Research with human subjects is a sensitive matter. Every now and then, cases in which research subjects are seriously harmed meet the eye of the public, which then calls for more governance of research. The result is that research with humans today is governed by an extensive and complex set of regulations.

The history of this regulatory system in the Netherlands is usually told as a story of a free, licentious medical profession that had to be put under control by externally enforced public regulations. The Central Committee on Research Involving Human Beings (CCMO), which supervises accredited medical research ethics committees (MRECs), highlights the establishment of the first MREC in 1976 and the Dutch Law on Research involving Humans (WMO), which was established in 1999.Footnote ¹ Before then, the CCMO suggests, many informal ethical review committees were doing their job but lacked central control and uniform criteria. Only the 1999 law, which established the CCMO, solved such problems.

The CCMO’s 2003 self-evaluation report presents the law as necessary, if not always popular: “The Law didn’t have any transitional arrangements and the field was hardly enthusiastic about the law and the central committee,” it notes. “Moreover, there were a lot of uncertainties: it was unknown how many local research ethics committees were active, and how many of these committees wanted to be eligible for accreditation. Also, a national register for research with human beings was lacking.”Footnote ² Henk Visser, the CCMO’s chairman, paints a more positive picture, but his statement also implies a radical improvement since legislation was established. He stated in the CCMO’s first annual report: “In our country since the early nineteen eighties procedures of medical research with human subjects—as well as ethics review—in practice was in general adequately arranged. When the WMO came into force on December 1, 1999, an integral regulation and review system was established.”Footnote ³

This historical account of the development of research regulation in the Netherlands shows a particular deterministic style. A common presumption or methodological premise in such determinist histories is that events in the historical sphere have a chain of causation with an inner logic, which is considered characteristic for the course of events.Footnote ⁴ Generally, all events in a chain ought to be explainable by specific laws. Typically, these laws only mention characteristics or variables in terms of which the chain is specified, which suggest completeness. Also, the explanations of events exclude everything outside this logic, which suggest the state of closure.Footnote ⁵ Determinism in this sense can also be found in the historiography of Dutch governance of ethical issues in research with human subjects. It suggests that strict and formal regulation offers the solution to all obstacles that might be encountered. Subsequently, historical events are defined and explained in this framework and seem to form a progressive path to the future. Such a narrow historical view might prohibit a thorough understanding and evaluation of current ethical review practice. It also seriously narrows the scope of potential alternatives, since formal regulations are regarded as the best and only logical way of governing research ethics.

In this article, I try to provide a more balanced history of ethics governance of human-subjects research. By taking seriously the controversies about governance issues, it argues that, instead of resulting from inevitable historical logic, things could have been otherwise, and regulation was not the only possible solution to governance dilemmas. It describes changes in Dutch governance of ethics in research with human subjects by exploring three controversial issues in the development of research governance. First, it will focus on the debate about internal and external control regarding the medical profession to show that different stakeholders held different views on how to govern ethics of research with human subjects. Second, it will describe discussions about centralized versus decentralized governance. This topic was especially relevant in the constitution of formal ethical review practices in the late twentieth century. Third, it will investigate the homogeneity versus heterogeneity issue with respect to substantive and procedural criteria for the assessment of research. Exemplary for this issue is the multicenter drug trial, which has become a paragon in ethics review for other related fields of research. The article concludes with suggestions on what we can learn from this alternative account of history.

SELF-GOVERNANCE OR EXTERNAL CONTROL?

Until the 1950s, the Dutch medical profession was fairly autonomous compared to other Western countries. As sociologist John Griffiths observed in 2000, the medical profession’s “traditional claim to autonomy … carries a bit of an heroic aura (at least among the older generation) because of the way Dutch doctors collectively and en masse asserted it during the War against Nazi attempts to gain control over the profession.”Footnote ⁶ Lawyers and politicians had no urge to interfere with medical practices. The growing cry for regulation of medical research after World War II implied a threat to this ideal of autonomy and stimulated fierce debates about “self-governance” or “external control.”

How did the perceived need for regulation develop? In the early twentieth century, medical researchers became more critical of one another’s work and more transparent about their own methods.Footnote ⁷ They emphasized objectivity and the exclusion of the “human factor.” By the 1950s, doctors embraced the randomized clinical trial as the standard for good research.Footnote ⁸ Such studies required large numbers of participants, so patients now became potential subjects, which required a different role of the medical professional. Discussions in medical literature show that physicians were struggling with the morality of their practice, posing such questions as: Were they doing research primarily in the interest of the patient, or mainly in order to increase general scientific knowledge? With the horrific experiments of the Nazis fresh in their minds, Dutch medical professionals discussed the implications of the Nuremberg trials for the medical domain and even expressed their concerns regarding experiments conducted in Western countries.Footnote ⁹ They widened their view as their professional networks expanded, discussing the ethics of research with human subjects not only on an institutional level but also at a growing number of national and international conferences, some even especially dedicated to the issue of human research.

Although Lucas Bergkamp claimed in his influential 1988 study on norms in ethical review practices that no specific case stimulated public debate, physicians did express their concerns about foreign cases they learned about.Footnote ¹⁰ Already in 1948, William Bernard Huddleston Slater referred to an American study in which volunteers were injected with gonococci to investigate the effectiveness of prophylactic drugs. He warned that “under the pretence of science a lot of things happen which cannot pass.”Footnote ¹¹ Similarly, in 1957, Leopold Meyler noted a disturbing case study in the prominent journal Blood in which a volunteer was injected with the plasma of a serious ill patient, diagnosed with thrombotic thrombopenic purpura, a sometimes fatal clotting disorder. He regretted that such practices were apparently considered normal by the researchers, the journal’s editors, and the Department of Internal Medicine, Washington University School of Medicine, where this test was conducted.Footnote ¹² Some physicians denied that such things could happen in the Netherlands or found it very unlikely.

Other medical professionals voiced concerns about research in the Netherlands. They became more critical of one another and increasingly expressed their concerns about responsible conduct in medical journals, especially the leading Dutch Medical Journal (NTvG). In 1957, for instance, the physician Willem Fokkens wrote a letter to the editor contesting the conduct of Dr. Jacob Borst, a professor in neuroscience at Erasmus University in Rotterdam. Fokkens claimed that Borst reported at a seminar, and he quoted: “We brought some sufferers from Addison disease slowly and under strict clinical control in a critical state.” “As far as I know,” complained Fokkens, “it is not allowed to put a patient in a state which is to say the least worse than at the beginning of a study, in order to gather scientific evidence.”Footnote ¹³ Borst did not disagree directly, but he replied that Fokkens “did not take into account the possibility that the gathered information could be necessary for the diagnoses and treatment of patients.”Footnote ¹⁴

In the same year, the physician Jan Roelof Prakken, who would become the editor in chief of the NTvG in the 1960s, expressed his concerns regarding the possible dangerous effects of the rise of a new powerful actor in the medical domain: the pharmaceutical industry.Footnote ¹⁵ Worried about drug advertisements, he asked that medical professionals demand scientific evidence and reject commercial methods. So the Dutch medical profession already reflected upon ethical issues in their practices without apparent strong public pressure.

Such pressure did come, however, in the form of accusations by the Anti-Vivisectionist Foundation. This movement was generally concerned with the growing power of modern medicine and was primarily active in the field of animal testing. In 1955, for instance, Cor van Dis, a member of the Social Reformed Party, claimed in a parliamentary discussion on large-scale vaccinations to be informed by the movement that some doctors were eagerly vaccinating children at schools against smallpox, but at the same time deliberately withholding their own children from such vaccinations.Footnote ¹⁶ The Anti-Vivisectionists also got notice in the daily press.Footnote ¹⁷ Their complaints persuaded the state secretary of public health to request a report on research with human subjects from the Health Council, an advisory body for the Dutch government. The Health Council in turn acknowledged that experiments with humans were a sensitive and urgent matter, especially since the international field of human research was expanding rapidly. But the Dutch government preferred preventive measurements rather than repressive strategies, which were reflected in its suggestions for self-governance of the medical field.

The Health Council developed guidelines for medical interventions, explicitly avoiding a strict distinction between experiment and regular care. The council acknowledged the complexity of the ethical issues in research practice, and even the distinction between research and regular care, and therefore suggested that in “gray area cases” advice would be needed from a permanent committee of people familiar with “human experimentation.”Footnote ¹⁸ It appealed to editorial boards of medical journals to reject unethical research for publication, and to universities to add teaching in medical ethics to the medical curriculum. Additionally, the Health Council suggested that in serious cases, disciplinary courts would have the task of assessing cases according to prevailing professional norms. However, the problem was that no common professional opinion was yet formed about experiments on human subjects and therefore professional guidelines were needed. To further promote responsible conduct, the Health Council asked the Royal Dutch Medical Association (KNMG), the main medical professional organization in the Netherlands, to use its power to prohibit publication of unethical research and to promote the substance of the council’s report among its members.

In 1961, the public learned of the potentially disastrous effects of new medical technologies when they saw the severely malformed babies whose mothers had taken the drug thalidomide, marketed in the Netherlands as Softenon. Citing this case, physician Jan Hendrik van den Berg argued that physicians, supported by patients and family members, should assume responsibility regarding their “medical power.”Footnote ¹⁹ Others agreed, and by the end of the 1960s various groups, including theologians, philosophers, and lawyers, sought a role in controlling developments in medical technologies and science.Footnote ²⁰

Although to some extent the medical profession shared these public concerns, the professional societies were reluctant to open up debates on their domain for other groups. A typical response, although already put forward some years earlier, came from the renowned physician Gerrit Arie Lindeboom. He acknowledged that some nonmedical disciplines might alert physicians to things they had missed, but he argued that decisions regarding the acceptability of research with human subjects could be made only by physicians. “Despite the fact that ethical norms might be easy to indicate,” he explained, “their scope and application to medical casuistry … is something that can only be adequately judged by him who is located in the situation of the casuistry, that is, the medical professional.”Footnote ²¹

Such insistence on physicians’ autonomy could not withstand additional challenges regarding abortion and euthanasia. According to Griffiths, the abortion debate remained in a legal vacuum for some time, when the Medical Association was very conservative and abortion was considered illegal, whereas, in practice, solutions like special abortion clinics were developed. Then, in the 1970s, abortion was decriminalized by the Medical Association, which termed abortion a “normal medical practice.” But it took five legal bills and several political crises to overcome the problem of regulating abortion.Footnote ²² Eventually, criteria for abortion had been regulated top-down, which the leadership of the medical profession found hard to accept.Footnote ²³

From the abortion case in the early 1970s, the KNMG learned the lesson that a conservative, closed attitude did not work and thus changed its strategy. Theo van Berkestijn, who held sway over the KNMG, explained that “there should absolutely not develop a renewed alienation between physicians and public opinion.”Footnote ²⁴ Still, rather than turning governance over to external bodies, the KNMG opened itself to other disciplines. In the 1980s, Van Berkestijn deliberately chose to engage people from outside the medical profession. He involved, among others, theologians and ethicists Heleen Dupuis and Harry Kuiert in an effort to create a certain level of public authority.Footnote ²⁵ This multidisciplinary group proposed a protocol for euthanasia that in essence is still operative today.Footnote ²⁶

Local medical research ethics committees (MRECs) emerged as part of this effort to break the monopoly of doctors on medical decisions. First established in the academic hospital of Leiden in 1965, these committees were mainly composed of experts with different disciplinary backgrounds, including doctors.Footnote ²⁷ As numerous hospitals and health-care institutions followed their example, the number of MRECs grew rapidly. Many of these committees also dealt with ethical policies on clinical care. Growing technical possibilities added a new set of moral dilemmas to everyday medical practices. Erik Noach, one of the founders of the first MREC, would later refer to the rise of MRECs as an illustration of shifting norms: “It was no longer assumed that physicians in science always do good. No, the professional community and lay persons should judge about that.”Footnote ²⁸

By the early 1970s, then, Dutch physicians had lost the unquestioned authority that had allowed them to make all the decisions about medical research and practice. Both at the national and local levels, they found themselves debating such decisions with lawyers and ethicists. But the process remained defined by voluntary guidelines rather than legislation. That soon would change.

CENTRALIZED OR DECENTRALIZED GOVERNANCE?

A second important controversy in the history of research regulation deals with the question of how to organize regulation. Should it be organized centrally or on a local level?

The Tokyo amendment to the Declaration of Helsinki of the World Medical Association in 1975 required that a biomedical research project be described in an experimental protocol, and that it be submitted to a specially appointed independent committee.Footnote ²⁹ According to Bergkamp, this amendment was the main reason for the development of medical research ethics committees.Footnote ³⁰ Also in 1975, Henk Leenen, the most prominent health lawyer, suggested that the American Institutional Review Board (IRB) system could serve as a model. His motivations were in line with the ideas of Noach, who believed research ethics committees should serve as a middle ground between self-regulation and state control: “It seems not adequate to assign this task to the government, as it is such a delicate matter, which can better be left outside the domain of the state,” Leenen argued. “On the other hand, experimenting can neither be left to the individual experimenter, as he has his personal interests, and his judgment might be blurred.”Footnote ³¹ The U.S. IRB system was, however, far more formalistic than the ethical review practices in the Netherlands. The Dutch committees lacked a strong legal status, which the American IRBs had since 1974. Nor were they constrained by regulations comparable to those in the United States, which featured detailed provisions concerning composition, tasks, powers, and working methods of the IRB.Footnote ³²

Further proposals for arranging research ethics review and searching for intermediate bodies between government and medical practice followed during the late 1970s and 1980s. There was no general consensus on the role of the state, what should be enacted in law and what should be left to the medical field. Questions included: Should we officially regulate only medical research, or ethics review as well? And who in the beginning has adequate expertise to judge the ethical reasonableness of medical research?

In 1978, the state secretary of health, welfare, and sports sought to prioritize the matter of ethics in human research on the political agenda and called for advice from the Central Council. The Central Council, a central advisory body of the Dutch government, concluded that public regulations were necessary to prohibit people from being harmed. The Dutch government, however, was generally in favor of deregulation, and the state secretary deemed legislation on research on human subjects unnecessary.Footnote ³³ In 1983, the government published a special report on deregulation in which each ministry discussed its measures for the following years. The deregulation measurements were part of a larger operation to reorganize state control and decentralize government structures. Moreover, at a time when health costs were rising quickly, politicians were, as critics claimed, more interested in reducing health-care costs than protecting patients’ rights.Footnote ³⁴

Still, Dutch doctors and scholars continued to debate the governance of biomedical research on humans in Medisch Contact, the leading policy journal of the Royal Dutch Society of Medicine. In 1979, Dr. Mathijs Visser, a biologist in the department of science and society at Wageningen University, published a critical paper discussing the need to control ethical issues in research with human subjects in light of the increasing interest for human rights and, more specifically, the importance of protecting the physical and mental integrity of human subjects involved in medical research. He noted the broader movement of patient empowerment and self-organization: “Public developments have made consumers, also of health packages, more critical and articulated. Blind trust in experts has been fairly damaged. Also physicians were not spared.”Footnote ³⁵ And although discussions about patients’ rights were ongoing, he expressed surprise that the rights of healthy subjects or patients in biomedical and psychological research seemed hardly worthy of discussion. Visser blamed researchers for resisting legislation. He argued that based on a random sample of recent articles in Dutch medical literature, researchers showed poor ethical judgment. In many cases, he concluded, patients were insufficiently informed or information about participants’ consent was lacking. (Visser acknowledged that the actual protocols might have contained good consent procedures, but he suggested that the Declaration of Helsinki required those procedures to be included in published results.) Seeing peer review as inadequate, Visser suggested that multidisciplinary committees (like IRBs) could help to improve everyday research practice and to stimulate the ethical consciousness of scientists and physicians.

Not everyone shared Visser’s faith in MRECs, which had yet to become part of regular practice at health-care institutions conducting research with human subjects. In 1984, CABLA, the Board for Counseling and Support for Religious Matters, reported that twelve ethics committees were active in the field, but they were concentrated at academic institutions and institutions with an evident role in medical research.Footnote ³⁶ In 1985, Inez De Beaufort noted fourteen such committees. She discussed the possibility of incremental, less bureaucratic alternatives, such as a selective review in which only high-risk studies would be systematically reviewed, while less risky research proposals would be randomly reviewed. She acknowledged that the lack of legislation caused problems regarding the structure and authority of ethics review but believed the real problem was a lack of clarity on the moral requirements of research with human subjects.Footnote ³⁷

Many doctors continued to press for a law governing research ethics review. In the 1980s, Bergkamp found that MRECs varied widely in their norms and rules regarding their composition, criteria, and work routines and that “some MRECs do not sufficiently observe ethical and legal problems. This results in the sometimes inadequate protection of human research participants in experiments.” He blamed the committees’ lack of lawyers and ethicists and called for a law to impose uniform review criteria and require adequate insurance of research participants.Footnote ³⁸ Gradually, lawmakers began to explore this possibility. In 1983, the state secretary of welfare, public health, and culture proposed a law on experiments on human subjects. In 1984, a preliminary arrangement was established in the Decree on Requirements for the Accreditation of Hospitals, which stated that all human research at hospitals should be reviewed by an independent committee.Footnote ³⁹ In 1985, a first bill was introduced in parliament. It suggested a license-based system in which experiments with human subjects was forbidden unless a researcher had a license provided by an ethics committee.Footnote ⁴⁰

Some doctors and researchers, however, had varying expectations regarding a law. Health professor Erik Noach, one of the first initiators of MRECs in an academic setting, hoped that a law would bring enough money to pay reviewers, rather than relying on unpaid committee members.Footnote ⁴¹ Dr. H. A. van Geuns claimed that a law would ensure effective quality control.Footnote ⁴² Legislation, he argued, would oblige researchers to have their work reviewed by a competent committee. It would also establish state responsibility for the control of compliance with the law, and the state would provide the tools for handling cases of misconduct. Others saw legislation as the answer to new ethical challenges. For example, comments on research with embryos, published by Medisch Contact in 1989, differed not so much on whether the issue should be enacted in law, but rather how it should be done.

Parliament, which had long been reluctant to establish a law on human research, began debating the issue again in the mid-1980s. In 1987, the bill was put forward after the National Council for Public Health stated that a law on the protection of research subjects should be established as soon as possible. At that time, two major parties, the Liberals and the Christian Democrats, controlled a parliamentary majority. Both parties agreed on the importance of legal protection for research subjects. The VVD, the Dutch People’s Party for Freedom and Democracy, a party with strong liberal ideas, stressed the protection of vulnerable groups such as children, mentally challenged persons, prisoners, and hospitalized patients. Spokeswoman Erica Terpstra also argued that the protection of human subjects should go beyond the medical domain to include “marginal cases with psychological, pedagogical, ecological and sociological research,” because some of those experiments have higher risks than medical experiments. She named changes in personality as an example.Footnote ⁴³ The protection of especially vulnerable people was also a key point in discussions on patients’ rights in general, especially for children and persons unable to give consent. Ton de Kok, a Christian Democrat, stressed the right of patients for legal control. He referred to Bergkamp’s finding of plural norms in ethical review practices, apparently as evidence for the need of better protections.Footnote ⁴⁴

By the end of the 1980s, formalization of patients’ rights was a hot issue, enough to move politicians away from their earlier focus on deregulation. Some politicians believed the government relied too much on the self-regulating competence of the medical profession, so they proposed several new laws: a law on Special Admission Psychiatric Hospitals (BOPZ), a law on Patient Rights (WGBO), and a law on Public Health Research (WBO). Members of the Christian-Democratic party, the Social Reformed Party, and Netelenbos (members of the Labor Party) all agreed on the importance of legislation.Footnote ⁴⁵

Other politicians warned of the bureaucratic effects of the proposed law. Several Dutch politicians liked the existing system of MRECs and were skeptical of the proposed central committee. They asked whether it should serve as an advisory board or as a controlling body. Should ethics review be mandatory for researchers? In 1987, parliament debated, but did not pass, a proposal that ethics review committees would have only an advisory role. This would allow research on human subjects without the “approval” of an ethics committee, which would lack any official authority.Footnote ⁴⁶

Meanwhile, international medical research in the Netherlands was becoming big business, as commercial partners took an important position in Dutch medical research networks. During the 1990s, the pharmaceutical industry increasingly argued that MRECs discriminated against industry-sponsored research, in comparison to purely academic research. It co-sponsored a study by Ron Berghmans and colleagues of the Institute of Health Ethics in Maastricht to compare academic and regional MRECs.Footnote ⁴⁷ The study was inconclusive on the question of discrimination, although it did show several inconsistencies among committees asked to review four hypothetical protocols. The committees varied both in their assessment of patient information leaflets and in the final decisions about the protocols, suggesting a lack of standards for ethics review.

Passage of a law was delayed by discussions on the protection of especially vulnerable groups, such as minors unable to give consent. This issue was so important to the government that it sought advice from a specially appointed committee. Eventually, it decided on a “no-unless” criterion.Footnote ⁴⁸ This criterion states that all medical scientific research with persons unable to give consent is forbidden unless the study (a) can be potentially beneficial to the research participant, (b) cannot be conducted without cooperation of the category to which the research subject belongs, and (c) has negligible risks and minimal difficulties.

Finally, in 1999, parliament passed the Law on Research involving Humans (WMO). The law imposed legal requirements regarding research on human subjects and ethical review practices. These requirements concerned the composition of a committee and other administrative demands. The law instituted a new regulatory body, the Central Committee on Research involving Human Beings (CCMO). Later, the CCMO presented this law as nothing more than a formalization of already existing practices, and only a reaction to increasing demands of the field.Footnote ⁴⁹ However, it was not really clear whether the MRECs needed legislation or guidance about how to conduct reviews. Kok had claimed in a parliamentary debate in 1989: “Progressively the patient/research subject has a right to a legal arrangement. By definition, there are complaints from the field about the delay of the intended law. The advisory bodies complain about being flooded with questions.” Parliament gave them the CCMO, which gradually began to further regulate practices not only on a substantive but also on a procedural level by publishing guidelines on how the law should be interpreted, which formats should be used, and which criteria MRECs should take into account.

In practice, the law did not settle the question of centralization. In 2003, for example, the chair of the Dutch association of MRECs (NVMETC) expressed his concerns about the endangerment of decentralized review by the latest implementation plan. “Our cabinet wants drug research to be double reviewed,” he complained, “marginally by the CCMO and substantially by the MRECs. When this proposal becomes established in law, MRECs will lose their autonomy on review.”Footnote ⁵⁰

But too much autonomy was also a problem, especially for multicenter trials.Footnote ⁵¹ Researchers had to seek the separate approval of each site’s MREC, which might differ in its judgment from all the others. In 2004, the CCMO tried to solve the problem by a change of rules, which entailed that in the case of a multicenter trial only one MREC had to review the protocol on its merits, while the rest had only to judge issues of local feasibility.Footnote ⁵² But MRECs continued to disagree on protocols. The CCMO offered yet more instructions to local committees to stick such criteria as expertise, facilities, and organization, rather than reassessing risks and benefits and other, more general parts of the study, such as methodological and scientific quality. The debate over centralization continues today, although in a slightly different form, as illustrated by the CCMO’s call in 2009 to different health-care institutions to leave judgments on local feasibility to the institution itself instead of mandating an MREC.Footnote ⁵³ Here the authority of MRECs to have a say on aspects of local feasibility was further pushed back.

The lawmakers intended to establish a legal framework that could be filled in by the field. MRECs would have some autonomy to apply the general regulations to their own practices. The CCMO would be the coordinating body, accrediting the individual local policies, overseeing the work of MRECs, and registering protocol reviews. In addition, the CCMO would review protocols in areas that required special expertise. In the years after the WMO came into force, the CCMO established guidelines, in line with its legal authority, that were intended to create clarity on how to interpret the scope of the law. Such standardization, of course, also meant narrowing MRECs’ discretionary powers. And although the CCMO tried to ensure a strict distinction between centralized and decentralized responsibilities, it was hard to change established practices.

DOES ONE SIZE FIT ALL?

While lawmakers tinkered with the legal requirements for human subjects research, physicians and researchers built their own institutions. In 1991, the Royal Dutch Medical Association (KNMG) and the National Hospital Board (NZR) established the National Association of Medical Research Ethics Committees (NVMETC), which promoted the advancement of expertise in ethics review. The association intended to organize meetings in which members could exchange experience and thus build coherence in ethics review. At those meetings, members offered scientific presentations on difficult issues in ethical review practices, such as ethical aspects of phase I and II trials, informed consent, and the difference between scientific and ethical review.Footnote ⁵⁴

Researchers had their own concerns. In 1990, the clinical epidemiologist Jan Vandenbroucke sparked discussion with an article on epidemiological research. He painted a historical picture of a free and well-intended medical practice in which important discoveries are made with the help of harmless research, and he doubted the wisdom of letting other disciplines meddle in discussions on sound medical research, especially when it concerns harmless methods such as studies on patient files or blood serum. “The medical ethicist and the lawyer,” he noted, “believe they have the primacy of the true principle based on the patient’s autonomy and on the constitution, which entails that nobody can be obliged to contribute to the benefit of others, even if it does not in the least bother them.”Footnote ⁵⁵ But, he argued, standard medical ethics worked poorly for fields like clinical epidemiology, clinical follow-up studies, and also more basic research on pathological-anatomic samples. He claimed that researchers were wasting time writing their protocols to anticipate both the competencies and incompetencies of an MREC. Vandenbroucke dismissed calls for uniformity in ethical review, overseen by a central, national committee. Instead, he stressed that ethical review remains human work, and he applauded approaches that were more sensitive to variations in actual research practices. As an example, he offered a disciplinary council conviction of a colleague who gathered information for research of another colleague’s patients. The court regarded this as negligence regarding duty of professional confidentiality. Vandenbroucke thought the court had unnecessarily hampered research.

The Dutch Federation of medical scientific associations (FMWV, also referred to as Federa), also remained skeptical of externally enforced regulations. The federation became actively involved in self-regulation and “rule taking” as it was opposed to the top-down rule making by governmental bodies and laws. “Rule taking” refers to the active involvement and lobbying in decision-making processes on laws that affect medical scientific professionals, and trying to create support for the implementation of such regulations. Therefore, the federation developed rather proactive policies and established professional guidelines regarding responsible conduct and behavior in research. For instance, in the mid-1990s and early 2000s, it established professional codes on privacy, personal data, and human tissue and fluid samples. The former secretary of the federation, a pathologist, claims that “this alliance has contributed to the idea that researchers increasingly have to consider preconditions set by the public on scholarly work.”Footnote ⁵⁶

Psychologists also grappled with the WMO. The law officially covered all human research that breaches the integrity of research participants, that is, research in which certain actions or behavior are imposed on participants. This definition at first might seem straightforward, but when the law was enacted in 1999, the field was not sure whether it covered psychological research. So Dutch psychologists struggled with the definition and questioned adequate review of their protocols in case their research was reviewed by accredited committees within the WMO framework. Psychologists claim that this is often done for safety’s sake.Footnote ⁵⁷ That is, research subjects could profit from the provided protection under the WMO.Footnote ⁵⁸

Eventually, in 2001, the CCMO announced an interpretation of the law implying that almost all psychological research would be covered. Sander Welie, Leo Blomert, Harald Merckelbach, and Rob de Vries, all psychologists, thought that was a bad idea. They were not opposed to ethics review, and they had established a psychological review committee in Maastricht, but they had done so outside the WMO framework. They felt that psychological research is often less risky, that some areas require special expertise, and that if ethics review was imposed on unwilling psychologists, these psychologists would deliberately hide information in their documents.Footnote ⁵⁹

The official MREC of Maastricht University disagreed with the establishment of this Ethical Committee in Psychology (ECP) and stressed the general character of the criteria in the WMO as well as the multidisciplinary composition of the committee. However, the ongoing discussion in Maastricht further encouraged other psychology faculties to establish their own specialized committees, and gradually psychological committees became more and more accepted. Later, educational researchers formed their own ethical review arrangements for research with human participants. They did so in part in response to the growing pressure of scientific journals to show ethics approval of the studies reported in the submitted papers.Footnote ⁶⁰

Henk Visser, the CCMO’s first chairman, acknowledged that the law was not without problems. Stakeholders in the field were skeptical. “The establishment of the WMO—and herewith also the CCMO—is expected in the research field with some caution. After all, it was going well in our country? Didn’t it mean even more paperwork, more bureaucracy regarding clinical scientific research? The MRECs saw the CCMO as a possibly difficult supervisor, which could disturb the established order.” For the purpose of the WMO evaluation, various stakeholders were interviewed on their experience with the WMO and asked for suggestions for improvement. This evaluation showed that stakeholders had different expectations of the law. One interviewee of a medical association stated: “The WMO is well intended and necessary from an international perspective, but the responsibility of researchers is undermined. If the starting point would be one of honest, accurate, and expert researchers, with a thorough morality, then these people should be autonomous and there should only be interference when problems occur.”Footnote ⁶¹

The evaluation showed widespread concerns about the law. In addition to perceived problems of delay in multicenter trials, four out of eleven institutional boards complained about the number of regulations and the administrative burdens. All forty MRECs confirmed the increased bureaucracy as a result of the WMO, as well as 74 percent of the researchers (192); 95 percent of committees also noted an increased workload for the researchers, and 73 percent saw a delay of the review procedure (143). Further, the applicability of the WMO framework was not straightforward. This was the conclusion of 67 percent of MRECs, who totally disagreed with the statement that “it is always clear whether or not the WMO applies to a study” (144). One scientific professional association suggested that “a review framework should be developed for observational research (within and beyond the scope of the WMO).” Footnote ⁶²

As a reaction to this criticism, in 2005 the CCMO circulated a new memo on the scope of the WMO. When the central research question is grounded in medical science, the CCMO considered it within the scope of the WMO. But if the research question was nonmedical, the law would not apply. The CCMO still wanted nonmedical research reviewed, arguing that “the protection level of research participants should be similar. Therefore, at the moment, the possibility is investigated to develop a framework for review for behavioral research.” Footnote ⁶³ And the law’s scope remained unclear since there was no consensus on the definition of “medical research.” In 2008, researchers at Utrecht Medical Center injected priobiotics, living microorganisms intended to help the patient, into pancreatitis patients. When they concluded that the probiotics had caused unnecessary deaths in the experimental group, scientists asked what regulatory framework should be applied to assess such research. Probiotics were generally not regarded as a drug, but what if these substances were not taken as food but were injected directly in the patient’s body?

Even today the issue of what the scope of the WMO should be is an urgent matter. In 2010, the Royal Dutch Academy of Science organized a symposium, and it became clear that the various stakeholders hold different views on whether the legal medical framework of the WMO should apply to all research. By then, other social faculties had followed Maastricht’s example and established their own ethics review committees. And Jan Willem Coebergh, chair of the Federation of Medical Scientific Associations (FMWV), proposed a differentiated system of ethics review for low-risk research, such as observational research and research with data and body tissue, in line with the report “Toetsing op Maat” (Tailor-made review).Footnote ⁶⁴ These examples show that not all professional researchers automatically adopt the framework for medical research. Rather than ending the debates on the oversight of human subjects research, the 1999 law had sparked new controversies.