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

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.

Primary endpoint discrepancies were found in one in ten clinical drug trials. Results of an inception cohort study

“…RCTs, respectively [10]. In the subgroup of the 126 academic trials in our cohort, discrepancies in primary endpoints were found in 10 of 54 RCTs (19%), and in 13 of 72 non-RCTs (18%).…”

“…In addition to the sponsor type, we analyzed the trial characteristics that were significantly associated with nonpublication in the same cohort [21]: phase, centers involved, prospective registration, and completion. Furthermore, in line with previous studies [9,10], we also analyzed the association of the trial design and the treatment arms with discrepancies in the primary endpoints. The protocol of our study [7] prescribed the analysis of determinants for all protocol-publication discrepancies separately.…”

“…Although the existence of selective publication has been convincingly established among clinical trials starting 15e20 years ago [9,10], its occurrence may have decreased due to subsequent countermeasures. Governments, journals, pharmaceutical companies, and research communities have implemented requirements for trial registration and data sharing [14e20].…”

“…Governments, journals, pharmaceutical companies, and research communities have implemented requirements for trial registration and data sharing [14e20]. However, more recent evidence suggests that only limited progress has been made [10]. Empirical evidence is very limited on whether other aspects of trials are transparently reported, such as the selection criteria, sample size, subgroup or other additional analyses, and the methods used for data analysis.…”

From registration to publication: A study on Dutch academic randomized controlled trials

“…Unfortunately, discrepancies between a registered trial protocol and its publication are still frequently reported. [5][6][7][8] Since July 2005, the International Committee of Medical Journal Editors requires trials to be registered before the enrolment of the first patient in order to prevent selective publication of trial outcomes in an effort to reduce this form of publication bias. 9 Besides the obligation to publish trial results, it is essential that these results become available within an appropriate period to ensure that clinical decisions can be made on the most recently available evidence.…”