In the Netherlands, first-in-human studies are approved by an autonomous panel of experts. This can either be an accredited Medical Research Ethics Committee (MREC) or The Central Committee on Research Involving Human Subjects (CCMO). You are not allowed to start your study without their regulatory approval. So, how do you make sure you get the green light for your first-in-human trial?
Does your study fall under the WMO-act?
Your study is subject to the WMO, Medical Research Involving Human Subjects Act, if it matches at least one of the two criteria:
- You are conducting medical scientific research. Even though there is not a set definition of medical scientific research it usually refers to the intention of contributing to medical knowledge.
- Study participants or volunteers must follow procedures and specific behavioral rules. This requires participants to be physically involved in your research. If you are conducting retrospective research, you do not have to deal with the WMO.
Your first-in-human trial most likely matches both criteria. As it is subject to the WMO your research file must first be approved by an accredited MREC or the CCMO. Moreover, if you start your study without approval, you are conducting an illegal offence.
Submit your standard research file for approval.
Your standard research file is a bundle of documents ranging from your study protocol till CVs from researchers. See the list below for a complete overview. Most of the documents for your standard research file are due for your primary submission, where others are to be submitted after a decision has been made (e.g., K4, L and M).
|A||Correspondence||A cover letter addressing the review panel, authorization of the sponsor if this is not you and your EudraCT number|
|B||Forms||This includes the EudraCT form (European trial register) and the ABR form (Dutch registry)|
|C||Protocol||Your research protocol and protocol amendments|
|D||Product information||Available description(s) and data on the product that will be investigated|
|E||Information research subjects||Any material you use to inform (potential) study participants, such as patient information leaflet, consent forms and promotional materials|
|F||Questionnaires etc.||Questionnaires and/or dairies study participants need to complete and their study card they carry with them|
|G||Insurances||Information regarding your insurance coverage|
|H||CVs||CVs of independent experts and coordinating investigator|
|I||Participating centers||Information on all participating centers and their PIs|
|J||Financial compensation||How much financial compensation participants receive and financial details of contracts between investigator and sponsor|
|K||Other documents||All other documents related to the clinical trial, such as clinical trial agreements and your Data Safety Monitoring Board|
|L||Safety information||Report on a suspected unexpected serious adverse reaction by one of the participants during the study and other safety information|
|M||Progress and results||An update of the study (minimal once a year) and a summary of the trial results|
Once you prepared all (needed) documents you can submit your standard research file. It is best to submit the documents in the above order. The moment you submit the complete research file study review starts.
When you receive approval from the accredited MREC or CCMO, including approval of the Board of the participating hospitals, you can start your recruitment study. Recruiting patients before approval has been granted is not allowed and the rules of Good Clinical Practices (GCP) need to be followed.
A new way to submit your standard research file.
From the January 31, 2022, the EU Clinical Trial Regulation (CTR) became applicable for any study needing approval. However, there is a three-year transition period. During the first year, sponsors may choose to submit a clinical trial application according to the current legislation, or according to the CTR via CTIS. Even though the submission process differs, the documentation you need to submit remains the same.
The Clinical Trials Information System (CTIS) will contain the centralized EU portal and database for clinical trials foreseen by the CTR. CTIS will be the single-entry point for submitting the clinical trial application in the EU. The system will support the day-to-day business processes of Member States and sponsors throughout the life-cycle of a clinical trial. The European Medicines Agency (EMA) sets up and maintains CTIS, in collaboration with the Member States and the European Commission.