‘Negative’ clinical trials in rare diseases and beyond: reclassification and potential solutions

Abstract

Currently, all clinical trials, including those in rare diseases, that do not demonstrate a statistically significant benefit (i.e., p < 0.05) on the primary end point are classified as ‘negative’. This classification does not take into account a myriad of factors, including whether the trial was sufficiently powered, or had other statistically significant end points, or was terminated before completion, or was even initiated. In this paper, I propose reclassification of these trials into five categories: true negative, underpowered, inadequate, terminated or uninitiated, and justifiable. These categories reflect the trial characteristics more accurately and will be more useful to all stakeholders, especially the patients who participated in the trial and their healthcare providers.