Phase III Failures for a Lack of Efficacy can be, in Significant Part, Recovered (Introducing Success Probability Estimation Quantitatively)


  • Daniele De Martini Università degli Studi di Genova



failure reasons, unexpected failures, ethics, waste, conservative sample size, software for sample size


The rate of phase III trials failures is approximately 42-45%, and most of them are due to a lack of efficacy. Some of the failures for a lack of efficacy are expected, due to type I errors in phase II and type II errors in phase III. However, the rate of these failures is far from saturating the global failure rate due to a lack of efficacy.
In this work, the probability of unexpected failure for a lack of efficacy in phase III trials is estimated to be about 14%, with credibility interval (9%, 18%). These failures can be recovered through an adequate planning/empowering of phase II, and by adopting conservative estimation for the sample size of phase III. The software SP4CT (a free web application available at allows these computations. This 14% rate of unexpected failures gives that every year approximately 270,000 patients uselessly undergo a phase III trial with a large damage in individual ethics; moreover, the unavailability of many effective treatments is a considerable damage for collective ethics. The 14% of unexpected failures also produces more than $11bn of pure waste, and generates a much higher lack of revenue given by drugs’ marketing.






Statistical Methods