Competing interests: The need to control conflict of interests in biomedical research

Individual and institutional conflict of interests in biomedical research have becomes matters of increasing concern in recent years. In the United States, the growth in relationships — sponsored research agreements, consultancies, memberships on boards, licensing agreements, and equity ownership — between for-profit corporations and research universities and their scientists has made the problem of conflicts, particularly financial conflicts, more acute. Conflicts can interfere with or compromise important principles and obligations of researchers and their institutions, e.g., adherence to accepted research norms, duty of care to patients, and open exchange of information. Disclosure is a key component of a successful conflict policy. Commitments which conflict with a faculty member's primary obligations to teaching, research, administrative responsibilities, or patient care also need attention. Institutional conflict of interests present different problems, some of which are discussed in an analysis of an actual problem posed by two proposed clinical trials. This paper is adapted from a lecture presented to a Symposium on Scientific Integrity, Warsaw, Poland, 23 November 1995. Daniel Steiner was Vice-President and General Counsel of Harvard University (1972–92) and in that capacity became familiar with conflict of interest issues. He is currently Counsel to the Boston law firm. Ropes and Gray, and is Adjunct Lecturer in Public Policy at the John F. Kennedy School of Government. Harvard University.     

The Meaning vs. The Medical Model in the Empirically Supported Treatment Program: A Consideration of The Empirical Evidence

A review of the debate on the Empirically Supported Treatment Program is presented. It is argued that underlying the specifics of the debate are fundamentally incompatible paradigms: a meaning vs. a medical model. The findings from two gold standard multi-site studies are reviewed to conclude that the control condition meets requirements for an empirically supported treatment. The empirical finding of the failure of clinical training to improve treatment outcomes is explained by the focus on rational factors in training. It is recommended that training of therapists focus on enhancing experiential capacity rather than mastery of manualized treatment approaches.     

A call to restructure the drug development process: Government over-regulation and non-innovative late stage (Phase III) clinical trials are major obstacles to advances in health care

The history of drug/vaccine development has included major advances guided primarily by risk/benefit analyses concerning the innovative agent, not by evidence-based clinical trials (Phase I–IV). Because the approval for new drugs is hindered under the present process, the system requires restructuring. The Phase I/II study period should be more flexible, using the “environment of knowledge” about the new agent, plus risk/benefit assessments. Phase III, as presently constructed, does not add new adverse events data, it provides a narrower profile of drug efficacy than properly done Phase II studies, and placebo-controlled trials continue to raise unresolved ethical and social issues. Phase III studies should be abandoned for most drugs, and substituted with properly powered Phase II doseranging studies plus careful post-marketing surveillance. Phase III should be a penalty for poor drug development, not a regulatory requirement. To accomplish efficient drug development, greater cooperation between pharmaceutical companies and governments in developing clinical trials is needed rather than over-regulation. These changes will synchronize the drug development and regulatory process with the current rapid drug discovery process, reduce drug development time and cost, and improve patient care. The author is Adjunct Professor of Medicine, Weill Medical College of Cornell University, New York, New York, USA.     

Informed consent and the use of placebo in poland: Ethical and legal aspects

The concept of informed consent was one of the most fruitful ideas that deeply changed the relationships between physicians and their patients from paternalism to respect for the personal autonomy of subjects needing professional medical care. The great progress in medicine, also involving the pharmaceutical industry, has created an increasing need to perform different clinical and experimental trials. The evolution of clinical research in the last decades has influenced strongly the design of these studies. One of the most important changes in this field has been the use of placebo groups in double-blind controlled studies. The controversies have involved not only the use of placebo when standard or proven treatment was available, but also some specific problems concerning the procedure of obtaining informed consent in such trials. This paper briefly presents the evolution of informed consent in Poland as well as different ethical and legal problems concerning informed consent and the use of placebo controls in clinical trials. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

The Ethics of Type 1 Diabetes Prediction and Prevention Research

There are approximately one million cases oftype 1 diabetes in the US, and the incidenceis increasing worldwide. Given that two-thirdsof cases present in childhood, it is criticalthat prediction and prevention research involvechildren. In this article, I examine whethercurrent research methodologies conform to theethical guidelines enumerated by the NationalCommission for the Protection of Human Subjectsof Biomedical and Behavioral Research, andadopted into the federal regulations thatprotect research subjects. I then offer twopolicy recommendations to help researchersdesign studies that conform to these ethicalrequirements.     

Effects of a meaningful, a discriminative, and a meaningless stimulus on equivalence class formation

Thirty college students attempted to form three 3-node 5-member equivalence classes under the simultaneous protocol. After concurrent training of AB, BC, CD, and DE relations, all probes used to assess the emergence of symmetrical, transitive, and equivalence relations were presented for two test blocks. When the A-E stimuli were all abstract shapes, none of 10 participants formed classes. When the A, B, D, and E stimuli were abstract shapes and the C stimuli were meaningful pictures, 8 of 10 participants formed classes. This high yield may reflect the expansion of existing classes that consist of the associates of the meaningful stimuli, rather than the formation of the ABCDE classes, per se. When the A-E stimuli were abstract shapes and the C stimuli became S(D)s prior to class formation, 5 out of 10 participants formed classes. Thus, the discriminative functions served by the meaningful stimuli can account for some of the enhancement of class formation produced by the inclusion of a meaningful stimulus as a class member. A sorting task, which provided a secondary measure of class formation, indicated the formation of all three classes when the emergent relations probes indicated the same outcome. In contrast, the sorting test indicated "partial" class formation when the emergent relations test indicated no class formation. Finally, the effects of nodal distance on the relatedness of stimuli in the equivalence classes were not influenced by the functions served by the C stimuli in the equivalence classes.     

The protection of patients’ rights in clinical trials

The Helsinki Declaration is a very important document regarding the protection of patients’ rights in clinical trials and one of the fundamental sources of operational principles for every ethics committee. Although they have been updated, the international guidelines for ethics committees continually fail to address certain issues pertaining to the protection of patients’ rights in clinical trials. These issues include, most significantly, the method of electing ethics committees (a free, secret ballot should be preferred to direct appointment), the avoidance of conflict of interest during the election of ethics committee members, and the necessary insurance coverage for the participants of clinical trials. Polish law should, on the other hand, be developed in such way as to not limit the effectiveness of ethics committees in protecting patients’ rights in clinical trials. The ideal solution would be to draft a uniform law concerning not only clinical trials, but all medical experiments. The opinions of experts who have been reviewing medical research projects for several years may prove to be especially valuable in this setting. This paper was presented at the 6th International Bioethics Conference on the subject of ‘The Responsible Conduct of Basic and Clinical Research’, held in Warsaw, Poland, 3–4 June 2005. The author is Chairman, Bioethics Committee of the Warsaw Regional Chamber of Physicians and Dentists.     

Combining Pharmacotherapy with Cognitive‐Behavioral Interventions for Obsessive‐Compulsive Disorder

This paper reviews the evidence‐based literature concerning the efficacy and effectiveness of cognitive behavior therapy (CBT), drug treatment and their combination for obsessive‐compulsive disorder (OCD). After a brief outline of the seminal studies, the state of the art is presented with reference to the consensual recommendations proposed in the last 10 years. Management of OCD rests on potent selective serotonin re‐uptake inhibitors and CBT, used separately, sequentially, or concurrently. A hierarchical model for clinical decision‐making is reported. With greater severity of OCD, it is recommended to add medications. However, the response rate is still too low in many patients, and some patients remain refractory to any kind of treatment. This stresses the importance of joint efforts of psychological and biological teams to develop new treatments.