Ethics in clinical research
Authors: Silvio Garattini, Vittorio Bertele’
Journal: 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. 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. Surrogate endpoints and non-inferiority trials in chronic viral hepatitisJournal of HepatologyVol. 52Issue 5PreviewWe read with great interest the recent article by Dr. Garattini and Dr. Bertelè [1]. We would just like to comment on the authors' statement that "Quality of life, morbidity and mortality should always be the primary hard end-points for evaluating new drugs". We believe that this rule should be applied with caution in the field of chronic viral hepatitis because of the slow progression of this disease and the availability of surrogate virological end-points. For example, we know that the quality of life and survival of chronic hepatitis B patients can be improved if HBV replication is suppressed in a sustained manner [2]. Full-Text PDF Open Access