Clinical Trials

❘❙❚■ Chapter 22 | Intention-to-Treat Analysis• From a statistical point of view, an ITT analysis aims to preserve thestrengths of randomization [1,2], ie, to minimize bias. An ITT analysisassumes that the rates of noncompliance or withdrawal are equal in bothgroups. If bias is introduced into such a model, an ITT analysis is morelikely to identify this bias. For example, if a large number of subjectswithdraw from the new treatment arm compared with the standardtreatment arm, the trial will either show no difference in outcomes (sincethese subjects might switch to standard treatment) or, if the withdrawingsubjects take no treatment until the end of the study, may show improvedoutcomes in the standard treatment arm.• An ITT analysis captures what happens in real-life more closely thanthe method that uses data only from subjects with perfect compliance,making it a particularly relevant method for treatments that are difficultto tolerate (ie, drugs with lots of side-effects, such as chemotherapeutics).• An ITT analysis uses the information from all the subjects in a trial at anygiven time point in the study, which enables an interim analysis to beperformed, while the PP method is best applied when the study is overand all noncompliant patients can be identified and excluded.• ITT analysis provides practical information on the administration of atreatment. If, for example, subjects are allocated to a surgical treatmentfor coronary artery disease instead of a less invasive percutaneouscoronary intervention and these subjects have to wait 3 months beforesurgery, during which time some die, an ITT analysis would correctlyassign this mortality rate (possibly due to the delay in surgery) to thesurgical group, rather than excluding these data as a PP analysis might do.Therefore, an ITT analysis gives a pragmatic estimate of the effect of a treatmentstrategy rather than just the specific efficacy of the treatment itself, as given by thePP method [4,5].What are the limitations of the ITT method?The main limitation of an ITT analysis is that it includes data from both compliantand noncompliant subjects, and also those who might switch treatment groupsunexpectedly during the study. It does not aim to determine the maximumpotential effectiveness of a treatment as a PP method would [1,2,4,5]. Therefore,in some studies, the ITT method might not show a statistically significant benefit,or might show the benefit to be smaller than that generated by a PP analysis [2].Consequently, a routine ITT analysis might find an efficacious treatment to be nomore effective than placebo.258