Which registries a sponsor has to satisfy
A sponsor may have to register a trial and post its results on several registries at once. The duties rest in law on a US statute and an EU regulation, the US, European and national registries differ in scope, content and deadline, and good clinical practice counts registration and results posting as part of a trial's transparency.
The legal duties
Prospective registration on a public registry has been an obligation for medical researchers since the FDA Amendments Act of 2007 and the World Medical Association's 2008 revision of the Declaration of Helsinki, and compliance with the registries now established across the globe is often mandatory. The legal disclosure duties rest on Regulation (EU) No 536/2014 in the EU/EEA, and in the US on Section 801 of the Food and Drug Administration Amendments Act and its final rule at 42 CFR Part 11. Failure to comply with either can lead to civil monetary penalties or the withholding of research funding. Penalties for not adhering to registry requirements include monetary fines, but in one 2024 account the risk to reputation is perhaps the greatest incentive, because lists of non-compliant organisations are frequently published. Paediatric clinical trials must be registered with the authorities.
A sponsor must upload protocol information to the registries before recruiting participants, maintain it during the trial and post summaries of the results after the trial is completed. Registration of a new trial draws on its protocol, and the posting of summary results, made once the trial has been completed or prematurely ended, draws on its clinical study report.
The US and EU registries
The registries share similarities, but their differences include the studies in scope, the information required and the timelines.
ClinicalTrials.gov, provided by the US National Library of Medicine, was launched in February 2000, and in 2024 it was the largest global registry, with approximately 500,000 studies from more than 200 countries. It gives patients and their advocates, health care practitioners, researchers and the general public access to information on publicly and privately funded trials for a wide range of diseases and conditions. In June 2024 the library launched a modernised version of the site with greater functionality for searching, viewing and downloading trial information.
The EU's registry, EudraCT, was launched in 2004, and in 2024 it held almost 44,000 trials with a EudraCT protocol. Regulation (EU) No 536/2014 increased the amount of trial information required for publication. That information is submitted during the clinical trial application through the Clinical Trials Information System, which in 2024 was due to replace EudraCT as the European Medicines Agency's registry from January 2025.
| Requirement | US | EU/EEA |
|---|---|---|
| Applicable regulation | Created under the FDA Modernization Act of 1997 and expanded by the FDA Amendments Act of 2007 | Governed first by Directive 2001/20/EC, and from 31 January 2022 by Regulation (EU) No 536/2014 |
| Scope | Controlled clinical investigations of drugs, biologics or devices, phase I studies excluded, that have at least one US site, are conducted under an investigational new drug application or device exemption, or involve a product manufactured in the US and exported for research | All interventional trials of medicinal products submitted to the national competent authorities, and trials outside the EEA that form part of a paediatric investigation plan or are conducted under Article 45 or 46 of Regulation (EC) No 1901/2006 |
| Information included | Trial information; summary results with some adverse event information; the redacted protocol and statistical analysis plan; an indication of plans to make participant data and data dictionaries available | Structured data fields containing trial information; documents including the protocol and its synopsis, an optional plain language protocol synopsis, patient-facing documents, subject information sheets and informed consent forms; the scientific summary of results, the plain language summary of results and clinical study reports |
| Timelines | Registration within 21 days of the first participant's enrolment; summary results within 12 months of the primary completion date | The timelines for publishing documents depend on the trial's category under the EU's revised transparency rules |
The revised transparency rules sort trials into three categories:
- Category 1: phase 0 and phase I trials in healthy volunteers or patients, bioequivalence and bioavailability trials, and biosimilarity trials.
- Category 2: integrated phase I and II trials, and phase II and III trials.
- Category 3: integrated phase III and IV trials, phase IV trials and low-intervention trials.
National registries
Dozens of national registries exist, because a country that runs its own can gather data to support local policymaking and healthcare decisions. As of 2024 the countries that mandated registration in a national registry or on a globally recognised registry or platform such as the WHO's included, among others, Australia, Brazil, China, India, Iran, Israel, Japan, South Africa, South Korea, Sri Lanka, Taiwan and Thailand.
As of 2018 the EU countries, the EEA countries Iceland, Liechtenstein and Norway, and the US were particularly active in advocating and enforcing disclosure. Some 40 further countries worldwide had national disclosure obligations, and certain countries had more than one relevant registry or database needing attention.
In the UK the Health Research Authority requires sponsors to register trials in a publicly accessible database before they begin, to report results within 12 months of completion, and to make lay summaries of the results available to the public. In March 2023 the UK government was to introduce a legal requirement to make public the results of all drug clinical trials within 12 months of trial completion, and the new law would also make it mandatory to pre-register trials and to share their outcomes with participants.
In March 2023 Health Canada had draft guidance for sponsors of Health Canada-authorised clinical trials on registering them and publicly disclosing their results using international registries. The draft guidance also described the clinical trial information Health Canada was publishing on its Clinical Trials Portal.
Keeping several registries current
A trial may need registering and its results posting at several sites. Some regions expect the sponsor to register a trial at regional or national level, and in some cases summary results must also be reported at study completion or after a milestone in the trial's conduct, such as completion of the primary endpoint. Keeping up with these requirements can be a challenge, especially for sponsors of multinational trials.
Trial information sits in global, regional and national databases, most of them freely accessible without a subscription. That spread makes timely management, updating and consistent content a challenge for those who implement and coordinate the entries.
As of 2018, internet sites gave the definitions of the elements required for registration and results disclosure in ClinicalTrials.gov and EudraCT, and their information was updated as new topics were raised. Sites of frequently asked questions covered the items trial sponsors and database users raised, and other sites explained how to enter data into the database fields and interpret the relevant laws and the requirements of other influential bodies, such as the International Committee of Medical Journal Editors, the World Medical Association and the World Health Organization.
Transparency under good clinical practice
Under ICH E6(R3), the transparency of clinical trials includes timely registration on publicly accessible and recognised databases and the public posting of trial results. Communicating the results to participants should be considered, and such communication should be objective and non-promotional.
Once the trial has been unblinded and the relevant analyses and conclusions have been completed and finalised, the sponsor should generally, in accordance with applicable regulatory requirements:
- Make the trial results publicly available.
- Provide the investigator with information about the treatment their participants took in a blinded trial.
- Provide investigators with the trial results. A summary of the results provided to participants should use language that is non-technical, understandable to a layperson and non-promotional.