June 2022: Netherlands Update

Netherlands Trial Register (NTR) No Longer Available

As per an update posted on Central Committee on Research Involving Human Subjects (CCMO) website on June 24, 2022, the NTR is no longer available. The National Trial Register, in which the CCMO register and the NTR will be merged, is not yet ready for use.

Guidelines provided to researchers for the time being are as below:

  • For ongoing investigations that were already reported to the NTR: The data as registered in NTR are automatically included in the International Clinical Trial Registry Platform (ICTRP) and can be consulted on the  ICTRP Search Portal. The researcher thus still meets the requirement of prospective registration as required by the International Committee of Medical Journal Editors (ICMJE) for publication in scientific journals. Unfortunately, the data can no longer be edited. If adjustment of the data is nevertheless necessary, the research will have to be registered again with another recognized register, see below. A reference to the trail ID of NTR must be included.
  • For registering new trials: New studies can be registered on any WHO recognized registers, such as  ClinicalTrials.gov. The full list of recognized registries can be found at Primary registries in the WHO registry network.

As soon as this situation changes, the CCMO will inform researchers. Click here for more information.

June 2022: What’s New on ClinicalTrials.gov

On June 09, 2022, the following updates were posted on the  Clinicaltrials.gov What’s New section.

The new FAQ for the deadline for submitting a good cause extension for prematurely terminated studies have been included and the information to be taken into consideration for registering expanded access records have been updated.

A responsible party must submit results information no later than one year after the primary completion date unless the responsible party has submitted a certification of delay, a request for an extension for good cause, or a request for a waiver of the requirements for submission of results information.

The standard results information submission deadline is one year after the actual Primary Completion Date. The termination date does not impact the actual Primary Completion Date or the standard results information submission deadline.

A good cause extension request submitted on or after the standard results information submission deadline date, would be late and would not be accepted, regardless of when the decision to terminate the trial was made.

More information can be found here: FAQ

Detailed considerations for registering expanded access records can be found here.

May 2022: Switzerland Update

An update posted on the Kofam portal on May 27, 2022, informs users of the most important new developments and changes relating to clinical trials with in-vitro diagnostic products (IVDs) which  are regulated by the Ordinance on Clinical Trials with Medical Devices (ClinO-MD) from May 26, 2022.

According to the update, in addition to the existing obligation to prospectively register clinical trials with IVDs, the results of trials with IVDs must now also be published in a trial registry. This also applies to clinical trials with IVDs already underway when the ClinO-MD entered into force on 26 May 2022. The updated ClinO-MD is also now available.

The update further informs users of the categorization of IVDs and classification of clinical trials regulated under ClinO-MD into clinical investigation and performance studies.

An online information event, to cover the new and changed requirements and clarify the specifications in Switzerland will be held on  3 November 2022. Participation is free of charge and individual presentations will be provided on the Swissmedic website in German, French, Italian, and English a few days before the event.  The presentations during the event will be given in German and will be interpreted simultaneously into French. The event will not be recorded. The presentations can not be viewed at a later date.

More information can be found here.

May 2022: Switzerland Update

An update posted on the SwissMedic portal on May 26, 2022, informs users of the change in legal requirements for clinical trials with in-vitro diagnostic products (IVDs) in Switzerland.

From 26 May 2022, at the same time as the application of the In Vitro Diagnostics Regulation (IVDR) in the EU, clinical trials with in vitro diagnostic medical devices will be regulated in the Ordinance on Clinical Trials with Medical Devices (CTO-MedD) and no longer in the Ordinance on Clinical Trials (ClinO).

These new transitional periods in the EU have also been taken into account accordingly in the Swiss Ordinance on In Vitro Diagnostic Medical Devices (IvDO). To avoid jeopardizing a sufficient supply of medical devices to Switzerland, the Federal Council has set lengthy transitional periods – over one year for most devices – for designating the CH-REP.

More information can be found here.

April 2022: Netherlands Update

Performance studies on in vitro diagnostics (IVDR)

On 26 May 2022, the EU Regulation on Medical Devices for In Vitro Diagnostics, also known as the In Vitro Diagnostics Regulation (EU no 2017/746, IVDR) will come into effect. The IVDR contains specific rules for the submission, assessment and execution of performance studies on in vitro diagnostics, IVDs. On the CCMO website, the necessary information for researchers is available on the special theme page Performance studies for in vitro diagnostics as of 29 April 2022.

Performance studies on in vitro diagnostics are divided into different legal frameworks. These frameworks are described in Legislation and regulations, guidelines and standards .

For information about the submission and content of the research file, please visit the Primary Submission and Standard Research File page.

On the During and after page, you will find information about what to report during and after an IVD performance study.

Results:

  • The client must submit a report on the performance study within one year of the end of the performance study. The requirements for the report are set out in Annex XIII of the IVDR (section 2.3.3 of Section A).
  • The sponsor must submit a layperson summary of results within one year of the conclusion of the performance study.
  • If it is not feasible for scientific reasons to submit the report and the lay summary within one year of the end of the performance study, the client must have laid down a different period with reasons in the plan for the performance study (Clinical Performance Study Plan — CPSP). The review committee assesses whether the extension of the term is justified.
  • If the performance study been suspended or terminated prematurely, a period of three months instead of one year applies for submitting the report and the lay summary.
  • If the performance study been suspended and restarted within three months, the client does not have to submit a report and a lay summary.

Once Eudamed is operational, the results of the performance study must be uploaded in Eudamed and the report and the lay summary will be made public via Eudamed (IVDR Article 73.7).

Information about starting an appeal or objection procedure against a decision by the accredited MREC or the CCMO can be found under  Appeals and objections.

April 2022: US Regulatory Update

FDA Takes Action For Failure to Submit Required Clinical Trial Results Information to ClinicalTrials.gov

The FDA issued a Notice of Noncompliance on April 15, 2022, to Ocugen for failing to submit required summary results information to ClinicalTrials.gov. The company’s applicable clinical trial evaluated the efficacy of Brimonidine Tartrate Nanoemulsion Eye Drop Solution in the Treatment of Dry Eye Disease (DED).

The prenotice was issued on July 21, 2021, alerting Ocugen to potential noncompliance with the requirement to submit clinical trial results. The company failed to update the study results for their applicable clinical trial (ACT) within 30 days after the prenotice was issued. Upon receiving this notice of noncompliance, FDA provides Ocugen 30 days to submit the required summary results information. The FDA is authorized to seek civil monetary penalties for Ocugen’s violation, including additional civil money penalties and other regulatory action, such as injunction and/or criminal prosecution, without further notice, if Ocugen fails to submit the required information within the 30-day period.

The Notice of Noncompliance has been posted to the FDA’s website and information about the noncompliance has also been posted on the study record on ClinicalTrials.gov by NIH. NIH will continue to update the ClinicalTrials.gov records for applicable clinical trials that are the subject of a Notice of Noncompliance with information regarding whether the noncompliance has been corrected and the amount of civil money penalties assessed, if any.

For more information, please refer to the Letter of noncompliance on the FDA Website: Non-Compliance Letter

April 2022: Netherlands Update

As of April 4, 2022, the CCMO’s 2021 Annual Report will be available and presented to the Minister of Health, Welfare and Sport, Ernst Kuipers and the presidents of the Senate and House of Representatives. In the annual report, the CCMO reports on its activities in the past year.

In addition to the introduction of the new legislation for research with medical devices, the MDR (Medical Device Regulation), 2021 was dominated by preparations for the European Medicines Regulation, the CTR (Clinical Trial Regulation) for everyone involved in clinical research. The CCMO pays extra attention to this subject in this annual report. In three interviews, professionals talk about the challenges of the CTR, but also about the opportunities that this regulation offers for clinical research in the Netherlands.

The annual report also provides insight into the legal duties of the CCMO. In addition, important national and international developments of the past year are discussed that have consequences for the Dutch assessment system and the CCMO. The annual report also contains figures and data about the research files that were assessed in 2021 by the recognized medical ethics review committees (MRECs) and the CCMO on the basis of the Medical Research Involving Human Subjects Act (WMO) and the Embryo Act.

Here is a quick link to the Annual Report.

April 2022: Combined Review – New Video Explains IRAS User Roles and Recent Changes

On 06 April 2022, HRA UK posted on its website, a short, animated video to explain how the different roles work in IRAS for combined review and the permissions each has in the system.

The clip focuses on collaborators, covering recent changes to IRAS for combined review of a CTIMP or combined CTIMP and device project.

  1. Changes are applicable only to the new part of IRAS, for applications submitted through combined review.
  2. Every project in the new part of IRAS must have a Chief Investigator (CI) and a Project Deputy.
  3. Now, all collaborators can have edit access in the system. Moreover, collaborators can now book the Research Ethics Committee (REC), respond to requests for further information (RFIs), create amendments or reports and provide end of trial notification.
  4. If the project is not yet authorised, all collaborators will have been upgraded to unlimited edit access. If the project has been authorised, all collaborators will be removed automatically by the system when this change is made. The Project Deputy or CI will need to re-add the collaborators.
  5. Changes made by people with edit access will be stored once saved.
  6. The person that sends the project to the Sponsor will receive the tasks in the system to book the REC, and then to respond to any RFIs, if needed.
  7. The email correspondence about the project is only sent to the contact listed in question C1.

To view the full video, click here.

March 2022: The Draft UK Resolution: Strengthening Clinical Trials to Improve Public Health

An article, “UK proposes global effort to strengthen clinical trial transparency” has been published on 30 March, 2022, on TranspariMED.

On 30 March 2022, an original draft resolution text by the United Kingdom – ‘Strengthening Clinical Trials to Improve Public Health’ was made available online. The UK will make a proposal at the 75th World Health Assembly (WHA) to be conducted between 22-28 May 2022, to improve clinical trial quality and conduct globally.

The following steps pertaining to clinical trial study design, registration, and results posting are proposed in this draft:

  • Ensuring new trials are not duplicative, are of sufficient size and appropriate design
  • Introducing grant conditions for funding clinical trials to encourage the use of standard data protocols and to mandate registration on a clinical trial registry within the World Health Organization’s International Clinical Trials Registry Platform (ICTRP)
  • Establishing mechanisms to secure a commitment from researchers to share pre-publication results with regulatory bodies
  • Establishing mechanisms to ensure the results of clinical trials are reported in a timely manner following primary study completion, including through registering the results on a clinical trial registry within the ICTRP, and encouraging timely publication of the trial results ideally in an open-access publication

Additionally, the draft requests the Director General of the WHO to develop a global action plan for implementing the principles of this resolution and to present the draft action plan for consideration by the 76th World Health Assembly in 2023.

Download the full text of the UK draft resolution here.

March 2022: Germany Regulatory Update

The German authority (BfArM) had recently updated the requirement for results posting according to Section 42b of the German Medicines Act (AMG) for trials conducted for medicinal products in humans on January 27, 2022.

According to this update, as of January 27, 2022, the previously applicable Section 42b paragraph 2 AMG has been repealed, i.e., there is no longer any obligation for the sponsors of clinical trials with medicinal products that have been approved/approved in the central procedure for placing them on the market to submit results reports to the competent higher federal authority.

The German authorities were asked a few questions to clarify the period/timeline from when this new regulation would be applicable.

The authorities confirmed that the new regulations do not provide for a transition period for the amendment of Section 42b AMG. The amendment applies directly as of January 27, 2022. Therefore, any studies that had a deadline to report results after January 27, 2022, no longer have to submit the results after January 27, 2022, regardless of when the study ended.

Further, it was also stated that for submissions of results reports according to Section 42b paragraph 2 AMG, which should have been done regularly until January 27, 2022, and for which the requirement was not met in time, the obligation to submit a result report remains unchanged.