An ethics committee assesses the ethical aspects of applications for the conduct of clinical trials of medicinal products and medical devices. First and foremost, this is meant to safeguard the rights and the safety of the patients. For this reason, an ethics committee reviews not only the study protocol, but also the investigators’ qualification, along with all documents that patients will receive during the course of the trial. These include, among others, the patient information sheet, the informed consent form, advertising material, the clinical trial insurance and the compensation offered to patients. However, the investigator agreements, especially the remuneration for investigators, must also be ethically reasonable; these aspects are thus also assessed by the ethics committee. The public ECs release the required documents to be submitted as per the German Medicinal Products Act (AMG) and Medical Devices Act (MPG). Minor deviations to others ECs may exist.
It is not always necessary to assess applications; in some cases, the ethics committee advises the sponsor of a trial, for example, in register trials.
Ethics committee members
In Germany, ethics committees comprise a number of interdisciplinary members. The members are generally physicians, natural scientists, lawyers, philosophers and theologians. This ensures that, ideally, all aspects to be considered are taken into account in the final assessment.
Application submissions and deadlines
The application for approval of a clinical trial of a medicinal product or medical device is submitted by the sponsor to the competent federal higher authority (BfArM or PEI) and to the ethics committee in writing. A clinical trial may only be commenced once the federal higher authority has given its approval and the ethics committee (EC) has issued a positive vote. Following the initial submission, amendments, changes of investigators or registrations of new trial sites must be additionally submitted to the EC.
In Germany, a distinction is made between the lead ethics committee and involved ethics committees. The lead EC is the EC responsible for the National Coordinator of the trial (NC). For multicentre trials, the ECs responsible for the respective site investigators are also involved. The lead EC makes the overall decision about the trial. To this end, all documents are submitted to the lead EC in full. The involved EC merely assesses the suitability of the respective trial site and investigators. Only the corresponding proof of qualification is sent to the involved EC.
The lead ethics committee acknowledges receipt of the application within 10 days. Any formal deficiencies must be resolved by the sponsor within 14 days. Once the application has been duly received, all involved ECs are given 30 days to send their assessments to the lead EC. After a total of 60 days (30 days for monocentric trials, 90 days for biotechnological drugs, 180 days when assessors are involved, no deadline for xenogeneic cell therapies), the lead EC must reach a final decision, which is then communicated to the sponsor and the federal higher authority in writing. The ethics committee can request additional information from the sponsor one single time. In this case, the deadline is suspended until any such content-related deficiencies are resolved.
What will change once Regulation EU No 536/2014 comes into application?
According to the new Regulation EU No 536/2014, ethics committees are required to meet certain requirements in the future and to register with the federal higher authorities by September 2017.
For mono- or multinational trials, the sponsor will only be required to submit the application for a clinical drug trial one single time via the EMA’s central online portal. The federal higher authority and the ethics committee will thus receive the same electronic-only application. The decision is then made jointly by the federal higher authority and the EC. It will thus be inevitable for the two institutions to collaborate closely. The applicant and the member states will only communicate with one another in writing via the EMA portal.
For multinational trials there will be a reporting member state (MS) and the involved member states. Upon receiving the application, the reporting MS will validate the completeness of the application within 10 days. The sponsor is obliged to resolve any formal deficiencies at the latest within 10 days. Upon duly receiving the application, the reporting MS publishes an initial report within 26 days. During this period, any content-related questions can be sent to the sponsor, who is then required to respond to the questions within 12 days at the latest. Once this deadline has passed, the application is considered rejected. As the reporting MS is given an additional 19 days to finalise the application, the clock is suspended (“clock-stop”) for at most 31 days. Within the next 12 days, the decisions of the involved MS are announced, and the initial report is coordinated and reviewed jointly by all member states. Based on this, the reporting MS issues an individual decision after another 7 days which is binding for all member states. This consolidated assessment report is thus sent to the sponsor via the EMA portal at the latest 45 (+31) days after the application was validated. If any of these deadlines are missed, the application is considered as “tacitly approved” in favour of the sponsor.
Due to this considerable shortening of the deadlines, and because the ethics committees in Germany only meet one to two times a month on a voluntary basis, their influence is expected to decrease in the future. In terms of time, this constellation will barely allow for requesting additional information or for involving patient organisations and external assessors anymore.
6 months after the EMA portal and the EMA database are operational (planned for October 2018), Regulation EU No 536/2014 will come into application. Delays owing to the relocation of the EMA from London to Amsterdam can be expected. A three-year transitional period will follow. Non-interventional studies and clinical trials of medical devices are not affected by the new EU Regulation.
The sponsor is responsible for submitting the application for approval of a clinical trial; whereby this task can be delegated to a CRO. Please do not hesitate to ask about our services! Our Clinical Trial Service team will be happy to support you in submitting your applications!