title: What are the appropriate methods for analyzing patient-reported outcomes in randomized trials when data are missing?
abstract: Subjective health measurements using Patient Reported Outcomes (PRO) are increasingly used in randomized trials, particularly for patient groups comparisons. Two main types of analytical strategies can be used for such data: Classical Test Theory (CTT) and Item Response Theory models (IRT). These two strategies display very similar characteristics when data are complete, but in the common case when data are missing, whether IRT or CTT would be the most appropriate remains unknown and was investigated using simulations. We simulated PRO data such as quality of life data. Missing responses to items were simulated as being completely random, depending on an observable covariate or on an unobserved latent trait. The considered CTT-based methods allowed comparing scores using complete-case analysis, personal mean imputations or multiple-imputations based on a two-way procedure. The IRT-based method was the Wald test on a Rasch model including a group covariate. The IRT-based method and the multiple-imputations-based method for CTT displayed the highest observed power and were the only unbiased method whatever the kind of missing data. Online software and Stata® modules compatibles with the innate mi impute suite are provided for performing such analyses. Traditional procedures (listwise deletion and personal mean imputations) should be avoided, due to inevitable problems of biases and lack of power.
authors.affiliation: 1 EA 4275, Faculty of Pharmaceutical Sciences, University of Nantes, France.|2 Biostatistics and Methodology Unit, LUNAM Angers, CHU Angers, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Hamel
authors.affiliation: 1 EA 4275, Faculty of Pharmaceutical Sciences, University of Nantes, France.
authors.forename: V
authors.initials: V
authors.lastname: Sebille
authors.affiliation: 1 EA 4275, Faculty of Pharmaceutical Sciences, University of Nantes, France.
authors.forename: T
authors.initials: T
authors.lastname: Le Neel
authors.affiliation: 1 EA 4275, Faculty of Pharmaceutical Sciences, University of Nantes, France.
authors.forename: G
authors.initials: G
authors.lastname: Kubis
authors.affiliation: 3 Unites MPR CHU Reims, Hospital Sebastopol Reims, France.
authors.forename: F C
authors.initials: FC
authors.lastname: Boyer
authors.affiliation: 1 EA 4275, Faculty of Pharmaceutical Sciences, University of Nantes, France.
authors.forename: J B
authors.initials: JB
authors.lastname: Hardouin
mesh_terms: D015982:Bias; D056808:Biostatistics / Q000379:methods; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D016014:Linear Models; D015233:Models, Statistical; D009136:Muscular Dystrophies / Q000503:physiopathology; D010147:Pain Measurement / Q000706:statistics & numerical data; D000071066:Patient Reported Outcome Measures; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*
keywords: Classical test theory; Rasch model; item response theory; missing data; simulations