Global sensitivity analysis of clinical trials with missing patient-reported outcomes

Stat Methods Med Res. 2019 May;28(5):1439-1456. doi: 10.1177/0962280218759565. Epub 2018 Mar 20.

Abstract

Randomized trials with patient-reported outcomes are commonly plagued by missing data. The analysis of such trials relies on untestable assumptions about the missing data mechanism. To address this issue, it has been recommended that the sensitivity of the trial results to assumptions should be a mandatory reporting requirement. In this paper, we discuss a recently developed methodology (Scharfstein et al., Biometrics, 2018) for conducting sensitivity analysis of randomized trials in which outcomes are scheduled to be measured at fixed points in time after randomization and some subjects prematurely withdraw from study participation. The methodology is explicated in the context of a placebo-controlled randomized trial designed to evaluate a treatment for bipolar disorder. We present a comprehensive data analysis and a simulation study to evaluate the performance of the method. A software package entitled SAMON (R and SAS versions) that implements our methods is available at www.missingdatamatters.org .

Keywords: Corrected estimator; exponential tilting; identifiability; missing not at random; plug-in estimator; smoothing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antidepressive Agents / administration & dosage
  • Bipolar Disorder / drug therapy
  • Data Interpretation, Statistical*
  • Humans
  • Patient Reported Outcome Measures*
  • Quetiapine Fumarate / administration & dosage
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Research Design
  • Software

Substances

  • Antidepressive Agents
  • Quetiapine Fumarate