Definitions of intention-to-treat in the face of missing outcome data: A systematic survey of methodology papers

Article type
Authors
Alshurafa M1, Guyatt G1, Akl E2, Haines T1, Gentles S1, Rios L1, Tran C3, Lamontagne F4, Moayyedi P5, Walter S1, Briel M6
1Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada
2Departments of Medicine and Family Medicine, State University of New York at Buffalo, Buffalo, USA
3Chau Tran Consulting, Toronto, Canada
4Centre de recherche clinique’Etienne-Le Bel, Universit’e de Sherbrooke, Sherbrooke, Canada
5Department of Medicine, McMaster University, Hamilton, Canada
6Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland
Abstract
Background: Intention-to-treat (ITT) has been established as a quality label for randomized clinical trials. However, surveys of randomized trials showed that trialists hold a variety of views on the relationship between missing outcome data (MOD) and ITT and how MOD should be handled under ITT.

Objectives: We surveyed articles addressing the methodology of ITT in relation to MOD.

Methods: We systematically searched MEDLINE up to December 2008 for methodological articles written in English that devoted at least one paragraph to ITT and two other paragraphs to either ITT or MOD/loss to follow-up. We excluded original trial reports, observational studies, or clinical systematic reviews. Working in teams of two, we independently extracted relevant information from each eligible article. Discrepancies between data extractors were resolved by consensus or by third party arbitration if necessary.

Results: Of 1007 titles and abstracts reviewed, 66 articles met our eligibility criteria. Five (8%) did not provide a definition of ITT; 25 (41%) mentioned MOD but did not discuss its relationship with ITT; and 36 (59%) discussed the relationship of MOD with ITT. These 36 articles described one or more of three distinct relationships: full-follow-up is required for ITT (58%); ITT and MOD are separate issues (17%); and ITT requires a specific strategy for handling MOD (78%); 17 (47%) described more than one relationship. The most frequently mentioned strategies for handling MOD were using the last outcome carried forward (50%), sensitivity analysis (50%), and use of available data to impute missing data (46%). Most articles (81%) specifically excluded complete case analysis under ITT.

Conclusions: We found that there is no consensus on the definition of ITT in relation to MOD. For conceptual clarity, we suggest considering deviations from randomization separately from issues of MOD when reporting randomized trials.