A Cost/Benefit Analysis of Clinical Trial Designs for COVID-19 Vaccine Candidates

I am very happy to see this new and urgently needed study.  They have heeded the stricture to show their work.  The authors are Donald A. Berry, Scott Berry, Peter Hale, Leah Isakov, Andrew W. Lo, Kien Wei Siah, and Chi Heem Wong, and here is the abstract:

We compare and contrast the expected duration and number of infections and deaths averted among several designs for clinical trials of COVID-19 vaccine candidates, including traditional randomized clinical trials and adaptive and human challenge trials. Using epidemiological models calibrated to the current pandemic, we simulate the time course of each clinical trial design for 504 unique combinations of parameters, allowing us to determine which trial design is most effective for a given scenario. A human challenge trial provides maximal net benefits—averting an additional 1.1M infections and 8,000 deaths in the U.S. compared to the next best clinical trial design—if its set-up time is short or the pandemic spreads slowly. In most of the other cases, an adaptive trial provides greater net benefits.

And what is an adapted trial you may be wondering?:

An adaptive version of the traditional vaccine efficacy RCT design (ARCT) is based on group sequential methods. Instead of a fixed study duration with a single final analysis at the end, we allow for early stopping for efficacy via periodic interim analyses of accumulating trial data…While this reduces the expected duration of the trial, we note that adaptive trials typically require more complex study protocols which can be operationally challenging to implement for test sites unfamiliar with this framework. In our simulations, we assume a maximum of six interim analyses spaced 30 days apart, with the first analysis performed when the first 10,000 subjects have been monitored for at least 30 days.

That means of course you might cut the trial short.  Kudos to the authors for producing one of the most important papers of this year.



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