How publication under Policy 0070 ran, stopped and restarted
Publication of clinical reports under EMA Policy 0070 began in October 2016, and its first year showed what the public could reach and who used the published data. Publication then stopped in 2018 and stayed suspended for years, broken only by exceptional publication for COVID-19 medicines, until the policy was relaunched with procedural changes and a second step planned for the documents the first left out.
The policy's course from launch to relaunch
The policy was launched in 2015, and its first publication was submitted in 2016. It originally had two phases, the first for clinical study reports and the second intended for individual patient data. It was suspended in 2018 because of operational changes brought by the United Kingdom's withdrawal from the EU, revised in 2019 to cover both clinical study reports and individual patient data, and resumed in 2020 with condensed reporting requirements for COVID-19 medicines. It was relaunched in 2023.
What the agency opened to the public
The first packages under Policy 0070 were published in 2016, when on 20 October the European Medicines Agency gave open access to clinical reports for new medicines for human use authorised in the European Union. This publication followed the agency's adoption of a policy on the publication of clinical data for human medicines. For every new medicine, citizens, including researchers and academics, can directly access thousands of pages from the clinical reports pharmaceutical companies submitted to the agency with their marketing-authorisation applications. Clinical reports give information on the methods used and the results of the clinical trials conducted to demonstrate the safety and efficacy of medicines. The agency described itself as the first regulatory authority worldwide to give such broad, open access to the clinical data companies submit in support of their marketing-authorisation applications.
In October 2016 the agency forecast that its clinical data website, at https://clinicaldata.ema.europa.eu, would offer access to approximately 4,500 clinical reports a year.
The first year of publication
On 16 July 2018 the agency published the first report on the implementation of Policy 0070, which it called its flagship policy on the publication of clinical data. The report covers one year from the launch of the agency's clinical data website on 20 October 2016 and lists the 50 medicines for which clinical data were published, including orphan, paediatric, biosimilar and generic medicines, with the corresponding 54 regulatory dossiers.
To implement the policy successfully, the agency made sure that the pharmaceutical industry received regularly updated guidance, and it gave individual companies one-to-one assistance to prepare them for the publication of clinical data. By the agency's account, this let it publish an average of six dossiers a month from October 2017 to May 2018, reaching its hundredth published dossier on 29 May 2018.
Who used the published data
The clinical data published for those 50 medicines attracted a total of 3,641 users, resulting in 22,164 document views and 80,537 downloads for non-commercial research purposes.
Of the respondents to a user survey of the clinical data website, 62% were affiliated with the pharmaceutical industry, 14% with academia, 8% were patients and 8% healthcare professionals. Very few respondents disagreed with the agency's rationale for developing the policy, and most strongly agreed that publishing clinical data increases public trust in the agency's decision-making and that it allows the reassessment of clinical data.
What the agency claimed for the policy
In July 2018 the agency described its open access to clinical data as a cornerstone of its commitment to openness and transparency, a commitment endorsed by the EU General Court's rulings on the limited scope of commercial confidentiality with regard to authorised medicines. It held that its proactive publication of clinical data had shaped the global debate towards more transparency, as other regulators, such as the US Food and Drug Administration and Health Canada, had subsequently implemented, or were considering implementing, similar transparency measures.
When and why publication stopped
In July 2018 the agency was preparing for its relocation to the Netherlands and implementing the next phase of its business continuity plan, which would also affect the publication of clinical data in the second half of 2018 and in 2019. It would liaise with the companies then preparing their submissions, and would do its utmost to resume the activity to the level outlined at the start of the policy once the relocation was complete.
Preparations for the United Kingdom's withdrawal from the EU affected the agency's activities broadly and clinical data publication specifically: the launch of new procedures was to be temporarily suspended from 1 August 2018, while data packages submitted up to the end of July 2018 would be processed and finalised.
By the end of October 2018 the agency had published all submitted clinical data, cancelled new submissions due after 1 August 2018 and suspended all new activities relating to clinical data publication. The agency was temporarily suspending clinical data publication until further notice. There was no timetable for lifting the suspension, and one practitioner wrote that the lull was ostensibly because the agency was focusing on its relocation from London to Amsterdam. One account dates the suspension to December 2018 and says it was only meant to be temporary.
Asked in the last quarter of 2018 whether submissions made between 2 August 2018 and the lifting of the suspension would be published retrospectively, the agency said it could not yet comment on how the process would resume or on retrospective publication. It was then processing only the applications that the CHMP, the agency's human medicines committee, had adopted up to the first quarter of 2017 and that had been submitted by 31 July 2018 on receipt of an invitation letter. It would contact the applicants and marketing authorisation holders concerned before restarting, once its relocation was complete, and it asked companies to pause any ongoing preparatory work until further notice.
In one practitioner's view, the lull in many ways gave time to reflect, fine-tune disclosure processes and consider what to improve before the suspension was lifted.
The guidance set for when publication resumed
By one account, the implementation guidance to apply once the suspension was lifted was Version 1.4, dated 15 October 2018. Its major changes from Version 1.3, to take effect when clinical data publication resumed, were these:
- clarification on publishing withdrawn applications where the application has been resubmitted or has an agreed resubmission date
- clarification on publishing clinical studies whose main period or phase is still ongoing at the time of publication
- an added timetable of the main steps of the end-to-end process for publishing clinical reports
- wording reflecting the review of the anonymisation report that takes place during the consultation phase
- wording on the potential need to submit an updated anonymisation report, written responses to the agency's comments on it, or both, before the final redacted document package is submitted
- wording flagging the availability of a checklist to help applicants prepare that final package
- template paragraphs and instructions for the cover letter on studies already published under the policy
- a new checklist for the final redacted document package, in addition to the one for the redaction proposal package
Several minor changes were also made.
By another account, the latest implementation guidance was Revision 4, dated 9 November 2018, with a published summary of its changes.
The hold through 2019 and 2020
In 2019 clinical data publication activities in the EU remained suspended, as they had been since October 2018, while regulatory public disclosure elsewhere gained pace.
In 2019 the agency's clinical data publication was still on hold, as was its guideline development. A management board meeting was planned for October 2019 to review the situation. One observer expected little, if any, movement, because the activities were not listed among the agency's 2019 priorities.
In 2020 the agency was still holding its clinical data publication activities, with no indication of when they might resume or whether disclosure would then apply retrospectively to documents.
The exception for COVID-19 medicines
In October 2020 the agency stated that it had had to suspend publication under the policy at the end of 2018 because of its move from London to Amsterdam, and that publication remained suspended because of ongoing business continuity linked to the COVID-19 pandemic and human resource constraints. Given the unprecedented public interest, the agency nonetheless decided to publish clinical data for COVID-19 medicines exceptionally. On 30 October 2020, in line with the policy, it published on its clinical data website the clinical data supporting the authorisation of Veklury (remdesivir): a package of 64 documents including the clinical overview and summaries, the final reports of pharmacokinetic and phase I studies, interim reports of phase III studies and data from the compassionate use programme. The data anonymisation report was also published; it explains the methods used to protect personal data, in line with a common approach agreed with Health Canada and the marketing authorisation holder.
On 2 March 2021 the agency and Health Canada jointly published, on the agency's clinical data website and Health Canada's Public Release of Clinical Information portal, the full clinical data they had reviewed for their authorisations of the Moderna COVID-19 vaccine: interim safety and efficacy data from three studies, with the anonymisation report explaining the methods used to protect personal data in the clinical reports. They described themselves as the only two jurisdictions in the world publishing such comprehensive information. Both held openness and transparency to be key to building confidence in COVID-19 vaccines, and committed to ensuring the public had as much information as possible to make decisions about vaccination. Both were working with manufacturers to expedite publication of the clinical information underpinning their authorisations of COVID-19 medicines and vaccines, with the Pfizer-BioNTech vaccine's clinical data expected shortly.
By late May 2021 the EU had publicly disclosed the clinical documentation for the Moderna and Pfizer-BioNTech vaccines. The agency's page on exceptional transparency measures for COVID-19 medicines set out how the transparency measures for a standard regulatory activity, such as scientific advice or rolling review, compared with those for the same activity for a COVID-19 medicine. Publication of clinical trial data, for example, remained suspended for non-COVID medicines, while COVID-19 data were published on the clinical data website.
What the 2023 relaunch covered
At the relaunch in September 2023 Policy 0070 was essentially unchanged in content, with only procedural updates. Some of the relaunch's changes were to improve efficiency and to continue the work with Health Canada begun during COVID-19. Clinical data publication for COVID-19 and other public health emergency products continued as before.
From September 2023 the relaunch applied to new active substances, including negative and withdrawn products; these were expected to be in CHMP assessment by then. From that month the clinical data submitted for initial marketing authorisation applications containing new substances with a CHMP opinion were made public. There was at that time no plan to request clinical data for products authorised during the suspension.
What the relaunch asked of sponsors
Sponsors in scope were to receive detailed invitation letters requesting their packages, with the first batch of letters due at the end of May or the beginning of June 2023. Product-specific pre-submission meetings were offered, and sponsors were encouraged to use them.
The agency held a webinar on the relaunch on 16 May 2023 and published its recording and slides. Its agenda covered the scope and updates, the timelines, the guidance and a new questions-and-answers document, and the anonymisation report template, a new document that would be needed once the policy relaunched in September.
A new questions-and-answers document specific to the 2023 relaunch was in preparation ahead of it. The agency developed it to address practical questions on procedural matters including timelines, commercially confidential information and the anonymisation process.
Before submission, the sponsor was to complete a full quality control check confirming that all necessary documentation was submitted. The updated cover letter includes a checklist to ensure validation success, based on the agency's experience with clinical data publication for COVID-19 and carried forward into publications after September.
When the relaunch took effect
Notice was given that clinical data publication for non-COVID indication studies would restart in the fourth quarter of 2023. The first packages of the restart announced in 2023 were published early in February 2024. Voydeya, part of the relaunch, was submitted in spring 2024 and published in June 2024.
Step two and the legacy documents
The agency called the relaunch step one; step two was to look at the backlog of studies and might require some of them to be published, for example on request for particular products, though the agency might also change that view. Step two was originally anticipated in 2024, but the agency postponed its requirements until 2025. It deals with the legacy documents left out of step one, and was to come into effect from the second quarter of 2025, probably from April. A new questions-and-answers document and new or updated regulations were also expected in 2025.