Data monitoring committees, interim analysis and early termination in paediatric trials

Aim: To evaluate whether paediatric randomized clinical trials (RCTs) adopt recent guidance on Data Monitoring Committees (DMCs), interim analysis and early termination.

Methods: We reviewed paediatric RCTs that reported on DMCs, interim analysis or early termination, published in eight general medical and paediatric journals (2005-2007). We searched full-text databases for eligible trials and recorded predefined parameters on each item. Reported activities were compared with current scientific guidance.

Results: A total of 110 of 648 paediatric trials (17%) reported on DMC, interim analysis or early stopping. Various approaches for convening a DMC were identified; information on DMC composition and independence was limited. Strict predefined statistical stopping 'rules' were reported in 10 of 23 trials, and interim analyses were more frequently performed on efficacy than on safety outcomes (39/45 vs 27/45). No adjustment for repeated testing was reported in 11 of 33 trials reporting monitoring methods and in 7 of 17 early terminated trials. Validity of results from early stopped trials was threatened by small sample sizes. Incomplete reporting hampered a full analysis.

Conclusion: Few paediatric trials report on DMCs' roles, interim analysis or early stopping. Heterogeneous practices and apparent shortcomings jeopardize the validity of trial results. Easily accessible guidelines for the design, conduct and reporting of paediatric DMCs are needed.