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?

Trials. 2019 Sep 13;20(1):566. doi: 10.1186/s13063-019-3671-2.

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: ANCOVA; Correlations; Health Technology Assessment; Patient-reported outcome measures; Publicly funded; Randomised controlled trials; Review; Sample size estimation.

MeSH terms

  • Comparative Effectiveness Research
  • Endpoint Determination*
  • Humans
  • Patient Reported Outcome Measures*
  • Randomized Controlled Trials as Topic / methods*
  • Sample Size*
  • Time Factors
  • Treatment Outcome