Two criteria that define the scope of the legislation

Here in the second theme, we will discuss which studies involving human subjects fall within the scope of the WMO, and we will discuss the criteria that determine when review by an accredited MREC and/or the CCMO is mandatory. The distinction between studies that require MREC/CCMO review and those that do not is not always clear to investigators, Contract Research Organizations (CROs), or companies; however, it is important to understand this distinction know before you start to design medical research in the Netherlands involving human subjects.

In this theme, we will also describe the mandatory review of clinical studies involving medicinal products or medical devices that do not fall within the scope of the WMO but are regulated by the Dutch Medicines Act and the Medical Devices Regulation (MDR), respectively. In addition, we will discuss the review of research involving medicinal products that are not covered by Dutch law but are covered by self-regulation. Finally, we will touch upon psychological, social, and behavioral studies involving human subjects, as well as biobanks, which are also covered by self-regulation.

We continue using the Committee Finder (CoF) tool, which we introduced in the first theme. This tool will help you identify the right committee for reviewing your application for a medical study involving human subjects (adults, minors, and/or incapacitated subjects), gametocytes, surplus embryos, and fetuses in utero; in addition, you can use this tool find other organizations (e.g., the competent authority, advisory committees, etc.) that are involved in reviewing specific cases such as clinical studies involving medical devices.

Most medical research involving human subjects falls within the scope of the WMO

Most medical studies involving healthy volunteers and/or patients fall within the scope of the WMO. As we discussed in the first theme, these studies must be approved by an accredited MREC or — in specific cases — the CCMO. You will therefore need to obtain this approval before you can approach subjects with a request to participate in the study. For the small percentage of medical studies involving human subjects that do not fall under the scope of the WMO, a different review procedure is in place.

Two criteria define whether a study involving human subjects falls under scope of the WMO

According to Dutch law, a study involving human subjects will fall within the scope of the WMO if both of the following two criteria are met:

1. The study involves medical scientific research, and
2. The research subjects will be subjected to medical procedures and/or required to follow certain rules of behavior.

Criterion 1

For the first criterion, the CCMO provides the following definition of “medical scientific research”:

Note that the last sentence in this definition indicates that a study designed to obtain results that are both time and place restricted (for example, a study performed in one particular hospital for a certain period of time of which the results are only locally used) without the intention of contributing to knowledge to the medical field does not fall under the WMO. An example of this scenario would be a hospital study in which the quality of a new reagent used to isolate stem cells from peripheral blood is compared with reagents that are currently used in that hospital.

Criterion 2

For the second criterion, it is important to realize that the procedures to which the research subjects will be subjected and/or the behavioral rules that they will be required to follow are specific to this study. In other words, the procedures and/or rules of behavior are not part of a standard medical treatment.

An example of this would be a research project in which an experimental medicine will be administered to a patient with the purpose of obtaining results that will answer a medical scientific question. In this case, medicine will be administered to the subjects specifically for the purposes of research and is not part of any current standard treatment. In this case, and assuming that criterion 1 is also met, it is clear that this study will fall within the WMO. In other cases, it may be less clear.

For example, when a patient will be requested to collect a single urine sample for a research project, the study would not fall under the scope of the WMO. However, if the patient will be requested to collect daily urine samples for a month, the study would be considered a WMO study (assuming that criterion 1 is met), and a research file will need to be submitted for mandatory review. In this case, the burden placed on the patient to collect urine so many days is not considered negligible.

A similar rationale applies for collecting mucosal swabs. Obtaining a single buccal mucosa swab from adult patients for a research project is not sufficient for the study to fall under the WMO; however, collecting a cervical swab from an adult female patient is sufficient for the study to fall under the WMO, due to the added burden placed on the patient. Similarly, collecting a single blood sample from healthy volunteers or patients is sufficient for the study to fall within the scope of the WMO (again, assuming the first criteria is also met).

Finally, asking study participants to complete a simple questionnaire regarding their food intake for a week or so (for example, for an obesity study) would not be sufficient for the study to fall under the WMO. However, if the participants are requested to complete a questionnaire regarding potentially traumatic events and/or factors such as sexual abuse, drug addiction, violent behavior, borderline personality disorder, etc., and again assuming that criterion 1 is met, the study would fall within the scope of the WMO.