Primary Outcome in Clinical Trials and Clinical Significance
- Pocock SJ, Stone GW.
- The Changing Face of Clinical Trials: The Primary Outcome Is Positive — Is That Good Enough? N Engl J Med 2016;375:971-979.
The following are key points to remember from this review about findings of a clinical trial when the primary outcome is positive:
- The achievement of statistical significance for the primary outcome is typically a necessary prerequisite for the adoption of a new therapy, but it is not sufficient.
- The totality of trial results will be scrutinized by numerous stakeholders, including regulators, payers, journal editors and reviewers, clinical experts, guidelines committees, physicians, patients, and critics.
- The determination of whether the findings provide evidence that is sufficient to modify medical practice requires in-depth interpretation of the trial data and the results of earlier, related trials.
- Answering the key questions listed below may help to identify which “positive” trials provide evidence that is sufficient to advance clinical practice.
- Does a p value of <0.05 provide strong enough evidence?
- What is the magnitude of the treatment benefit?
- Is the primary outcome clinically important (and internally consistent)?
- Are secondary outcomes supportive?
- Are the principal findings consistent across important subgroups?
- Is the trial large enough to be convincing?
- Was the trial stopped early?
- Do concerns about safety counterbalance positive efficacy?
- Is the efficacy–safety balance patient-specific?
- Are there flaws in trial design and conduct?
- Do the findings apply to my patients?
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