inaccurate or biased conclusions and may thereby compromise the advancement of objective medical knowledge.
Clinical drug trials constitute a scientific endeavor with a major impact on the millions of people who utilize the medications studied in these trials. The clinical consequences of inaccurate or biased conclusions derived from clinical drug trials may be serious and widespread. A variety of remedies to protect against inaccurate or biased conclusions from clinical drug trials should be pursued. These remedies must be carefully constructed to maximize scientific objectivity without jeopardizing needed industry funding of clinical drug trials.
CONFLICTS OF INTEREST IN CLINICAL RESEARCH
Two seminal events have driven the increasingly intimate intermingling of academic biomedical researchers and industry. First was invention in 1973 of recombinant DNA technology, which revolutionized the pace of discovery in biomedical science, laid the cornerstone of the biotechnology industry, and led to the veritable collapse of the time and distance parameters historically separating biomedical discovery from commercial interest. Second was the Bayh-Dole Act of 1980, which revolutionized the pace of invention disclosure and patenting in research universities and academic medical centers. Relationships of academic faculty with industry are not new, and universities have long had policies on faculty consulting and conflicts of interest and commitment to govern these relationships. Typically, these policies have been sparse, light of hand, and rooted in trust in faculty integrity. The recent intensification of university-industrial relationships is not unique to biomedicine; computer science has had a similar course and poses comparable challenges to university leaders.
What then makes biomedical research, and especially clinical research that involves human subjects, different? First, Congressional and media interest in the 1980s to misdeeds in human subjects research confounded conflict of interest with scientific misconduct and forever wedded them in the public's mind. The recent gene transfer deaths only reinforce that confusion. Second, the unprecedented public support that biomedical research enjoys rests on public trust, which is badly strained when clinical researchers appear to be driven by self-interest. Finally, the progressive erosion of boundaries between academic and industrial research undermines the privileged status of academic medicine as a trusted independent arbiter of knowledge about human health and disease.
Institutional Review Boards (IRBs) are currently struggling with their roles and responsibilities pertaining to the review and management of conflicts of interest as they relate to research protocols involving human subjects. Over the past 10 years, the IRB of Children’s Hospital, Boston developed some preliminary policies and practices to address some of the issues. Children’s Hospital faculty must comply with the conflict of interest guidelines of Harvard Medical School. In addition, they are required to complete and submit a financial interest disclosure form for each protocol submitted. The Department Chairperson reviews this form. At the discretion of the Department Chairperson, issues raised in the form may be referred to institutional officials assigned the responsibility for managing conflicts of interest. When the Chairperson signs the IRB protocol application, his or her signature designates that no conflict of interest exists or that an existing conflict of interest has been appropriately managed. Budgets are carefully reviewed and approved by members of Research Administration for industrial and nonindustrial research. During this process, investigators need to justify the amount of money they will receive and how it will be spent. IRB approval for industry-sponsored research is not released until a clinical trial agreement is negotiated and signed. The IRB also has a policy against the acceptance of finder’s fees and the requirement to disclose in the informed consent when the hospital owns equity, which was obtained as part of a licensing agreement with the company for intellectual property, invented at the hospital. The IRB frequently communicates with investigators about the situations which may constitute a conflict of interest and the need to avoid them.
RAISING ETHICAL QUESTIONS CONCERNING
CONFLICTS OF
INTEREST THROUGHOUT THE PROCESS OF CLINICAL RESEARCH
Conflicts of interest are embedded in clinical research. Such conflicts are present at multiple steps in the research process: deciding to conduct a particular project, the design of research, its prospective review, the recruitment of subjects, the compensation of subjects, and the reporting of research results. These conflicts can pose ethical challenges for sponsors, institutions, investigators, research assistants, and patient-subjects. Given the ethical requirement for those designing and conducting clinical research to protect the rights and interests of research subjects as well as future patients, it is essential to be able to recognize these conflicts of interest and take steps to mitigate them.
POLICY OF THE AMERICAN SOCIETY OF GENE THERAPY ON FINANCIAL CONFLICT OF INTEREST IN CLINICAL RESEARCH
Potential financial conflicts of interest in clinical gene transfer studies have become a concern to both the public and the scientific community. The American Society for Gene Therapy Board of Directors has accordingly adopted a set of ethical standards to achieve the following objects. First, to ensure that the safety and the interests of patients who participate in clinical trials involving gene transfer are protected. Second, to assure the public that clinical gene transfer studies will be carried out by investigators in an objective manner, free from financial conflicts of interest. The following policy was published in the May 2000 issue of Molecular Therapy, the official scientific journal of the Society.