Handling informative dropout in longitudinal analysis of health-related quality of life: application of three approaches to data from the esophageal cancer clinical trial PRODIGE 5/ACCORD 17

B. Cuer (1, 2) , C. Mollevi (2) , A. Anota (3, 4, 5) , E. Charton (6, 3, 4) , B. Juzyna (7) , T. Conroy (8) , Célia Touraine (1)

1 ICM - UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle
2 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
3 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
4 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
5 UBFC - Université Bourgogne Franche-Comté [COMUE]
6 Centre Léon Bérard [Lyon]
7 UNICANCER [Paris]
8 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]

Background: Health-related quality of life (HRQoL) has become a major endpoint to assess the clinical benefit of new therapeutic strategies in oncology clinical trials. Typically, HRQoL outcomes are analyzed using linear mixed models (LMMs). However, longitudinal analysis of HRQoL in the presence of missing data remains complex and unstandardized. Our objective was to compare the modeling alternatives that account for informative dropout. Methods: We investigated three alternative methods—the selection model (SM), pattern-mixture model (PMM), and shared-parameters model (SPM)—in relation to the LMM. We first compared them on the basis of methodological arguments highlighting their advantages and drawbacks. Then, we applied them to data from a randomized clinical trial that included 267 patients with advanced esophageal cancer for the analysis of four HRQoL dimensions evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. Results: We highlighted differences in terms of outputs, interpretation, and underlying modeling assumptions; this methodological comparison could guide the choice of method according to the context. In the application, none of the four models detected a significant difference between the two treatment arms. The estimated effect of time on HRQoL varied according to the method: for all analyzed dimensions, the PMM estimated an effect that contrasted with those estimated by the SM and SPM; the LMM estimated effects were confirmed by the SM (on two of four HRQoL dimensions) and SPM (on three of four HRQoL dimensions). Conclusions: The PMM, SM, or SPM should be used to confirm or invalidate the results of LMM analysis when informative dropout is suspected. Of these three alternative methods, the SPM appears to be the most interesting from both theoretical and practical viewpoints. Trial registration This study is registered with ClinicalTrials.gov , number NCT00861094 .

Mots clés: Pattern-mixture model; Selection model; Shared-parameters model; Joint modeling; Health-related quality of life; Informative dropout; Cancer clinical trial

Domaines: Méthodologie [stat.ME]; Cancer; Hépatologie et Gastroentérologie; Santé publique et épidémiologie

B. Cuer, C. Mollevi, A. Anota, E. Charton, B. Juzyna, et al.. Handling informative dropout in longitudinal analysis of health-related quality of life: application of three approaches to data from the esophageal cancer clinical trial PRODIGE 5/ACCORD 17. BMC Medical Research Methodology, 2020, 20 (1), pp.223. ⟨10.1186/s12874-020-01104-w⟩. ⟨hal-03696198⟩