Abstract
The intention-to-treat (ITT) approach to randomized controlled trials analyzes data
on the basis of treatment assignment, not treatment receipt. Alternative approaches
make comparisons according to the treatment received at the end of the trial (as-treated
analysis) or using only subjects who did not deviate from the assigned treatment (adherers-only
analysis). Using a sensitivity analysis on data for a hypothetical trial, we compare
these different analytical approaches in the context of two common protocol deviations:
loss to follow-up and switching across treatments. In each case, two rates of deviation
are considered: 10% and 30%. The analysis shows that biased estimates of effect may
occur when deviation is nonrandom, when a large percentage of participants switch
treatments or are lost to follow-up, and when the method of estimating missing values
accounts inadequately for the process causing loss to follow-up. In general, ITT analysis
attenuates between-group effects. Trialists should use sensitivity analyses on their
data and should compare the characteristics of participants who do and those who do
not deviate from the trial protocol. The ITT approach is not a remedy for unsound
design, and imputation of missing values is not a substitute for complete, good quality
data.
Keywords
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Article info
Publication history
Accepted:
November 18,
2002
Identification
Copyright
© 2003 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
