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Abstract
The Effect of "Strength of Evidence" Requirements and HIV Incidence on the Size of Phase III trials for Microbicides
Coplan P.1, Rosenberg Z.1
Introduction: The US FDA has stated that a single pivotal efficacy trial may suffice for licensure of microbicides under certain conditions if the “strength of evidence” of efficacy is p<0.005. Alternatively, two trials need to be done with the strength of evidence of efficacy for each trial of p<0.05. Microbicide sponsors may therefore conduct one large pivotal trial or two smaller efficacy trials. We assess the impact of the strength of evidence requirements and HIV incidence on the size of Phase III trials.
Methods: Sample size was calculated for a randomized placebo-controlled trial with 1:1 randomization and 90% power for a 1-yr long study, assuming 20% drop-out rate and 50% intent-to-treat efficacy (per protocol efficacy may be higher once incomplete adherence is accounted for) using Stata Version 8.
Results: Required sample size for the whole trial is shown below:
The ratio of sample size for p<0.05 versus p<0.005 was 0.64 for all incidences. The sample size decreased by ½ from 1% to 2% HIV incidence, by 1/3 from 2% to 3%, by 1/4 from 3 to 4%, and by 1/5 from 4% to 5%. Trials with 3 or 4 arms would be proportionally larger.
Conclusions: The sample size required for one pivotal efficacy trial is 22% smaller than two Phase III trials. Changes in HIV incidence have a large effect on sample size between 1 to 3% and relatively smaller effects above 4%.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
WePe6.3C02
Suggested Citation
"CoplanP., et al.
The Effect of "Strength of Evidence" Requirements and HIV Incidence on the Size of Phase III trials for Microbicides.
Poster Exhibition:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
WePe6.3C02"
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