Methodological characteristics of academic clinical drug trials – a retrospective cohort study of applications to the Danish Medicines Agency 1993–2005

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • From 1993 to 2005, the number of academic clinical drug trials in Denmark decreased by 38% with a small increase in 2006. Commercial clinical drug trials in Denmark were subject to a similar decrease. Implementation of the European Clinical Trials Directive in 2004 had no immediate effect on the number of either academic or commercial clinical drug trials. WHAT THIS STUDY ADDS • Our study shows that randomization, definition of primary endpoint, monitoring according to the principles of Good Clinical Practice (GCP monitoring), and control of medicine compliance form part of a significantly increasing percentage of academic clinical drug trials. This indicates an increasing quality of these trials. • However, high numbers of unblinded randomized controlled trials and randomized controlled trials utilizing unacceptable methods for generation of allocation sequence emphasize the potential for further improvement of the methodological quality. AIM The aim of this study was to investigate the temporal trends in characteristics of academic clinical drug trials. We here report characteristics on trial methodology. METHODS A review of 386 approved applications of academic clinical drug trials submitted to the Danish Medicines Agency 1993–2005 was carried out. Data on 11 methodological characteristics were collected, e.g. statement of primary endpoint, use of control group, blinding, randomization, method for generation of allocation sequence, monitoring according to the principles of Good Clinical Practice (GCP monitoring) and publication. RESULTS Statement of primary endpoint increased from 60 to 90% of trials (P < 0.0001). Comparing the period before and after implementation of the Clinical Trials Directive in 2004, intention of GCP monitoring increased from 13% to 94%. Control of medicine compliance increased from 42% to 76% (P < 0.0001) among trials with self‐administration of the investigational medicinal product. Among controlled trials use of randomization increased from 78% to 94% (P= 0.0063) of trials. Remaining characteristics did not change significantly. In total 68% (264/386) were randomized controlled trials. CONCLUSIONS Our study shows that randomization, definition of primary endpoint, GCP monitoring, and control of medicine compliance form part of a significantly increasing percentage of academic clinical drug trials. This indicates an increase in the quality of academic clinical drug research in Denmark