Research Roadmap

WMO - Research 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).

To facilitate the medical ethical review process, researchers must submit a complete research file with a number of standard documents depending on the type of study. General information on the standard research file is available on the CCMO website. Researchers are responsible for verifying that all documents comply with the various submission requirements. MREC Amsterdam UMC prepared a checklist for WMO submissions and a list of mandatory documents.

There are costs involved in the review process by the MREC Amsterdam UMC. For more information, consult the MREC website.

Research subject to the WMO must be submitted digitally via the national Research Portal. An exception applies to clinical trials involving medicinal products, which needs to submitted via the EU portal Clinical Trial Information System (CTIS) . Detailed information on submission procedures can be found on the CCMO website.

Besides approval from a medical ethical review committee, all WMO research conducted in Amsterdam UMC must obtain local approval of the Executive Board. This procedure takes place via Research Manager. For further details, consult Local approval Executive Board Amsterdam UMC and the MREC Amsterdam UMC website.

WMO - Medicinal products

For clinical trials involving medicinal products, the European Clinical Trial Regulation (CTR) is applicable. The CTR aims to simplify and accelerate the medical ethical review process through standardized procedures, and fixed timelines and deadlines for both the sponsor and review committee(s).

Sponsors submit their application for medical ethical review via an EU web portal: the Clinical Trial Information System (CTIS). More information is available in the CTIS Sponsor Handbook and CTIS online training modules.

A clinical trial falls under the scope of the CTR 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 participants are randomized to a treatment
   - The medicine is prescribed as part of the study and not as part of standard care;
   - More or different procedures are performed on the participant than in the context of standard care.

Researchers can use the Clinical Trial Tool (CCMO) to determine if a study falls under the scope of the CTR.
Non-interventional studies with medicinal products, such as observational studies on long-term effects of a medicine, do not fall under the CTR and are not assessed through CTIS.

A low-intervention trial is a study involving a registered drug, with minimal burden and risk to the participant compared to standard care. For this type of study, the CTR has less strict requirements regarding insurance, subject information letters and the collection of safety information (such as AEs and SAEs).

For more details, consult the CCMO website. A Q&A about the CTR in the Netherlands is also available.
For local procedures in Amsterdam UMC, consult the website of the Clinical Monitoring Center (CMC).
If you have any questions about the CTR submission process, contact the CMC via ctis@amsterdamumc.nl.

WMO - Medical devices

Specific rules for the submission, assessment and conduct of clinical investigations involving 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 involving a medical device. This applies to both non-CE-marked medical devices and CE-marked medical devices that will be investigated outside their intended use.

All investigations involving 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 research file is first validated by the national clinical trial office of the CCMO (in Dutch: Landelijk Bureau, CCMO_LB). After a positive validation decision, the CCMO_LB forwards the research file to either an accredited MREC or the CCMO for review.
Clinical investigations involving 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_LB 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). Each framework has different requirements and procedures for submission and review.

All studies using in-vitro diagnostics (IVD) 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) for non-CE-marked IVDs.

For performance studies involving risks to participants (IVDR Article 58 an Article 70.2), the research 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) and performance studies with companion diagnostics (IVDR Article 58.2) may be reviewed directly by an accredited MREC. Validation by the CCMO is not necessary.
An exception applies for IVDR Article 58.2 studies using only leftover materials; in that case a notification to the CCMO via devices@ccmo.nl is sufficient.

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

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

Non-WMO

Research not subject to the WMO does not require approval from an accredited MREC or the CCMO. However, Amsterdam UMC does assess all non-WMO research according to predefined ethical and legal criteria. For this purpose, a dedicated review committee is established under the responsibility of the MREC Amsterdam UMC: the non-WMO Review Committee.

Submission procedure

Non-WMO applications must be submitted digitally via the online portal of the MREC Amsterdam UMC: 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 for the Non-WMO research file 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, under certain conditions, use data from an existing database to answer a specific research question (a data issuance or 'data uitgifte').

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

Data issuances (or 'data uitgiftes') from an existing database do not require review by the non-WMO Review Committee beforehand if specific conditions are met and the issuance is without risk. However, for registration purposes, the 'data uitgifte' must be uploaded in Research Manager under the tab 'Rapportages' of the existing database.
High-risk issuances always require submission 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 Amsterdam UMC Biobank Review Committee (Commissie Toetsing Biobanken, CTB) reviews requests to set-up a biobank ('biobank opzetten') or to conduct research with material from an existing biobank ('biobank uitgifte'). The CTB is under the responsibility of the MREC Amsterdam UMC and evaluates the legal and ethical aspects of biobank research based the Biobank Assessment Regulation.

Submission procedure

Requests for 'biobank opzetten' and 'biobank uitgifte' must be submitted digitally via 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.

Research with animals

Research involving laboratory animals is regulated by the Animal Experiments Act (WOD). In compliance with the WOD, both Amsterdam UMC locations have an institutional license to perform experiments on animals. Moreover, for each project the 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).