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The subject of research in children invariably generates strong emotions. On the one hand, children are vulnerable because of their limited autonomy and hence capacity, their predisposition to adverse effects resulting from their unique physiology and anatomy, and the severity of complications they might suffer (and the ‘size’ of the loss should permanent harm or death occur, in terms of the number of years and the potential that are lost). On the other hand, overprotection of vulnerable groups (not just children but others including the elderly and pregnant women – indeed all women, historically) by excluding them from research risks depriving society of the knowledge required to treat them effectively. It is not surprising, therefore, that an article reporting how anaesthetised children were exposed to a provocative test in order to study the treatment of the (potentially serious) complication thus caused [1] would generate controversy [2-4].

In the article, published in this issue of Anaesthesia, Erb et al. describe how they studied the effect of intravenous lidocaine on laryngeal and respiratory reflexes in children anaesthetised with sevoflurane [1]. Responses were elicited by spraying distilled water on to the patients’ laryngeal mucosa before, and at 2 and 10 min after, the lidocaine bolus. The incidence of laryngospasm was significantly reduced from 38% at baseline to 15% and 18% at 2 and 10 min after lidocaine administration, respectively. The authors concluded that intravenous lidocaine significantly reduced the incidence of induced laryngospasm but that the effect was shortlived – knowledge that could be both important and useful for treating intra-operative laryngospasm.

Irrespective of the study's scientific value (which is itself contested, not just its ethics [2]), the ethical issues it raises are important ones for those involved in regulating and conducting – and consenting to and benefiting from – clinical research. At their core are three main issues: first, the balance of risk and benefit, both in terms of quantity and distribution. Thus, how much risk is it acceptable for a group of individuals to be exposed to in order to obtain knowledge that might benefit others in the future (or possibly some of the same individuals should they present for further treatment)? And, how much should consideration of this question be affected by the potential for benefit to this study group, and to society at large? At first glance, one might conclude that the patients in Erb et al.'s study were only exposed to risk, with no possibility of deriving any benefit. But could it be argued that the presence (and readiness) of highly trained specialists during the provocation test might confer additional benefit compared with, say a routine case anaesthetised by a less experienced practitioner, with no warning of an impending complication? And even if Erb et al.'s patients did derive no benefit, how big a benefit to future children might justify the risk to those in the study – and how would one (or could one) ever quantify the amount of either? This is where the science comes back into the equation – in truth it never went away, since the ethics of research depends on the quality of the science [5]: the better the science the more the potential for benefit (or at least, the weaker the science the less the potential). And so Durward, in order to discuss the ethics of Erb et al.'s study, must cover the science too [2].

The second issue concerns the nature (some would say the impossibility [6]) of informed consent – difficult enough for treatment, let alone research, and let alone research involving one's children. The three editorials that accompany this one, including responses from the investigators and from the research ethics committee (REC) involved [2-4], all discuss the importance of providing information to the parents – a central part of clinical research and treatment and yet such a difficult one in practice. Is it really possible to explain such complicated physiological and ethical issues in order for parents to understand what is involved and why? Does the low uptake in Erb et al.'s study represent good understanding or poor understanding?

Documentation of consent, and the role of REC in ensuring this [4], leads us to the third main issue – one that is at the heart of the regulatory process for clinical research: what is the actual role of the REC? Is it merely procedural: checking that local processes have been followed, confidentiality ensured, and consent obtained properly, irrespective of the actual risk/benefit ratio (surely the true expression of respect for autonomy: so long as adequate information is given, it's up to the participants (or in this case, their parents) to decide)? Or should the REC go further: stepping in to prevent a study that its members feel represents an unacceptable risk/benefit ratio, even if informed consent is granted (a more paternalistic approach)? Perruchoud's account [4] describes the latter, with the REC considering the risks and benefits of Erb et al's study carefully before approving it. We suspect that most readers (and possibly most REC members) would feel uncomfortable with a purely procedural role for RECs: weighing up risks and benefits is a fundamental part of considering ethical dilemmas. Which brings us back to where we started.

These are difficult questions, and the nature of ethical dilemmas is that there are never clear, easy answers. As to Erb et al.'s study itself, it has taken considerable time to reach publication, reflecting the difficult issues it raised. The article was reviewed by no less than nine internal and three external reviewers, the process including our obtaining a translation (from the original Swiss) of the information provided to the children's parents and several communications to/from the investigators and REC addressing the concerns raised during the article's review. As might be expected, a range of opinions was obtained – some quite extreme (both for and against publication). After considerable thought, our decision was to publish the article, inviting an independent expert to summarise the concerns [2] and the investigators [3] and REC chairman [4] to respond to them. We are grateful to all of them for their patience and willingness to contribute to the debate. The final stage is to invite readers to come to their own decision and contribute themselves, through the Journal's Correspondence website (see www.anaesthesiacorrespondence.com).

Competing interests

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SMY is a former chairman of Riverside REC and a former Council member of the Committee on Publication Ethics. No external funding declared.

References

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  2. Competing interests
  3. References