The Netherlands: Call for reform of Dutch legislation on medical research involving the paediatric population

02 March 2010

Machteld Hiemstra

On 26 November 2009 the Committee on Medical Scientific research involving minors presented its findings on its study of the desirability of relaxing Dutch legislation applicable to medical research involving minors. The Committee concluded that Dutch legislation prevents essential medical research and therefore tends to be counter productive in protecting the interests of minors. The Committee recommends relaxing the circumstances in which medical research may involve minors. The Minister of Health has informed the Parliament that she will respond to the report in spring of this year.

Medical research involving minors is governed by the law on medical scientific research involving humans, which implements the Clinical Trials Directive.  Also relevant are the Paediatric Regulation 1901/2006 and the Dutch civil rules governing the contract to provide medical treatment.

Dutch law requires that, in situations where participation in a study cannot be demonstrated to have beneficial effects to the study subjects, often referred to as "non-therapeutic research", only “negligible risks” are acceptable. In this respect, Dutch legislation is much more strict than the legal framework created by the Clinical Trials Directive, which has set as standard for permission for non-therapeutic research that a study must be designed to minimise pain, discomfort, fear and any other foreseeable risk in relation to the disease and development”. Clearly, this “minimalisation criterion” still leaves discretion to ethics committees to decide that the minimum risks as identified may still be regarded unacceptable and for that reason not allow the study to be conducted. From the Dutch legislative history, it becomes clear that the difference in terminology is not just semantic but intended to introduce a very rigorous and strict legal framework - “negligible” is to be interpreted as; “a risk which may not extend the risk exposure in daily life in a reasonably safe environment or ordinary routine interventions in health care”. The Central Committee on research involving humans, responsible for safeguarding the interests of participants in clinical trials, as well as patient representation bodies and medical practitioners, have expressed their dissatisfaction with the current situation and now find the Committee on their side.

The Committee points out that application of the “negligible” criterion leaves no space for ethics committees to take into consideration during the assessment process elements like the necessity and proportionality of involving minors and the actual risks faced even in well designed and necessary studies.

The Committee stresses that the strict Dutch legal regime does not serve the interests of minors as they may be deprived of the chance of development and implementation of treatment and therapies adapted for minors and progression in research in this field. Not performing research amongst the paediatric population may be as unsatisfactory as continuing the established practise of experimental treatment and care based on evidence and information gathered by adult studies and use or ‘off label’ use of medicines not authorised for minors. It was of course these types of considerations that induced the introduction of the Paediatrics Regulation in the EU to improve availability of therapies suitable and tested for the paediatric population. However, and contradictory to achieving this purpose, particularly in the case of "non-therapeutic investigations", conducting human research of pharmaceutical compounds is practically impossible as the study participant will not have any direct, personal benefits resulting from participation. The Committee points out that the automatic assumption that phase 1 medicinal research qualifies as "non-therapeutic research" is not justified as it cannot be excluded per se that minors, including healthy minors, will benefit from this type of medical research, albeit not directly or individually.

An important element in the report of the Committee is the acknowledgement of the rights of potential minor participants in medical research as well as the individual motivating factors to participate. In this context the Committee distinguishes “aspirational benefit”, “collateral benefit” and “future potential benefit” and suggest that these individual motivating aspects should be taken into account in the assessment of a proposal for research involving minors.

Important suggestions for revision of the law include:

  • Permission for medical research involving minors should be based on the “yes, but”, principle, instead of the currently applied “no, unless”. The Committee finds that this principle would do more justice to the importance of and need for medical research for the benefit of the paediatric population as a whole or in individual cases.

  • The Dutch law should implement article 4 (g) of the Clinical Trials Directive introducing the “minimalisation criterion” for all types of research involving minors.

  • Adoption of the element of proportionality and particular circumstances of potential study participants in the study assessment protocols in order to take account of and balance aspects like age, severity, stage and harm of illness. This requires amendment of article 3 of the Dutch law.

  • Involvement of minor participants in the decision making process should be increased by requesting informed consent from minor participants aged 12 years and older.