13 October 2023
Clinical trials are an essential building block in the (further) development of medicines and research into diseases. They do not just make a significant contribution to the progress of medical development and the provision of comprehensive healthcare, but are also part of a German economic sector worth billions. Despite this enormous significance and based on an international comparison, Germany is losing its importance as a location for the research and development industry.
An evaluation carried out by the German Association of Research-Based Pharmaceutical Companies (vfa) based on the public study register Clinicaltrials.gov revealed a decline in the number of drug trials conducted in Germany. In 2016, Germany hosted 641 clinical trials conducted by the pharmaceutical industry, ranking second in the world behind the USA, but since the beginning of the Covid 19 pandemic, these numbers have been steadily declining. In 2021, only 589 studies were carried out in Germany, which puts Germany in sixth place behind the USA, China, Spain, the UK and Canada .
The reasons for this decline are various. Delays in the start of planned clinical trials can be attributed, among other things, to the high level of bureaucracy in Germany compared to the rest of the world and frequently extensive negotiations between companies and research institutions. Data protection requirements in the EU, which are already high, are exacerbated in Germany by the large number of data protection commissioners at a federal state level and the restricted access to health data even for research purposes.
The EU Regulation 536/2014 has already provided some reduction in bureaucracy. Following the establishment of a functioning EU portal, this Clinical Trials Regulation 536/2014 entered into force with a delay on 31 January 2022. In its adjustments to the new the legal situation, Germany has, among other things, newly regulated the procedure for involving the ethics committee in the application and evaluation process for clinical trials. Whereas before the new Regulation separate applications to the higher federal authority and the ethics committee were required, which were decided independently and therefore also partly differently from each other, a joint assessment procedure by the higher federal authority and the ethics committee is now envisaged.
This innovation not only brings administrative relief, but also leads to a uniform decision on the approval of the conduct of a clinical trial. Problems arise in the practical implementation due to the lack of user-friendliness of the new European “Clinical Trials Information Systems” (CTIS). Since February 2023, all applications to conduct a clinical drug trial in the EU must be submitted via the CTIS system. Numerous ethics committees complain about a considerable additional effort in the evaluation of study applications due to unnecessary formalities of the unstructured and error-prone CTIS platform. In a press release dated 8 March 2023, the Working Group of Medical Ethics Committees in the Federal Republic of Germany (AKEK) and the German Medical Association (Bundesärztekammer) called for a systematic review of the CTIS platform and to refrain from transferring data from studies previously approved in the conventional procedure to CTIS. The EMA (“European Medicines Agency”) periodically publishes a list of known CTIS application issues and management options for Member States, the EU Commission and EMA users, most recently on 6 March 2023. Possible solutions through a restructuring of the CTIS have not been officially announced; use is still mandatory throughout the EU.
For Germany, an announced national legislative initiative could bring further relief. Federal Health Minister Karl Lauterbach (SPD) wants to present a law by the end of this year which will ease the conditions for research so that Germany does not lose any more of its attractiveness as a research location. Lauterbach announced this planned law to accelerate research and approval of medicines at the side-lines of the meeting of the G20 health ministers in Gandhinagar, India. In addition to medicines, the planned law will also cover medical devices such as magnetic resonance tomographs.
It remains to be seen which adjustments the German draft law will seek to introduce. Since the regulatory framework is standardised across the EU through the Clinical Trials Regulation 536/2014, it will presumably be a matter of simplifying the administrative processes for authorisation procedures in Germany.
Even on the basis of the existing legal framework, sponsors of clinical trials can work towards fast processes in coordination with the trial times. In this context, recourse to uniform model contracts can help to shorten the negotiation period.
In 2019, the vfa published individual model clauses for study contracts together with Deutsche Hochschulmedizin and the KKS network. The vfa describes the model clauses as an orientation aid for recurring points, since no two studies are completely the same.
Even more specific is an initiative in the field of oncology by the Bavarian Centre for Cancer Research (BZKF) and all six Bavarian university hospitals, which have agreed on a uniform model contract for clinical trials in the field of oncology with a total of seven pharmaceutical companies (Novartis, MSD, Servier, Ipsen, Amgen, BMS and Roche). If a sponsor uses the uniform contract template, all six oncology clinics in Bavaria will accept it.
The BZKF sample contract, without appendices, comprises 18 pages and contains the essential provisions that are to be expected in the context of a typical study contract. The agreement is within the scope of usual regulations; whereby regulations that are accommodating to the university hospitals were often chosen. For example, the liability of the executing university hospitals is excluded in the BZKF for slight negligence (section 9). The general vfa model clauses from 2019 provide for limits on the amount for slight negligence (e.g. in relation to the contract value) but no general exclusion of liability.
The BZKF sample contract assigns the work results obtained in the study that are not eligible for patent protection to the company as sponsor. Regarding the frequently discussed sub-issue of employee inventions, the sample contract provides for a transfer of rights to the sponsor only in return for financial consideration. This remuneration of inventions can either consist of a fixed amount which can be renegotiated or an open remuneration which is determined in a separate agreement still to be negotiated. The deadlines given to the sponsor for notifying whether a reported invention is to be transferred to the sponsor or whether there are comments on a planned publication is a comparatively short 30 days.
It remains to be seen whether the project of a model contract will be limited to research in oncology in Bavaria or will have an exemplary effect due to the expected acceleration of procedures.