Approvals Of Medicines from Regulatory Agencies Despite Omitted Clinical Trials

As per a post dated 3rd January, 2022 on TranspariMED, a drug to treat attention deficit hyperactivity disorder (ADHD) was approved by several regulatory agencies without all relevant clinical trials having been reviewed, a study published in November 2021 suggests.

The omitted trials accounted for a median of 45% of all data from participants in relevant studies, raising concerns that regulators may not be looking at all relevant trials when assessing the safety and efficacy of new treatments.

Six regulators did not consistently list all relevant trials in public approval documents: BfArM (Germany), FDA (United States), Health Canada, MHRA (United Kingdom), PMDA (Japan) and TGA (Australia). With the exception of Health Canada, regulators did not explain why certain trials were omitted.

The researchers identified 18 relevant trials and 13 drug applications filed with 7 different regulators by four pharma companies: Janssen, Medice, Novartis, and Purdue. They found that in just over half of regulatory documents, relevant clinical trials were not mentioned.

The authors recommend that regulatory agencies should systematically search for trials themselves, rather than relying on drug companies to identify all relevant studies, and that pharma companies should be held accountable if they fail to inform regulatory agencies about all available evidence.

For more details, please refer to this post on TranspariMED.


December 2021: Netherlands Update

New online tool provides insight into the scope of CTR

The CCMO on December 23, 2021, has released an update to provide information about the Clinical Trial Decision Tool which was jointly developed by the Paul Janssen Futurelab and the CCMO.

The new Clinical Trial Decision Tool helps determine whether the drug research falls within the scope of the Clinical Trial Regulation (CTR). The CTR will become applicable in the European Union on January 31, 2022.

After answering a maximum of 13 questions, the Clinical Trial Decision Tool shows whether or not the research falls within the scope of the CTR. The tool also shows whether that is a low-intervention clinical trial. Adapted rules apply to such research.

For more information, follow this link.

December 2021: Webinars for Transitioning to Combined Review

The HRA UK on December 22, 2021, has released an update for the Combined Review process.  They will be running a series of free, live webinars during December and January to provide an overview of upcoming changes and how they can affect individually the CTIMP applicants, sponsors, and NHS/HSC organizations depending on the role.

Bookings would be done online and the user needs to register for an account on the Learning Management System.

December 2021: Netherlands Update

Dutch Institutions Finally Make Progress on Clinical Trial Reporting

As per the news article posted on TranspariMED on 14-Dec-2021, over 700 clinical trials run by the ten largest Dutch institutions are still missing results, but major institutions are now working to fix the problem, new data suggest.

Full results are publicly available on the European trial registry for only 52 clinical trials run by the Dutch cohort, less than 7% of all due trials. This is still far below the European average reporting rate of 28% for major non-commercial trial sponsors.

The country’s largest sponsor, Radboudumc, has the strongest transparency record with 21 reported trial results, while estimated 102 Radboudumc trials are still missing results or are not marked as completed and 124 trials are not yet due to report results.

On the positive side, nearly all major Dutch institutions have uploaded additional results over the course of 2021. Between February and November 2021, Radboudumc uploaded 10 due trial results as part of an ongoing systematic effort to clear its backlog of unreported trials. Erasmus University uploaded 6 additional due results. Only HOVON Foundation has made no visible progress.

Netherlands may finally be starting to catch up with the rest of Europe in terms of clinical trial transparency.

For additional details, please follow this link.

December 2021: Czech Republic Update

Decree No 463/2021 on “Detailed Conditions Governing the Conduct of Clinical Trials on Medicinal Products” has been published in the Collection of Regulations of the Czech Republic by the Ministry of Health, Czech Republic on December 10, 2021.

Decree No 463/2021 shall be applicable only to clinical trials conducted in Czech Republic and submitted via the Clinical Trials Information System (CTIS) portal and assessed pursuant to  EU Regulation No 536/2014. Decree No 463/2021 will come into effect on January 31, 2022.

More information can be found here.

December 2021: Netherlands Update

Transition from NTR to CCMO

Some additional information is available in continuation to the service announcement displayed on the Netherlands Trial Registry (NTR) website:

  • It is currently not possible to register a new study with the NTR since it is permanently closed for new study registrations
  • The NTR will get a restart with the Central Committee on Research Involving Human Subjects (CCMO) registry. The new Dutch Trial Register is not yet available and there is no clarity as to when it will go live
  • New studies cannot be registered in the NTR during the transition phase, however, studies already registered in the NTR will be included in the New Trial Register and the registration number (NL XXXX) can continue to be used when publishing the study in a scientific journal
  • In addition, as a researcher it remains possible to make changes to already registered studies in NTR
  • It is further advised to register studies with another WHO recognized registry, such as ISRCTN Registry or

For more details, please follow this link.

December 2021: An IQWiG Update: Call for a Central Portal for Clinical Study Reports

An update about a journal article, Call for a Central Portal for Clinical Study Reports (CSRs) was posted, on the Institute for Quality and Efficiency in Health Care (IQWiG) website on December 01, 2021.

The IQWiG is a professionally independent scientific institute under the Federal Joint Committee (G-BA) or the Federal Ministry of Health (BMG), Germany. Two authors from IQWiG have published an open-access article in the Journal of European CME. This article discusses the need for a central, public, and worldwide portal for accessing CSRs of all the clinical studies carried out worldwide.  The authors also suggest the use of the CSRs not only for dossier assessments but also for developing other information formats such as clinical practice guidelines, continuing medical education (CME) materials, and patient information.

The article acknowledges that the quality of clinical practice guidelines has improved in the form of prospective study registration as a precondition for publication in scientific journals in 2004 and mandatory registration of studies and summaries of study results. Even then, the information related to any intervention, is scattered in different information sources. These sources could be journal publications, public and industry study registries, as well as regulatory and health technology assessment (HTA) agency websites, which results in extensive resources required for retrieving and screening of this information.

As a way of providing a solution to these problems of scattered information sources and the possible influence of the industry on certain scientific materials like the CME, the article suggest establishment of a digitised clinical study portal containing all CSRs which would enable the resource-efficient production of unbiased evidence synthesis, not only to inform health policy decisions, but also for use in other information formats described above, and thus ultimately improve treatment outcomes. The article also provides the basic structure of the portal for each clinical study, including a unique identifier as well as the corresponding CSR (provided proactively) and anonymized IPD (provided on request).

Since experience has shown that voluntary commitments by industry in disclosing trial information are insufficient, the legislators are called upon to establish such a central portal and to make the submission of CSRs mandatory.

For more details of this article can be found here.

November 2021: HRA Announces a New e-Learning Module

The UK, Health Research Authority (HRA) announced a new e-learning module for lay summaries on 26 November 2021.

A plain language summary is mandatory for all the clinical studies registered on the ISRCTN registry. To support researchers in communicating results, the HRA has developed an e-learning module that will give a better understanding of how to produce consistent plain language summaries of research.

For access to the e-learning module, an account needs to be set up on the learning system. This account can be created for free here.

November 2021: Webinars for Combined Review

On 24 November 2021, HRA UK has updated that the Combined review will come into effect for all Clinical Trials of Investigational Medicinal Products (CTIMPs) from 1 January 2022. It was initially run as a pilot that started in 2018 under the name ‘Combined Ways of Working’ (CWoW) but from January 2022 it will be the only way to submit CTIMPs to MHRA and REC. Applications will be completed and submitted in the new part of IRAS.

To facilitate the transition there will be 3 webinars held-Combined Review as an Applicant, Combined Review for Sponsors, and Combined Review for NHS/HSC Participating OrganisationsThe webinars will provide an introduction to upcoming changes, help check the impact of the changes on the organization so as to update any internal processes/procedures as required thereof and provide guidance to available resources for further information and support.

November 2021: Netherlands Update

Information on EU Clinical Trial Regulation available on CCMO’s website

On 31 January 2022, the EU Clinical Trial Regulation (CTR) 536/2014 will apply in the European Union. All required information for investigators is available on the Central Committee on Research Involving Human Subjects (CCMO) website in a special section for research with medicinal products in accordance with the CTR.

The section consists of six parts:

The information is currently only available in English. A Dutch translation will be published soon.

The CTR replaces the current Clinical Trials Directive 2001/20/EC, which has been embedded in the Dutch Medical Research Involving Human Subjects Act (WMO). In contrast to the Clinical Trials Directive, the CTR stipulates that the procedures for the submission, assessment and conduct of research with medicinal products are the same throughout the EU. A transition period of three years applies. Partly due to the transition period for the CTR, the page Guide to the review procedure has been revised. Here you can find information on the legal frameworks and procedures for medical research, including research with medicinal products.