The U.S. Food and Drug Administration (FDA) issued a draft guidance suggesting the agency adopt an International Council for Harmonization (ICH) to a 1998 clinical trials statistics guideline. The original ICH guideline (ICH E9) focused on the use of sensitivity analyses and targets for trial estimation and measurement, ACRP reports.
The draft guidance, entitled “E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials” presents a “structured framework to link trial objectives to a suitable trial design and tools for estimation and hypothesis testing.”1 Clarifying trial objectives and accounting explicitly for intercurrent events when describing the treatment effect of interest at the planning stage should inform choices about trial design, data collection, and statistical analyses.
ICH states that “it remains undisputed that randomization is a cornerstone of controlled clinical trials and that analyses should aim at exploiting the advantages of randomization to the greatest extent possible…However, the question remains whether understanding the effect of a treatment policy always targets the treatment effect of greatest relevance to regulatory and clinical decision making.”1
The draft guidance also suggests that clinical trial sponsors demonstrate their rationale for any uncollected data when conducting analyses of results. Additionally, FDA recommends avoiding “a bevy of simultaneous changes to a study” when conducting a sensitivity analysis and instead wants trial practitioners to “investigate any impact one change at a time.”2
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