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.
Keywords: accelerated access; conditional approval; efficacy; ethics; randomized placebo-controlled trials; research.
To determine whether a treatment is effective, clinical trials often compare an experimental treatment with an inactive substance (placebo). There are rules about when placebos can be used so that patients receiving them are not deprived of a proven treatment if such exists. Disregarding these rules may harm patients. In some cases, it is difficult to estimate whether a proven treatment exists and, thus, whether an experimental treatment can be compared with a placebo. These cases are when experimental treatments are made available to patients only on the condition that more data about their effectiveness is collected in subsequent clinical research, following this so-called conditional approval. There are many issues raised by such approvals, including treating patients with therapies the effectiveness of which is only assumed, but not known. For various reasons, it may become difficult to collect further evidence about the effectiveness of conditionally approved treatments. For example, patients may be unwilling to participate in trials when they can access experimental treatments without participating; companies may be unwilling to conduct costly trials when preliminary efficacy data was enough to get the therapy on the market and so on. This paper discusses why this is the case and suggests what could be done about it.