A systematic review of on-site monitoring methods for health-care randomised controlled trials.

BACKGROUND: Monitoring the conduct of clinical trials is recommended by International Conference of Harmonisation Good Clinical Practice (ICH GCP) guidelines and is integral to trial quality assurance. On-site monitoring, that is, visiting trial sites, is one part of this process but little is known about the procedures that are performed in practice.
PURPOSE: To examine and summarise published on-site monitoring methods for health-care clinical trials, including evaluations of their benefits and costs to trials.
METHODS: A systematic literature review identified all articles reporting the methods and practices of on-site monitoring of randomised controlled trials (RCTs). Articles were categorised into (1) reports from research groups and organisations, (2) reports from individual RCTs, (3) randomised trials of on-site monitoring interventions, (4) cost simulations, or (5) surveys of trial staff and monitors. Data were extracted on the characteristics of the trials and groups reporting on-site monitoring (e.g., geographical origin, sponsor, and trial focus). Information from articles in categories (1)-(3) was summarised on the frequency and scope of site monitoring visits, monitoring team size and composition, activities during site visits, and reporting structures. Evaluations of the benefits and disadvantages of on-site monitoring were examined for all included articles.
RESULTS: In total, 57 articles were identified, comprising 21 articles about the on-site monitoring practices of 16 research groups, 30 articles from 26 RCTs, 1 on-site monitoring intervention RCT, 2 cost simulations, and 3 surveys. Publications in categories (1)-(3), mostly originated from the United States (33/52, 63%) or Europe (15/52, 29%), were predominantly describing non-commercial organisations or trials (45/52, 87%), with heart disease (9/26, 35%) or cancer (5/26, 19%) the commonest focus of individual RCTs. The frequency of visits ranged from every 6-8 weeks up to once every 3 years, with mostly all trial sites visited. The number of monitors visiting a site varied between 1 and 8. The most common on-site monitoring activity was verifying source data and consent forms, with a focus on data accuracy. Only six articles evaluated their on-site monitoring process, with improvements observed in recruitment rates and protocol adherence but with direct costs and staff time viewed as the major disadvantages. The on-site monitoring RCT ended prematurely so preventing full assessment. LIMITATIONS: Trialists and organisations may utilise additional unpublished on-site monitoring systems. The varied terminology used to describe monitoring may have limited identification of some relevant articles.
CONCLUSIONS: This review demonstrated that on-site monitoring is utilised in trials worldwide but systems vary considerably with little evidence to support practice. These on-site monitoring practices need to be evaluated empirically, including costs, to provide robust evidence for the contribution of site visits to trial performance and quality.