Pressure grows on German regulators and universities to make clinical trial results public
Europe’s largest medical association and a member of the European Parliament have urged German medicine regulators and universities to improve clinical trial reporting.
These calls for greater transparency come in the wake of a report showing that 445 clinical trials of medicines run by German universities are missing results on the European database EudraCT, in violation of long-standing transparency rules.
The report by TranspariMED and BUKO Pharma-Kampagne, which was released in late December, was widely covered by national and regional media.
1. Medical association calls status quo “completely unacceptable”
The Marburger Bund, an association of 124,000 German doctors that is reportedly the largest medical association in Europe, condemned universities’ failure to make all clinical trial results public “completely unacceptable”. Dr Susanne Johna, who chairs the association, stated that:
“The results of clinical research have to be made accessible to the public. It is completely unacceptable for universities to not fully comply with this transparency obligation. Every new insight from clinical trials can result in new treatment approaches… At the end of the day, such studies always have the goal of improving the quality and safety of patient care.
"Therefore, their results have to be completely and openly accessible in the data bases of German and European medicines regulators. Even when a study was terminated, the reasons for this must be made public. Die universities involved need to answer questions about whether negative results in particular are being withheld.
"This behaviour also damages universities’ own interests, as they let down patients and trial participants who are recruited into clinical trials with the argument that they can contribute to the development of better treatments.”
According to the Standing Committee of European Doctors (CPME), which represents national medical associations across Europe:
"Transparency of clinical trial data and results is essential to the good conduct of medical research, to the development of new medicines and medical treatments, to expand scientific knowledge on those medicines and treatments and for patient safety. CPME insists that all results of clinical trials, whether they are positive, negative or inconclusive, should be made publicly available."
2. Parliamentarian seeks clarity on rules and regulations
In parallel, member of the European Parliament and data transparency expert Dr Patrick Breyer raised the issue of hidden trial results with Germany’s Minister for Health and the European Commission.
Is reporting clinical trial results mandatory in Germany?
Dr Breyer’s letter to Jens Spahn, the German Minister for Health, notes that one of the country’s medicines regulators, Paul Ehrlich Institut, reportedly told a university that there was no obligation to make clinical trial results public on the European database.
(Paul Ehrlich Institut has yet to release a formal statement setting out its position. Germany’s second regulator, BfArM, has repeatedly stated that it regards uploading onto the database as mandatory.)
The letter asks the Minister to clarify:
Whether posting results onto the database is currently mandatory for universities
Whether Germany is monitoring the submission of results to the database
Whether national legislation on trial reporting is aligned with European guidelines
Is Germany in breach of European law?
Dr Breyer’s written enquiry to the European Commission also seeks clarification on the rules governing trial reporting, on whether Germany is monitoring compliance with these rules, and on the possible misalignment of national legislation.
In addition, the enquiry asks:
“Has the European Commission initiated an infringement procedure against Germany for possibly failing to implement European Union law, or else how does the Commission intend to resolve this issue (please provide a justification)?”
The full text of both letters is reproduced further below.
What does all of this mean?
More pressure on German universities
First and foremost, these developments increase the pressure on German universities to upload missing clinical trial results onto the database, and to ensure that in future, results are routinely uploaded in a timely manner.
Previous research has shown that German universities never reported the results of clinical trials involving 56,730 patients, neither in journals nor on public databases, leaving important gaps in our understanding of how safe, effective and cost-effective medicines are.
In addition, 75% of all university trials were not prospectively registered - a clear breach of medical research ethics.
Some German universities have reportedly already begun tackling these issues. This excellent news for patients and taxpayers in Germany and beyond.
More clarity and better regulation
Second, German trial sponsors will hopefully soon receive clear guidance from regulators on the ethical, scientific and legal expectations around clinical trial registration and reporting. In the past, largely due to mixed or muted signals from regulators, universities across Europe have struggled to understand what exactly the rules and expectations are.
More clarity would be good news for universities because clear standards will support their efforts at achieving compliance.
Making the European Clinical Trial Regulation work
The European Clinical Trial Regulation was adopted and entered into force in 2014, but it will only be fully applied in late 2020 or early 2021. At that point, individual Member States (including Germany) will adopt it into national law. Sanctions for breaching the Regulation will also be defined at the national level.
Hopefully, the current discussion will help to ensure that Germany imposes effective sanctions on universities and pharmaceutical companies that fail to make clinical trial results public within 12 months of trial completion.
Warning: The new regulation will NOT solve all problems
The incoming European Clinical Trial Regulation only applies to some trials of medicines. Therefore, withholding the results of trials of medical devices such as pacemakers will remain completely legal in Europe post 2020 – hard to believe but true. In addition, enforcement of the regulation will be the responsibility individual member states.
Getting all clinical trials conducted in Germany registered and their results reported would require two things:
First, the German government would have to monitor registration and reporting of all trials nationwide, as the UK is currently planning to do.
Second, the government would have to adopt legislation that imposes effective sanctions for failures to register or report the results of any and all clinical trials, not only the minority of drug trials covered by the incoming European regulation.
No country has to wait for permission from Brussels to make clinical trial registration and reporting mandatory. Germany can and should adopt rules that exceed European standards.
Please click on the report below to learn more about clinical trial transparency policies.
Over the coming year, TranspariMED will focus its advocacy efforts on Germany. Together with German partners, we will regularly publish reports tracking universities’ progress on clinical trial reporting, and closely follow legal and regulatory developments. Stay tuned.
FULL TEXT OF ENQUIRIES BY DR PATRICK BREYER,
MEMBER OF THE EUROPEAN PARLIAMENT
Written enquiry to the European Commission
Anfrage zur schriftlichen Beantwortung an die Kommission
Artikel 138 der Geschäftsordnung
Betrifft: Unveröffentlichte Ergebnisse von Arzneimittelprüfungen
Die Organisationen „Buko Pharma-Kampagne“ und „Transparimed“ meldeten Ende 2019, deutsche Universitätskliniken hätten von 477 klinischen Arzneimittelprüfungen, deren Ergebnisse unionsrechtlich binnen 12 Monaten in die Datenbank EudraCT hätten eingestellt werden müssen, nur die Ergebnisse von 32 Prüfungen eingestellt (6,7%). Das in Deutschland zuständige Paul-EhrlichInstitut soll einer Universität mitgeteilt haben, dass in Deutschland gemäß § 13 Abs. 9 GCP-V keine Verpflichtung von Sponsoren zur Veröffentlichung von Prüfungsergebnissen in der Datenbank EudraCT bestehe.
1. Sind deutsche Universitäten als öffentlich-rechtliche Körperschaften gegenwärtig unionsrechtlich verpflichtet, Ergebniszusammenfassungen und/oder den vollen Datensatz von ihnen gesponsorter pädiatrischer und nicht-pädiatrischer klinischer Prüfungen binnen 12 Monaten in EudraCT einzustellen? Wenn ja, auf welcher Rechtsgrundlage?
2. Überprüft die Bundesrepublik Deutschland entsprechend Abs. 4.7 der Leitlinie 2012/C 302/03, ob Ergebnisse von klinischen Prüfungen bei der EMA eingereicht werden, und steht § 13 Abs. 9 GCP-V im Einklang mit Unionsrecht?
3. Hat die Kommission wegen etwaigen Unionsrechtsverstößen nach Ziff. 1 oder 2 ein Vertragsverletzungsverfahren gegen die Bundesrepublik eingeleitet oder wie sonst will sie für Abhilfe sorgen (bitte begründen)?
Letter to German Minister of Health
Sehr geehrter Herr Minister,
die Organisationen „Buko Pharma-Kampagne“ und „Transparimed“ meldeten Ende 2019, deutsche Universitätskliniken hätten von 477 klinischen Arzneimittelprüfungen, deren Ergebnisse unionsrechtlich binnen 12 Monaten in die Datenbank EudraCT hätten eingestellt werden müssen, nur die Ergebnisse von 32 Prüfungen eingestellt (6,7%). Das in Deutschland zuständige Paul-Ehrlich-Institut soll mitgeteilt haben, dass in Deutschland gemäß § 13 Abs. 9 GCP-V keine Verpflichtung von Sponsoren zur Veröffentlichung von Prüfungsergebnissen in der Datenbank EudraCT bestehe.
Vor diesem Hintergrund frage ich Sie:
1. Sind deutsche Universitäten als öffentlich-rechtliche Körperschaften gegenwärtig Ihrer Auffassung nach unionsrechtlich verpflichtet, Ergebniszusammenfassungen und/oder den vollen Datensatz von ihnen gesponsorter pädiatrischer und nicht-pädiatrischer klinischer Prüfungen binnen 12 Monaten in EudraCT einzustellen? Wenn ja, auf welcher Rechtsgrundlage?
2. Überprüft die Bundesrepublik Deutschland entsprechend Abs. 4.7 der Leitlinie 2012/C 302/03, ob Ergebnisse von klinischen Prüfungen bei der EMA eingereicht werden, und steht § 13 Abs. 9 GCP-V im Einklang mit Unionsrecht?
Mit freundlichem Gruß
Dr. Patrick Breyer MdEP