How proven is a ‘proven intervention’? Ethics of placebo controls in light of conditional approval programs

Abstract

This article discusses the difficulties of establishing whether there exists a proven therapeutic intervention when regenerative experimental treatments are made accessible to patients under conditional approval programs (outside clinical trials). Conditional approvals are often made on the basis of less robust efficacy evidence than otherwise required for the registration of new treatments. Lower quality of evidence affects the ethical justification of using a placebo-control design. The absence of a proven intervention is important in evaluating whether it is ethically justifiable to use such a design in a clinical trial and is present in major ethical guidelines. The main argument in this paper is that conditionally approved therapies, if referred to as ‘proven interventions’, would make placebo-control design ethically unjustifiable. Conducting rigorous clinical trials after conditional approvals is crucial to establish the efficacy of therapeutic approaches under such approvals. Hindrances to running such trials and generating further efficacy evidence are brought to attention.