Rules for clinical trials
Clinical trials involving human subjects must be safe and the welfare of the subjects must be protected. The results from clinical research must also be reliable. Therefore, clinical trials involving human subjects should be conducted according to national and international legislation and regulations. Moreover, additional rules apply for clinical trials with medicinal products or medical devices.
On this page you will find an overview of the legislation and regulations for clinical trials. On separate pages you will find more specific information on:
Laws, decrees and regulations
Are you an investigator or sponsor involved in a clinical trial with test subjects that falls under the Medical Research Involving Human Subjects Act (WMO)? Then you must comply with the provisions of this law. However, there are several other relevant decrees and regulations such as:
- Medical research involving human subjects compulsory insurance decree (in Dutch)
- Scientific research involving medicines decree (in Dutch)
- Medical research involving human subjects regulation (in Dutch)
- European directives (2001/20/EC and 2005/28/EC)
- Individual healthcare professions act (BIG Act) (in Dutch)
- Healthcare quality, complaints and disputes act (Wkkgz) (in Dutch)
Additional legislation may also apply to a clinical trial. For example, the Medicines Act or the Medical Devices Act (see also clinical trials with medical devices). The ICH-GCP guidelines describe what clinical trials with a medicinal product require in order to comply with good clinical practice (GCP). This also applies to other clinical trials for which the research protocol states that it is or has been carried out according to GCP. The Helsinki Declaration also contains ethical principles for conducting clinical trials.
By the end of 2018, the European regulation 536/2014 will replace the European directive 2001/20. The regulation applies to clinical trials with medicinal products.
The ICH-GCP guidelines explain what is covered by the term Good Clinical Practice. An 'Integrated Addendum’ is also available on the ICP-GCP website. The ICH-GCP guidelines are a set of rules adopted during the International Conference on Harmonisation (ICH). It is a quality standard for designing, conducting, recording and reporting on clinical trials involving human subjects. The protection of the test subjects, their rights, health and safety is thereby guaranteed. This also applies to the integrity of the trial and the data obtained. The ICH-GCP guidelines are endorsed by the European Union, Japan and the United States as well as Australia, Canada, the Nordic countries and the World Health Organization (WHO).
When is the WMO applicable?
Prior to approval, clinical trials must be submitted to an accredited medical research ethics committee (MREC) or the Central Committee on Research Involving Human Subjects (CCMO). This concerns research that falls under the Medical Research Involving Human Subjects Act (WMO). The scientific research is explained as follows in the WMO:
medical research that includes subjecting people to treatment or requiring people to behave in a particular way‘ (Article 1, paragraph 1b of the WMO).
An online help tool is available on the CCMO website. This tool is helpful in determining whether a specific trial falls under the WMO and whether the trial should be assessed by an MREC and/or the CCMO. For questions on research not subject to the WMO, please consult the website 'Assessment framework for research not subject to the WMO’ (in Dutch).
Clinical trials with medicinal products
According to the WMO, clinical research involving medicinal products must adhere to additional national requirements. The CCMO website provides additional information on these additional requirements (in Dutch).
Clinical trials with medicinal products and the/in relation to the Food and Drug Administration (FDA) 1572 form
Clinical trials with medicinal products conducted in the Netherlands can be part of an international trial in the framework of an Investigational New Drug (IND) application for the FDA. All investigators (including European) are requested to sign a 1572 form. This is a mandatory requirement in the framework of an application dossier for the FDA in the USA.
The FDA 1572 form is in fact a statement by the investigators and is considered a (legally binding) agreement signed by the investigators. In addition to providing the investigators with specific information, the 1572 form also safeguards compliance (by the investigators) with specific FDA legislation (Code of Federal Regulations, CFR) relevant to the conduct of clinical trials with medicinal products.
In The Netherlands, conduct of clinical trials with medicinal products, must comply with all applicable European and national regulations and legislation as stated above under “Laws, degrees and regulation”. These European and national legal requirements can (and do) differ from or can even conflict with some specific aspects from FDA requirements (CFR). Therefore, the 1572 form cannot be signed by Dutch (and in fact any European) investigators.
In case a clinical trial conducted in The Netherlands (or other EU member states) is part of an IND application and hence has to comply with all necessary requirements, FDA allows the applicant of the study/sponsor to apply for a specific waiver under 21 CFR 312.10.
In March 2018 the FDA has adopted ICH E6(R2) as an official FDA Guidance (document). Based on this, the FDA (developed and) published an exemption procedure and requirements for an alternative (or adapted) 1572 form. This new form comprises specific commitments by the investigators and sponsor.
This exemption process should be documented by an alternative form signed by the principle investigator and sponsor, declaring compliance with ICH-GCP. In addition, there must be a letter from the FDA approving the absence of a signed 1572 form.
Clinical trials with medical devices
Clinical trials with medical devices must adhere to both the WMO and the specific legislation for medical devices. See also additional information on this website on clinical research with medical devices.
Parties involved in clinical trials
Different parties may be involved in clinical trials, each with different responsibilities:
- Sponsor: sponsor/commissioning party. This may be the pharmaceutical industry or a non-commercial institution. For investigator-initiated research, it is the board of directors of the institution.
- Agent: investigator (specialist, general practitioner, etc.).
- Third parties: these can be hired by the sponsor. They include contract research organisations (CROs), pharmacies, laboratories and manufacturers of investigational medicinal products.
- Test subject: the participant in the trial.