Fig: Mitka et al. JAMA 2012
Determining the sample of participants to be analysed is a crucial step in reporting clinical trials. For such analyses, the gold standard is the “intention-to-treat” principle.
Intention-to-treat analysis is a comparison of the treatment groups that includes all patients as originally allocated after randomization. This is the recommended method in superiority trials to avoid any bias.
- Retains balance in prognostic factors arising from the original random treatment allocation
- Gives an unbiased estimate of treatment effect
- Admits non-compliance and protocol deviations, thus reflecting a real clinical situation
Requirements for an ideal ITT analysis
- Full compliance with randomised treatment
- No missing responses
- Follow-up on all participants
- Estimate of treatment effect is generally conservative because of dilution due to non-compliance
- In equivalence trials (attempting to prove that two treatments do not differ by more than a certain amount), this analysis will favour equality of treatments
- Interpretation becomes difficult if a large proportion of participants cross over to opposite treatment arms
- Full application of intention to treat is possible only when complete outcome data are available for all randomised subjects
Application of ITT Analysis in clinical trials:
- About half of all published reports of randomised controlled trials stated that intention to treat was used, but handling of deviations from randomised allocation varied widely.
- Many trials had some missing data on the primary outcome variable, and methods used to deal with this were generally inadequate, potentially leading to bias.
- Intention to treat analyses are often inadequately described and inadequately applied.