September 2021: UK Regulatory Update

Implementation of UK HRA’s New Reporting Standards for Clinical Research

As per the latest update from UK Health Research Authority, new reporting standards have been implemented to ensure that all researchers fulfill their responsibilities to make their research open and transparent. This is in line with the commitments set out in the Make it Public research transparency strategy.

From Wednesday 15 September health and social care researchers are expected to submit information at the end of their research study to the HRA online, explaining how they have fulfilled their transparency responsibilities. This is part of a set of changes which make it easy for researchers to be transparent and enable the HRA to know whether they are meeting the requirements.

This will also enable to see more clearly what proportion of studies are fulfilling transparency requirements, including information about study registration, publication of results, informing participants of the outcome of the study and the sharing of data and tissue (if applicable).

In order to standardize the information submission, a New Final Report Form had been published.

August 2021: Integrated Research Application System (IRAS)

On August 31, 2021, MHRA launched new systems functionality to support the combined review of Clinical Trials of Investigational Medicinal Products (CTIMPs). The combined review service (previously known as ‘combined ways of working’) offers a single application submission route and a coordinated review for CTIMPs, resulting in a combined regulatory and ethics decision on a clinical trial.

The trial sponsors can now manage their complete trial lifecycle via combined review using the Integrated Research Application System (IRAS) – from initial application through to amendments, safety reporting, end of trial notification and submission of summary results. From January 01, 2022, the combined review will become the only way to apply for CTIMP approvals.

August 2021: Combined Review Service for CTIMPs applications

Formerly known as the Combined Ways of Working (CWoW), the new Combined Review Service, will be utilised to submit new Clinical Trials of Investigational Medicinal Products (CTIMPs) applications from January 01, 2022. It encompasses a “single submission, a coordinated review, and combined communications” process to facilitate all communications between the authority and all the CTIMP sponsors and applicants.

The system will allow the sponsor or applicant to submit a single application to both the MHRA and Research Ethics Committee (REC). The consequent MHRA authorization and REC opinion would thereby be delivered together in one step. This streamlined process will also apply to further requests sponsors or applicants make for any substantial amendments to the trial authorisation. The system will also allow viewing and revision of the application information directly in the system.

The facilitate the transition, NHS has released a step by step guide to using IRAS for combined review – Health Research Authority (hra.nhs.uk).

UK HRA Business plan: 2021 – 2022

The Business Plan 2021/2022 released by the UK HRA focuses on 3 main objectives: High-quality research integrating the interests of participants, public involvement, and iterating the importance of transparency standards. Making services user-friendly and efficient to improvise research environments and lastly to strengthen the organization in terms of integrity and values.

The plan specifies the delivery of the next phase of the Make It Public transparency strategy in the form of definitive timelines. Provisions to facilitate registration of all clinical trials of medicinal products prospectively, and releasing a tool that would allow the public to see all approved research studies and their findings.

August 2021: CTIS Training Update

Dissemination guidelines for training materials: CTIS training programme

European Medicines Agency published a new guideline document related to the Clinical Trial Information System (CTIS) training programme, on August 05, 2021.

This guide is intended to support instructors in using the training materials prepared for the CTIS Training Programme. It is suggested that trainers follow a blended learning approach combining asynchronous with synchronous activities for an optimal learning experience of end-users while making efficient use of their time.

Combining the two training methods, by sharing some materials with participants ahead of a real-time training session, will ensure that participants can assimilate some contents individually and reflect on questions they may have. The training session can then be used to check participants’ knowledge absorption, address their questions, and collect input on the training materials and methodology.

For more information, refer to the guideline here.

July 2021: Clinical Trial Data Reporting in EU Countries

In Europe, the enthusiasm for trials is not matched with a zeal for reporting the results to the public. Nearly 28% of completed European trials in the EU Clinical Trials Register (EUCTR) on 1 July—had not posted their results according to the latest data from the EU Trials Tracker, set up by U.K. researchers in 2018. Public research hospitals and universities are responsible for the vast majority of the lapses, which appear to violate European rules that require sponsors to post their results within 1 year of a trial’s conclusion.

Some researchers from public trial centers aren’t keen to disclose negative results and others believe publishing results in a journal fulfills the reporting requirement, even though journal articles can come years later and are often not made public. The Public Assistance Hospitals of Paris (AP-HP), the largest clinical trial center in Europe has reported results for just one of 35 trials completed more than 12 months ago, according to the EU tracker. More than 200 of the center’s trials are listed on EUCTR as ongoing, even though more than half of them began more than 10 years ago.

The current rules stem from 2001 European guidelines are considered as “soft legislation” and some nations seem to be taking advantage. According to current French regulations, there is no obligation to post results in the EU database, their priority has been to publish both positive and negative results in peer-reviewed journals. In the Netherlands, it is sufficient if sponsors post results in the Dutch trial registry, run by the Central Committee on Research Involving Human Subjects (CCMO). The CCMO website states that sponsors must also post results of medicines trials in the EU database, but Amsterdam University Medical Center (AUMC) does not follow that rule seeing any advantage in double registrations or in doubling researchers’ administrative burden.

Europe is getting more serious about enforcing the reporting requirements. Since the launch of the EU tracker in 2018, timely reporting of results has risen from 50% to 72% of completed trials. The European Medicines Agency (EMA) has stepped up reminders to trial leaders and has sent out about 30,000 reminders to overdue trial sponsors since 2018, another possible driver of improvement. Special notices go out for COVID-19 trials.

EMA’s new trial registry Clinical Trials Information System (CTIS) launch scheduled for Jan 2022 will eventually replace the EUCTR portal after a 3-year transition period and will end the tedious process of registering trials in each participating country. Sponsors will upload all trial data, from start to finish and the relevant national regulators will review the data before the information becomes public in one, linear, straight-through process. Once CTIS goes live, a 2014 European regulation will take effect, empowering national regulators in the European Economic Area to enforce the reporting of results. It will be for governments to decide how the national regulators should enforce reporting and what penalties they should impose for lapses.

Denmark, known for its vigilant regulation of drugs and trials already has a law that allows authorities to fine or imprison clinical trial leaders who do not meet deadlines for reporting results.

Additional details are found here.

July 2021: Regulatory Update

Health Research Authority (HRA) “Make it Public” 1st Virtual Conference

HRA is hosting its first virtual conference, “Make it public: transparency and openness in health and social care research” on November 3 and 4, 2021.

In this conference, HRA will display UK-wide case studies for transparent research and discuss working together on improving the visibility of studies. One can submit the case study as an example of transparency done well by following the guidance for submitting case studies. The deadline for submission is July 23, 2021.

May 2021: New Database from National Institute for Health Research

The United Kingdom’s National Institute for Health Research (NIHR) Innovation Observatory has launched ScanMedicine, a searchable database of global clinical trials, for use by researchers, clinicians, and the public.

ScanMedicine is free to access, draws data from 11 major clinical trial databases around the world, including US ClinicalTrials.gov, and features data on medical devices, diagnostics, and digital apps.

The tool collates and presents the latest data in a readily accessible format, enabling users to filter results by trial type, phase, registry and more, as well as to view searches as visualisations and infographics for a ‘quick-look’ version of their results, identifying gaps and trends.

March 2021: UK MHRA Pilots Patient Involvement In New Applications

The MHRA has announced a new pilot, which will request, on a voluntary basis, applicant companies of new active substances and new indications to provide evidence of the patient involvement activities they undertook when developing their product.

For clinical trials, whilst additional information won’t be requested at this early exploratory stage of the pilot, the MHRA will be documenting in medical assessment reports if there is evidence of patient involvement in clinical trial applications in order to better understand the current scope of activities.

In considering how patient involvement is integrated into the approvals process, the MHRA hopes to learn from any patient-related activities that take place during development, and use this knowledge to improve the quality of clinical drug development and health outcomes in the future. During the pilot, the information provided by the applicants will be voluntary and will not alter the outcome of their application. However, in future, the agency hopes that a successful pilot will lead to patient involvement playing a greater role in the final assessment process, when clinical trials are approved, or medicines are licensed.

The agency will undertake a detailed analysis of the evidence submitted. This crucial patient-focused pilot supports the ambitious vision of The Future of UK Clinical Research Delivery. As a partner, the MHRA is proud to be part of strengthening and contributing to this project.

For more information, please click here.

December 2020: UK Regulatory Update

An FAQs document was published by MHRA on 21 December 2020. The guidance document referred to in the FAQs is the guidance document published on September 01, 2020 (LINK).

Section C, questions 3, 4, 5, 7, 8 and 9 deal with disclosure related aspect. Below are the summarized points based on the questions and answers:

  1. For the UK clinical trials (CTs) approved and entered in EudraCT prior to January 01, 2021, the results posting can still be completed in EudraCT. This will meet the UK publication requirement.
  2. For CTs approved after January 01, 2021, results can be posted on a public database, where the study is registered.
  3. Once the results are made public, an email confirmation must be sent to MHRA about the same.
  4. If a clinical trial is not on a public register (e.g. Phase 1 healthy volunteer), summary results should be submitted to the MHRA.
  5. The Health Research Authority (HRA) at [email protected] will need to be contacted, in case deferral is required.
  6. If a Phase 1 healthy volunteer study is approved before December 31, 2020, and entered on the EU Clinical Trials Register (but not visible to the public), then either a copy of the EU Clinical Trials Register upload or a copy of the CSR synopsis has to be submitted to MHRA