Intention to treat analysis
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Overview
In epidemiology, an intention to treat (ITT) analysis is an analysis based on the initial treatment intent, not on the treatment eventually administered. The ITT analysis includes all patients randomized to a therapy irrespective of protocol deviations, discontinuation of study drug, drug administration errors, cross-over to another strategy, or withdrawal from the study by the subject. For example, in a trial comparing medical therapy to angioplasty for coronary artery disease, those patients who were initially randomized to medical therapy but who crossed-over to receive an angioplasty instead due to a failure of medical therapy are analyzed as part of the medical therapy cohort. This form of analysis differs significantly from a per protocol (PP) analysis in which only those subjects are included who actually received study drug as specified in the study protocol.
Philosophy of an ITT Analysis
In a way, an ITT analysis tests a strategy of administering the therapy, rather than the therapy itself. It is based on the assumption that, as in real life, sometimes patients cannot all tolerate the initial treatment, they may stop the initial treatment, there may be errors in administering the initial treatment or they may switch to another treatment despite the initial treatment. For the purposes of analysis, the reasons why the patient did not receive the treatment are ignored.
Rationale
Randomization of subjects at the beginning of a trial assures that any imbalances in risk factors, demographics and confounders will be minimized. An ITT analysis preserves that initial randomization, and avoids the effects of crossover and drop-out, which may break the randomization to the treatment groups in a study. Patients who discontinue study drug therapy may do so due to side effects or a perceived lack of effectiveness. As a result, the remaining population is enriched with those patients who could tolerate the drug or perhaps had their symptoms improved on the treatment. Simply put, this remaining "per protocol" cohort harvests out those subjects who were "success stories", and eliminates those patients who failed. An ITT analysis is a more conservative form of analysis because it incorporates patients who failed therapy, could not take therap and who may have crossed over to other therapies. A per protocol analysis of those patients who successfully followed the protocol may overestimate the efficacy of a treatment.
In contrast, efficacy subset analysis selects the subset of the patients who received the treatment of interest--regardless of initial randomization--and who have not dropped out for any reason. This approach can :
- introduce biases to the statistical analysis
- inflate the type I error; this effect is greater the larger the trial[1].
Full application of intention to treat can only be performed where there is complete outcome data for all randomised subjects.
Although intention to treat is widely cited in published trials, it is often incorrectly described and its application may be flawed.
References
- ↑ Lachin JM (2000). "Statistical Considerations in the Intent-to-Treat Principle". Statistics in Medicine. 21 (3): 167–189. PMID 10822117. Unknown parameter
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See also
External links
- Intention to Treat - Bandolier's definition
- Intention to Treat - Tufts.edu
- What is meant by intention to treat analysis? Survey of published randomised controlled trials - BMJ