Intention-to-treat analyses and missing data approaches in pharmacotherapy trials for alcohol use disorders
A C Del Re, Natalya C Maisel, Janet C Blodgett, John W Finney, A C Del Re, Natalya C Maisel, Janet C Blodgett, John W Finney
Abstract
Objectives: Intention to treat (ITT) is an analytic strategy for reducing potential bias in treatment effects arising from missing data in randomised controlled trials (RCTs). Currently, no universally accepted definition of ITT exists, although many researchers consider it to require either no attrition or a strategy to handle missing data. Using the reports of a large pool of RCTs, we examined discrepancies between the types of analyses that alcohol pharmacotherapy researchers stated they used versus those they actually used. We also examined the linkage between analytic strategy (ie, ITT or not) and how missing data on outcomes were handled (if at all), and whether data analytic and missing data strategies have changed over time.
Design: Descriptive statistics were generated for reported and actual data analytic strategy and for missing data strategy. In addition, generalised linear models determined changes over time in the use of ITT analyses and missing data strategies.
Participants: 165 RCTs of pharmacotherapy for alcohol use disorders.
Results: Of the 165 studies, 74 reported using an ITT strategy. However, less than 40% of the studies actually conducted ITT according to the rigorous definition above. Whereas no change in the use of ITT analyses over time was found, censored (last follow-up completed) and imputed missing data strategies have increased over time, while analyses of data only for the sample actually followed have decreased.
Conclusions: Discrepancies in reporting versus actually conducting ITT analyses were found in this body of RCTs. Lack of clarity regarding the missing data strategy used was common. Consensus on a definition of ITT is important for an adequate understanding of research findings. Clearer reporting standards for analyses and the handling of missing data in pharmacotherapy trials and other intervention studies are needed.
Keywords: Clinical Pharmacology; Statistics & Research Methods.
References
- Gupta SK. Intention-to-treat concept: a review. Perspect Clin Res 2011;2:109–12
- Hollis S, Campbell F. What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ 1999;319:670–4
- Little RJ, Rubin DB. Statistical analysis with missing data. Wiley New York, 1987
- Ruiz-Canela M, Martínez-González MA, de Irala-Estévez J. Intention to treat analysis is related to methodological quality. BMJ 2000;320:1007.
- Moher D, Schulz K, Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. BMC Med Res Methodol 2001;1:2.
- Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Int J Surg. Published Online First: 2011. (accessed 6 Mar 2013).
- Zwarenstein M, Treweek S, Gagnier JJ, et al. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ. Published Online First: 2008. (accessed 6 Mar 2013).
- Polit DF, Gillespie BM. Intention-to-treat in randomized controlled trials: recommendations for a total trial strategy. Res Nurs Health 2010;33:355–68
- Schulz KF, Grimes DA. Sample size slippages in randomised trials: exclusions and the lost and wayward. Lancet 2002;359:781–5
- Avins AL, Pressman A, Ackerson L, et al. Placebo adherence and its association with morbidity and mortality in the studies of left ventricular dysfunction. J Gen Intern Med 2010;25:1275–81
- Granger AL, Fehnel SE, Hogue SL, et al. An assessment of patient preference and adherence to treatment with Wellbutrin SR: a web-based survey. J Affect Disord 2006;90:217–21
- Schwartz D, Lellouch J. Explanatory and pragmatic attitudes in therapeutical trials. J Clin Epidemiol 2009;62:499–505
- Maisel NC, Blodgett JC, Wilbourne PL, et al. Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? Addiction 2013;108:275–93
Source: PubMed