Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency.

OBJECTIVE: To characterize and quantify barriers towards the publication of academic drug trials. STUDY DESIGN: We identified academic drug trials approved during a 3-year period (2004-2007) by the Danish Medicines Agency. We conducted a survey among the trial sponsors to describe the rates of initiation, completion, and publication, and the reasons for the failure to reach each of these milestones. Information on size and methodological characteristics of the trials was extracted from the EudraCT database, a prospective register of all approved clinical drug trials submitted to European medicines agencies since 2004. RESULTS: A total of 181 academic drug trials were eligible for inclusion, 139 of which participated in our survey (response rate: 77%). Follow-up time ranged from 5.1 to 7.9 years. Most trials were randomized controlled trials (73%, 95% CI 65-81%). Initiation and completion rates were 92% (95% CI: 88-97%) and 93% (95% CI: 89-97%) respectively. The publication rate of completed trials was 73% (95% CI: 62-79%). RCTs were published faster than non-RCTs (quartile time to publication 2.9 vs. 3.1 years, p = 0.0412). CONCLUSIONS: Many academic drug trials are left unpublished. Main barriers towards publication were related to the process from completion to publication. Hence, there is much to gain by facilitating the process from analysis to publication. Research institutions and funders should actively influence this process, e.g. by requiring the publication of trial results within a given time after completion.

From protocol to published report: a study of consistency in the reporting of academic drug trials.

BACKGROUND: Unacknowledged 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. METHODS: A 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, χ(2), and Fisher's exact test. RESULTS: A 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. CONCLUSIONS: Overall consistency between protocols and their corresponding published reports was low. Motivators for the inconsistencies are unknown but do not seem restricted to economic incentives.

[Effect of the GCP Directive on academic drug trials]. / Effekten af GCP-direktivet på forskerinitierede kliniske laegemiddelforsøg--sekundaerpublikation

Since 2004, adherence to Good Clinical Practice has been mandatory for all clinical drug trials. This was new to the investigator-initiated trials. Our study showed no association between the implementation of the Directive and investigator or industry-initiated trials. However, a steady decline was observed over the entire period. Presumably, the introduction of GCP did not entail a decline because of the presence of GCP units at university hospitals. Thus, researchers can conduct clinical drug trials under the same regulations as drug companies.

Effect of European Clinical Trials Directive on academic drug trials in Denmark: retrospective study of applications to the Danish Medicines Agency 1993-2006.

OBJECTIVE: To determine the impact of the European Union's Clinical Trials Directive on the number of academic drug trials carried out in Denmark. DESIGN: Retrospective review of applications for drug trials to the Danish Medicines Agency, 1993-2006. REVIEW METHODS: Applications for drug trials for alternate years were classified as academic or commercial trials. A random subset of academic trials was reviewed for number of participants in and intended monitoring of the trials. RESULTS: Academic and commercial drug trials showed an identical steady decline from 1993 to 2006 and no noticeable change after 2004 when good clinical practice became mandatory for academic trials. CONCLUSION: The Clinical Trials Directive introduced in May 2004 to ensure good clinical practice for academic drug trials was not associated with a decline in research activity in Denmark; presumably because good clinical practice units had already been in place in Danish universities since 1999. With such an infrastructure academic researchers can do drug trials under the same regulations as drug companies.