Dataset Information

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

ABSTRACT:

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Many academic drug trials are left unpublished.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.

SUBMITTER: Berendt L

PROVIDER: S-EPMC5423601 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Berendt Louise L Petersen Lene Grejs LG Bach Karin Friis KF Poulsen Henrik Enghusen HE Dalhoff Kim K

PloS one 20170509 5

<h4>Objective</h4>To characterize and quantify barriers towards the publication of academic drug trials.<h4>Study design</h4>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 f ...[more]

PMID: 28486523

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Project description:AimsWe have previously described the European Medicines Agency's (EMA) and the US Food and Drug Administration's guidelines, each for a specific psychiatric indication, on how to design pivotal drug trials used in new drug applications. Here, we report on our efforts over 3 years to retrieve conflicts of interest declarations from EMA. We wanted to assess potential internal industry influence judged as the proportion of guideline committee members with industry conflicts of interest.MethodsWe submitted Freedom of Information requests in February 2020 to access EMA's lists of committee members (and their declared conflicts of interest) involved in drafting the 13 'Clinical efficacy and safety' guidelines available on EMA's website pertaining to psychiatric indications. In our request, we did not specify the exact EMA committees. Here, we describe the received documents and report the proportion of members with industry interests (i.e. defined as any financial industry relationship). It is a follow-up paper to our first report (http://doi.org/10.1017/S2045796021000147).ResultsAfter 2 years and 9 months (November 2022), the EMA sent us member lists and corresponding conflicts of interest declarations from the Committee for Medicinal Products for Human use (CHMP) from 2012, 2013 and 2017. These member lists pertained to 3 of the 13 requested guidelines (schizophrenia, depression and autism spectrum disorder). The 10 remaining guidelines were published before 2011 and EMA stated that they needed to require permission from their expert members (with unknown retrieval rate) and foresaw excessive workload and long wait. Therefore, we withdrew our request. The CHMPs from 2012, 2013 and 2017 had from 34 to 36 members; 39%-44% declared any interests and we judged 14%-18% as having industry interests. For the schizophrenia guideline, we identified two members with industry interests to companies who submitted feedback on the guideline. We did not receive declarations from the Central Nervous System (CNS) Working Party, the CHMP appointed expert group responsible for drafting and incorporating feedback into the guidelines.ConclusionsAfter almost 3 years, we received information, which only partly addressed our request. We recommend EMA to improve transparency by publishing the author names and their corresponding conflicts of interest declarations directly in the 'Clinical efficacy and safety' guidelines and to not remove conflicts of interest declarations after 1 year from their website to reduce the risk of stealth corporate influence during the development of these influential guidelines.

Project description:BACKGROUND:Clinical study reports (CSRs) have been increasingly utilised within academic research in recent years. European Medicines Agency (EMA) Policy 0070 'Phase 1,' which came into effect in January 2015, requires the publication of regulatory documents such as CSRs from central applications in an anonymised format. EMA Policy 0070 requires sponsors to demonstrate careful consideration of data utility within anonymised CSRs published within the scope of the policy, yet the concept of data utility is not clearly defined in the associated anonymisation guidance. OBJECTIVE:To review the use of data from CSRs in published academic research and to hypothesise the potential data utility of CSRs anonymised under the objectives of EMA Policy 0070 for future academic research. METHODS:Review of the objectives, research methodologies and findings of academic research reports using unpublished data from CSRs (prior to EMA Policy 0070). Semi-structured interviews with authors of academic research reports, including questions related to data utility of anonymised CSRs published under EMA Policy 0070. RESULTS:Thirteen academic research reports were identified and reviewed. The research purposes ranged from assessment of reporting bias, comparison of methods and results with published data sources, detailed evaluation of harms and adverse events, re-analysis and novel analyses including systematic reviews and meta-analysis. All of the examples identified required access to the methods and results sections of CSRs (including aggregated summary tables) and research purposes relating to evaluation of adverse events also required access to participant narratives. Retaining anonymised participant narratives relating to interventions, findings and events, while maintaining an acceptably low risk of participant re-identification, may provide an important gain in data utility and further understanding of drug safety profiles. CONCLUSIONS:This work provides an initial insight into the previous use of CSR data and current practices for including regulatory data in academic research. This work also provides early guidance to qualitatively assess and document data utility within anonymised CSRs published under EMA Policy 0070.

Project description:ObjectivesTo evaluate the added benefit and revenues of oncology drugs, explore their association, and investigate potential discrepancies between added benefit and revenues across different approval pathways of the European Medicines Agency (EMA).DesignRetrospective cohort study.SettingOncology drugs and their indications approved by the EMA between 1995 and 2020.Main outcome measuresAdded benefit was evaluated using ratings published by seven organisations: health technology assessment agencies from the United States, France, Germany, and Italy, two medical oncology societies, and a drug bulletin. All retrieved ratings were recategorised using a four point ranking scale to indicate negative or non-quantifiable, minor, substantial, or major added benefit. Revenue data were extracted from publicly available financial reports and compared with published estimates of research and development (R&D) costs. Finally, the association between added benefit and revenue was evaluated. All analyses were performed within the overall study cohort, and within subgroups based on the EMA approval pathway: standard marketing authorisation, conditional marketing authorisation, and authorisation under exceptional circumstances.Results131 oncology drugs with 166 indications were evaluated for their added benefit by at least one organisation within the required timeframe, yielding a total of 458 added benefit ratings; 189 (41%) were negative or non-quantifiable. The median time to offset the median R&D costs ($684m, £535m, €602m, adjusted to 2020 values) was three years; 50 of 55 (91%) drugs recovered these costs within eight years. Drugs with higher added benefit ratings generally had greater revenues. Negative or non-quantifiable added benefit ratings were more frequent for conditional marketing authorisations and authorisations under exceptional circumstances than for standard marketing authorisations (relative risk 1.53, 95% confidence interval 1.23 to 1.89). Conditional marketing authorisations generated lower revenues and took longer to offset R&D costs than standard marketing authorisations (four years compared with three years).ConclusionsWhile revenues seem to align with added benefit, most oncology drugs recover R&D costs within a few years despite providing little added benefit. This is particularly true for drugs approved through conditional marketing authorisations, which inherently appear to lack comprehensive evidence. Policy makers should evaluate whether current regulatory and reimbursement incentives effectively promote development of the most effective drugs for patients with the greatest needs.

Project description:AimsTo systematically assess the level of evidence for psychotropic drugs approved by the European Medicines Agency (EMA).MethodsCross-sectional analysis of all European Public Assessment Reports (EPARs) and meta-analyses of the many studies reported in these EPARs. Eligible EPARs were identified from the EMA's website and individual study reports were requested from the Agency when necessary. All marketing authorisation applications (defined by the drug, the route of administration and given indications) for psychotropic medications for adults (including drugs used in psychiatry and addictology) were considered. EPARs solely based on bioequivalence studies were excluded. Our primary outcome measure was the presence of robust evidence of comparative effectiveness, defined as at least two 'positive' superiority studies against an active comparator. Various other features of the approvals were assessed, such as evidence of non-inferiority v. active comparator and superiority v. placebo. For studies with available data, effect sizes were computed and pooled using a random effect meta-analysis for each dose of each drug in each indication.ResultsTwenty-seven marketing authorisations were identified. For one, comparative effectiveness was explicitly considered as not needed in the EPAR. Of those remaining, 21/26 (81%) did not provide any evidence of superiority against an active comparator, 2/26 (8%) were based on at least two trials showing superiority against active comparator and three (11%) were based on one positive trial; 1/26 provided evidence for two positive non-inferiority analyses v. active comparator and seven (26%) provided evidence for one. In total, 20/27 (74%) evaluations reported evidence of superiority v. placebo with two or more trials. Among the meta-analyses of initiation studies against active comparator (57 available comparisons), the median effect size was 0.051 (range -0.503; 0.318). Twenty approved evaluations (74%) reported evidence of superiority v. placebo on the basis of two or more initiation trials and seven based on a single trial. Among meta-analyses of initiation studies against placebo (125 available comparisons), the median effect size was -0.283 (range -0.820; 0.091). Importantly, among the 89 study reports requested on the EMA website, only 19 were made available 1 year after our requests.ConclusionsThe evidence for psychiatric drug approved by the EMA was in general poor. Small to modest effects v. placebo were considered sufficient in indications where an earlier drug exists. Data retrieval was incomplete after 1 year despite EMA's commitment to transparency. Improvements are needed.

Dataset Information

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

Objective

Study design

Results

Conclusions

Publications

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

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