ABSTRACT

BackgroundUnacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the results of the trials. Little is known about inconsistency in the reporting of academic clinical drug trials. Therefore, we investigated the prevalence of consistency between protocols and published reports of academic clinical drug trials.MethodsA comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory), primary objective, primary endpoint, and – for confirmatory trials only – hypothesis and sample size calculation. We used logistic regression, χ2, and Fisher’s exact test.ResultsA total of 282 applications of academic clinical drug trials were submitted to the Danish Health and Medicines Authority in 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding published report reporting data on trial subjects. Overall consistency was observed in 39 % of the trials (95 % CI: 29 to 49 %). Randomized controlled trials (RCTs) constituted 72 % (95 % CI: 63 to 81 %) of the sample, and 87 % (95 % CI: 80 to 94 %) of the trials were hospital based.ConclusionsOverall consistency between protocols and their corresponding published reports was low. Motivators for the inconsistencies are unknown but do not seem restricted to economic incentives.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• 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. AIMThe aim of this study was to investigate the temporal trends in characteristics of academic clinical drug trials. We here report characteristics on trial methodology. METHODSA 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. RESULTSStatement 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. CONCLUSIONSOur 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 1993-2005. 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 trial methodology.