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WHO to place clinical trial registries “on probation” over missing and outdated information

The World Health Organization today announced that trial registries that fail to comply with WHO standards may be placed on probation, and may eventually have their official status revoked, a document released today explains.

The move will increase pressure on registries such as (United States) and EUCTR (European Union) to meet key benchmarks, including:

  • Registration before recruitment of the first participant

  • Complete, accurate and meaningful data provided during registration

  • Clinical trials report results within 12 months of their primary completion date

  • Registered records are updated at least once each year

Both and EUCTR currently fail to publicly flag trials that are violating existing rules on posting summary results, and entries that are missing data or have not been updated for a long time. In addition, both the US authorities and the European Medicines Agency currently fail to routinely contact – let alone sanction – trial sponsors who are in breach of registry rules.

As a result, trial registry users, including TranspariMED, have repeatedly found that registries frequently contain data that is incomplete, inconsistent and out of date. Some entries even fail to specify a trial’s primary outcome measure. Most recently, the EBM Data Lab found that the completion date of 3,392 European trials was impossible to determine.

The current substandard data management by trial registries makes it difficult for patients to locate ongoing trials that they can enrol in, and impossible for the scientific community to access the complete evidence base on any given drug, medical device, or treatment – which were the main rationales for setting up trial registries in the first place.

For example, it is impossible to determine from European registry entries whether and when 486 clinical trials sponsored by the drug company Novartis have been completed. While the primary responsibility for failing to provide adequate data lies with Novartis itself, this number also highlights the European registry's failure to adequately oversee and manage its database.

According the new WHO International Standards for Clinical Trial Registries:

“Registry staff must routinely check all data submitted about a trial for completeness and meaningfulness… If one or more items… are incomplete or not meaningful, Registries must contact the Responsible Registrant and attempt to obtain complete and meaningful data. Registries must have quality control procedures in place to ensure all items… contain meaningful data.”

“The Registry will make an effort to keep registered information up-to-date. The users of information in clinical trial Registries need to be aware of how current the information in each record might be. A trial record in a registry will be considered out-of-date when the last update was made more than 12 months previously (and no publication has been recorded).”

“Each registry will be required to provide a written commitment to comply with the minimum standards and agree to site visits and random audits… All Registries should conduct regular internal audits and monitor their continued compliance with the Standards… The intention is… to audit registries to ascertain compliance with the standards described in this document.”

The WHO document sets out the following minimum standards:

  • “Registry staff must routinely check all data submitted about a trial for completeness and meaningfulness to ensure that all TRDS fields are populated... If one or more items… submitted for registration are incomplete or not meaningful, Registries must contact the Responsible Registrant and attempt to obtain complete and meaningful data.

  • Registry database systems must apply automated checking procedures... to data items to facilitate validity checking.

  • Registries must undertake regular internal quality control audits to assess the level of completeness and accuracy of the data collected. Registries may consider making the results of these audits public through publication on the registry's web site or in peer reviewed journals or similar publications.

  • Registries must make available a publicly accessible audit trail of any changes…”

The WHO's 'ideal standard' sets the bar even higher:

  • “Registries will have a reminder system to facilitate the submission of updated information by the Responsible Registrant. The recommended frequency for updating trial information (and for reminding Registrants to do so) is at least annually.

  • Registries will display the date the trial record was last updated so readers will be aware that information contained in trial records may be out of date. Registries may also choose to flag records that are out of date.

  • Update reminders will continue to occur annually until the Registrant has recorded meaningful information about the publication of the trial results within the trial record”

Addtional key points:

  • A trial should only be included on more than one registry if it is absolutely necessary. If a trial involves more than one site in a single country, it should not be necessary to register that trial more than once. If a trial is, by necessity, registered in more than one registry then the Responsible Registrant is responsible for ensuring that all known identifiers for the trial are included in each registry's record. Registries should attempt to determine whether a submitted trial has been registered in another Primary Registry.

  • “[R]egulatory authorities and funding agencies can all play a major role in ensuring complete research transparency by requiring trials under their auspices to be prospectively registered. Regardless of any national policies that may exist, trials registered after the date of first enrolment are considered… to be retrospectively registered. [However] it is better for trials to be registered retrospectively than not at all.”

TranspariMED strongly welcomes the updated WHO International Standards for Clinical Trial Registries.

Till Bruckner, founder of TranspariMED, said:

“At present, many registry entries are a complete mess, limiting what scientists can learn from trials that cost millions to run. Patients and taxpayers deserve better. The US Food and Drug Administration and the European Medicines Agency should immediately start contacting those responsible and prompt them to update their registry entries.

The WHO should use its power to place those registries that fail to meet its standards on probation in February 2019, and publicly communicate this decision. This will send a strong message to political decision-makers in Washington, Brussels and other capitals that they urgently need to take action to curb the rampant waste of medical knowledge, including by providing trial registries with the political support, resources and mandates required to safeguard patient interests.”

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