Standardisation of global clinical trial and results databases "desperately needed"

There is a desperate need to standardise the increasingly differing transparency requirements around the world for clinical trials, delegates at the recent Drug Information Association's 22nd Annual EuroMeeting, were told last week.

"We have multiple [clinical trial] registries, with multiple formats and requirements – with more coming on line all the time," said Jacqueline Sayers, quality projects manager, pharma development quality, Roche Products Ltd, UK. Moreover, regulators are now starting to focus on results databases rather than just registries, "which will make the problem even worse", Dr Sayers said during her EuroMeeting presentation, in which she also provided an update of imminent and impending transparency requirements in some of the major markets.

Inconsistencies in clinical registry and transparency requirements result in duplicate and multiple efforts on the part of companies and individual investigators, Dr Sayers explained. This, in turn, leads to confusion for patients and doctors trying to find details on a specific trial. It also creates the potential for discrepancies between entries and increases the likelihood of inadvertent non-compliance.

public access to EudraCT results imminent

In the EU, the dates are drawing closer for new requirements to make available to the general public both protocol information and results of trials held in EudraCT, the EU database on clinical trials. The provisions are being made in accordance with two rules: Article 57(2) of Regulation (EC) No 726/2004, which relates to all clinical trials in EudraCT; and Article 41 of Regulation (EC) No 1901/2006, which relates to paediatric clinical trials.

The requirement to make trial protocol information available will be implemented via EudraCT Version 8. According to Dr Sayers, Version 8 is due to go live in July 2010. However, she warned that this date may be pushed back, as previous launch dates have been missed.

The requirement to make trial results available to the public will be implemented via EudraCT Version 9, which, according to Dr Sayers, will be launched no earlier than the end 2010.

For paediatric trials, results-related information will have to be submitted within six months of a trial's completion and made public immediately after submission, Dr Sayers said. Data entry is to be completed by the marketing authorisation holder, sponsor or paediatric investigation plan (PIP) addressee via the European Medicines Agency. For all other EudraCT database trials (except for Phase I trials), including trials of products without a marketing authorisation, results must be submitted within one year of the end of the trial, via the EMA. As with the paediatric trial results, the information will be made public after it is submitted.

Dr Sayers said that while the format for posting results had not yet been confirmed, it would probably be based on the International Conference on Harmonisation E3 guideline on structure and content of clinical study reports, a format with which industry is already familiar.

expanded results disclosure nears in the US

In the US, there is a provision in the Food and Drug Administration Amendments Act of 2007 to expand, by rulemaking, clinical trial results disclosure on the FDA's ClinicalTrials.gov database no later than 27 September 2010.

Currently, ClinicalTrials.gov requires the submission of results from trials of drugs, biological products and medical devices that have been approved by the FDA; unlike in the EU, results are made available in the US only after a product is approved. In general, results must be submitted not later than 12 months after the trial completion date, which is defined as the date that the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome. Protocols must be registered on ClinicalTrials.gov within 21 days of the first patient being enrolled. The US database requires tabulated data and does not accept ICH E3 format.

Dr Sayers noted that the US regulators have not yet confirmed what the expanded disclosures will involve. There might be requirements to post lay and technical summaries of results and full protocols if they are needed to interpret results. There might also be a requirement to post results from trials of unapproved drugs.

Complicating clinical trials transparency requirements in the US, the state of Maine has adopted its own clinical trials transparency requirements and other states, such as Minnesota, New York and Pennsylvania, have legislation pending on the matter, Dr Sayers noted.

rest of the world

As for the rest of the world, Dr Sayers said that mandatory transparency requirements are in place – or soon will be – for the following countries: Argentina, Brazil, Croatia, the Czech Republic, France, India, Iran, Israel, Italy, Malaysia, the Netherlands, Norway, Peru, South Africa, Spain, Taiwan and Turkey. Most of these countries have – or will have – their own registry, Dr Sayers said. "France is the only country on the list at the moment that requires mandatory posting of results [in French] but many of the others are likely to follow."

Voluntary registration is in place or pending in Africa (Pan African Registry), Australia, Canada, Chile, China, Cuba, Germany, Hong Kong, Japan, Latin America, New Zealand, Sri Lanka and the UK. Registration may become compulsory in many of these countries, Dr Sayers predicted.

call for standardisation

The global clinical trial registry and results database arena is becoming increasingly complex. Standardisation "is desperately needed", Dr Sayers said, adding that inconsistencies in clinical transparency requirements are likely to become worse as regulators shift their focus from registries to results databases. "With registries you've got basic information that needs to be posted so requirements are only slightly different," Dr Sayers explained. "But different bodies are asking for different things with regards to the postings they want for results."