The intention-to-treat approach in randomized controlled trials: Are authors saying what they do and doing what they say?

Abstract

Background Intention-to-treat (ITT) is an approach to the analysis of randomized controlled trials (RCT) in which patients are analyzed as randomized regardless of the treatment actually received.

Purpose To ascertain the proportion of RCT reporting the use of intention-to-treat and the accuracy of that report and to examine the distribution and analysis of missing data for the studies reporting an ITT analysis.

Method We conducted a cross-sectional literature review of RCTs reported in 10 medical journals in 2002. All articles were assessed using a standardized form. Two evaluators independently reviewed a 10% sample of articles to assess reliability. Subsequently, one evaluator reviewed the remaining articles. The proportion of articles reporting the use of ITT was calculated. Among these, the proportion of articles that `analyzed patients as randomized' and the proportion and analysis of missing data were evaluated using standardized definitions.

Results Of the 403 articles, 249 (62%) reported the use of ITT. Among these, available patients were clearly analyzed as randomized in 192 (77%). Authors used a modified ITT in 23 (9%); clearly violated a major component of ITT in 17 (7%), and the approach used was unclear in 17 (7%). More than 60% of articles had missing data in their primary analysis. Few articles reported a strategy for missing data. The main reason for missing data was loss to follow-up.

Limitations A single evaluator evaluated most articles, but the high concordance obtained during the inter-rater evaluation suggests that the assessments were consistent. In addition, the small spectrum of journals limits generalizability. Finally, there could be a difference between what was reported and what was performed.

Conclusions This study emphasizes that authors use the label `intention-to-treat' quite differently. The most common use refers to the analysis of all available subjects as randomized regardless of the missing data aspect. Clinical Trials 2007; 4: 350—356. http://ctj.sagepub.com

Get full access to this article

View all access options for this article.

References

Junker CA Adherence to published standards of reporting: a comparison of placebo-controlled trials published in English or German. JAMA 1998; 280: 247—49.

Adetugbo K. , Williams H. How well are randomized controlled trials reported in the dermatology literature? . Arch Dermatol 2000; 136: 381—85.

Thornley B. , Adams C. Content and quality of 2000 controlled trials in schizophrenia over 50 years . BMJ 1998; 317: 1181—84.

Hotopf M. , Lewis G. , Normand C. Putting trials on trial— the costs and consequences of small trials in depression: a systematic review of methodology. J Epidemiol Community Health 1997; 51: 354—58.

Dickinson K. , Bunn F. , Wentz R. , Edwards P. , Roberts I. Size and quality of randomized controlled trials in head injury: review of published studies. BMJ 2000; 320: 1308—11.

Ruiz-Canela M. , Martinez-Gonzalez MA , Irala-Estevez J. Intention to treat analysis is related to methodological quality. BMJ 2000; 320: 1007—008.

DerSimonian R. , Charette LJ , McPeek B. , Mosteller F. Reporting on methods in clinical trials. N Engl J Med 1982; 306: 1332—37.

Altman DG Better reporting of randomized controlled trials: the CONSORT statement. BMJ 1996; 313: 570—71.

Begg C. , Cho M. , Eastwood S. et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA 1996; 276: 637—39.

10.

Huston P. , Hoey J. CMAJ endorses the CONSORT statement. CONsolidation of standards for reporting trials. CMAJ 1996; 155: 1277—82.

11.

Rennie D. How to report randomized controlled trials. The CONSORT statement. JAMA 1996; 276: 649.

12.

Altman DG , Schulz KF , Moher D. et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 2001; 134: 663—94.

13.

Moher D. , Schulz KF , Altman DG The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Lancet 2001; 357: 1191—94.

14.

Moher D. , Schulz KF , Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA 2001; 285: 1987—91.

15.

Moher D. , Schulz KF , Altman DG The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Ann Intern Med 2001; 134: 657—62.

16.

Shapiro S. The revised CONSORT statement: honing the cutting edge of the randomized controlled trial. CMAJ 2001; 164: 1157—58.

17.

Bradford HA Principles of Medical Statistics, 1961.

18.

Last JM A Dictionary of Epidemiology. 4th ed. New York, Oxford University Press, 2001.

19.

Newell DJ Intention-to-treat analysis: implications for quantitative and qualitative research. Int J Epidemiol 1992; 21: 837—41.

20.

Hollis S. , Campbell F. What is meant by intention to treat analysis? Survey of published randomized controlled trials. BMJ 1999; 319: 670—74.

21.

Cochrane collaboration. Cochrane controlled trials register. http://www.ovid.com/site/products/ovidguide/cctrdb.htm. 2002.

22.

Cohen J. A coefficient of agreement for nominal scales. Educational and Psych Meas 1960; 20: 37—46.

23.

Shrout PE , Fleiss JL Intraclass correlations: uses in assessing rater reliability. Psychological Bulletin 1979; 2: 420—28.

24.

Bravo G. , Potvin L. Estimating the reliability of continuous measures with Cronbach's alpha or the intraclass correlation coefficient: toward the integration of two traditions . J Clin Epidemiol 1991; 44: 381—90.

25.

Muller R. , Buttner P. A critical discussion of intraclass correlation coefficients. Stat Med 1994; 13: 2465—76.

26.

Landis JR , Koch GG The measurement of observer agreement for categorical data. Biometrics 1977; 33: 159—74.

27.

Kruse RL , Alper BS , Reust C. et al. Intention-to-treat analysis: who is in? Who is out?. J Fam Pract 2002; 51: 969—71.

28.

Mora-Duarte J. , Betts R. , Rotstein C. et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Eng J Med 2002 ; 347: 2020—29.

29.

Engels JM , Diehr P. Imputation of missing longitudinal data: a comparison of methods. J Clin Epidemiol 2003; 56: 968—76.

30.

Revicki DA , Gold K. , Buckman D. et al. Imputing physical health status scores missing owing to mortality: results of a simulation comparing multiple techniques. Med Care 2001; 39: 61—71.

31.

Streiner DL The case of the missing data: methods of dealing with dropouts and other research vagaries. Can J Psychiatry 2002; 47: 68—75.

32.

Peto R. , Pike MC , Armitage P. et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer 1976; 34: 585—612.

33.

Sackett DL , Gent M. Controversy in counting and attributing events in clinical trials. N Engl J Med 1979; 301: 1410—12.

34.

Fergusson D. , Aaron S. , Guyatt G. , Hérbert P. Postrandomisation exclusions: the intention to treat principle and excluding patients from analysis. BMJ 2002; 325: 652—654.

35.

Peduzzi P. , Detre K. , Wittes J. , Holford T. Intent-to-treat analysis and the problem of crossovers. An example from the Veterans Administration coronary bypass surgery study. J Thorac Cardiovasc Surg 1991; 101: 481—87.

36.

Peduzzi P. , Wittes J. , Detre K. , Holford T. Analysis as-randomized and the problem of non-adherence: an example from the Veterans Affairs Randomized Trial of Coronary Artery Bypass Surgery. Stat Med 1993; 12: 1185—95.

37.

Farwell JR , Lee YJ , Hirtz DG et al. Phenobarbital for febrile seizures—effects on intelligence and on seizure recurrence. N Engl J Med 1990 ; 322: 364—9.