Double-blind coumadin research—An ethical dilemma (original) (raw)
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Journal of Thrombosis and Haemostasis, 2008
To cite this article: Bü ller HR, Halperin JL, Bounameaux H, Prins M. Double-blind studies are not always optimum for evaluation of a novel therapy: the case of new anticoagulants. J Thromb Haemost 2008; 6: 227-9. See also Furberg CD, Soliman EZ. Double-blindness protects scientific validity. This issue, pp 230-1; Casteels M, Flamion B. Open-label trials and drug registration: a European regulatorÕs view. This issue, pp 232-4.
Are double-blind controlled trials always necessary?
Human Psychopharmacology: Clinical and Experimental, 1992
The use of double-blind controlled trials to assess treatment receives almost universal praise (e.g. Paykel, 1989). Some Anglo-Saxon commentators have congratulated themselves on a major contribution to world medicine. Thanks to our native pragmatism, prejudice has been ousted and reason now dominates therapeutics. Major studies such as those of streptokinase in myocardial infarction (Isis 2, 1988) or tamoxifen in breast cancer (Nolvadex Adjuvant Trial Organization 1983) are indeed impressive. Characteristics of obviously worthwhile trials include: (1) A lot of time, effort and money goes into them. (2) Sufficient patients are entered to allow detection of significant differences between treatments. (3) A fair percentage of patients eligible for the trials actually enter them.
Fundamental & Clinical Pharmacology, 1999
The current reference guideline about ethics in clinical trials is the Declaration of Helsinki of human rights in medical research. Three major principles are emphasised: respect of the patient to accept or not to participate in a trial, the constraints and the presumed risks must be acceptable for patients included in a study, and vulnerable subjects should not participate in studies. The investigator is responsible for obtaining a free and well-informed consent from patients before their inclusion in a study. Where possible, a new drug should always first be compared to placebo in order to prove its superiority. Else, a small-sized trial comparing a new drug versus a reference treatment can lead to an erroneous conclusion of absence of difference. Moreover, good results or improvement are obtained in at least 30% of cases with placebo, whatever the disease. The use of placebo is unethical in life-threatening diseases and when an effective proved drug exists. The use of placebo is ethical in severe diseases with no efficient drug, in some severe diseases even when an active reference treatment is available, and in all moderate and functional diseases. In order to detect flawed studies, most journals now ask for any manuscript submitted and reporting results of a randomised clinical trial to join a checklist in order to verify the quality of the trial. Finally, it remains the responsibility of the doctor to decide whether or not a protocol is ethical, to participate or not and to include patients or not. research ethics / randomised controlled trials / informed consent / ethics committee / placebo / publication ethics * Correspondence and reprints This paper is based on a lecture given on 4th June 1998, at the International Symposium: "Ethical and Economical aspects of Pharmacotherapy", Faculty of Pharmacy, Charles University, Hradec Kr&lovb, Czech Republic, organised for the 650th anniversary of the Charles University.
Journal of Hepatology, 2009
R&D of new drugs is driven by pharmaceutical companies that invest considerable amounts of money for this purpose. This may introduce bias, to emphasize the clinical value of drugs to be allowed onto the market. Bias is caused by methodological flaws including the population under study, the choice of inadequate comparators or of their dosage, the adoption of surrogate or composite endpoints, the decision to publish mainly positive findings or to overlook some safety concerns, etc. All this happens in a legal context that requires no added value for new drugs to be approved for the market. This encourages the use of placebo even when active comparators are available, or the search for non-inferiority of new products in comparison with active comparators. Superiority over placebo and non-inferiority to active comparators may allow drugs onto the market that are in fact less active (or safe, tolerable, convenient, etc.) than those already available, usually with consolidated properties and lower costs. In addition, they do not meet patients' or physicians' needs of defining the place in therapy and respective roles of new and available treatments. The current legislative and regulatory setting seems designed to meet commercial interests rather than public health needs. Ó