Dynamic data-enabled stratified sampling for trial invitations with application in NHS-Galleri

BACKGROUND: Participants of health research studies such as cancer screening trials usually have better health than the target population. Data-enabled recruitment strategies might be used to help minimise healthy volunteer effects on study power and improve equity. METHODS: A computer algorithm was developed to help target trial invitations. It assumes participants are recruited from distinct sites (such as different physical locations or periods in time) that are served by clusters (such as general practitioners in England, or geographical areas), and the population may be split into defined groups (such as age and sex bands). The problem is to decide the number of people to invite from each group, such that all recruitment slots are filled, healthy volunteer effects are accounted for, and equity is achieved through representation in sufficient numbers of all major societal and ethnic groups. A linear programme was formulated for this problem. RESULTS: The optimisation problem was solved dynamically for invitations to the NHS-Galleri trial (ISRCTN91431511). This multi-cancer screening trial aimed to recruit 140,000 participants from areas in England over 10 months. Public data sources were used for objective function weights, and constraints. Invitations were sent by sampling according to lists generated by the algorithm. To help achieve equity the algorithm tilts the invitation sampling distribution towards groups that are less likely to join. To mitigate healthy volunteer effects, it requires a minimum expected event rate of the primary outcome in the trial. CONCLUSION: Our invitation algorithm is a novel data-enabled approach to recruitment that is designed to address healthy volunteer effects and inequity in health research studies. It could be adapted for use in other trials or research studies.