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Abstract
Objective To evaluate the opinions of parents of newborns following their infant’s enrolment into a neonatal research study through the process of deferred consent.
Design Mixed-methods, observational study, interviewing 100 parents recently approached for deferred consent.
Setting Tertiary-level neonatal intensive care unit, Melbourne, Australia.
Results All 100 parents interviewed had consented to the study/studies using deferred consent; 62% had also experienced a prospective neonatal consent process. Eighty-nine per cent were ‘satisfied’ with the deferred consent process. The most common reason given for consenting was ‘to help future babies’. Negative comments regarding deferred consent mostly related to the timing of the consent approach, and some related to a perceived loss of parental rights. A deferred approach was preferred by 51%, 24% preferred a prospective approach and 25% were unsure. Those who thought prospective consent would not have been preferable cited impaired decision-making, inappropriate timing of an approach before birth and their preference for removal of the decision-making burden via deferred consent. Seventy-seven per cent thought they would have given the same response if approached prospectively; those who would have declined reported that a prospective approach under stressful conditions was unwelcome and too overwhelming.
Conclusion In our sample, 89% of parents of infants enrolled in neonatal research using deferred consent considered it acceptable and half would not have preferred prospective consent. The ability to make a more considered decision under less stressful circumstances was key to the acceptability of deferred consent.
- ethics
- neonatology
- qualitative research
Data availability statement
Data are available on reasonable request.
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What is already known on this topic?
Obtaining prospective consent for neonatal resuscitation research is ethically challenging; consent sought in the immediate perinatal period may not be valid.
Alternative options for consent include consent waiver and deferred consent; use of deferred consent improves recruitment and results in a more representative study sample.
Parental opinion, from those who have experienced deferred consent for neonatal research, is not well explored. Given hypothetical scenarios, parents prefer prospective antenatal consent.
What this study adds?
This study showed that in our sample of families who had recently experienced deferred consent, the majority found it to be a satisfactory process.
Parental concerns around deferred consent mostly related to the early timing of the consent approach, and a minority were concerned about perceived loss of parental rights.
Half of parents thought prospective consent would not have been preferable; the ability to make decisions under less stressful circumstances was key to acceptance of deferred consent.
Introduction
Participants in clinical research must provide informed consent. In neonatal research, the parent/legal guardian provides proxy consent.1 Obtaining prospective consent for newborn resuscitation research can be challenging. Distress,2 3 pain,4 clinical urgency and effects of maternal medication5 may prevent researchers from approaching parents and erode their ability to obtain ethically valid consent. Reliance on prospective (antenatal) consent for neonatal resuscitation trials can introduce selection bias, reducing generalisability; mothers admitted antenatally have greater opportunity for inclusion in research, are more likely to receive protective antenatal treatments and their infants have a less risk of adverse outcomes. Secondary analysis of a delivery room (DR) trial using prospective antenatal consent6 demonstrated over-representation of lower-risk infants with higher survival than eligible unenrolled infants.7
Regulatory bodies such as the National Health and Medical Research Council, Australia (NHMRC),8 European Commission9 and the U.S. Department of Health & Human Services10 11 can waive the requirement for prospective consent under certain circumstances. Some processes require later ‘consent’ to use collected data and continue data collection, referred to as ‘deferred’ (retrospective) consent.12 13 This may be more accurately termed ‘research without prior consent’,14 where ‘consent’ seeks permission to use collected data or to identify objections to the research undertaken. Regulatory bodies waive requirements for prospective consent when specific criteria are fulfilled. These criteria vary between countries,12 but typically include that research risk is deemed either ‘low’, ‘minimal’ or ‘justified by benefit’. The Australian NHMRC stipulates that deferred consent should be sought ‘as soon as reasonably possible’ after randomisation.
Deferred consent may overcome the limitations of generalisability, but it raises complex ethical issues. Secondary analyses of paediatric and neonatal trials have demonstrated higher recruitment15 16 and more representative sampling16 when deferred consent was permitted than when only prospective consent was used. However, parental opinion of deferred consent in neonatal research is not well explored. Studies posing hypothetical scenarios have reported that parents of newborns can be uncomfortable with the idea of deferred consent.17 18 We evaluated the opinions of parents of newborns who had been asked for deferred consent following their infant’s enrolment into a study.
Methods
The study was completed at The Royal Women’s Hospital, Melbourne, a large, tertiary referral centre. A sample of 100 parents was planned; all families approached for deferred consent between May 2015 and October 2017 were eligible, regardless of the consent decision. Most studies involved interventions in the DR; therefore, the approach for deferred consent typically occurred after study intervention was complete. Researchers usually approached parents in the first few days after birth, with timing dependent on individual trial regulations, the clinical situation and parental availability. Parents were asked to consent to use of data already collected, ongoing data collection, follow-up and, in a few cases, to ongoing trial intervention. Face-to-face structured interviews with one/both parents were performed; parents of multiples completed one interview. During the study period, six neonatal resuscitation and respiratory support trials were ongoing; five used prospective and deferred consent, one used only deferred consent, three studies recruited only in Australia and three recruited internationally (table 1).19–24 Eleven trials requiring prospective consent were recruiting concurrently (online supplemental table). Infants could potentially be enrolled into any of these 17 trials, regardless of the mode of consent.
Supplemental material
Index studies recruiting using deferred consent
Interview questions were devised and assessed for content validity. Face validity was established via pilot interviews with eligible parents, with subsequent question refinement. During the infant’s admission, eligible parents were approached for consent for interview. Interviews were undertaken by a research nurse (n=3) or clinician researcher not otherwise involved in the infant’s care or original approach for deferred consent (n=3). Interviews occurred at a location of the parent’s choice, typically the bedside, lasting approximately 15 min.
Interviews included closed and open-ended questions with responses recorded verbatim by the interviewer (see online supplemental material). Inter-interviewer variation was minimised by a single interviewer (JAD) training other interviewers in a standardised approach. Data saturation analysis was not used; data were manually extracted (following full recruitment) by a single researcher (SS) and stored using REDCap (Host; Murdoch Children’s Research Institute, Melbourne). Two researchers (SS, JAD) inductively derived themes independently. SS read interview transcripts to develop a coding framework used by both researchers. Discrepancies were reviewed by SS and JAD. Analysis of quantitative data used descriptive statistics. Verbatim excerpts are included in the results; […] signifies omitted text and [text] signifies text added for clarification.
Results
One hundred and ninety families were approached for deferred consent (online supplemental figure); 184 (97%) consented. We approached 113/190 families (59%); 77 (41%) were not approached due to researcher unavailability or infant discharge/transfer (n=60), or decision not to approach (bereaved families/unwell mothers, n=17). All 113 parents initially approached had consented to the index trial using deferred consent. Eight of the 113 declined interview participation, a further five were excluded as they did not speak English and this study did not have resources to offer interpreters. Interviews occurred at a median 16 days after deferred consent approach (IQR 2–63 days); 62 questionnaires were completed on behalf of the mother, 22 for the father and 16 on behalf of both parents together. Seventy-nine had been approached for one deferred consent trial, 16 for two, and five for three studies. No infant became eligible for more than three trials using deferred consent. Twenty-one interviewees were parents of twins. Sixty-two families (62%) had also been approached for at least one study using prospective consent, of which 50 (81%) had consented. The mean total number of studies (deferred±prospective consent studies) parents were approached for was 3 (range 1–7). Demographic details of participants are shown in table 2. For both consent processes, parents typically chose two reasons for consenting (table 3); most frequently cited reasons were ‘to help future babies’ and ‘to help the researchers’.
Parent and infant demographics
Reasons given for consenting to or declining from research studies
Overall satisfaction with deferred consent
Eighty-nine parents (89%) involved in a deferred consent encounter were ‘satisfied’ with the process, no comments provided. Nine (9%) were ‘unsatisfied’ or thought ‘improvements could be made’; two (2%) were unsure. These 11 parents provided comments (table 4), and five comments focused on the timing of consent approach: “not during cuddles” and to “perhaps wait a little longer […] when things have calmed down”; three reported discomfort at being asked afterwards: “disappointment to have been asked after the event” and “would have preferred to have been asked before, was in antenatal ward for a week”. Fifty-seven of 62 parents (92%) involved in a prospective consent encounter were ‘satisfied’ with that process, and five (8%) were ‘unsatisfied’ or thought improvements were needed (table 4). For either process, parents disliked being approached while holding their infant (table 4).
Comments regarding concerns and suggested improvements to consent processes
Attitude towards prospective consent as a potential alternative
Seventy-seven parents (77%) felt that they would have given the same answer if approached prospectively instead, 16 (16%) were unsure and seven (7%) thought they would have declined if approached prospectively (table 5). Of those who thought they would have declined prospectively, the predominant themes were feeling too stressed prior to birth (both mothers and fathers) and feeling too overwhelmed to process information: “too much… at a time when things are overwhelming” and “would have been overwhelmed… wouldn’t have made a logical decision” and “… glad you came afterwards. Too stressed beforehand […] would have made the decision harder”. Those unsure what their response would have been prospectively cited the circumstances: “depends how busy I was or what other stresses were going on”.
Comments on potential responses had prospective consent been available and on which process would have been potentially have been preferred
Is prospective consent considered preferable?
Fifty-one parents (51%) thought prospective consent was ‘not preferable’ to deferred consent, 25 (25%) were unsure and 24 (24%) thought prospective consent would have been preferable. Themes that emerged from parents who thought prospective consent was not preferable (n=18) described their feeling of impaired decision-making “they came too early” and “better to come the next day, [I] would not have understood”, inappropriate timing of approaches before birth “a horrible time to ask parents for consent”, and a preference for removal of decision-making burdens via deferred consent “preferred afterwards, prior [I] had other worries” (table 5). Of the 24% who thought prospective consent was preferable, comments included the appreciation of a “heads up”, and prospective consent “where possible”, but were “unsure [they] could have made this decision in the hours leading up to birth”. One parent stated that “prospective consent gave [me] hope that [my babies] would survive, or if not their existence meant something as they helped with research”. Parents who were ‘unsure’ which consent process was preferable (25 parents, 5 comments) expressed concern about the available time for consent antenatally, remained neutral or were concerned about their ability to make a decision at that time.
Discussion
This is the first study to explore opinions of parents recently involved in neonatal trials using deferred consent. Both deferred and prospective consent were deemed ‘satisfactory’ by a large majority (89% and 92%, respectively), 24% considered prospective consent preferable to deferred consent and 51% did not. Key themes regarding attitudes towards decision-making were parents’ perceptions of being overly stressed, or not thinking clearly at the time of a prospective antenatal or early postnatal approach, or that making research decisions was not a priority at that time, and that a deferred approach allowed more time flexibility. Most reasons stated for preferring deferred consent related to emotional and practical reactions, rather than ethical opinions of the research or consent process.
Previous investigation of this subject sought opinions from parents presented with hypothetical scenarios.17 18 The one prior study that sought opinions from families exposed to deferred consent emailed parents a year after recruitment,25 where 71% of 49 parents of infants enrolled in a US DR trial recalled a positive experience. Although our results are more positive, they remain less positive than findings from paediatric trials in emergency settings that found ‘no parents were dissatisfied with the [deferred] consent process’,26 where deferred consent was considered to ‘protect[s] the interests of both patients and researchers’.27 Importantly in our study, three comments from the nine parents ‘not satisfied’ with the deferred process suggested disappointment in being asked afterwards, implying a perceived loss of autonomy or parental rights. Such concerns were also described in a paediatric emergency study; however, the authors noted that parents’ initial reservations were allayed following explanation of the reasons deferred consent was used.26
Parents in our study were altruistic in their decisions to participate in research, as reported previously.28–30 However, our data demonstrated inconsistencies: despite 95% responding that they consented to ‘help future babies’, 26% also indicated (from presented options) that they consented because their child had ‘already received the study intervention’. This could be viewed positively: it alleviated distress “because the study intervention had already been done it took the decision making burden away”, or negatively: “only said yes because [I] felt [I] had no choice…”. This concern was raised previously by Songstad et al who noted that parents might consent to a study to avoid disruption to clinical care when the study intervention was ongoing, that is, risking having to return to ‘standard care’ after randomisation to the intervention if consent was declined,16 suggesting that parents may feel obliged to consent to studies using deferred consent.
We posed the hypothetical question whether, if it had been possible under the perinatal circumstances they faced, parents would have preferred prospective consent. Acknowledging the responses are subject to considerable bias, parents who thought a prospective approach was potentially preferable were most concerned about timing; a discussion about research before birth was only preferred “if there was sufficient time”, with some acknowledging that they may have been unable to make a decision at that time. More than three-quarters thought that they would still have consented if it had been possible to approach them prospectively. Those who were unsure or who thought they would have declined prospectively reported being too stressed and overwhelmed antenatally. Conversely, studies report that in hypothetical and real situations, families say they would prefer to discuss research during scheduled antenatal visits18 31 and that seeking consent once in labour is unacceptable.17 A recent report found 52% of parents thought prospective consent was still necessary in emergency scenarios but acknowledged that 28% thought they would feel pressured to consent.18 Researchers must acknowledge the risk of applying inadvertent coercion while seeking consent during times of crisis.32 Indeed, the ability to provide informed consent in the perinatal period is limited, less than 30% of parents may give valid consent in the immediate antenatal period28 and many have no recollection of the process.27
In our study, most of those dissatisfied with the deferred consent approach were concerned with its timing. Guidelines regarding the timeframe for obtaining deferred consent suggest it should be “as soon as reasonably possible”. 8 Ethical review boards typically stipulate consent approaches within 24–48 hours of enrolment. However, comments such as “perhaps wait a little longer […] when things have calmed down” support consideration of a later time point, and this warrants exploration. Woolfall et al reported lasting parental dissatisfaction when consent (of any type) was sought at a time parents felt was inappropriate, too stressful or too early.26 In practical terms, parents in our study specifically disliked being approached for consent while feeding or holding their infant.
Regulations for research without prior consent differ around the world, leading researchers to draw up frameworks to guide clinicians in best practice.12 33 Regardless, individual ethics review boards interpret and apply the regulations differently,34 35 meaning that the studies used to source our pool of parents may not have been granted deferred consent at other study sites. Studies typically suited to deferred consent include comparative effectiveness trials, comparing two or more clinically accepted practices. The implication being that as both/all practices are acceptable standards of care, the risk of comparing them ought to be ‘minimal’, a typical requirement for deferred consent acceptance. However, this may not be the case, especially in critically unwell newborns, where care is inherently high risk. If one intervention ultimately proves to be superior, the inferior intervention(s) potentially convey worse morbidity or mortality outcomes not considered to be ‘minimal risk’. So, despite potential advantages of reduced enrolment bias, improved generalisability and more representative study samples, deferred consent remains ethically challenging. Autonomy and non-maleficence must be balanced against the need for evidence-based research to prevent unregulated use of unproven, potentially harmful therapies. One parent captured this conundrum, stating “[it] would have been nice to know [they] were involved before. However, catch 22, it was nice to be spoken to when we were less stressed, after the event”.
A strength of our study is its direct evaluation of families soon after exposure to deferred consent decision-making. However, our study also has important limitations. First, the consent rate to the index studies was very high (97%), and despite our efforts to interview parents who had declined a deferred consent study (n=6), we failed to capture these families, potentially biasing our results. Although there is no evidence to suggest how the views of families who declined participation in studies using deferred consent may have differed from those who consented, the issue warrants exploration. It is possible that families declined the initial study due to concerns over the mode of consent, or distress that their infant had received an intervention without their knowledge or permission. If so, our results may represent an overly favourable view. However, it is also possible that these families declined for reasons entirely unrelated to the mode of consent. Second, we excluded those with limited English who may have had different opinions. Third, we chose not to approach families whose child had already died (n=12), potentially introducing selection bias. In older children, it has been shown that bereaved parents are as likely to want their child included in a trial as those with surviving children,36 they have similar views on the acceptability of deferred consent,36 but they are more likely to decline deferred consent than those whose infant lived.15
While acknowledging these biases, our results demonstrate good acceptability of deferred consent in our sample. However, parental opinions were not unanimous and it will be important to repeat this research in settings where the culture and attitudes towards research processes may differ.37
Conclusion
Eighty-nine per cent of families in our sample were satisfied with the deferred consent process. Twenty-four per cent thought prospective consent would have been preferable and 51% did not. Negative comments related to deferred consent mostly concerned early timing of the approach, with some to perceived loss of autonomy. The ability to make a more considered decision under less stressful circumstances was key to deferred consent acceptability.
Data availability statement
Data are available on reasonable request.
Ethics statements
Ethics approval
This study was approved by the institutional Human Research and Ethics Committees.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors SS contributed to data collection and interpretation and wrote the first draft of the manuscript. JAD contributed to data collection and interpretation and manuscript revision. LMcG contributed to study design, data collection and manuscript revision. ARR contributed to data collection and manuscript revision. PGD contributed to study conception and design and manuscript revision. LSO contributed to study conception and design, data collection and interpretation and manuscript revision.
Funding National Health and Medical Research Council Fellowships: PGD: Australian National Health and Medical Research Council Programme Grant #1113902, Australian National Health and Medical Research Council Practitioner Fellowship #105911; LSO: Australian National Health and Medical Research Council Early Career Fellowship #1090678.
Disclaimer The NHMRC had no role in study design, data collection, analysis, or interpretation, manuscript writing or decision to publish.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.