Competent Authority
Contact Details
Since 1 October 2020, the Central Committee on Research Involving Human Subjects (Centrale Commissie Mensgebonden Onderzoek, CCMO) has been the (sole) competent authority for all notifications relating to clinical trials with medical devices.
Clinical Investigation Authorisation / Registration / Notification
Dutch Medical Devices Act contains organisational matters that are left to the national governments to regulate: wetten.nl - Regeling - Wet medische hulpmiddelen - BWBR0042755 (overheid.nl)
Clinical investigation into the safety and/or (clinical) performance of the medical device falls within the scope of the EU Medical Device Regulation (MDR).
Other research in which medical devices are used as part of a study (for example, to measure an endpoint), but in which the safety, performance and/or effectiveness of the medical device itself are not investigated, falls outside the scope of the MDR. These studies may fall under the scope of the Dutch Medical Research Involving Human Subjects Act [Wet Medisch-wetenschappelijk onderzoek met mensen, WMO] or the Dutch Embryo Act [Embryowet].
Submission Format
Pending the availability of Eudamed, investigational applications must be register by completing the ABR form (General Assessment and Registration form) (version May 2021) in ToetsingOnline (available until July 2025, link to the new portal here).
Clinical investigations in the context of conformity purposes (MDR article 62/74.2)
- For clinical investigations in the context of conformity purposes (MDR article 62/74.2) the research file is first validated by CCMO.
- After a positive decision on the validation, CCMO will transfer your file to the review committee (accredited MREC or CCMO) for assessment.
- You are required to submit your research file digitally to CCMO, by email at devices@ccmo.nl (don't forget to state the file number (NL number) listed on the ABR form in your email).
Other clinical investigations (MDR article 82) or post-market clinical follow-up investigations (MDR article 74.1)
- Submit a file directly to the MREC of your choice. Please follow the instructions of the MREC concerned.
- Submit your file to tc@ccmo.nl if CCMO serves as review committee.
Available on the website ToetsingOnline (until July 2025). New portal after this date.
When finalising the ABR form you are required to select either an accredited MREC or CCMO to submit your file to. In the case of clinical investigations that fall under article 62 or 74.2 of the MDR, the study must be submitted to CCMO for validation. After a positive validation decision, CCMO forwards your file to the review committee (accredited MREC or CCMO) which you have indicated as your preference in the cover letter. If you have not indicated a preference, CCMO determines which review committee will assess your clinical investigation. CCMO transfers the ABR form in ToetsingOnline to this review committee. In all other cases you may submit the file directly to the review committee that you have selected in the ABR form.
Related information are available on the CCMO website in section: Home>Investigators>clinical Investigations with medical devices.
The Dutch Medical Devices Act [Wet medische hulpmiddelen] contains organisational matters that are left to the national governments to regulate.
Language of Submission
For the primary submission to an accredited MREC or CCMO, the list of documents to be submitted are listed here.
More precision: Overview of documents to be submitted for clinical investigations with medical devices
Submission Fees
In the Netherlands, national fees are set for medical-ethical review of research with a medical device and a medical device for in-vitro diagnostics.
For the evaluation of clinical trials on medical devices carried out for compliance purposes, Article 62/74.2 of Regulation (EU) 2017/745 on medical devices (MDR) applies.
For other research files falling within the scope of the MDR (MDR article 74.1 or 82), the fee of the review committee concerned applies instead of the national fee. These fees are collected by the relevant ethics committee (accredited MREC).
An overview of all the conditions that apply to the fees, can be downloaded via: Terms and conditions fees.
In the Netherlands, national fees are set for medical-ethical review of research with a medical device and a medical device for in-vitro diagnostics.
Timelines Autorisation
Validation of clinical investigations for conformity purposes (MDR article 62/74.2) is carried out by CCMO. CCMO checks whether the clinical investigation falls within the scope of the MDR and whether the research file is complete. The check for completeness only concerns the presence of all documents; it is not a substantive assessment.
If the clinical investigation falls within the scope of the MDR and the research file is complete, CCMO sends the file to the review committee of your choice, after which the assessment of the investigation begins.
See the procedure and the deadline in the figure here.
Amendments/Substantial Amendments
Modifications of the research file during the investigation should be reported to the review committee (accredited MREC or CCMO).
No need to report modifications to CCMO as competent authority.
Safety Reporting
End of trial
More information available here
Art 13(5) Medical Devices Decree (Dutch)
Additional Information & Specifics
Ethics Committee
Contact Details
Primary submission investigations with clinical devices
To select an authorised MREC you may use the online tool Committee Finder.
Ethical Review - General
The EU Medical Device Regulation (MDR) stipulates that clinical investigations for conformity purposes (MDR article 62/74.2) must be validated before they can be assessed by a review committee. In Netherlands, validation of clinical investigations for conformity purposes is carried out by CCMO. CCMO checks whether the clinical investigation falls within the scope of the MDR and whether the research file is complete.
After a positive decision on the validation, CCMO will transfer your file to the review committee (accredited MREC or CCMO) for assessment.
CCMO will transfer your file to the review committee of your preference. If you did not indicate a preference for a review committee, CCMO will assign your file to a review committee.
Single-Centre Studies - Ethical Review
To select an authorised MREC you may use the online tool Committee Finder.
A limited number of review committees are authorised for clinical investigation with high-risk medical devices in the context of conformity purposes (see table here).
Multi-Centre Studies - Ethical Review
Submission of Application
The procedure and the content of the submission of a research file is provided on the CCMO website in section: Home>Investigators>Clinical investigations with medical devices >Primary submission investigations with clinical devices>How to submit
Art 13(3) Medical Devices Decree (Dutch)
Submission Format
You are required to register your clinical investigation with a medical device before submitting your research file to the review committee.
Pending the availability of Eudamed, investigational applications must be register by completing the ABR form (General Assessment and Registration form) (version May 2021) in ToetsingOnline.
ABR form (General Assessment and Registration form) (version May 2021) in ToetsingOnline (until July 2025)
When finalising the ABR form you are required to select either an accredited MREC or CCMO to submit your file to. In the case of clinical investigations that fall under article 62 or 74.2 of the MDR, the study must be submitted to CCMO for validation. After a positive validation decision, CCMO forwards your file to the review committee (accredited MREC or CCMO) which you have indicated as your preference in the cover letter. If you have not indicated a preference, CCMO determines which review committee will assess your clinical investigation. CCMO transfers the ABR form in ToetsingOnline to this review committee. In all other cases you may submit the file directly to the review committee that you have selected in the ABR form.
Related information are available on the CCMO website in section: Home>Investigators>clinical Investigations with medical devices.
Language of Submission
For the primary submission to an accredited MREC or CCMO, the list of documents to be submitted are listed here.
More precision: Overview of documents to be submitted for clinical investigations with medical devices
Submission Fees
In the Netherlands, national fees are set for medical-ethical review of research with a medical device and a medical device for in-vitro diagnostics.
For the evaluation of clinical trials on medical devices carried out for compliance purposes, Article 62/74.2 of Regulation (EU) 2017/745 on medical devices (MDR) applies.
For other research files falling within the scope of the MDR (MDR article 74.1 or 82), the fee of the review committee concerned applies instead of the national fee. These fees are collected by the relevant ethics committee (accredited MREC).
An overview of all the conditions that apply to the fees, can be downloaded via: Terms and conditions fees.
In the Netherlands, national fees are set for medical-ethical review of research with a medical device and a medical device for in-vitro diagnostics.
Timelines Ethical Review
Related information is provided on the CCMO website in section Home>Investigators>Primary submission to the reviewing committee>Validation by CCMO of clinical investigations for conformity purposes
Different deadlines are used for the assessment of clinical investigations with medical devices for the primary submission and for amendments depending on the medical device class.
Please click here to find out which time limit applies to your investigation.
Amendments/Substantial Amendments
According to the amendment, f the content of information in the ABR form (B1) changes, you need to make and submit a new version of the ABR form. It is not required to modify the blocked questions at C17a for studies with a positive decision before May 26, 2021.
More information here.
Documents which need to be submitted are listed here.
A signed cover letter (A1) with a description of the amendment(s) and an overview of all documents submitted is required.
It is up to the review committee to determine whether a further assessment is required.
Safety Reporting
The procedures for safety reports are described in MDCG guidance 2020-10/1
Because Eudamed is not available as yet, the sponsor is required to upload the safety information through ToetsingOnline. The review committee will receive a message that the safety information (SAE, line listing) has been uploaded and can start the assessment. Safety reports of studies with a positive decision prior to 26 May 2021 and not subject to the Dutch Medical Research Involving Human Subjects Act [Wet medisch-wetenschappelijk onderzoek met mensen, WMO] may be reported at devices@ccmo.nl. These should also be reported to the review committee.
End of trial
More information available here
Art 13(5) Medical Devices Decree (Dutch)
Study Specific Requirement
Sponsor
"the person conducting the scientific research: a person, company, institution organisation that assumes responsibility for the start-up, management and or the funding of scientific research"
Investigator
Study participants - informed consent
Templates for the Dutch informed consent form, the Dutch Patient Information Form (PIF) and for other information material for research subjects are provided on the CCMO website in section Home>Investigators>Standard research file>E. Information for the research subjects.
The templates are updated regularly. At all times, use de most recent versions of the templates as available on following website.
“informed, written, dated and signed consent to take part in a clinical trial” (pursuant to Section 1(1.u) WMO (en)).
There are special provisions regarding informed consent including consent obtained in vulnerable populations are specified in section 6 of WMO (en)
Section 1(1.u) WMO (en): Definition
Section 6 of WMO (en): Provisions, vulnerable populations
"the person carrying out the scientific research means a doctor or a person referred to in Article 3(f) who is responsible for carrying out the scientific research research at a particular location. If the actual implementation is carried out by an employee or other auxiliary person, the person who uses that person shall be as the person conducting the investigation"
Study participants - vulnerable population
Clinical trials including minors are possible under special provisions according to the section 4, 6 and 13(e) of WMO (en).
The WMO applies the “no, unless” principle.
Related information and specific documents (“Non-therapeutic research on minors and incapacitated subjects: 'no, unless” and “Code of conduct involving minors”) are provided on the CCMO website in section: Home>Investigators>Additional information on certain types of research>Research with subjects under the age of 16 years (children) or Research with incapacitated subjects.
Clinical investigations on MD in emergency situations are possible under special provisions.
"If the clinical trial can be conducted only in medical emergencies in which the consent required pursuant to subsection 1 cannot be given and if inclusion in the trial may benefit the person in urgent need of medical treatment, procedures to implement the trial may be undertaken without such consent for as long as circumstances continue to prevent the giving of consent.“
Section 6(4) WMO (en)
Specific rules exist for research on fetuses, pregnant and/or breastfeeding women
Study participants - compensation & reimbursement
There are no detailed instructions regarding the amount of compensation for research subjects for participating in a clinical trial.
The most important elements for the review of a proposed financial compensation for the research subjects are:
- any expenses made are always reimbursed;
- financial compensation is based on invested time, on the basis of the minimum wage and the burden of the research;
- a higher financial compensation is not ruled out, as long as there is sufficient reason for doing so;
- the compensation is not based on the risks;
- the type of research (therapeutic or non-therapeutic) and the phase of research can be used for determing the amount of the financial compensation deemed acceptable for/appointed to the patients.
Study participants - recriutment & trial outcome >> end of study
The investigator will inform the study participant about the most important results of the study, and about the treatment /group the study participant was in.
If the participant prefers not to know, he has to tell the investigator who won't inform him.
Data protection
The DPA is the supervisory body and monitors the compliance with the laws governing the use of personal data.
The Dutch Personal Data Protection Act lays down the main rules for handling and protecting personal data. It has been translated into a code of conduct known as the Use of Data in Health Research (Code Goed Gedrag)
NB! There is a new law that enables the Dutch government to give (very, very high) penalties (in euros) if you break the law on this point.
Archiving & data management
A minimum retention period of 10 years is required for the documentation of research with medical devices after the end of the study with the device. When the medical device is put on the market, the minimum retention period of 10 years starts when the last device has been put on the market.
A minimum retention period of 15 years is required for research with an implantable medical device.
These retention periods have been laid down in Annex XV Chapter III section 3 of the EU Medical Device Regulation 2017/745 (MDR). Information available here.
National Legislations
General Information
Investigations on Medical Devices
In the case of clinical investigations with medical devices, first of all it must be determined whether the study falls within the scope of the EU Medical Device Regulation (MDR) and if so, which legal frame applies. Which legislation and transitional arrangements apply? Information on relevant topics related to the MDR can be found here.
Combination studies (IMP/MD)
Research in which medical devices are used as part of a study (for example, to measure an endpoint), but in which the safety, performance and/or effectiveness of the medical device itself are not investigated, falls outside the scope of the MDR. These studies may fall under the scope of the Dutch Medical Research Involving Human Subjects Act [Wet Medisch-wetenschappelijk onderzoek met mensen, WMO] or the Dutch Embryo Act [Embryowet].
Radiation & Radiotherapy
During some types of medical scientific research, subjects are exposed to ionizing radiation. Since this can lead to certain health risks for the subjects, it is important to make a comparative assessment of these risks and the potential benefits of the research.
In order to develop univocal guidelines regarding this subject, a subcommittee of the Netherlands Commission on Radiation Dosimetry (NCS) summarized the existing literature about the risks of radiation exposure for patients and healthy volunteers participating in clinical research. The conclusions of this literature study and the resulting recommendations are described in the report Human exposure to ionizing radiation for clinical and research purposes which was published in May 2016. Investigators and MRECs can use this report to make a comparative assessment of the risks of ionizing radiation for subjects and the possible benefits of the research for the individual patient, a group of patients, society and/or science.
Data protection
Dutch Personal Data Protection Act (unofficial English translation) / Wet Bescherming Persoonsgegevens WBP:
WBP lays down the main rules for handling and protecting personal data
WBP has been translated into a code of conduct known as the Use of Data in Health Research (Code Goed Gedrag).
Insurance
Insurance Decree (Verzekeringsbesluit) - 1th of July 2015 &
Section 7 WMO (en)
People participating in research covered by the Medical Research Involving Human Subjects Act (WMO) must be insured against any potential damages incurred as a result of participating in the research. The insurance must comply with specific regulations stated in the Compulsory Insurance Decree in Medical Research Involving Human Subjects (dd 1-7-2015). Exemption from this insurance obligation is possible under certain conditions. In this case, a request must be included in the submitted application. Even if exemption from the WMO insurance obligation is granted, the liability insurance must still be covered.
If the research is carried out by an ministerial appointed institution, service or governmental organization, such as those which fall under the Ministry of Health, Welfare and Sport, or the Ministry of Defence, then a WMO human subject insurance or a liability insurance is not needed (section 7, sub 10 WMO).
Definitions
MD/MD Investigation
see Art 1 Medical Device Act (Dutch)
Combination studies:
The question of whether a research with a medical device or active implant falls under the scope of the regulations for research with a medicinal product as laid down in the WMO, is important when the medical device (or active implant) also contains a medicinal product.
The CCMO (Central Committee on Research Involving Human Subjects) does not consider medical devices combined with medicinal products as a medicinal product as long as the effect of the medicinal product has a subordinate function with regards to the function of the medical device. A drug eluting stent is an example of this. The legislation for research with medicinal products is not applicable in this case.