An open science pathway for drug marketing authorization—Registered drug approval

ackgroundBefore drug approval, health authorities like the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) evaluate findings from the relevant clinical trials to assess the balance between clinical benefit and safety.When requesting marketing authorization for their drug products, pharmaceutical companies are allowed to choose the indication, design the trials, and choose assessments.In the US, pharmaceutical companies and drug manufacturers must submit full trial protocols to the FDA before those trials can begin.In Europe, companies can, at their discretion, obtain prior scientific advice from the EMA.This consultative process between sponsor and regulator is not fit for purpose, as there is, in practice, no clear a priori consensus on the exact criteria that will be applied to adjudicate success.Although the FDA lays out a set of a priori rules, all too often, it later bends those rules post hoc.For instance, for esketamine, for treatment of resistant depression, the FDA decided post hoc that a maintenance trial could substitute for a second positive short-term trial [1].OAU : Pleaseche ther examples include nalmefene for alcohol use disorder (approved by the EMA), which was based on a post hoc subgroup analysis of the pivotal trials [2], or eteplirsen for muscular dystrophy (approved by the FDA) despite a lack of clinical evidence [3].Even the initial standards agreed upon between the sponsor and regulator can be too lax.Too often, trials ask the wrong question: Trials may explore superiority over an inappropriately weak comparator such as placebo when superiority versus an already approved active comparator would be more clinically relevant [4].Trials can also be underpowered [4], focus on surrogate markers, or omit clinically relevant outcomes [5].Moreover, the regulator is laissez-faire with respect to trial publication in journal articles, allowing the sponsor to freely choose which findings to include and how to frame them, often diverging starkly from the