Post-trial access and the new version of the Declaration of Helsinki

Abstract

In October 2013, the World Medical Association (WMA) approved the latest version of the Declaration of Helsinki (DoH) in Fortaleza, Brazil. Post-trial access of favorable interventions was again one of the critical issues raised during the meeting. The call to clinical research actors, other than physicians, in this discussion is not new, but this is the first time, after 49 years and nine amendments, when governments are requested to take responsibilities.

The primary purpose of the DoH is the protection of human subjects involved in clinical research, but since the 2000 amendment, the WMA extended their concerns to what happens to the trial participants after the study. This issue, along with the use of placebo, was one of the key points that led to the withdrawal of the DoH as reference in the United States regulation. However, only the 2013 version acknowledges that the burden of providing post-trial access for those patients on continuous treatment is far beyond the investigator’s scope.

The delay between the end of a blind study and the unblinding could take several months. Meantime, the investigator is unaware if the participant received either control or experimental product. In case of therapeutic response, the investigator should provide to the participant the same treatment until the unblinding, even if it is the control product, i.e. placebo?

A trial participant can get therapeutic response with an experimental product that during the unblinded analysis has failed. The risk benefit analysis on individual basis might be challenging if one considers that the clinical development can stop due to safety concerns, lack of efficacy or release of alternatives more advantageous than the investigational product. Before retaining a product still under development after a study, the physician should consider safety and efficacy information as well as therapeutic alternatives to take decisions on an individual participant, even if the patient has a favorable response with acceptable tolerance. Furthermore, product manufacturing can be discontinued, raising the need to switch the experimental product to a sustainable alternative.