New WHO rules: Protocols and results of all clinical trials must be published within 12 months

New guidance issued by the World Health Organisation states that all interventional trials, including trials that were terminated early, must make their protocols and results public on trial registries within a year of trial completion.

To facilitate the rapid publication of results directly on trial registries, WHO’s guidance identifies eight new items that all registries should add to their platforms. These include a field for uploading or linking the “most recent study protocol and statistical analysis plan,” and several fields intended to capture key trial outcomes including adverse events.

What is the problem?

Currently, 20 separate trial registries feed data into the central ICTRP platform, which in theory provides a comprehensive overview of over one million past, present and future clinical trials worldwide, with over 70,000 new entries being added every year.

In practice, ICTRP is a very basic platform that is riddled with incorrect, incomplete and out-of-date data. Many of its contributing registries lack fields where trial results could be entered, the guidance notes.

Meanwhile, researchers and patients often wait in vain for medical research results to be made public. The traditional publication route through scientific journals is slow and open to widespread manipulations. Many trial results are never made public at all. Finding out whether and where a trial has published results typically requires time consuming manual searches.

What is new?

1. REPORTING ‘SUMMARY RESULTS’ ON TRIAL REGISTRIES BECOMES A REQUIREMENT.

The new guidance specifies that key data have to be entered directly into trial registries, and calls on all registries to adopt new features allowing this functionality.

With regard to widespread ‘outcome switching’ in journals, it notes that:

“Any changes to outcome definitions or the choice of primary or secondary outcomes should be transparently documented in registries so that it is clear which outcomes were not pre-specified and why the change was made.”

While WHO has long called for the publication of results directly on registries, many registries only included a field where a hyperlink to a paper in a scientific journal could be added, or a PDF with results uploaded. This made results easier to find, but did not remove the slow speed and quality problems associated with journal publication.

2. MAKING PROTOCOLS AVAILABLE ON TRIAL REGISTRIES BECOMES A REQUIREMENT.

The new guidance makes publishing study protocols an explicit requirement:

“The protocol and full statistical analysis plan should be available in the registry alongside the trial results”

Going forward, trial registries will enable protocols to be shared either as document uploads, or by posting a hyperlink to a DOI.

Publishing the full text of study protocols has long been seen as a best practice in medical research.

3. ALL TERMINATED TRIALS HAVE TO MAKE THEIR RESULTS PUBLIC.

Up to now, institutions have sometimes argued that terminated trials – some of which only recruited a handful of people – should not be required to make results public. The new WHO guidance clearly refutes this stance:

“Even if there are insufficient data to conduct the protocol-specified analysis, reporting of outcome data on benefits and harms enables their inclusion in meta-analyses and can help inform future research. The availability of results in registries is particularly important when trials are stopped early, as they are less likely to be published in journals than trials that are completed as expected.”

What remains unresolved?

1. NOBODY IS ACCOUNTABLE FOR ANYTHING.

This is a classic WHO pathology: “Investigators and sponsors” are responsible for results posting. So if results are not posted, investigators can point the finger at their institutions, and institutions can point the finger back at individual investigators.

The WHO too is not accountable for anything. The central ICTRP data platform run by WHO is the nerve centre of the global clinical research data infrastructure. It desperately requires an overhaul, but the guidance contains no commitment by WHO to modernise and upgrade its own systems.

2. WHERE WILL THE MONEY COME FROM?

There is no WHO commitment to technically or financially assist registries with the demanded upgrades.

Instead, the guidance states that:

“Governments and registry funders should provide sufficient resources for registries to implement the 2025 WHO guidance. This includes resources for improving infrastructure to meet existing ICTRP-defined standards, for incorporating the new results-related fields in their database, and for conducting quality control of submitted data.”

TranspariMED has long argued that providing registries with adequate funding is key to creating a useful overview of the global clinical trial landscape, and that in most cases national governments should make that money available.

However, this money is unlikely to just fall from the sky. Cochrane South Africa and the government of Lebanon probably cannot be realistically expected to find the sums required to significantly upgrade the registries that they manage. (Even India’s and Thailand’s registries temporarily ran out of money a few years back.)

The WHO could plausibly have filled those gaps by assuming responsibility for providing financial or remote IT support to cash-strapped registries - but it seems to have decided not to take this road.

3. THE DETAILS OF THE FUTURE REGISTRY ARCHITECTURE REMAIN UNCLEAR.

The new guidance leaves unclear to what extent WHO intends to ensure that structured data fields are consistent across multiple registries.

This is necessary to avoid the whole registry landscape from getting even messier than it already is. Consistency across registries would also make life far easier for universities and pharma and medical device companies who sometimes have to enter data into more than one registry.

However, the guidance lacks the detail essential to ensure consistency and interoperability:

“It is recommended that registries offer structured data formatting for applicable items. Structured data fields with defined response options allow for more comprehensive and efficient search queries and analyses compared with unstructured, free-text fields or document uploads. Machine readability also facilitates quality checks for errors.”

In this context, the vague phrase “for applicable items” provides little confidence. However, the guidance does announce that:

“Over the coming years, ICTRP will work closely with registries to operationalise and implement the 2025 WHO guidance for reporting summary results.”

Let’s hope for the best.

The document “Reporting summary results in clinical trial registries: updated guidance from WHO” is available online.