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Published in: Trials 1/2015

Open Access 01-12-2015 | Research

The ethical issues regarding consent to clinical trials with pre-term or sick neonates: a systematic review (framework synthesis) of the empirical research

Authors: E. Wilman, C. Megone, S. Oliver, L. Duley, G. Gyte, J. M. Wright

Published in: Trials | Issue 1/2015

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Abstract

Background

Conducting clinical trials with pre-term or sick infants is important if care for this population is to be underpinned by sound evidence. Yet approaching parents at this difficult time raises challenges for the obtaining of valid informed consent to such research. This study asked: what light does the empirical literature cast on an ethically defensible approach to the obtaining of informed consent in perinatal clinical trials?

Methods

A systematic search identified 49 studies. Analysis began by applying philosophical frameworks which were then refined in light of the concepts emerging from empirical studies to present a coherent picture of a broad literature.

Results

Between them, studies addressed the attitudes of both parents and clinicians concerning consent in neonatal trials; the validity of the consent process in the neonatal research context; and different possible methods of obtaining consent.

Conclusions

Despite a variety of opinions among parents and clinicians there is a strongly and widely held view that it is important that parents do give or decline consent for neonatal participation in trials. However, none of the range of existing consent processes reviewed by the research is satisfactory.
A significant gap is evaluation of the widespread practice of emergency ‘assent’, in which parents assent or refuse their baby’s participation as best they can during the emergency and later give full consent to ongoing participation and follow-up. Emergency assent has not been evaluated for its acceptability, how such a process would deal with bad outcomes such as neonatal death between assent and consent, or the extent to which late parental refusal might bias results.
This review of a large number of empirical papers, while not making fundamental changes, has refined and developed the conceptual framework from philosophy for examining informed consent in this context.
Appendix
Available only for authorised users
Footnotes
1
NIHR Programme in Applied Health Research, Improving quality of care and outcome at very preterm birth (RP-PG- 0609-10107).
 
2
In philosophical work this is sometimes arrived at using a mind-map technique.
 
3
As Additional file 4 shows only 3 studies included questions about hypothetical scenarios as opposed to actual consent processes, and 2 of these were with clinicians not parents.
 
4
Scare quotes are used here as, to the extent the parents are deciding whether or not to enter their child, it is not directly altruism on their behalf, since the child is the one entering the trial, not the parents. Of course in some cases, as in cord-clamping trials, it might be both mother and child that enter the trial. As will be discussed later, one gap in the empirical literature was study of cases of maternal-fetal research.
 
5
We follow the convention of referring to the baby as ‘him’ (using the ungendered form) to distinguish the baby from the mother in what follows.
 
6
Additional file 3 gives additional findings for this section and for further sections.
 
7
More recently Nathan found – using a competence assessment tool – that parents of sick neonates gave significantly more valid consent than patients with Alzheimer’s or schizophrenia, though comparison with previously published control groups using the same assessment tool gave variable results [58]. But this does not necessarily show that their consent was valid.
 
8
Voluntariness, informedness and competence (rationality) are the three standard criteria for informed consent.
 
9
The authors raise the question of whether the initial consent is really ‘permission to be approached later’ and the ‘actual consent’ for the study then takes place at the second discussion.
 
10
Full tabulated results are presented in Additional file 1.
 
11
Though not all the reasons are good ones. The consent process might be seen as having a very small role in protecting neonates from risk, but the main responsibility for that lies with research designers and research ethics committees which are much better placed than most lay parents to make such judgements of risk. This is pretty clear on philosophical grounds alone, but one piece of data in the studies (about parental assessment of risks) also supports this.
 
12
It might be suggested that with respect to these second and third claims the force of an appeal to empirical data alone is less compelling. This is because, although parental claims about how comfortable they felt in a consent process are of interest, it is very likely that parents in general will not have thought through the criteria for valid informed consent, so not appreciate fully the challenges to providing genuinely valid informed consent in certain neonatal research contexts. So even where a parent reports ‘comfort’ with a consent process this is not sufficient to show that such a process was a satisfactory means of gaining valid consent.
 
13
Allmark’s suggestion is similar to this, but his version is expressed in terms of continuous consent [46].
 
14
A review by Claire Snowden et al. on the BRACELET research has now reported on views of bereaved parents, but this research was published after the our review was completed. A reviewer notes that they were also considered by Allmark and Mason [46]
.
 
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Metadata
Title
The ethical issues regarding consent to clinical trials with pre-term or sick neonates: a systematic review (framework synthesis) of the empirical research
Authors
E. Wilman
C. Megone
S. Oliver
L. Duley
G. Gyte
J. M. Wright
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Trials / Issue 1/2015
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-015-0957-x

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