Prospective cluster-randomized evaluation of strategies for on-site monitoring adapted on a study-specific basis in conjunction with additional quality assurance measures.

ADAMON is a project to evaluate risk-adapted monitoring strategies for clinical trials. The adapted monitoring strategies investigated have been developed with a methodology that was initially developed heuristically in preliminary projects, integrating numerous experts. It allows risk classification of non-commercial clinical trials and assigns each of those risk classes an adapted monitoring strategy.

The efficiency of this method is now evaluated in a prospective cluster-randomized investigation. The focus is on the question:

Is a focused, reduced monitoring strategy that is adapted to the design and objectives of the clinical trial and implemented by monitors specifically trained for the study sufficient to ensure achievement of the objectives of good clinical practice and does it help to obtain meaningful results?

For this purpose, ADAMON cooperates with numerous clinical studies in which for each participating trial site a randomized decision is taken as to whether the site will be monitored on site using a specifically adapted monitoring strategy or an intensive monitoring strategy ("full monitoring“). A final audit is planned for each trial site. The audit results are crucial for a comparison of the two monitoring strategies.

The funding period is December 2008 to 30 June 2016. The project is being funded by the German Federal Ministry of Education and Research (BMBF). The project application was developed within the scope of preliminary TMF projects, integrating the TMF working group "Management of Clinical Studies". ZKS Leipzig (project leader: Dr. Oana Brosteanu) is in charge of filing the application and implementation. The project team consists of representatives of the network of Coordination Centres for Clinical Studies (KKS Network) and Competence Networks in Medicine (KN) and cooperates with employees of the German Federal Institute for Drugs and Medical Devices (BfArM).

Results

Risk-adapted monitoring is not inferior to extensive on-site monitoring.

Compared with risk-adapted monitoring, the potential benefit of extensive on-site monitoring is small relative to overall finding rates, although risk-adapted monitoring requires less than 50% of extensive on-site monitoring resources. Risk-adapted monitoring has a part to play in quality control. It appears sufficient to control only a sample of patients to identify systematic problems in the conduct of clinical trials.

Clusters of findings within trials suggest that complicated, overly specific or not properly justified protocol requirements contributed to the overall frequency of findings. However, no monitoring strategy can remedy defects in quality of design. On-site monitoring should be embedded in a comprehensive quality management approach, including central monitoring strategies and covering the entire trial lifecycle.

(cited from the original publication)

The results of the study were published in Clinical Trials in 2017.