An open science pathway for drug marketing authorization
Our essay "An open science pathway for drug marketing authorization -Registered drug approval" won the "Reimagine Biomedical Research for a Healthier Future Essay Challenge" sponsored by the Health Research Alliance and PLOS.
Before drug approval, health authorities lay out a set of a priori rules by which clinical trials will be judged as “positive” or “negative”.
All too often, they bend those rules post-hoc. This results in contentious debates as to whether appropriate thresholds for success were met. Examples include nalmefene for alcohol use disorder (approved by EMA), which was based on a post-hoc subgroup analysis of the pivotal trials or eteplirsen for muscular dystrophy (by FDA) despite a lack of clinical evidence or more recently aducanumab for Alzheimer disease.
Weak evidence leads to persistent uncertainty, and to difficult and controversial decisions for caregivers. In previous works, we have pointed toward these problems. For instance, we showed that too often, pivotal trials for psychiatric drugs ask the wrong question: trials explore superiority over an inappropriately weak comparator such as placebo when superiority versus an already-approved active comparator would be more clinically relevant. Trials can also be underpowered and/or focus on surrogate markers, and/or omit clinically relevant outcomes.
It is therefore timely to develop and test solutions that could be effective to solve these issues.
Our essay proposes to adapt the concept of Registered Reports to the process of regulatory drug approval and marketing authorization. We propose a pathway of ‘registered drug approvals’ that values the clinical importance of research questions, with in-principle approval granted on pre-specified criteria of success. This is done before data collection, precluding any post hoc rule-bending and enabling full transparency.
Our essay, published in PLOS Medicine, was written in collaboration with colleagues from Lyon, Pavia and Portland. Please have a look.