Risks in a Trial of an Innovative Treatment of Duchenne Muscular Dystrophy.

Studies of innovative therapies for muscular dystrophy raise unique ethical issues. The disease is currently untreatable and relentlessly progressive. A number of potentially efficacious treatments are being developed, but like all treatments, they may have unforeseen adverse effects. Nevertheless, patients and families, facing a bleak future, may be willing to take the gamble and try the treatments. Many doctors are eager to study them. But should institutional review boards approve them? This article discusses these issues and recounts the ways that one such study elicited different responses from different institutional review boards.

Perceived discomfort levels in healthy children participating in vaccine research.

When assessing the risks of a research protocol, review boards need to consider not only the possible harms but also the expected discomfort levels caused by the various study procedures. However, data on how children experience various study procedures are scarce. This study assessed perceived discomfort levels in 671 healthy children aged 0-2 years under-going vaccinations, venipunctures, and nasopharyngeal swab taking. In half of the study participants, venipunctures caused a moderate or high level of discomfort (49%). Corresponding figures for nasopharyngeal swabbing and vaccinations were 28% and 12%, respectively. Within the reported age group, increasing age was related with higher discomfort levels. In a majority of cases for all study procedures, the perceived levels of discomfort met the parents' expectations.

Discomfort in children undergoing unsedated MRI.

Magnetic resonance imaging (MRI) scans for research purposes usually do not directly benefit the children scanned, so that review boards need to assess whether the risk of harm or discomfort is minimal. This study aimed at providing empirical data on discomfort related to unsedated MRI in children aged 5-12 years. Secondary objectives were to determine whether lower age is associated with higher levels of discomfort and to investigate which other characteristics of subjects and/or procedures may be associated with higher levels of discomfort. Self-report scores, observation scores, heart rate standard deviation scores, and incremental salivary cortisol levels were obtained from 54 children aged 5-12 years with non-acute conditions undergoing diagnostic MRI. Of the 54 children, 10 scored relatively high values on the self-report score and on one or two of the other measures, and another 15 scored relatively high on the self-report score alone. Rather than an age effect, associations were found between parents' trait anxiety and observation score values and between use of contrast fluid (requiring the insertion of a venous cannula) and high incremental salivary cortisol levels. In conclusion, MRI-related discomfort may be regarded as minimal for more than half of children aged 5-12.

[Medical research in children: should the rules be eased?]. / Wetenschappelijk onderzoek met kinderen: maak de regels niet te ruim.

'Non-therapeutic research' in children, i.e. research that will not directly benefit the patients involved, is indispensable for improving the quality of paediatric care. However, as children cannot give consent, such research is strictly limited. According to the Dutch Medical Research Involving Human Subjects Act (WMO) non-therapeutic studies with children are only allowed if the risks are negligible and the burdens are minimal. A Dutch expert committee ('committee Doek') investigating whether the WMO should be made less rigid, recently recommended discouraging the use of the distinction between 'therapeutic' and 'non-therapeutic' research and maintaining the absolute limit regarding risks and burdens only for observational studies in children younger than 12 years. This paper discusses these recommendations and argues that in principle, the risks and burdens of all research that has no direct benefit for the subjects should be kept to a minimum.

Acceptable risks and burdens for children in research without direct benefit: a systematic analysis of the decisions made by the Dutch Central Committee.

OBJECTIVES: To evaluate whether the requirement of "minimal risk and burden" for paediatric research without direct benefit to the subjects compromises the ability to obtain data necessary for improving paediatric care. To provide evidence-based reflections on the EU recommendation that allows for a higher level of risk. DESIGN AND SETTING: Systematic analysis of the approval/rejection decisions made by the Dutch Central Committee on Research involving Human Subjects (CCMO). REVIEW METHODS: The analysis included 165 proposals for paediatric research without direct benefit that were reviewed by the CCMO between January, 2000, and July, 2007. A separate, in-depth analysis of all drug studies included 18 early phase drug studies and nine other drug studies without direct benefit. RESULTS: 11 out of 165 studies were definitively rejected because the CCMO did not regard the risk and/or burden to be minimal. In three of these 11 cases (including two early phase drug studies) the requirement of minimal risk and burden was cited as the only reason for rejection. Four other early phase drug studies also involved risks and/or burdens that were not regarded to be minimal but were nevertheless approved. CONCLUSIONS: The requirement of minimal risk and burden, aiming to protect research subjects, occasionally leads to rejection of protocols. Early phase drug studies relatively often do not comply with the requirement. Committees may find ways to approve important studies that formally should be rejected, but that is not a desirable solution. The regulatory framework should be revised to make such occasional exceptions to the requirement legitimate and transparent.

Communicating with Muslim parents: "the four principles" are not as culturally neutral as suggested.

The "four principles approach" has been popularly accepted as a set of universal guidelines for biomedical ethics. Based on four allegedly trans-cultural principles (respect for autonomy, nonmaleficence, beneficence and justice), it is supposed to fulfil the need of a 'culturally neutral approach to thinking about ethical issues in health care'. On the basis of a case-history, this paper challenges the appropriateness of communicating in terms of these four principles with patients with a different background. The case describes the situation in which Muslim parents bring forward that their religion keeps them from consenting to end-of-life decisions by non-religious paediatricians. In a literature analysis, the different meanings and roles of the relevant principles in non-religious and Islamic ethics are compared. In non-religious ethics, the principle of nonmaleficence may be used to justify withholding or withdrawing futile or damaging treatments, whereas Islamic ethics applies this principle to forbid all actions that may harm life. And while the non-religious version of the principle of respect for autonomy emphasises the need for informed consent, the Islamic version focuses on "respect for the patient". We conclude that the parties involved in the described disagreement may feel committed to seemingly similar, but actually quite different principles. In such cases, communication in terms of these principles may create a conflict within an apparently common conceptual framework. The four principles approach may be very helpful in analysing ethical dilemmas, but when communicating with patients with different backgrounds, an alternative approach is needed that pays genuine attention to the different backgrounds.