Abstract
BACKGROUND: Few randomised controlled trials (RCTs) recruit centres representatively, which may limit the external validity of trial results.
OBJECTIVE: The aim of this study was to propose a proof-of-concept method of assessing the generalisability of the clinical and cost-effectiveness findings of a given RCT.
METHODS: We developed a generalisability index (Gix), informed by centre-level characteristics, as a measure of centre and trial representativeness. The centre-level Gix quantifies how representative a centre is in relation to its jurisdiction, e.g. a country or health authority. The trial-level Gix quantifies how representative trial recruitment is in relation to clinical practice in the jurisdiction. Taking a real-world RCT as a case study and assuming trial-wide results to represent 'true jurisdiction values', we used simulation methods to recreate 5000 RCTs and investigate the relationship between trial representativeness, reflected by the standardised trial-Gix, and the deviation of simulated trial results from the 'true values'.
RESULTS: The simulation study provides evidence that trial results (odds ratio for the primary outcome and incremental quality-adjusted life-years) were influenced by the representativeness of the sample of recruiting centres. Simulated RCTs with the closest results to the 'true values' were those whose recruitment closely mirrored the jurisdiction-wide context. Results appeared robust to six alternative specifications of the Gix.
CONCLUSIONS: Our findings suggest that an unrepresentative selection of centres limits the external validity of trial results. The Gix may be a valuable tool to help facilitate rational selection of trial centres and ensure the generalisability of results at the jurisdiction level.
Original language | English |
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Pages (from-to) | 1195-1214 |
Number of pages | 20 |
Journal | PharmacoEconomics |
Volume | 33 |
Issue number | 11 |
Early online date | 12 Jun 2015 |
DOIs | |
Publication status | Published - Nov 2015 |
Keywords
- Incremental Cost
- Simulated Trial
- Trial Recruitment
- Patient Throughput
- Representative Centre