Background: Randomized trials provide pivotal evidence for evaluation and approval of therapies. Nonetheless, such trials are often plagued by noncompliance, especially in the form of premature discontinuation of treatment. While intent-to-treat (ITT) analysis can provide valid tests of no-effect hypotheses, some trials may make ITT analysis impossible by ceasing follow-up when patients go off assigned treatment. Furthermore, estimates based on ITT, on-treatment, or per-protocol comparisons can seriously understate harm or benefit VSports手机版. .

Purpose: To show how g-estimation based on randomization status is a natural generalization of ITT null testing to estimating efficacy from trials with important discontinuation or noncompliance. V体育安卓版.

Methods: We contrast with an analysis of the effect of a tiotropium inhaler on the occurrence of chronic obstructive pulmonary disease (COPD) events in a six-month double-blind placebo-controlled trial of 1829 patients with good but imperfect compliance V体育ios版. .

Results: The covariate-adjusted point estimates, 95% confidence limits (CL), and null P-values comparing expected COPD event times in placebo versus tiotropium patients were: ITT, 1. 21, CL = 1. 02, 1. 43, P = 0 VSports最新版本. 027; on-treatment, 1. 27, CL = 1. 06, 1. 52, P = 0. 009; per-protocol, 1. 36, CL = 1. 13, 1. 63, P = 0. 001; and g-estimation, 1. 31, CL = 1. 03,1. 72, P = 0. 027. Thus g-estimation preserved the ITT test of the null, but exhibited more uncertainty about the size of the tiotropium effect than the other methods. In particular, it allowed for a much larger potential effect than did ITT analysis, but produced a much larger null P than exhibited by per-protocol analysis. .

Limitations: Like ITT analysis, g-estimation requires all patients be followed to the end of the trial protocol, regardless of whether they comply with the protocol V体育平台登录. Like on-treatment and per-protocol analyses, it also requires accurate compliance information be recorded. .

Conclusion: G-estimation should become a standard procedure for the analysis of trials with noncompliance. Software to do so is available in major packages, and the procedure is easily coded for other packages. VSports注册入口.