Today publication of drug trial results becomes mandatory in 30 European countries
The European Union today launches its new clinical trial registry, marking a watershed in medical research transparency.
Companies, universities and hospitals are now legally obliged to make the results of drug trials public within one year completing a trial.
NEW LEGAL REQUIREMENTS AND PENALTIES
All 27 European Union countries plus Norway, Iceland and Liechtenstein have integrated the regulation into their national legal frameworks, meaning that sponsors that fail to share trial results will be in violation of national law.
Each country has also adopted penalties for violating this transparency requirement. Penalties vary from one country to the next.
Nobody seems to have compiled a comprehensive overview, but TranspariMED has previously reported that trial sponsors in Denmark and France could face prison as well as a fine.
The more important question is whether and to what extent national medicines regulators will use their new powers in practice.
In 2020, the Danish regulator announced that it will take to court sponsors that break the law, and the Belgian regulator recently outlined an innovative sanctions process involving fines only.
Other regulators’ enforcement strategies are currently unknown. A 2021 TranspariMED report documented strong differences in regulatory performance across Europe.
NEW EUROPEAN TRIAL REGISTRY
The new European trial registry, called the Clinical Trials Information System (CTIS), went live today.
For the next year, sponsors have the choice of registering new drug trials in either in the existing EudraCT registry or in CTIS. From 31 January 2023 onwards, all new trials must be registered in CTIS. Any old trials registered on EudraCT that are still ongoing in January 2025 will have to then be transitioned to the new registry.
Additional functionalities will be added over the next year. CTIS is expected to streamline and accelerate the launch of clinical trials that have sites in more than one country, making it easier to conduct large trials.
The new registry includes novel transparency features, according to Fergus Sweeney, head of the Clinical Studies and Manufacturing Task Force at EMA:
“We can track these processes: both the sponsors are alerted—‘it’s time for you to submit your results’—and the member states— ‘sponsor X didn’t submit, 12 months has passed now.’ . . . Also, the public will be able to see when results should have been posted and if they are there or not.”
WHAT SHOULD TRIAL SPONSORS DO?
Consistently making trial results public on trial registries requires central oversight and management of trial portfolios by universities and hospitals. The TranspariMED website contains useful resources to help institutions set up appropriate systems.
Trial sponsors should also review the CTIS Sponsor Handbook, keep up to date by subscribing to a dedicated CTIS newsletter, and take advantage of training opportunities and training resources.
Upcoming training courses are listed here.
WHAT SHOULD NATIONAL REGULATORS DO?
International regulatory experience clearly shows that trial reporting rules are widely ignored unless and until regulators monitor compliance and impose sanctions.
The WHO recommends that “Legislation or supporting regulations [should include] sanctions if a clinical trial is not registered and/or results are not reported.”
TranspariMED and allied groups across Europe will now advocate for national regulators to set out clear, credible and time-specific plans for imposing sanctions on sponsors that violate the law.
Till Bruckner, founder of TranspariMED, said:
“Regulators have repeatedly acknowledged that clinical trial transparency benefits patients and public health. From today, national medicines regulators across Europe finally have the power protect patient interests and deliver on long-standing promises of greater transparency".
" TranspariMED calls on all European regulators send a loud and clear message to trial sponsors that the days of impunity are finally over, and that the new laws will be promptly, consistently and fully enforced.”
In addition, lawmakers across Europe should put into place national legal requirements to make the results of all clinical trials public. Patients who are implanted with medical devices deserve the same level of transparency as patients that take medicines.
HOW DOES EUROPE COMPARE INTERNATIONALLY?
WHO best practices state that the results of all clinical trials should be made public on trial registries within one year of trial completion.
Europe’s new transparency rules fall short of WHO standards because their scope is limited to certain drug trials (see below). Note that EU Member States are free to adopt national legislation that goes above and beyond European transparency requirements.
The United Kingdom is poised to become the first country worldwide to fully meet WHO standards. The UK recently started tracking all clinical trials to ensure that their results are made public. The UK’s medicines regulator now plans to enshrine this obligation in law.
In the United States, a trial reporting law has been on the books since 2007, but so far has not been effectively enforced. The U.S. law also only covers a minority of all clinical trials, but it does cover certain trials of medical devices as well as drug trials.
According to an industry expert, 30 jurisdictions outside Europe already have rules, regulations or laws requiring clinical trials to be registered and/or reported.
LEGAL AND REGULATORY BACKGROUND
The launch of the new Clinical Trial Information System (CTIS) means that the 2014 Clinical Trials Regulation is now fully applicable throughout all European Union member states.
As is currently the case, European rules only cover so-called Clinical Trials of Investigative Medicinal Products (CTIMPs). Other clinical trials, including trials of medical devices and non-drug treatments, cannot be registered on the old and new European trial registries, and are not subject to the new transparency laws.
According to the European Commission, around 3,700 CTIMPs are authorised each year.
The regulation states that:
“Irrespective of the outcome of a clinical trial, within one year from the end of a clinical trial in all Member States concerned, the sponsor shall submit to the EU database a summary of the results of the clinical trial.” – Article 37(4)
“Where the clinical trial protocol provides for an intermediate data analysis date prior to the end of the clinical trial, and the respective results of the clinical trial are available, a summary of those results shall be submitted to the EU database within one year of the intermediate data analysis date.” – Article 37 (8)
“In addition to the summary of the results, where the clinical trial was intended to be used for obtaining a marketing authorisation for the investigational medicinal product, the applicant for marketing authorisation shall submit to the EU database the clinical study report within 30 days after the day the marketing authorisation has been granted, the procedure for granting the marketing authorisation has been completed, or the applicant for marketing authorisation has withdrawn the application.” – Article 37 (4)
“Member States shall lay down rules on penalties applicable to infringements of this Regulation and shall take all measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate and dissuasive. [This is to include] non-compliance with the provisions laid down in this Regulation on submission of information intended to be made publicly available to the EU database” – Article 94
Correction 31 January 15:20 CET: The original version of this blog erroneously stated that the Danish regulator announced its intention to take trial sponsors to court in 2000. In fact, the announcement was made in March 2020. This typo has now been corrected in the blog above.