Sample size estimation for randomised controlled trials with repeated assessment of patient-reported outcomes: what correlation between baseline and follow-up outcomes should we assume?

Abstract

Abstract Background Patient-reported outcome measures (PROMs) are now frequently used in randomised controlled trials (RCTs) as primary endpoints. RCTs are longitudinal, and many have a baseline (PRE) assessment of the outcome and one or more post-randomisation assessments of outcome (POST). With such pre-test post-test RCT designs there are several ways of estimating the sample size and analysing the outcome data: analysis of post-randomisation treatment means (POST); analysis of mean changes from pre- to post-randomisation (CHANGE); analysis of covariance (ANCOVA). Sample size estimation using the CHANGE and ANCOVA methods requires specification of the correlation between the baseline and follow-up measurements. Other parameters in the sample size estimation method being unchanged, an assumed correlation of 0.70 (between baseline and follow-up outcomes) means that we can halve the required sample size at the study design stage if we used an ANCOVA method compared to a comparison of POST treatment means method. So what correlation (between baseline and follow-up outcomes) should be assumed and used in the sample size calculation? The aim of this paper is to estimate the correlations between baseline and follow-up PROMs in RCTs. Methods The Pearson correlation coefficients between the baseline and repeated PROM assessments from 20 RCTs (with 7173 participants at baseline) were calculated and summarised. Results The 20 reviewed RCTs had sample sizes, at baseline, ranging from 49 to 2659 participants. The time points for the post-randomisation follow-up assessments ranged from 7 days to 24 months; 464 correlations, between baseline and follow-up, were estimated; the mean correlation was 0.50 (median 0.51; standard deviation 0.15; range − 0.13 to 0.91). Conclusions There is a general consistency in the correlations between the repeated PROMs, with the majority being in the range of 0.4 to 0.6. The implications are that we can reduce the sample size in an RCT by 25% if we use an ANCOVA model, with a correlation of 0.50, for the design and analysis. There is a decline in correlation amongst more distant pairs of time points.

Keywords

• Sample size estimation
• Review
• Randomised controlled trials
• Health Technology Assessment
• Publicly funded
• Correlations