Submission to review committees

  • WMO
  • Non-WMO

WMO - Involving human subjects

Research subject to the Medical Research Involving Human Subjects Act (WMO) must be reviewed and approved beforehand by an independent accredited Medical Research Ethics Committee (MREC) or the Central Committee on Research Involving Human Subjects (CCMO). The purpose of the review is, among other things, to safeguard the rights, safety and welfare of the participants. It weighs scientific importance against the burden and risks to participants.

Research is subject to the WMO if the following criteria are met:

  1. It concerncs medical-scientific research; and
  2. Participants are subjected to procedures or are required to follow rules of behaviour.

If you're not sure, more details and guidance is available on the CCMO website.

To facilitate the review process, you are required to submit a complete research file with a number of standard documents. General information on the standard research file is available on the CCMO website.

The investigator/submitter is responsible for verifying that all submitted documents comply with the various requirements depending on the type of study. MREC Amsterdam UMC prepared a checklist for WMO submissions and a list of mandatory documents.

In the case of multicentre research, additional documents must be included in the research file. These include a list of participating centres, Research Declerations or VGOs, the Curriculum Vitae of the principal investigator per participating centre and a (draft) Clinical Trial Agreement.

There are costs involved in the review of a research file by the MREC Amsterdam UMC. For more information, see the MREC website.

Research subject to the WMO - excluding research involving medicinal products (see below) - must be submitted digitally via a national online portal: the Research Portal. Detailed information on the submission procedure can be found on the CCMO website.

WMO - Medicinal products

For clinical trials involving medicinal products, the European Clinical Trial Regulation (ECTR) is applicable.

The ECTR aims to simplify and accelerate clinical trials involving medicinal products within the European Union. The ECTR ensures that the medical ethical review process is regulated with uniform procedures and fixed timelines and deadlines, for both the sponsor and the reviewing Ethics Committee(s).

Sponsors submit their application for medical ethical review via an EU web portal: the Clinical Trial Information System (CTIS). For more details, see the CTIS Sponsor Handbook and CTIS online training modules.

A clinical trial falls under the scope of the ECTR if:

  1. The clinical, pharmacological or pharmacodynamic effects of a medicinal product are investigated; and
  2. The study meets one or more of the following conditions:

    • Patients or subjects are randomized to a treatment;
    • The medicine is prescribed as part of the research and not as part of standard care;
    • More or different procedures are performed on the subject than in the context of standard care.

Non-interventional research with medicinal products, such as observational studies of the long-term effects of a medicine, does not meet the standards of the ECTR and is not assessed through CTIS.

Consult the Clinical Trial Tool (CCMO) to determine if your research falls within the scope of the ECTR.

A low-intervention trial is considered to be a study which is conducted with a registered drug, where the burden and risk to the subject is minimal compared to standard of care. For this type of research, the ECTR has less strict requirements for insurance obligations, subject information letters and the collection of safety information, such as AEs and SAEs.

For more details, see the CCMO website. A Q&A about the ECTR in the Netherlands is also available.

For local procedures in Amsterdam UMC, see the website of the Clinical Monitoring Center (CMC)

If you have any questions about the ECTR submission process, please contact the CMC via ctis@amsterdamumc.nl.

WMO - Medical devices

Specific rules for the submission, assessment and conduct of clinical investigations with medical devices are set out in the EU Medical Devices Regulation (EU No. 2017/745, MDR). Three legal frameworks are defined, which can be found in articles 62, 74 and 82 of the MDR (see also Clinical trials involving medical devices). Each framework has different requirements and procedures for submission and review.

The CCMO is the authorized agency for registering clinical investigations with a medical device. This applies to both medical devices without a CE-mark and medical devices with a CE-mark that will be investigated outside the intended usage.

All investigations with medical devices must be submitted digitally via the Research Portal. Consult the CCMO website for general information on the primary submission and detailed guidance on using the Research Portal. The CCMO also provides a standard research file for clinical investigations with medical devices.

For clinical investigations conducted for conformity purposes (MDR article 62/74.2), the submission file is first validated by the CCMO. After a positive validation decision, the CCMO forwards the file to either an accredited MREC or retains it for review by the CCMO itself.
Clinical investigations with medical devices that are invasive in nature (risk classification IIa, IIb or III) fall under article 62 or 74.2 and can only be reviewed by an accredited MREC or the CCMO.

Post-market clinical follow-up investigations (MDR article 74.1) and other clinical investigations (MDR article 82) may be reviewed directly by an accredited MREC. Validation by the CCMO is not necessary.

For details on local procedures in Amsterdam UMC, consult the MREC Amsterdam UMC website.

WMO - IVD performance studies

Specific rules for submission, assessment and conduct of performance studies using in-vitro diagnostics are outlined in the EU In Vitro Diagnostics Regulation (EU No. 217/745, IVDR). Four legal frameworks are defined, which can be found in articles 57, 58 and 70 of the IVDR (see also Performance studies using in-vitro diagnostics). Per framework, different requirements and procedures for submission and review apply.

All studies using in-vitro diagnostics must be submitted digitally via the Research Portal. Consult the CCMO website for general information on the primary submission and detailed guidance on using the Research Portal. The CCMO also provides a standard research file for IVD performance studies, including a template for the Investigational In Vitro Diagnostic Medical Device Dossier (IMDD-IVD) in case of a non-CE-marked IVD.

For performance studies involving risks to subjects (IVDR Article 58 an Article 70.2), the submission file is first validated by the CCMO. After a positive validation decision, the CCMO forwards the file to either an accredited MREC or retains it for review by the CCMO itself.

Post-market performance follow-up (PMPF) studies with additional invasive and/or burdensome procedures (IVDR Article 70.1) may be reviewed directly by an accredited MREC. Validation by the CCMO is not necessary.

Performance studies with companion diagnostics (IVDR Article 58.2) may reviewed directly by an accredited MREC. Validation by the CCMO is not necessary. An exception applies if only leftover material is used; in that case a notification to the CCMO via devices@ccmo.nl is sufficient.

Performance studies without risk to the subject (IVDR Article 57) do not have to be reviewed by an accredited MREC or the CCMO.

For details on local procedures in Amsterdam UMC, see the MREC Amsterdam UMC website.

Non-WMO

If your research does not fall within the scope of the WMO, it does not need to be approved by an accredited MREC or the CCMO. However, Amsterdam UMC does in principle assess all non-WMO research according to certain pre-defined ethical and legal criteria. For this purpose, a dedicated review committee is established under the responsibility of the MREC Amsterdam UMC.

Submission procedure

Non-WMO applications can be submitted to the non-WMO Review Committee of the MREC Amsterdam UMC. The MREC Amsterdam UMC uses an online portal for digital submissions of a research dossier: Research Manager. Detailed instructions on the submission procedure are available on the MREC website, including manuals for Research Manager. A checklist with additional information on the required documents and how to prepare them is also provided.

Non-WMO databases

A database is a collection of data from patients or research participants that is kept for future (medical) scientific research. Researchers can set up a new database or use data from an existing database under certain conditions to answer a specific research question (a data issuance).

Setting up a database

To set up a new database, the 'Protocol opzetten databank'' must be submitted to the non-WMO Review Committee of the MREC Amsterdam UMC instead of the standard non-WMO research protocol. Furthermore, the same documents must be submitted as for a regular non-WMO application.
All non-WMO database applications must be submitted digitally via Research Manager. Templates and further instructions are available on the MREC website, including manuals for Research Manager.

Request for assessment of a data issuance

Researchers wishing to use data from an existing database for a specific research question (a data issuance or 'data uitgifte') may proceed without prior review by the non-WMO Review Committee, provided that specific conditions are met and the issuance is without risk.
For registration purposes the 'data uitgifte' must be uploaded in Research Manager under the tab 'Rapportages' of the existing database. However, high-risk issuances must always be submitted to the Non-WMO Review Committee for review beforehand.

The 'protocol uitgifte databank' and further instructions can be found on the MREC website.

Biobank

The Biobank Review Committee of the Amsterdam UMC (Commissie Toetsing Biobanken, CTB) reviews requests to set-up a biobank (a 'biobank opzetten') or to conduct research with material from an existing biobank (a 'biobank uitgifte'). The CTB is under the responsibility of the MREC Amsterdam UMC and focuses on evaluating the legal and ethical aspects of biobank research on the basis of the Biobank Assessment Regulation.

Submission procedure

The CTB uses an online portal for digital submissions of a biobank request: Research Manager. Detailed instructions on the submission process are available on the MREC website, including manuals for Research Manager. A checklist with additional information on the required documents and how to prepare them is also provided.

Research with animals

Research involving laboratory animals is regulated by the Experiments on Animals Act (WOD). In compliance with the WOD, both Amsterdam UMC locations have an institutional license to perform experiments on animals. Moreover, for each project responsible researchers have to apply for a project license at the Central Authority for Scientific Procedures on Animals (CCD). Project permission is based on ethical assessment by an independent local committee of experts known as the Animal Ethics Committee (DEC).