Why did clinical trial registries fail to prevent Covid research chaos?

“There is a long-standing global ethical obligation to register all trials before they start, shored up by regulatory requirements in some jurisdictions. Data from 18 registries worldwide feed into the WHO-managed International Clinical Trials Registry Platform (ICTRP), providing a continuously updated overview of who is researching what, when, where and how – at least in theory.

 

 

If the registry infrastructure had worked and been used as intended, much of the COVID-19 research chaos would have been avoided.

 

 

For example, researchers considering launching a hydroxychloroquine trial could have searched ICTRP and discovered that the drug was already being investigated by numerous other trials. Those researchers could accordingly have focused on investigating other treatment options instead, or aligned their outcome measures with existing trials. …

The global registry infrastructure has long been inadequately supported by legislators and regulators, and is woefully underfunded.

 

 

 

This persistent neglect of the world’s only comprehensive directory of medical research led to costly research waste on an incredible scale during the pandemic.

 

 

The WHO recommends that member states should by law require every interventional trial to be registered and reported. In addition, WHO recommends that all trial results should be made public specifically on a registry within 12 months, and that registry data should be kept up to date.

 

 

 

By enforcing these three simple rules, regulators would ensure that there is a comprehensive, up-to-date global database of all trials and their results.

 

In reality, existing laws in the EU and the US only cover a small minority of trials and are not being effectively enforced, while many other jurisdictions have no relevant laws at all. …”

 

 

CERN moves closer to achieving full open access | CERN

“Since 2014, CERN has required that all peer-reviewed primary research articles from CERN authors are published open access (OA), i.e. freely available for anyone around the world to read and re-use with appropriate attribution. This policy reflects the moral imperative of CERN as a publicly-funded organisation – supported by contributions from its Member States – to ensure that the results of our work accrue benefits to all.

I’m pleased to report that we are close to achieving full policy compliance: in 2021, 93.7% of the 1058 publications from CERN authors were published OA. …”

‘The EMA is withholding too much information”, 1 May 2022

“Transparency is a requirement for better and safer patient care. There is no valid reason to hide information about clinical trials, their methodology or their results, or evaluation data obtained on drugs after their market introduction, particularly data on adverse effects.

The creation of the European Medicines Agency (EMA) in 1995 constituted a step forward, compared with the practices of France’s drug regulatory agency at the time. For example, the EMA’s online publication of information on drug evaluations, such as European Public Assessment Reports, was a major advance in transparency as to the data in its possession….

It is one thing for pharmaceutical companies to consider that data showing the limitations of their drugs are commercially sensitive. But it is quite another – and utterly unacceptable – for the EMA to actually orchestrate the concealment of these data by pharmaceutical companies.

Transparency is not a fad or an end in itself. In the pharmaceutical field, it is a requirement for better and safer patient care. There is no valid reason to hide information about clinical trials, their methodology or their results, or evaluation data obtained on drugs after their market introduction, particularly data on adverse effects.

 

Perhaps there are certain individuals within the EMA who are dissatisfied with this situation? Or who are simply resigned to the power relations at play? Or who feel that the way the EMA operates is a necessary compromise, given the varying legislation? If so, these individuals are not speaking up and their opinions are not reflected in the EMA’s practices. Whatever the case may be, Prescrire’s negative assessment of the level of transparency at the EMA is intended as a wake-up call for policy makers and for legal bodies (such as the Ombudsman) who are in a position to improve the EMA’s operational practices….”

 

Publication of clinical trials on medicinal products: follow-up on trials authorized in Hungary | Trials | Full Text

Abstract:  Background

Clinical research should provide reliable evidence to clinicians, health policy makers, and researchers. The reliability of evidence will be assured once study planning, conducting, and reporting of results are transparent. The present research investigates publication rates, time until publication, and characteristics of clinical trials on medicinal products associated with timely publication of results, measures of scientific impact, authorship, and open access publication.

Methods

Clinical trials authorized in Hungary in 2012 were followed until publication and/or June 2020. Corresponding scientific publications were searched via clinical trial registries, PubMed (MEDLINE), and Google.

Results

Overall, 330 clinical trials were authorized in 2012 of which 232 trials were completed for more than 1?year in June 2020. The proportion of industry initiation was high (97%).

Time to publication was 21 (22) months [median (IQR)]. Time to publication was significantly shorter when trials involved both European and non-European countries (26 vs 69?months [median]; hazard ratio = 0.38, 95% CI 0.22–0.66, p<?0.001), and were registered in both EU CTR and clinicaltrials.gov (27 vs 88?months; hazard ratio = 0.24, 95% CI 0.11–0.54; p<?0.001) based on survival analyses.

A significant amount (24.1%) of unpublished clinical trial results were accessible in a trial register. The majority of available publications were published “open access” (70.93%). A minority of identified publications had a Hungarian author (21.5%).

Conclusions

We encourage academic researchers to plan, register and conduct trials on medicinal products. Registries should be considered as an important source of information of clinical trial results. Publications with domestic co-authors contribute to the research output of a country. Measurable domestic scientific impact of trials on medicinal products needs further improvement.

European parliamentarians urge action on missing clinical trial results

“A cross-party group of members of the European parliament has sent an open letter to regulators urging them to not drop the ball on over 3,400 clinical trial results that are still missing on the EudraCT trial registry, in violation of long-standing transparency rules.

 

 

Under European rules, institutions running investigative drug trials must make their results public within 12 months of trial completion. While the rules are set at the European level, responsibility for encouraging and enforcing compliance lies with the national medicines regulators in each country….”

Substantial delays in clinical data published by the European Medicines Agency – a cross sectional study – Journal of Clinical Epidemiology

Abstract:  

Background

Reporting bias poses a fundamental threat to the transparency and validity of interpretations of clinical trials, which may, in part, be mitigated through access Clinical Study Reports (CSRs). The European Medicines Agency (EMA), under their Policy 0070, prospectively publishes clinical data, including CSRs, submitted as part of marketing authorization applications or post-authorization procedures, although this practice is currently suspended for non-COVID-19 medicines, and have set out planned timelines for publication.

 

Methods

We conducted a cross-sectional study assessing the content and characteristics of all clinical data packages released by the EMA under Policy 0070 and the time to their publication. We extracted the number and characteristics of trials included in the clinical packages, assessed the delay to publication relative to the EMAs planned timeline and whether it differed between the EMAs various transparency measures and types of application procedures.

 

Results

We identified 148 clinical data packages that contained data on a total of 1,005 clinical trials, of which 261 (26%) were labelled as phase 3 trials. Full CSRs were available for 913 (90•8%) of the trials. The median time to publication was 511 (IQR 411 to 574) days. Only 2 (1•4%) of the clinical data packages were published within the EMA’s planned timeline. The delay was shorter for clinical data packages released under the EMAs transparency measures for COVID.19 medicines compared with their standard transparency measure.

 

Conclusion

The clinical data packages released by the EMA under Policy 0070 contained CSRs on many trials but were published with considerable delays relative to the timeline set forth by the EMA, reducing their potential impact on reporting bias.

Journal Checker Tool: Plan S Compliance Validator | Self Archiving Exceptions

“Self-archiving Approved List

This is a list of titles from publishers which have directly acknowledged their intention to honour the self-archiving agreements which authors/institutions make with Plan S funders….

Self-archiving Prohibited List

 

This is a list of titles from publishers which have explicitly expressed an intention to “desk-reject” manuscripts containing the Rights Retention Strategy (RRS) clause….”

4 weeks until new UKRI open access policy – key points about the green route – Cranfield University Blogs

“Did you know?

The policy permits two routes to compliant OA (open access) publishing. Route 2 is to go green.

Green route key points:

The AAM (author accepted manuscript) must be made publicly available on CERES at the same time as the version of record (publisher branded version). No embargo is permitted.
You must include a sentence of prescribed text in your acknowledgements and any cover letter accompanying the submission. This text reads: ‘For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence (where permitted by UKRI, ‘Open Government Licence’ or ‘Creative Commons Attribution No-derivatives (CC BY-ND) licence’ may be stated instead) to any Author Accepted Manuscript version arising’.
Depending on where you choose to publish, you may need to negotiate with the publisher to get permission to include the text in the AAM and publish it with no embargo. Some publishers do not impose an embargo (e.g. IEEE, AIAA, Emerald)….”

NIH issues a seismic mandate: share data publicly

“In January 2023, the US National Institutes of Health (NIH) will begin requiring most of the 300,000 researchers and 2,500 institutions it funds annually to include a data-management plan in their grant applications — and to eventually make their data publicly available.

Researchers who spoke to Nature largely applaud the open-science principles underlying the policy — and the global example it sets. But some have concerns about the logistical challenges that researchers and their institutions will face in complying with it. Namely, they worry that the policy might exacerbate existing inequities in the science-funding landscape and could be a burden for early-career scientists, who do the lion’s share of data collection and are already stretched thin….

Such a seismic shift in practice has left some researchers worried about the amount of work that the mandate will require when it becomes effective….

Others worry that data-management activities will further sap funds from under-resourced labs. Although the policy outlines certain fees that researchers can add to their proposed budgets to offset the costs of compliance with the mandate, it doesn’t specify what criteria the NIH will use to grant these requests….

Despite its potential pitfalls, Ross thinks that the policy will have a ripple effect that will persuade smaller funding agencies and industry to adopt similar changes. “This policy establishes what people expect from clinical research,” he says. “It’s essentially saying the culture of research needs to change.” ”

France rules Google Analytics non-compliant with GDPR | Matomo

The French Data Protection Agency, CNIL (Commission nationale de l’informatique et des libertés), has concluded that the use of Google Analytics is illegal under GDPR. The CNIL has begun issuing formal notices to website managers using Google Analytics.

Trends and variation in data quality and availability on the European Union Clinical Trials Register: A cross-sectional study – Nicholas J DeVito, Ben Goldacre, 2022

Abstract:  Background/Aims:

The European Union Clinical Trials Register is a public facing portal containing information on trials of medicinal products conducted under the purview of the European Union regulatory system. As of September 2021, the registry holds information on over 40,000 trials. Given its distinct regulatory purpose, and results reporting requirements, the European Union Clinical Trials Register should be a valuable open-source hub for trial information. Past work examining the European Union Clinical Trials Register has suggested that data quality on the registry may be lacking. We therefore set out to examine the quality and availability of trial data on the registry with a focus on areas that fall under the authority of regulators in each European Union/European Economic Area country.

Methods:

Using data scraped from the full European Union Clinical Trials Register public dataset, we examined the extent of issues with three areas of trial data availability linked to European Union regulations. We examined whether there is evidence for missing registration of protocols in the public database, whether information on the completion of clinical trials is being made available and how often the results of trials are posted to the registry. We assessed each area overall, and examined variation between national regulators and over time.

Results:

Major issues with the availability of expected protocols and information on trial completion were focused in a few countries. Overall, when comparing enrolment countries from tabular results to available registrations, 26,932 of 31,118 (86.5%) expected protocols were available and 22 of 30 (73%) countries had over 90% of expected protocols available. The majority of missing protocols, totalling 2764 (66%), were from just three countries: France, Norway and Poland. Evidence for this issue is further supported by data on trends in new registrations by country over time. Low availability of data on trial completion is also most pronounced in a minority of countries, like Spain and the Netherlands, with consistent trends for missingness over time. Finally, overall results availability is substantially worse among the 23,623 trials with a single registered European Union protocol (n = 6259, 26.5%) compared to 13,897 of those taking place in multiple countries (n = 8423, 60.6%). Reporting for single-protocol trials was consistently low across both time and location.

Conclusion:

Deficiencies in the public availability of trial protocols, trial completion information and summary results complicate the utility of the European Union Clinical Trials Register for research, transparency and accountability efforts. Users of the registry would benefit from a more complete and accurate accounting of the European research environment via the official European Union registry. We recommend regulators at the national and pan-national level undertake routine audits of approved trials to ensure national-level issues are proactively and transparently identified, documented and addressed.

Trends and variation in data quality and availability on the European Union Clinical Trials Register: A cross-sectional study – Nicholas J DeVito, Ben Goldacre, 2022

Abstract:  Background/Aims:

The European Union Clinical Trials Register is a public facing portal containing information on trials of medicinal products conducted under the purview of the European Union regulatory system. As of September 2021, the registry holds information on over 40,000 trials. Given its distinct regulatory purpose, and results reporting requirements, the European Union Clinical Trials Register should be a valuable open-source hub for trial information. Past work examining the European Union Clinical Trials Register has suggested that data quality on the registry may be lacking. We therefore set out to examine the quality and availability of trial data on the registry with a focus on areas that fall under the authority of regulators in each European Union/European Economic Area country.

Methods:

Using data scraped from the full European Union Clinical Trials Register public dataset, we examined the extent of issues with three areas of trial data availability linked to European Union regulations. We examined whether there is evidence for missing registration of protocols in the public database, whether information on the completion of clinical trials is being made available and how often the results of trials are posted to the registry. We assessed each area overall, and examined variation between national regulators and over time.

Results:

Major issues with the availability of expected protocols and information on trial completion were focused in a few countries. Overall, when comparing enrolment countries from tabular results to available registrations, 26,932 of 31,118 (86.5%) expected protocols were available and 22 of 30 (73%) countries had over 90% of expected protocols available. The majority of missing protocols, totalling 2764 (66%), were from just three countries: France, Norway and Poland. Evidence for this issue is further supported by data on trends in new registrations by country over time. Low availability of data on trial completion is also most pronounced in a minority of countries, like Spain and the Netherlands, with consistent trends for missingness over time. Finally, overall results availability is substantially worse among the 23,623 trials with a single registered European Union protocol (n = 6259, 26.5%) compared to 13,897 of those taking place in multiple countries (n = 8423, 60.6%). Reporting for single-protocol trials was consistently low across both time and location.

Conclusion:

Deficiencies in the public availability of trial protocols, trial completion information and summary results complicate the utility of the European Union Clinical Trials Register for research, transparency and accountability efforts. Users of the registry would benefit from a more complete and accurate accounting of the European research environment via the official European Union registry. We recommend regulators at the national and pan-national level undertake routine audits of approved trials to ensure national-level issues are proactively and transparently identified, documented and addressed.

Kakai | An analysis of the factors affecting open access to research output in institutional repositories in selected universities in East Africa | Journal of Librarianship and Scholarly Communication

Abstract:  INTRODUCTION Institutional repositories (IRs) present universities with an opportunity to provide global open access (OA) to their scholarship, however, this avenue was underutilised in two of the three universities in this study. This study aimed at proposing interventions to improve access to research output in IRs in universities in East Africa, and it adds to the depth of knowledge on IRs by pointing out the factors that limit OA in IRs, some of which include lack of government and funder support for OA and mediated content collection workflows that hardly involved seeking author permission to self-archive. METHODS A mixed methods approach, following a concurrent strategy was used to investigate the low level of OA in IRs. Data was collected from three purposively selected IRs in universities in East Africa, using self-administered questionnaires from 183 researchers and face-to-face interviews from six librarians. results The findings revealed that content was collected on a voluntary basis, with most of the research output deposited in the IR without the authors’ knowledge. The respondents in this study were, however, supportive of the activities of the IR, and would participate in providing research output in the IR as OA if required to do so. CONCLUSION The low level of OA in IRs in universities in East Africa could be increased by improving the IR workflow, collection development, and marketing processes. Self-archiving could be improved by increasing the researchers’ awareness and knowledge of OA and importance of IRs, while addressing their concerns about copyright infringement.