Research with a medicinal product and the WMO

The Medical Research Involving Human Subjects Act (WMO) offers the following definition of research with a medicinal product:

‘an investigation intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of any investigational medicinal product, and/or to identify adverse reactions to any investigational medicinal product and/or to study the absorption, distribution, metabolism and excretion of any investigational medicinal product with the object of ascertaining its safety and/or efficacy; (section 1 WMO) (non-official translation)

In short: if your research has the aim of studying the mechanism of the effect, safety or effectiveness of a medicinal product, then it is research with a medicinal product. Your research must then undergo the extra, marginal review by the competent authority.

 A clear definition of the term research with a medicinal product is not always easy to make. Discussion is currently ongoing on this. A handy tool is the Algorithm on the last pages of the Q&A-form part of CT Directive 2001/20/EC.

Phase I, II, III and IV

The WMO applies to all medical research in which people are subjected to procedures or are required to follow rules of behaviour, irrelevant of whether it applies to phase I, II, III or phase IV research, or whether it is carried out with an authorised or non-authorised product.

Phase IV research with an authorised medicinal product does not always have to be reviewed. If you only use existing patient data for the phase IV study, then it does not fall under the WMO (this is file research). In this case the patient may not be prescribed a different product.

Research with a medicinal product is arranged into the following phases:

  • Phase I: Human pharmacological: First administration in people, generally in a small number of healthy volunteers. Tolerance and safety are observed, generally by increasing the dosage. It also often concerns an evaluation of pharmacodynamics and pharmacokinetics.
  • Phase II: Explorative therapeutic: research into the activity in (a small number of) patients with a particular medical ailment. Verification of the active mechanism in patients or healthy volunteers and the safety when used for a short period of time.
  • Phase III: Confirmative therapeutic: testing the final dosage in a medical practice on its usability and effectiveness in a larger number of patients. Comparing with an existing product or placebo. Safety in the short and longer terms are also observed.
  • Phase IV: Research after authorisation and related to the indication area for which the product is authorised. These types of research are not necessary for authorisation purposes, though are important for optimalisation of the use of the medicinal product.

Research with a medicinal product: extra review competent authority

Research with a medicinal product must undergo an extra review alongside the medical ethical review. This review is carried out by the competent authority. See also Research with a medicinal product & extra review competent authority for practical information on the marginal review.

The same set of documents are to be submitted to the reviewing committee and the competent authority: see the standard research file.

Within this you will also find information specific to research with a medicinal product, such as the IB, the IMPD, labeling and licences. Sections specific to research with a medicinal product are marked with a ‘pill’ symbol:

Are you unsure who acts as competent authority? Go to Help-me-on-my-way.

Registration

On the website of the Medicines Evaluation Board (CBG/MEB) you can find information on the registration of medicinal products.

Research with medical devices in combination with a medicine

The question whether research with a medical device, or an active implant, falls under the category research with a medicinal product in accordance to the WMO, is of interest when the medical device (or an active implant) is used in combination with a medicine. See research with a medical device for more information on medical devices and research with a medicinal product.