Clinical Trials

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❘❙❚■ Chapter 22 | Intention-to-Treat AnalysisHow should the ITT strategy be implemented in clinical trials?An ITT strategy should be considered to be both a method of analysis and a wayof conducting an entire research study, including trial design [6,7]. When designinga trial, it should be specified whether the study aim is pragmatic (to determinethe practical impact of a treatment strategy in a trial setting) or explanatory(using a trial to determine the maximal effectiveness of a treatment strategy).For pragmatic trials the ITT method is optimal, while for an explanatory triala combination of PP and ITT methods will provide insights. The distinctionbetween these methods is relevant only when a significant number of subjectswithdraw, have missing data, or are noncompliant. If these aspects are minimalthen the results of both the ITT and PP analyses are likely to be similar.In addition, more complex statistical methods beyond ITT can be explored to takeinto account the issue of noncompliers or crossovers. It might also be possible todetermine factors that influence compliance, such as genetics. For example,tamoxifen – a treatment for breast cancer – is targeted at subjects in whom aparticular type of receptor is present, and some asthma therapies work better insubjects who are also susceptible to hay fever.What considerations are there when reporting trial results?When reporting a trial, it should be stated that an ITT strategy has been used toconduct the trial and compile the results. The handling of missing values,noncompliant subjects, and those deviating from the treatment allocated to themat randomization should be clearly described. Lastly, while the main conclusionsof the study should be drawn from the results of the ITT analysis, supplementalresults using other strategies, such as the PP method, can be shown in addition.ConclusionThe ITT approach is used to provide an unbiased assessment of a treatmentstrategy and is usually the optimal method for analyzing the results of a trial.In essence, the ITT method provides the basis for designing, conducting, andreporting an entire clinical trial and comparing treatment strategies. It accountsfor treatment effects, difficulties in administering the drug, and complianceissues. Meanwhile, a PP analysis evaluates the maximum benefit possible from atreatment, given perfect compliance. When noncompliance is considerable, theresults of both ITT and PP analyses might be unreliable and other statisticalmethods should be explored.262
<strong>Clinical</strong> <strong>Trials</strong>: A Practical Guide ■❚❙❘References1. Ellenberg JH. Intention-to-treat analysis versus as-treated analysis. Drug Inf J 1996;30:535–44.2. Senn S. Intention to treat. Section 11. In: Statistical Issues in Drug Development.Chichester: John Wiley and Sons, 1997:153–60.3. Chappell LC, Seed PT, Briley AL, et al. Effect of antioxidants on the occurrence of preeclampsiain women at increased risk: a randomised trial. Lancet 1999;354:810–16.4. Goetghebeur EJT, Pocock SJ. Statistical issues in allowing for noncompliance and withdrawal.Drug Inf J 1993;27:837–45.5. Sommer A, Zeger SL. On estimating efficacy from clinical trials. Stat Med 1991;10:45–52.6. Hollis S, Campbell F. What is meant by intention to treat analysis? Survey of publishedrandomized controlled trials. BMJ 1999;319:670–4.7. Lewis JA, Machin A. Intention to treat—who should use ITT? Br J Cancer 1993;68:647–50.263
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❘❙❚■ ContributorsStephen L
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Clinical Trials: A Practical Guide
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Clinical Trials

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