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Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial
Yumi Kubo1, Lulu Ren Sterling1, Patrick S Parfrey2
1Amgen, Inc., Thousand Oaks, CA, USA.
Pharmaceutical Statistics
|April 9, 2015
Summary
Intention-to-treat (ITT) analysis may underestimate cinacalcet
Area of Science:
- Cardiovascular Medicine
- Clinical Trials Methodology
- Nephrology
Background:
- Intention-to-treat (ITT) analysis is standard for randomized clinical trials.
- Non-adherence in long-term studies can underestimate treatment effects.
- The EVOLVE trial investigated cinacalcet for cardiovascular events in hemodialysis patients.
Purpose of the Study:
- To assess the on-treatment effect of cinacalcet.
- To evaluate the impact of non-adherence on efficacy estimates.
- To compare ITT analysis with sensitivity analyses for cinacalcet's cardiovascular outcomes.
Main Methods:
- EVOLVE trial: double-blind, placebo-controlled, event-driven study.
- Pre-specified sensitivity analyses for non-adherence: lag-censoring, IPCW, RPSFTM, IPE.
- Comparison of relative hazards for mortality and major cardiovascular events.
Main Results:
- ITT analysis showed a relative hazard of 0.93 (0.85, 1.02).
- Sensitivity analyses suggested a stronger effect: lag-censoring (0.85), IPCW (0.81), RPSFTM (0.85), IPE (0.85).
- These results indicate a potential on-treatment effect of cinacalcet.
Conclusions:
- ITT analysis is standard but may underestimate effects with significant non-adherence.
- Sensitivity analyses suggest cinacalcet may reduce risks during treatment.
- Consider additional analyses to assess on-treatment effects in trials with non-adherence.
Keywords:
intention-to-treatinverse probability of censoring weightsiterative parameter estimationlag-censoringnon-adherencerank preserving structural failure time modelMore Related Videos
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