Abstract
Randomized trials with dropouts or censored data and discrete time-to-event type outcomes are frequently analyzed using the Kaplan-Meier or product limit (PL) estimation method. However, the PL method assumes that the censoring mechanism is noninformative and when this assumption is violated, the inferences may not be valid. We propose an expanded PL method using a Bayesian framework to incorporate informative censoring mechanism and perform sensitivity analysis on estimates of the cumulative incidence curves. The expanded method uses a model, which can be viewed as a pattern mixture model, where odds for having an event during the follow-up interval $$({t}_{k-1},{t}_{k}]$$, conditional on being at risk at $${t}_{k-1}$$, differ across the patterns of missing data. The sensitivity parameters relate the odds of an event, between subjects from a missing-data pattern with the observed subjects for each interval. The large number of the sensitivity parameters is reduced by considering them as random and assumed to follow a log-normal distribution with prespecified mean and variance. Then we vary the mean and variance to explore sensitivity of inferences. The missing at random (MAR) mechanism is a special case of the expanded model, thus allowing exploration of the sensitivity to inferences as departures from the inferences under the MAR assumption. The proposed approach is applied to data from the TRial Of Preventing HYpertension.
MeSH Terms
Bayes Theorem
Biostatistics
Humans
Hypertension/prevention & control
Models, Statistical
Prehypertension/drug therapy
Randomized Controlled Trials as Topic/statistics & numerical data
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kaciroti Niko A
Department of Biostatistics, Center for Human Growth and Development, University of Michigan, Ann Arbor, MI 48109, USA.
[email protected].
Raghunathan Trivellore E
Taylor Jeremy M G
Julius Stevo
References (11)
11 references, click to expand
-
On the performance of random-coefficient pattern-mixture models for non-ignorable drop-out.
Stat Med. 2003 Aug 30;22(16):2553-75
PMID: 12898544
-
Reparameterizing the pattern mixture model for sensitivity analyses under informative dropout.
Biometrics. 2000 Dec;56(4):1241-8
PMID: 11129486
-
A Bayesian sensitivity model for intention-to-treat analysis on binary outcomes with dropouts.
Stat Med. 2009 Feb 15;28(4):572-85
PMID: 19072769
-
Incorporating prior beliefs about selection bias into the analysis of randomized trials with missing outcomes.
Biostatistics. 2003 Oct;4(4):495-512
PMID: 14557107
-
Methods for conducting sensitivity analysis of trials with potentially nonignorable competing causes of censoring.
Biometrics. 2001 Mar;57(1):103-13
PMID: 11252584
-
Feasibility of treating prehypertension with an angiotensin-receptor blocker.
N Engl J Med. 2006 Apr 20;354(16):1685-97
PMID: 16537662
-
A general class of pattern mixture models for nonignorable dropout with many possible dropout times.
Biometrics. 2008 Jun;64(2):538-45
PMID: 17900312
-
Inference in randomized studies with informative censoring and discrete time-to-event endpoints.
Biometrics. 2001 Jun;57(2):404-13
PMID: 11414563
-
TROPHY study: Outcomes based on the Seventh Report of the Joint National Committee on Hypertension definition of hypertension.
J Am Soc Hypertens. 2008 Jan-Feb;2(1):39-43
PMID: 20409883
-
A Bayesian model for longitudinal count data with non-ignorable dropout.
J R Stat Soc Ser C Appl Stat. 2008 Dec 1;57(5):521-534
PMID: 21072316
-
An index of local sensitivity to nonignorable drop-out in longitudinal modelling.
Stat Med. 2005 Jul 30;24(14):2129-50
PMID: 15909292