Economic Evaluations Alongside Efficient Study Designs Using Large Observational Datasets: the PLEASANT Trial Case Study

Matthew Franklin, Sarah Davis, Michelle Horspool, Wei Sun Kua, Steven Julious

Large observational datasets such as Clinical Practice Research Datalink (CPRD) provide opportunities to conduct clinical studies and economic evaluations with efficient designs. Our objectives were to report the economic evaluation methodology for a cluster randomised controlled trial (RCT) of a UK NHS-delivered public health intervention for children with asthma that was evaluated using CPRD and describe the impact of this methodology on results. CPRD identified eligible patients using predefined asthma diagnostic codes and captured 1-year pre- and post-intervention healthcare contacts (August 2012 to July 2014). Quality-adjusted life-years (QALYs) 4 months post-intervention were estimated by assigning utility values to exacerbation-related contacts; a systematic review identified these utility values because preference-based outcome measures were not collected. Bootstrapped costs were evaluated 12 months post-intervention, both with 1-year regression-based baseline adjustment (BA) and without BA (observed). Of 12,179 patients recruited, 8190 (intervention 3641; control 4549) were evaluated in the primary analysis, which included patients who received the protocol-defined intervention and for whom CPRD data were available. The intervention's per-patient incremental QALY loss was 0.00017 (bias-corrected and accelerated 95% confidence intervals [BCa 95% CI] -0.00051 to 0.00018) and cost savings were £14.74 (observed; BCa 95% CI -75.86 to 45.19) or £36.07 (BA; BCa 95% CI -77.11 to 9.67), respectively. The probability of cost savings was much higher when accounting for BA versus observed costs due to baseline cost differences between trial arms (96.3 vs. 67.3%, respectively). Economic evaluations using data from a large observational database without any primary data collection is feasible, informative and potentially efficient. Clinical Trials Registration Number: ISRCTN03000938.