Intention to treat analysis

If there are separate analysis plans for the clinical and economic evaluations, efforts should be made to make them as consistent as possible (e.g., shared use of an intention-to-treat analysis, shared use of statistical tests for variables used commonly by both analyses, etc.). At the same time, the outcomes of the clinical and economic studies can differ (e.g., the primary outcome of the clinical evaluation might focus on event-free survival, while the primary outcome of the economic evaluation might focus on quality-adjusted survival). Thus, the two plans need not be identical. 

Gillings D and Koch G (1991) The application of the principle of intention-to-treat analysis of clinical trials Drug Information Journal, 25, 411-424 Greenwood M (1926) The errors of sampling of the survivorship tables Reports on Public Health and Statistical Subjects, No. 33, Appendix 1. London HMSO Grieve AP (2003) The number needed to treat a useful clinical measure or a case of the Emperor s new clothes Pharmaceutical Statistics, 2, 87-102 Haybittle JL (1971) Repeated assessment of results in clinical trials of cancer treatment British Journal of Radiology, 44, 793-797... 

Adequate handling of dropouts (e.g., intent-to-treat analysis)... 

Based upon these observations and following Phase I safety studies, a Phase II randomized, double-blind, controlled clinical trial was undertaken to treat active ulcerative colitis with escalating doses of ISIS 2302. Based on an intent-to-treat analysis, 59% (13/22) of patients treated daily with 240 mg ISIS 2302 enema over six weeks achieved a positive response, as measured by Disease Activity Index (DAI)... 

In many clinical trials, especially trials that occur later in a new drug development program, analyses are first conducted on the il l population. These analyses are considered to be the primary analyses. Intent-to-treat analysis provides a conservative strategy in the sense that it tends to bias against finding the results that the researcher hopes for (recall the discussion in Section 7.2.1 regarding hope). The ITT population therefore comprises the purest population of subjects in the... 

An intention to treat analysis is an analysis of outcome of the original groups produced by randomisation with everyone analysed according to the treatment they were intended to receive. 

One should be careful to assess the effects of dropping patients with available data from analyses. An intent-to-treat analysis including all available data from all patients should be performed. 

It is usually required to perform an intent-to-treat analysis that will include data on all patients who were enrolled and began treatment, regardless of whether they followed protocol, finished the study, violated protocol, or dropped out.The purpose here is to ensure the safety of the investigational substance, because substantial bias would be built into the overall analysis with the exclusion of patients who could not tolerate medication and dropped out, or who were not helped by the medication and switched to another treatment. In addition, of course, there might be an analysis of the results from all patients who followed the entire protocol properly.The intent-to-treat analysis should include patients who withdrew from the study the last clinical measurements taken for these patients should be carried forward as the last observation or final score—the so-called end point analysis. 

The final report submitted to the FDA must discuss both safety and efficacy. In the efficacy section, a precise definition of which specific patients are included in the efficacy analysis is necessary. The Guidelines suggest doing an intent-to-treat analysis, including all patients randomized in the study. This is done in addition to the study sample that is defined as clinically relevant. 

Demographic and baseline features of individual patients and the comparability of treatment groups for these features are needed. If the patients in the intent-to-treat analysis and the clinically relevant analysis differ in number and identity, the comparability in both sets must be examined. In multicenter studies, comparability should be assessed both within and across centers. Tabular listings of individual patient demographic and baseline data should be provided. 

Information on both categories (use effectiveness and method effectiveness) is valuable. Sheiner L B et al 1995 Intention-to-treat analysis and the goals of clinical trials. Clinical Pharmacology and Therapeutics 57 1. 

Capell HA, Maiden N, Madhok R, Hampson R, Thomson EA. Intention-to-treat analysis of 200 patients with rheumatoid arthritis 12 years after random allocation to either sulfasalazine or penicillamine. J Rheumatol 1998 25(10) 1880-6. 

Module HI Presents the detailed efficacy findings including the intent-to-treat analysis population and the efficacy data listings. 

A. Tsiatis, Analysis and interpretation of trial results intent-to-treat analysis. / Acquir Immune Defic Syndr 3(Suppl 2) S120-S123 (1990). 

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