When PACE-Gate Meets Sample Size, 2025, Sepúlveda

[forestglip]

When PACE-Gate Meets Sample Size

Nuno Sepúlveda

[Conference paper]

Abstract
PACE-Gate is the name by which the case surrounding the high-profile PACE clinical trial became publicly known. This case ended up in controversy due to a change in the pre-trial primary endpoint and a re-definition of the treatments' efficacy.

The present paper concerns a different angle of the case: the statistical argumentation of the reported sample size calculations. The analysis of the per-trial research protocol and the post-trial statistical analysis plan revealed inconsistencies between the theoretical assumptions underpinning the sample size calculations and the prior beliefs of the trial's research team. The reported sample sizes also seemed inaccurate for not accounting for multiple pairwise comparisons contemplated in the trial's objectives.

In conclusion, the statistical argumentation of the trial sample size is suboptimal. The question is whether PACE is either an exception or the norm with respect to incongruous sample size determination.

Link (New Frontiers in Statistics and Data Science) [Paywall]

Most pages are available to read on Google Books.

 

[Nightsong]

This study identified four problems in the sample size calculations of the PACE trial. First, the trial protocol did not report the name of the test that supported these calculations. Second, the prior beliefs about the treatment efficacies suggested the use of one-sided tests rather than two-sided tests.

Three, the sample size calculations did not account for multiple treatment comparisons included in the trial’s objectives. Four, concerning the losses-to-follow, there was an inconsistency between the MCAR assumption used in the sample size calculations and the MNAR mechanism that the authors acknowledged to be more appropriate for the statistical analysis. In conclusion, the reported sample size calculations were suboptimal.

...

To conclude, the pre-trial research protocol includes the following statement at the end (Ref. [7], p. 18):

This paper should not be used as the protocol for executing the study, and is not the complete protocol considered to be ethically satisfactory by the relevant MREC [Multi- centre Research Ethics Committee], having been subject to shortening and revision to enhance communication for publication.

The above statement is somehow a safeguard for the authors to modify the trial protocol according to their will. It is again reasonable to ask about the intrinsic value of a pre-trial research protocol. It is worth remembering that the decision of making trial registration mandatory and accessible to the public was exactly motivated by recurrent episodes of selective reporting, especially, the clinical trials with the potential to reach mainstream clinical practice

 

[rvallee]

The above statement is somehow a safeguard for the authors to modify the trial protocol according to their will. It is again reasonable to ask about the intrinsic value of a pre-trial research protocol

And especially notable that this is the reason, pre-registering their protocol, Horton gave for fast-tracking publication. Which is a special kind of con: technically they did pre-register it, they just didn't do what they pre-registered.