Processes in recruitment to randomised controlled trials of medicines for children (RECRUIT): a qualitative study

Recruitment, information and understanding

By far the largest body of evidence on recruitment to children’s trials has been gathered from parents, and largely from paediatric oncology (specifically leukaemia) and neonatology. There is little work beyond these specialties. Research on parents is dominated by quantitative investigations of the recruitment process in terms of the information families receive and how much of that information they understand and recall. 12–15

Information can affect parents’ satisfaction and willingness to participate in a trial. 16–18 However, what constitutes the ‘right’ level and type of information is probably impossible to define,19 not least because information can simultaneously serve different functions20 and parents can vary in their preferences for trial information. 21,22 More information is not necessarily better: Miller and colleagues23 reported a trend for more information to be associated with greater parental anxiety and less control. While a baseline level of information may be necessary for informed consent and informed decline,24 research suggests that parents benefit from an approach in which practitioners select and tailor information according to individual need and preference. 23,25

Researchers consistently report that parents’ understanding of trials is poor. 26–28 Families whose first language is different from that used by practitioners, minority group members and those from disadvantaged backgrounds may experience particular difficulties. 27 It can also be a struggle for patients and families to separate discussions about treatment options and management from those about trial participation,29–31 particularly when faced with serious illness. 24,32 Based on a series of investigations of paediatric oncology trial discussions, followed by assessments of parents’ understanding, Simon and colleagues33 emphasised the need for a clearer distinction between trial-related issues and standard treatment issues, along with clearer explanations of randomisation, confirming findings from previous studies. 12

Interventions to improve understanding

When asked for feedback on how to improve informed consent discussions, parents of children with leukaemia who were approached about trial entry advocated a sequenced or staged approach to informed consent,21,34 including scheduling discussion of the trial after patients have achieved a basic understanding of the disease and treatment. An intervention based on this feedback, and on studies stressing the importance of encouraging parental participation,12,23,33 was used to train practitioners in communication techniques, such as simplifying information, prompting parents’ interactions and encouraging them to ask questions. 35 The training was evaluated using researcher-assessed measures of parental understanding. Improvements were found in parents’ understanding of the voluntary nature of the trial but not in their understanding of randomisation. Parents found nurse–family research education sessions helpful to prepare them for the trial discussion with their doctor, and felt that the sessions helped them ask questions and understand the information provided by the doctor. 36

Qualitative work on the recruitment of adults into trials has also indicated that patients find trials hard to understand; concepts such as voluntariness, equipoise and randomisation can be particularly difficult for patients to grasp. 37–39 These studies further indicated that a failure to understand these concepts can result in patients becoming distrustful of the trial or the doctor, and simple interventions to provide more or ‘better’ information may not always be sufficient to ameliorate these difficulties. 37–39 Adaptations to the practitioners’ communication, such as changing the way in which the trial arms were presented to emphasise their equivalence, increased the perceived acceptability of a trial to patients39 and its randomisation rate. 7 Wade and colleagues40 reported that styles of consultation that were participant led rather than practitioner led, and which involved practitioners using open questions, pauses and ‘ceding the floor’, enabled participants to express their concerns more easily.

The context and experience of trial recruitment

While these adaptations to practitioner presentation and communication about trials may be transferable to the paediatric context, parents considering trial entry for their child have a very different role from the adult considering trial entry for him or herself. 41 Parents are responsible for their child and are entrusted to act in the child’s best interests, a difficult and complex position when trials, by their nature, cannot promise to act in the best interests of the individual child. 42–44 Consent can often be sought soon after diagnosis, at birth or when the child is very ill and the parents are distressed and vulnerable. 30,45,46 Despite such challenges, parents have reported that they, rather than doctors or nurses, should be the ones who make the decision about whether a child should enter a trial,15,32,43,47,48 although parents value doctors’ advice. 49 Making a decision for one’s child is further complicated by the need to make the ‘right decision’ and the anticipation that one might later regret a decision. 31,50,51

The generally high rates of recruitment to trials in neonatology52 and childhood cancer53 suggest that the threat of a child’s illness and parents’ consequent need for hope could be important influences on how parents view trials. Parents of chronically ill children may, in general, be prepared to take greater risks in treatment in the hope of helping their child42 than the parents of healthy children considering participation in vaccine research, who have been found to believe that children should take part in research only when the medical benefits outweigh any potential risk. 54

Influences on parents’ decision to enter their child into a trial

Most studies on the reasons why parents choose whether or not to enter their child in a trial have used questionnaire and survey methods. Particularly common worries for parents when considering a trial are that their child might be randomised to the treatment arm that they perceive to be less effective50,55 and the responsibility that they would feel if the child later deteriorated. 56 Nevertheless, parents do perceive several benefits of trial participation for their own child, such as receiving extra medical attention. 57–60 Such benefits can be influential in their decision. However, evidence indicates that parents’ primary concern when considering a trial is their child’s safety61 and to protect their child from harm. 43 Altruism, although frequently cited by parents as a motivation for participation in trials,49,62,63 may be a secondary consideration in their decision. 26,45,64

The seriousness of the child’s condition and the urgency surrounding trial entry and parents’ resulting sense of vulnerability have also been found to be important influences on how parents experience recruitment to trials. 31,32,55,65 However, the relationship between anxiety, vulnerability and trial decisions may be mediated or moderated by factors such as trust in medical research66 and the parent–practitioner relationship. 23,56,67–70 The practicalities of trial participation are less commonly mentioned;71 this may reflect the fact that most studies have been conducted in neonatology and oncology, when the child is usually in hospital at the time of the trial approach.

Summary

A relatively large body of work has been conducted on parents and trial recruitment within oncology and neonatology; however, other areas have been largely overlooked, including trials in other specialties and studies investigating the experiences of parents who decline trials. The quantitative nature of much of the existing literature reflects the priorities of researchers and presupposes what is important to parents when they are approached about a trial. 72 In adult clinical trials, the information content of the trial discussion and the patient ratings of the interpersonal aspects of communication, such as a belief that the doctor listened to them, has been found to influence the trial decision and the patient’s confidence in that decision. 73 With a few notable exceptions, little research has addressed how the trial approach is experienced by parents in a way that allows them to define what they consider meaningful and important during this process. 21,30,55,74 Finally, no studies have compared parents’ experience of trial recruitment with the actual content of the trial discussion.

Young people’s understanding of research

Like their parents, young people may struggle to understand trials. 77–79 The voluntary nature of research and the right to withdraw were understood by young people in some studies78,80 but not in others. 81 In their study of young people with cancer or human immunodeficiency virus (HIV), Chappuy and colleagues81 link this difference to the young people’s lack of information and understanding of their life-threatening condition and proximity to diagnosis. Like parents, young people may find it difficult to distinguish between their treatment and research,82 and this may be particularly true in the cancer setting, where the two are particularly entwined. One study reported that young people with diabetes were much better able to differentiate between the research they were involved in and their treatment regimen than those with cancer,82 whereas one-half of the young people participating in one oncology research project did not know that their treatment was part of a clinical research study. 83

Young people’s reasons for participation in research

Like the available studies in parents, most studies on the reasons why young people choose whether or not to participate in research has been conducted using questionnaire and survey methods. Personal benefit is the most popular reason cited by young people consenting to an actual or hypothetical trial; the desire to help others is significantly less influential in young people’s decisions than perception of personal benefit,84–86 as it also is for their parents,87 although occasionally young people cite benefit to others as more important than personal benefit. 88,89 Young people give a number of reasons for declining a trial, including worries about blood or urine samples or the doctor’s examination,89 extra clinic visits,90 belief that the trial will take up too much time,88 belief that the ‘research methods are too involved or too burdensome’ and lack of interest in the research topic. 91 Refusal rates have been found to be higher in studies that include blood sampling, and higher in boys than in girls. 91

Young people’s role in the trial discussion

Discussions about young people’s participation in a trial entail more complex dynamics than is usually typical of adult trial recruitment. 92,93 Compared with adult trials, such dynamics are likely to present additional challenge to paediatric trial recruiters in managing the consultation and balancing the involvement of each party. 94 However, studies of health-care consultations, in general, report that young people often play little active part. 95,96 While few studies have investigated their role in discussions about trial entry, Olechnowicz and colleagues94 reported that young people recently diagnosed with cancer said very little in the trial discussion. There was considerable variability in the extent to which practitioners directed the discussion towards the patient. Older patients spoke more than younger ones, largely because they asked more questions, but few of their questions were about the trial.

Young people’s role in the trial decision

The role of young people in the decision about trial entry is complex. Some researchers have argued that while young people’s dissent should be respected, they are not in a position to make a decision on trial entry without significant guidance from their parents,97,98 and that, while it is important that they are consulted, they should be protected from decisions that they are unwilling, or unable, to make. 99 A key complexity in considering research in this area is that much of it has investigated young people’s decision-making about entry into hypothetical trials or non-therapeutic clinical research,87,100–105 rather than focusing on young people who have been approached about a ‘real’ clinical trial. Moreover, some research in this area has been conducted with samples of healthy children, rather than children who have recent experience of illness. Because of the uncertainties in interpreting the relevance of such research, we have limited our discussion of it in this section; we draw on it only where other evidence is unavailable.

Young people approached for assent to clinical anaesthesia and surgery research80 or to clinical trials of treatments for cancer or HIV81 are strongly influenced by their parents when making a decision on trial entry. This probably stems from young people’s reliance on their parents to guide and protect them, and from both parties’ concern to make the ‘right’ decision. 92 Sometimes, parents encourage or persuade children to take part in research if they think it is in their child’s best interests. 57,85

The potential for tension between young people and parents regarding decisions about research participation, and the difficulty for practitioners in balancing their needs, is highlighted by several studies. A survey of 7- to 14-year-olds who were enrolled in clinical research or receiving clinical care for cancer or asthma reported that approximately 90% of young people felt that they should be involved in decisions, whereas only approximately 60% of parents agreed. 84 Just over 40% of parents were against or unsure about whether children should have decisional authority over participation in non-therapeutic clinical research,100 while nearly 70% of parents responding to a hypothetical research scenario said that they would impose their own views on research participation regardless of their child’s wishes. 102

Particularly where the child has a life-threatening illness, some parents report excluding the child from the decisions about research altogether in order to protect them from distressing information, or including their child in discussions but making the trial decision themselves. 94,106 In a departure from much of the decision-making literature, which has largely focused on young people in hypothetical research scenarios, Unguru83 presented the views of young people in relation to the cancer research in which they were participating. Many young people in Unguru’s study felt minimally involved in decision-making. They had wanted to be involved but did not want to make the decision on their own – rather they wanted to decide jointly with their parents and doctors. By contrast, some healthy young people102,104 and those with a chronic condition (asthma, diabetes or epilepsy) responding to hypothetical research scenarios want the ultimate decision to be theirs, although other research has indicated that some young people feel that their parents ‘know best’ and take the view that if their parents did not want them to participate then they would not do so. 105

Among the challenges for triallists when considering the young person’s role in decision-making are the conflicting legislative frameworks governing consent for research versus those governing consent for treatment. While legislation governing consent to treatment recognises young people’s agency and autonomy,107 Medicines for Human Use (Clinical Trials) Regulations give power of legal consent to parents. The wishes of under-16-year-olds are ‘considered’ but they do not have legal force in the context of clinical trials of medicines. 76 Interestingly, evidence provides some support for this legislation. Young people are more willing to take part in above-minimal-risk hypothetical studies than their parents,87 and adolescents are particularly more likely to ‘consent’ than parents. 87 If they are less risk averse than their parents in actual clinical trials, parental consent may serve a valuable function in helping to protect young people from accepting inappropriate research risks. 105 Where family decisions are initially discordant about hypothetical research scenarios, the final decision usually reflects the parents’ opinions, although the young people are less happy with the final family decision as a result. 101

Summary

Considered alongside the legislative frameworks governing consent for children’s trials,108,109 data on hypothetical scenarios and non-therapeutic clinical research can alert us to some important considerations. However, as we outline above, the applicability of these findings to families of seriously ill children approached about a real clinical trial is questionable. Moreover, the survey nature of much research on young people means that, like the literature on parents, it assumes rather than explores what is important to young people when they are invited to join a clinical trial.

Practitioners’ communication in the trial discussion

Clinical trials have a long and successful history in paediatric oncology. It is no surprise then that almost all research on practitioners’ communication about clinical trials has been conducted in this area. In an early survey of clinicians’ practice and parents’ opinion, practitioners noted the need for a flexible and adaptable approach to accommodate families’ individual needs, but they also sometimes noted a conflict between the need to start treatment and the ‘deliberate pace necessary for an optimal consent’. 46 However, practitioners’ concerns about informed consent were not shared by parents, who were generally more satisfied with the consent process than practitioners, 50% of whom felt that families were given too much information. 46 These disparities between parents and practitioners are important. However, the brief survey data gathered from this and similar studies limit interpretation. In response to an open-ended question in another survey, one-quarter of practitioners’ suggestions for improving the informed consent process related to simplifying information for parents, while suggestions for improving the timing and staging of the discussions were a close second. 110

Barriers to recruitment

A relatively large body of work has investigated so-called barriers to recruiting adults and children to clinical research. Evidence from adult trial recruitment suggests that, when offered a trial, most patients accept,73 and some paediatric practitioners described selectively approaching those families who they thought most likely to consent. 111 Non-invitation of eligible participants is therefore likely to contribute to trial recruitment difficulties in trials in all specialties. In paediatric trials, where the pool of eligible participants may already be relatively small,111 this source of recruitment difficulty is an important concern.

Many studies in adult care settings cite practitioners’ time constraints as one of the most common barriers to recruitment or involvement in research at all. 112–115 However, based on a study of general practitioners (GPs) who declined to facilitate an adult trial, Salmon and colleagues112 pointed out that such justifications may be markers of the low priority that practitioners give to research and the perception that research has limited relevance to their clinical work. Other evidence on practitioners’ reasons for not approaching patients about research has indicated that practitioners do not recruit to studies because they see their patients as vulnerable,113 in need of protection;116 have concerns about the impact of research on the doctor–patient relationship,113,117 which may be a particular difficulty in community-based trials;52 or have strongly held preferences for one treatment over another118 and perceive other ethical difficulties. 115

Practitioners also cite time constraints as a barrier to recruitment in paediatric trials. 119 They are also concerned about the impact of research on the doctor–patient relationship,119,120 the use of placebo and randomisation,111,119 the practical burden of participation for families,111 potential harms to participants and unpleasant procedures, such as venepuncture. 111,119 Some practitioners describe an allegiance to the patient, which they regard as being in conflict with the uncertainty inherent in trials,120 and believe that families are liable to be confused by, or mistrust, trials. 119

Particular barriers exist in paediatric research in critical care settings where parents may be unavailable for consent or be so emotionally distraught as to make an approach about research untenable. 121 In a personal account of avoiding approaching vulnerable families, Walterspiel122 described the ‘emotional burden’ of obtaining informed consent under such circumstances. Particularly in critical situations, as is often the case in neonatal trials, practitioners express concern about parents’ competence to give informed consent because of their vulnerable position and emotional state, as well as their lack of knowledge and time to decide. 32

Practitioners may also have concerns over their own skill and confidence in approaching patients. 113 While some practitioners regard trials more positively, for example as a chance to offer their patients potentially effective therapies at an early stage,115 a prominent feature of much of the research on practitioners is the negative way in which they construct trials and oppose the interests of trials and the interests of the doctor–patient relationship. One study123 reported that a significant proportion of clinicians in adult cancer care rated seeking consent to clinical trials as their main communication problem – ranking it as more difficult than breaking news of serious illness to patients. In one focus group study, some paediatricians described how they disliked approaching parents and felt ‘rejected’ if parents said ‘no’ to a trial, while others described discomfort at expressing uncertainty because they were concerned it might damage parents’ trust in their expertise. 119

Summary

Recruiting to children’s trials brings additional complexities compared with recruiting adults to trials, which probably affects the practitioner’s experience of recruitment. Paediatric trials also confer specific potential risks – such as patient discomfort, pain and fear of separation from parents or familiar surroundings – that are either absent in adult trials or harder to assess in paediatric settings. 124 Much of the research on practitioners in both adult and paediatric settings indicates that they construct trials in rather negative ways, but evidence directly comparing practitioners’ and parents’ constructions of the same trials is limited.

MASCOT – Management of Asthma in School-aged Children On Therapy

• This was an RCT comparing the add-on treatments salmeterol (long-acting β₂-agonist) and montelukast (leukotriene receptor antagonist) for young people whose asthma was poorly controlled with fluticasone (low-dose inhaled corticosteroid).

• The initial approach about the trial was usually via a letter from the GP (interested families returned a slip to the trial team) or a personal approach when the child was attending a secondary care centre. Interested families received participant information leaflets (PILs) and a telephone call from a research nurse before attending an appointment with a respiratory consultant and research nurse, specifically arranged to discuss trial entry.

• The parent PIL was 12 pages long (approximately 5500 words), excluding consent forms.

• Prior to randomisation, there was a 4-week run-in period, during which families were provided with information about asthma and its management. All young people were prescribed the same low-dose inhaled corticosteroid (fluticasone), which was continued throughout the trial period. Families also completed an asthma diary throughout the trial period. Young people whose asthma control had not improved after the run-in phase were randomised to one of the three treatment arms. There was a 48-week treatment period. Including the screening and baseline assessments, families made five clinic visits and received one telephone call. There was a genetic substudy for which consent was taken separately after the run-in phase.

• At the time this report was prepared, 772 patients had been assessed for eligibility, 151 had registered for the trial, 54 had declined the trial, and 567 were ineligible or excluded for other reasons.

MENDS – the use of MElatonin in children with Neurodevelopmental Disorders and impaired Sleep

• This was an RCT of melatonin in young people with neurodevelopmental disorders and impaired sleep.

• The initial approach about the trial was usually made by community paediatricians at a routine clinic visit. Interested parents received PILs from their community paediatrician or by post, and had a telephone conversation with a research nurse before attending an appointment with a consultant neurologist and research nurse, specifically arranged to discuss trial entry.

• The parent PIL was 11 pages long (approximately 5500 words), excluding consent forms. Melatonin was not licensed in the UK for children at the time the trial was conducted, and this was stated in the parent PIL.

• Prior to randomisation there was a 4-week behavioural intervention using established techniques to reduce the child’s sleeping problems. During the trial parents completed a sleep diary every day and the child wore an ActiGraph (Ambulatory Monitoring Inc., Ardsley, NY, USA; www.ambulatory-monitoring.com) watch to record movement. Saliva samples were collected before randomisation and towards the end of the treatment phase to measure melatonin levels. There was a 12-week treatment period. Families made three additional hospital visits, and received four home visits by the research nurse and three telephone calls. There was a genetic substudy for which separate consent was taken.

• At the time this report was prepared, 241 patients had registered for the trial. A further 147 had not proceeded to registration because of an inappropriate referral, or ineligibility at screening or because the family was not contactable; 170 had refused screening.

POP – Prevention and treatment of steroid-induced OsteoPenia in children and adolescents with rheumatic diseases

• This was an RCT to establish if the bisphosphonate risedronate or the vitamin D analogue 1-alphahydroxycholecalciferol was better than placebo in preventing/reducing bone loss in young people (aged 4–18 years) with rheumatic diseases who were treated with corticosteroids.

• Usually the trial was briefly introduced to families by a doctor from the rheumatology clinical team. The trial design allowed considerable flexibility so practitioners could select an appropriate time to approach the family. After the initial introduction, a more formal discussion would be arranged to coincide with a routine hospital appointment with the rheumatology team. Research nurses and doctors had trial discussions with families, although only doctors took consent.

• The parent PIL was 6.5 pages long (approximately 3500 words), excluding the consent forms.

• There was no run-in phase and the treatment phase lasted for 1 year. All groups received calcium and vitamin D supplementation daily. Young people were seen seven times over the course of the year. However, this was timed to coincide with routine clinic visits where possible. Blood samples were also taken, but at the same time as routine visits and tests. Young people gave regular urine samples and had three DEXA (dual-emission X-ray absorptiometry) scans and two bone radiographs taken as part of the trial. There was a genetic substudy that was discussed at the time of consent; young people could participate in the main trial without consenting to the storage of their genetic material.

• At the time this report was prepared, 318 patients had been screened for the study, 132 had been recruited, 63 had declined the trial, 60 were potential future participants, 42 were ineligible and 41 did not take part for another or unstated reason.

TIPIT – Thyroxine In Preterm Infants Trial

An RCT of thyroxine in preterm infants under 28 weeks’ gestation.

• As the trial name indicates, this was a trial of thyroid hormone supplementation in babies born before 28 weeks’ gestation. The primary outcome related to brain growth.

• Necessarily, the initial trial discussion was often conducted either on the neonatal unit or at the mother’s bedside and with a practitioner unknown to the parents. A research nurse was not usually present during these discussions.

• The PIL was three pages long (approximately 1700 words), excluding the consent forms.

• Trial medication commenced within 5 days of birth and was given every day, through intravenous or feeding tube, until the baby was 32 weeks old, with follow-up until the baby went home. The mother had a single blood test and bloods were taken at several points from the baby alongside those for routine care (no bloods were taken from the baby specifically for the trial). There was a brain magnetic resonance imaging (MRI) study for which there was a separate consent, taken at a later date.

• The trial closed to recruitment in 2009 when target accrual was reached. In total, 153 babies took part in the trial (20 twin pairs) and the parents of 210 babies were approached for the trial.

Parents

We asked parents to describe the trial discussions from their perspective, how they felt about the encounter, the recruiter, the written and verbal information exchanged, whether there was anything that was unclear or surprising about this information, and whether anything might have been handled differently. Each interview was informed by the interviewers’ detailed knowledge of the features of the particular trial concerned. The interviewers used this knowledge to develop specific prompts about, for example, what the trial involved for families such as hospital visits, or about the trial run-in period.

Parents were also prompted about (1) other (unrecorded) experiences of family–practitioner discussions about the trial; (2) their broader views on clinical research involving children; (3) their prior knowledge and experience of such research; (4) how they saw trial participation in the context of the child’s illness and future well-being and their relationships with health professionals; and (5) how trial decision-making was negotiated within the family. We consulted with the RECRUIT steering group, which included two parent representatives, on the content of the parent and practitioner prompt guides. We also consulted with the study steering group and MCRN young persons’ advisory group on the prompt guides for young people.

Young people

Where possible we interviewed parents and young people separately. This was to avoid the difficulties of interpreting individual experiences from data collected at joint interviews, which may be particularly difficult in the case of young people interviewed in the presence of their parents.

Individual interviews with young people followed the same topics as those with their parents, although the number and complexity of prompts was greatly reduced, particularly for younger participants (7–10 years). We explored young people’s feelings about particular aspects of the trial and the extent to which they felt involved and able to influence trial decision-making.

Prior to the interviews, we usually consulted with parents about how best to approach interviewing their child and to select a time for the interview that would be convenient for the young person. Where possible we met with the young person some days before the interview so that we were not complete strangers to them by the time the interviews took place. On the day of the interviews we spent some time building rapport with the young person before starting the interview and we used various activities to conduct the interviews in a developmentally appropriate and child-friendly way. With younger children we sometimes used a ‘spidergram’ to find out about their likes and dislikes prior to starting the interview. Here the young person is shown a picture of a ‘friendly’ spider’s body and together with the interviewer they suggest four likes and four dislikes, making up the spider’s legs. To demystify and allay any potential fears that younger participants might have had about the audio-recording we encouraged them to listen to a short sample recording that was made during the warm-up questions if they wanted to, and help to switch on and off the digital recorder.

Interviews with older children and adolescents were very similar in style to the parent interviews and, where appropriate, followed the same prompt guide or one that was slightly simplified. However, with younger members, if they chose to, we introduced picture cards so as to vary the question-and-answer format; this also provided a shared reference point for the young person and the interviewer and avoided the young person potentially feeling ‘in the spotlight’ by an exclusive focus on him or herself. Each card had a familiar picture on one side, and a question on the other. These were spread on the floor and the interviewer asked the young person to find the card with a certain picture on it. Depending on the individual’s preference and reading ability, the young person or the researcher would ask the question out loud. The researcher then used additional prompts to explore the topic further. When the topic was finished, the young person could choose a sticker to place on the card to mark it as complete.

Irrespective of their age or developmental level, for all of the young people we took particular care to emphasise that:

1. their responses to the questions would not get anyone into trouble

2. there were no right or wrong answers and we were interested in their thoughts and feelings.

Practitioners

Interviews with practitioners followed a similar course to the parent interviews, but we steered these using a separate topic guide. We prompted practitioners to (1) contrast their experiences of this trial discussion with their experiences of other trial discussions [although, as we describe later (see Other clarifications and changes to the methodology), this was often not possible]; (2) describe their experiences of families who declined and those who agreed to trials; (3) describe what information children and parents required to inform their decision-making, and their experiences of managing the involvement of each party; (4) describe how they responded to the needs and requirements of families; (5) describe their experiences of deciding which families to approach, including their accounts of deciding not to approach eligible families; and, finally, (6) compare their role in approaching families about trials with other aspects of their role as clinical practitioners or researchers.

General interview and transcription procedure

The pace, sequencing and duration of all the interviews were shaped by the participants. All participants were given the opportunity to ask questions before and after their interviews. We audio-recorded and then transcribed all of the interviews, reviewed the transcripts for accuracy and pseudoanonymised them. Transcription was verbatim, recording all words spoken, as well as hesitation and overlapping speech; for the recorded trial discussions we also recorded markers of disfluency. We continually reviewed the transcripts from trial discussions and interviews, as the study was ongoing, to develop the prompt guides and thereby ground and inform subsequent interviews. VS and ES conducted all of the interviews and kept reflexive notes to record systematically the contextual details of the interviews and to inform the analysis.

Trial discussions

In order to link trial discussions and interviews, the sample of families interviewed largely comprised those for whom recorded trial discussions were available. However, during the course of the study we also included families for whom there was no recorded trial discussion but who had potentially informative experiences of recruitment. The recruitment of families is summarised in Figure 1, which shows the numbers of families with and without recorded trial discussions.

FIGURE 1.

(a) Recruitment of families with recorded trial discussion to RECRUIT, showing families’ trajectory in relation to the trials. a, Five families with recorded discussions from TIPIT were not approached for interview. Two had transferred to another hospital before they could be approached. Three babies had died; the RECRUIT steering group advised the team not to approach bereaved parents. (b) Recruitment of families without recorded trial discussion to RECRUIT, showing families’ trajectory in relation to the trials.

Families

We interviewed 84 members of 60 families: 58 mothers, 4 fathers and 22 young people. Figure 1 illustrates the recruitment process, recruitment rates and families’ trajectories in relation to the trials, i.e. those who consented to the trial, declined, were ineligible or withdrew. Table 2 shows family demographics and trial participation status for each of the four trials. Each trial had an initial target to enrol 15 families in RECRUIT. The MENDS trial reached this target in January 2009 and from that point we purposively sampled only those families who declined MENDS, as decliners were under-represented in the wider RECRUIT sample. Families who declined MENDS did so before attending a clinic appointment and, as such, no recorded trial discussions were available for them.

In total, 22 young people were interviewed, with the permission of their parents. [Through the remaining chapters of this report, we usually use the terms ‘young person/people’ in preference to ‘child/children’ unless the term child/children is used by the parent or patient themselves or is necessary for accuracy (e.g. when referring to the child of a parent).] Our protocol stated that, in the case of children < 7 years old, only the parents would be interviewed, as very young children are more likely to experience difficulties in articulating their experiences in interviews. Of the 22 young people interviewed, two were from MENDS, both of whom were aged 9 years, seven were from MASCOT, with a median age of 10 years (range 8–14 years), and 13 from POP, median age 13 years (range 8–16 years). We did not interview any 7-year-olds. Figure 2 shows the number of parents and young people interviewed by trial.

FIGURE 2.

Number of parents, young people and practitioners by trial. We interviewed 84 members of 60 families (58 mothers, 4 fathers and 22 young people). In one MENDS family and two POP families, both parents were interviewed. In one POP family, the parent declined to be interviewed but the young person was. Five doctors were also interviewed who regularly recruited to trials but were not recruiting to the four participating trials.

Interviews with families took place a median of 42 days after the recorded trial discussion (range 14–126 days). Table 3 shows the time lag between the recorded discussion and the RECRUIT family interviews by trial. We interviewed 48 of the 60 families in their homes, nine at the trial site and three by telephone interview. Interviews with parents lasted approximately 45–60 minutes and those with young people lasted approximately 15–30 minutes. Of the 22 young people interviewed, eight chose to be interviewed with one of their parents (sometimes for pragmatic reasons if the interviews were being conducted in the hospital). An interview with one young person was excluded from analysis as it contained no content relating to the trial.

Practitioners

We interviewed 31 practitioners: 12 were research nurses who were part of the trial teams for one of the four trials and 19 were doctors (14 of whom were also members of the trial teams). Twenty practitioners were directly involved in approaching the families who participated in RECRUIT; of these, 11 had audio-recorded trial discussions included in the study; nine were directly involved in approaching families within the study but were not present during or did not lead the recorded trial discussion. A further six were directly involved in recruiting families to the participating trials but had not been involved in the recruitment of specific families within this study. The remaining five practitioners did not recruit families to any of the participating trials, but we interviewed them because they had considerable experience of recruiting families to other trials. These were practitioners who responded to a request at one of the participating centres inviting those with extensive experience of recruitment to children’s trials to be interviewed. Table 2 and Figure 2 show the numbers of practitioners by trial, alongside those for families. The majority of interviews with practitioners were conducted at the trial site and lasted approximately 45–60 minutes.

Parents’ interactivity in the trial discussion

A striking finding from the trial discussions was that parents’ observed level of interactivity was generally low – the median percentage of speech by parents was 16% and ranged from just 1% to 49%. We categorised the discussions into three groups according to the amount of speech contributed by the parents: those discussions where parents contributed ≤ 10% of the speech (n = 12), those where parents contributed 11%–24% (n = 16) and those where parents contributed 25%–50% of the speech (n = 13) (Table 4).

Typically, a ‘low-interactivity’ discussion was the first time that a family had heard about the trial in any great detail – sometimes it was the first time the trial had been mentioned to them – and its purpose was to impart information. Often families had not received the information sheet in advance. In three cases consent was taken after one of these discussions. These discussions, which were usually very brief, typically began with an explanation of the rationale for the trial and moved on to cover the key procedural and methodological aspects of the trial. Practitioners presented trial information in a systematic way and did not actively try to involve the parent. A frequent goal of these discussions was to set the scene for future discussion, and invariably they concluded with the practitioner encouraging the parent to read the PIL and discuss it with his/her family.

Practitioners rarely asked families any questions other than to gain required information, such as the date of next appointments or discharge, although occasionally they asked questions pertinent to the trial which might have allowed parents to influence the direction of the discussion, for example ‘do you know much about thyroid at all?’ (F10). It was relatively unusual for practitioners in these discussions to elicit parents’ thoughts or questions about the trial, although 6 out of 12 discussions had at least one such instance, for example ‘That’s a lot of information so far. Have you any questions you want to ask me?’ (F42). (The 41 recorded trial discussions were made by 16 practitioners. The 12 discussions in which parents contributed ≤ 10% of the speech were recorded by five different practitioners.) Practitioners in this group often imparted a ‘chunk’ of trial information and then loosely checked back with the parents for confirmation that they were happy with what they had been told, often in one word such as ‘alright?’ or ‘OK?’. These questions generally elicited one-word responses from parents, such as ‘OK’, ‘right’ or ‘yeah’. For some parents, these responses formed the main content of their turn taking in the discussion. Practitioners made few enquiries to explore whether the parent had understood the information, this being the case in only 3 out of 12 discussions, for example ‘Obviously there’s a one in two chance he may get the dummy medicine. Um, do you understand that part?’ (F29).

For ‘high-interactivity’ discussions, parents had typically received the PIL prior to the discussion and had taken part in at least one brief conversation about the trial prior to the recorded discussion. Where the parent had received the PIL in advance, practitioners often used it as a starting point for the discussion and to offer parents the opportunity to ask questions at an early stage (n = 6), for example ‘You’ve had the information sheets […] about the study? And what did you think of that when you, you read through it?’ (F18). In five of the six discussions that began in this way, the practitioner also asked questions later in the discussion, for example ‘so, reading over it, were there any concerns you had?’ (F20).

When the parent had not read the PIL in advance, the discussion was initially much closer in style to those of the low-interactivity group, but, over time, it gradually became more interactive as the focus shifted to the child’s condition. In all four discussions, the practitioner asked questions that appeared to be aimed at exploring the parents’ understanding, but because the discussion had not been preceded by a written information sheet, the questions were necessarily more closed, for example ‘In a nutshell, does that make sense?’ (F3), ‘Are you with me so far?’ (F2).

In all 13 of these high-interactivity discussions, the practitioners asked parents lots of questions. These were almost all related to the child’s condition and seemed aimed at establishing eligibility rather than eliciting parents’ thoughts or questions about the trial. Although the agenda was always set by the practitioner, the parents in this group were more able to influence the direction of the discussion because they had valuable input about their child’s condition to contribute. Conversation directly related to the trial was dominated by practitioners.

Irrespective of their level of interactivity in the trial discussion, parents asked few questions. Ten families asked no questions at all and a further 13 asked just one. Questions asked by families were most often concerned with the practical and procedural requirements of the study (n = 37) although questions relating to safety and potential side effects (n = 16) and to clarify aspects of methodology and rationale (n = 17) were also common. Parents rarely asked questions relating to potential benefits to their child (n = 4). Examples of the types of questions parents asked are shown in Box 1.

Practitioners always gave reassurances on safety and absence of procedures that might be distressing to a child, irrespective of the level of a parent’s interactivity in the discussion, for example:

All the treatments that we are using in the study are licensed in children of [your child’s] age […] They’re all fully available so there’s nothing new or unusual about them.

(F48)

But if she wasn’t having bloods normally she wouldn’t give bloods for the study.

(F37)

It is therefore possible that in some cases practitioners’ reassurances pre-empted parents’ questions and contributed to their relatively low number.

Mismatches and misunderstandings

In this section we present several cases in which parents appeared to have misunderstood some aspect of the trial. We identified potential misunderstandings by reading the parent interview transcripts several times to search for descriptions or explanations that were not consistent with the trial rationale or methodology. We then cross-referenced these with the transcripts from the recorded trial discussions to examine whether the source of the misunderstanding could be potentially linked to the trial discussion. In most cases no direct link could be identified; however, in a few cases it was conceivable that a misunderstanding could have had its origins in the trial discussion, although other sources cannot be excluded. These misunderstanding cases are intended to indicate topics that might warrant particular attention from practitioners when recruiting families. An important aspect of our interviews was that they were led by parents and their beliefs. We explored their beliefs or misunderstandings sensitively as our aim was to describe parents’ experiences in a way that avoided influencing, ‘testing’ or altering their beliefs about the trials.

Parents often made general statements about having experienced a sense of misunderstanding and confusion that they linked to their emotional situation at the time of the trial approach (e.g. F12 and F25). Three parents in the neonatal trial told us that they were comfortable with the limitations of their understanding because they felt that their baby was in safe hands (F41, F45 and F46). However, we have identified several possible cases in which parents had specific misunderstandings had the potential to influence families’ decisions on trial entry.

A number of parents, particularly from the TIPIT and MENDS trials, had some degree of misunderstanding linked to equipoise and/or the rationale for the trial. In TIPIT particularly, a number of parents did not seem to recognise that the trial had been designed to test whether or not the trial medication was beneficial to that group of babies; rather they saw the trial as an opportunity to receive a medication that would be of benefit to their child, and which was otherwise unavailable to them.

Her only real way of getting it is to go and take part in the trial because then, I’ve got sort of a 50/50 chance of either she gets the drug or she gets the placebo. But she wouldn’t be getting it otherwise.

(F21)

These ‘therapeutic misconceptions’ represent a misunderstanding of the rationale of the trial but do not represent a direct misunderstanding of what parents had been told; practitioners often began the trial discussions by mentioning previous positive research. Therefore, the framework for parents’ understanding was that they had a 50 : 50 chance of ‘getting the right medication’ (F31). Indeed, the practitioner’s use of the term ‘I’m afraid’ in one trial discussion might have indicated to the parent that the practitioner was not in equipoise.

So we are running this study for the last year now, where I’m afraid half the [babies] get the supplement and half the [babies] doesn’t get it.

(F29)

In the MENDS trial, parents most common area of ‘misunderstanding’ also comprised a general lack of equipoise. Additionally, parents were often under the impression that the trial medication was not available outside the trial. One family told us:

We’d already made our mind up that we were going to. Before we’d even got the information […] we just weren’t getting sleep […] it’s like, we have to do something.

(F22)

Like a number of other parents, they entered the trial as a means, albeit randomised, of accessing the trial medication ‘in order to get that tablet he has to participate in the trial’ (F32). In fact, the trial medication was regularly prescribed outside the trial; in the trial discussion with one of these families the practitioner explained:

We’ve been using it for […] ten years or so […] and the whole idea of this study is to do it properly and to get the proof that it works so that we can use it more widely and for many more doctors to prescribe it, if it, if it is successful.

(F22)

This potentially sent mixed messages about the efficacy and availability of medication to parents who, in some cases, had asked for help and felt that trial participation was the only option open to them.

A few parents were confused about randomisation. Here, a practitioner explains randomisation to a parent during the trial discussion:

We will randomise [your son] into the study […] which means there’s a lottery as to whether he gets the trial medication […] or a thing called placebo dummy […] and they look exactly the same […] and no one knows which one contains [trial medication] and which one contains placebo.

(F1)

But in her interview the parent wondered whether the allocation of medicine might be more individually tailored:

You do kind of think ‘I wonder who does actually make the decision, who goes on what and who doesn’t’. I mean, do they actually look at all the information before they decide who goes on what?

(F1)

A second parent seemed to grasp the concept of randomisation in the trial discussion:

And by randomised, what we mean is that we just randomly pick one. So it’s almost like a sort of, it’s usually a computer program that just sort of.

A lucky dip?

Yeah it is exactly like that. Like a lucky dip […] so it’s almost like just, you know, saying well we just picked this out of a hat and [your son]’s got this treatment.

However, this parent’s comments in her interview indicate that she had misunderstood the explanation to mean that the drugs to be studied would be selected at random:

A bit wary, […] because I thought, ‘Oh what’s, just going to give him some random tablets or anything’.

(F48)

For one parent (see Case 1, below), a relatively straightforward misunderstanding of the procedures involved in the trial led her to decline to participate in the trial because she felt it would cause distress to her child. While the mother did not say that she would be put off research in the future, this type of misunderstanding has the potential to leave parents with negative views about research as well as having an immediate adverse impact on trial enrolment.

Other examples of ‘misunderstandings’ could perhaps be better thought of as ‘positive projections’ whereby the parent had constructed the trial around what they ‘wanted’ or hoped from it, rather than what the trial had been designed to investigate. This is illustrated in Case 2, below, where the parent believed that her child’s steroids would be reduced as part of participation in the POP trial. The parent’s perception of the trial was some distance from its actual purpose. Such examples can be distinguished from situations in which parents believed that the trial medication would benefit their child. While strictly speaking this is also a misunderstanding of the trial’s rationale, such a misunderstanding is arguably not so far removed from the purpose of the trial, which although designed to assess the efficacy of the trial medication, would not be conducted unless there was reason to believe that it might offer benefit above standard treatment.

The importance of practitioners’ continued careful exploration of parents’ understanding is highlighted in Case 3 (F28). We have no recorded trial discussion for this family (F28) so it is not possible to trace the particular source of the parent’s misunderstanding, and the trial discussion had been some months before the interview. However, the excerpts from the parent’s interview show an important misunderstanding of the trial methodology: the mother describes how pleased she is that her child is ‘just on a placebo thing’ and not taking any more medication even though the trial was blinded.

In a second similar case, the mother appeared to be unaware not only of the rationale of the trial, but also of the fact that her baby was involved in research at all – a misunderstanding that was compounded by language difficulties (Case 4).

Young people’s interactivity in the trial discussion

Of the 41 recorded trial discussions, 12 were from the neonatal trial and one was conducted between the parent and research nurse by telephone. Young people were present in the remaining 28 discussions; 12 of these young people took part in interviews for this study. A further nine interviews with young people are included where there was no trial discussion.

Young people said very little in the 12 recorded trial discussions. Two said nothing at all and a further three said just one, two or four words. The remaining seven uttered between 1% and 4.5% of the total words spoken (calculated in the same way as their parents’ speech had been). One young person who did not speak in the recorded discussion observed ‘I don’t think we really said anything. I think it was just [the nurse]’ (F35, 15–16 years).

Few young people asked any questions during the trial discussion. Parents’ accounts suggested that when young people had questions they tended to direct them to their parents after the consultation. However, two young people did ask one question each. Both were considering entry to the POP trial. Their questions were ‘Are they big tablets?’ (F60, 11–14 years) and ‘Even though one of them might not work for the bones and things will it do some good for me?’ (F49, 11–14 years).

Interestingly, practitioners did invite young people’s questions; 8 of the 12 young people were asked if they had any questions. Practitioners also asked other questions of the young people, although, as with the parents, these were often closed questions, such as ‘Does all that make sense?’ (F54, 8–10 years), which prompted one-word responses from young people. Two young people were asked open questions:

Do you know what an evidence base means?

Yeah.

What does it mean?

Err, proof that they actually work.

Exactly.

(F42, 15–16 years)

Can I ask, what do you understand by randomised? […] it’s a funny word isn’t it? What, what do you think it means?

(F20, 11–14 years)

(*For labelling of young person excerpts with more than one speaker, ‘YP’ is used for the young person.)

One way in which practitioners sought to involve young people in the discussion was to direct questions about their condition (which were necessary to establish eligibility) towards the young people themselves, rather than the parents. These attempts were not always successful, however. In two of the recorded trial discussions the practitioner attempted to specifically direct questions to the child by name but the parent answered for them.

Even when a young person was unlikely to contribute much to the discussion, owing to his or her age or developmental level, a number of practitioners placed the child at the centre of the discussion by speaking directly to him or her at the beginning of the consultation and explaining what was going to happen:

My name is [doctor], I’m one of the consultants here. And do you know why you’re here today?

Yeah, because I can’t go, go to sleep.

That’s right. And there’s a, there’s a new type of medicine, which we’ve been using for a few years, but we’re doing a study to see how well it works and whether it works for everybody or not. So that’s what I’m going to talk to your mum about.

OK.

Yeah, is that alright?

(F18, 8–10 years)

Similarly, in two discussions during which neither the young person nor parent spoke a great deal, the practitioner’s comments are directed towards the young person, for example ‘your’ appointments ‘your’ condition (F42, F60). However, in 2/12 discussions no attempt was made to involve the young person at all. Both of these were the first formal discussions that the family had had regarding the trial and both were ‘low-interactivity’ discussions for the parents also.

Research nurses often had an important role in talking to young people about the trial, going through the information leaflet with them while the parent was in discussion with the doctor. In two of the trial discussions in this study, it was the nurse who enquired whether the young person had read the information leaflet and whether he or she had any questions.

In some cases young people were absent for a considerable amount of the trial discussion because they were being weighed and measured by nurses as part of the trial while the parent was in discussion with the doctor. This constrained the potential for practitioners to involve young people, as well as for the young person to contribute.

Practitioners asked five of the young people if they were happy to proceed with the trial. As with the other questions, these tended to be closed questions to check that the young person accepted participation rather than open invitations for his or her thoughts, for example ‘And are you OK with this?’ (F18), ‘Happy to move forward?’ (F42). Although 10 out of 12 discussions recorded were consent discussions, the actual consent and assent forms were not always completed while the recorder was switched on, and it is possible that the other young people were asked at the time of their assent.

Parents’ experiences of the trial approach

Parents’ interactivity in the trial discussions was often low, but they did not tell us that they felt inhibited or constrained in any way. On the contrary, parents often described positive experiences of the verbal information that they had received, and emphasised their sense of ease in asking questions despite their low interactivity.

Some explained that they had not asked questions during the trial discussion because they were happy with the information that they had received, ‘It was explained the way it was meant to be explained. Anybody could have understood it’ (F2), and because the trial team were highly accessible and they felt comfortable in contacting the team with any questions as these occurred to them, ‘most doctors wouldn’t say, ‘Here’s my mobile. Any worries, just phone me there and then’ (F48) or ‘ring her anytime’ (F36). Indeed, parents described practitioners as ‘friendly’ (F56), ‘approachable’ (F13), ‘open and honest’ (F51), ‘relaxed’ (F60) and ‘comfortable to talk to’ (F38).

No parents commented on their lack of interactivity or involvement in these trial discussions. Rather, parents emphasised their overall experience of the discussion as a social encounter and their experiences of the practitioners.

I thought it was perfect and I don’t think there is any room for improvement, to be honest. [the nurse] was totally friendly and, and thoughtful and she just, she approached us and asked us whether we would like to participate in this study. Really I, I don’t see where she could have done it in a better way.

(F3)

Parents spoke of their sense of comfort during the discussion, their confidence in, and liking for, the practitioner, and their sense that the trial was safe and that their child’s health (rather than the trial) was the practitioners’ over-riding concern. Flexibility, consideration, kindness and effort on the part of the trial team were also appreciated. Parents praised practitioners for being confident, knowledgeable and enthusiastic about the trial, and spoke of how this helped them to also feel confident and enthusiastic, and fostered a sense that the trial was worthwhile. While parents valued practitioners for conveying a sense that the trial was important, they also spoke of how their child’s and family’s well-being, rather than the trial and the need to recruit participants, was the primary concern of practitioners. Therefore, a practitioner’s focus on the young person and the difficulties of the family’s situation helped to convey a sense of confidence and safety to parents. Excerpts from parents’ accounts of the trial approach are given in Box 2.

Parents who declined (n = 10) were also positive about their experiences of the trial, and the majority were indistinguishable from those who consented. It was not unusual for these families to also describe the practitioner as ‘really friendly’ (F36) or ‘absolutely lovely’ (F23). Nor did these families report feeling pressurised by the trial practitioner to take part: ‘we knew we wouldn’t be pushed into something’ (F24), ‘everything in terms of mannerisms, conduct, behaviour was absolutely spot on’ (F52). However, in two cases, the parents voiced criticisms of the approach:

He was fine […] he just explained the thing. (F34) Later in the interview the same parent said No I didn’t feel pushed, but I think the place was wrong. (F34) (parent was approached on a busy ward)

He was alright. It was just the fact that I got annoyed with all the waiting and when I tried to explain to him about the [medication] he wasn’t listening at first.

(F2)

In both cases the parent had strong reasons for declining; one as a result of a misunderstanding of the practitioner’s explanation of a trial procedure and the potential for distress to her child (see Case 1), while the other believed that her child had an adverse drug reaction to the trial medication in the past.

Parents’ experiences of the timing of the trial approach

In two of the trials parents were sometimes approached when they were fearful for their child’s survival or well-being, and it was not uncommon for these parents to acknowledge that they had found it difficult to concentrate during the trial discussion. As one mother commented, ‘it went sort of like in one ear and out the other […] she was so small and so poorly’ (F46). However, when asked if the trial discussion could have been better handled this mother echoed other parents in remarking:

No, I don’t think so. The doctor was really nice, he was clear and asked if we needed, you know, if had any questions either that day or later on then, you know, just arrange to speak to them.

(F46)

Parents acknowledged the difficulty of discussing clinical trials in the circumstances they faced. However, they were generally accepting of the need for research and the need for the approach to be made.

I didn’t really have a problem with it, her coming to see me so soon […] the sooner really you get in there, it’s the better isn’t it?

(F9)

I knew they needed to start it straight away and I think even the day after wouldn’t have been no good […] The day I was coming home wouldn’t have been any better or […] I don’t think there is a perfect time for stuff like that.

(F45)

I think the doctors definitely [should] feel like they should be able to approach the parents. I definitely think that because without approaching them obviously they won’t be able to do the trials.

(F40)

Parents are sometimes asked to consider entry to more than one trial. One mother’s (F29) experience highlights the importance of paying attention to the parent as an individual and the timing of the approach, as she described very different responses to being approached about two trials when her baby was in a critical condition. The mother and father consented to both trials having evaluated the information given to them, but their experiences of each trial’s recruitment contrasted sharply (Case 5).

Two parents of children with a chronic condition felt that the timing of the trial approach could have been better: ‘the timing of when they asked as opposed to how they explained it […] if they’d given us even an hour for the diagnosis to sink in’ (F25), ‘It wasn’t just that, it was everything else […] it was her first admission […] I was worried about that’ (F12). However, this contrasted with one parent who viewed being approached when her child was unwell and an inpatient as appropriate because ‘there were a lot more people on hand’ (F13) to ask questions. What mattered for this mother was the manner of the approach rather than its timing: ‘I think if they do it in the right way then it’s OK to approach’ (F13).

Interestingly, several parents described being ‘excited’ (e.g. F1, F10 and F21) at being asked if their child would participate and remarked on how ‘passionate’ (F51) and ‘enthusiastic’ (F10) practitioners were about research. This seemed to inspire parents’ confidence in practitioners’ expertise and commitment. A few parents described how they would have felt disappointed if they had not been invited:

You don’t want to think […] there’s some sort of a trial that could improve your child’s [condition] and your child hasn’t been offered that […] I would like to be asked and be given the opportunity to say no.

(F50)

Parents also emphasised how making a decision about their child at such a difficult time gave a sense that they were involved in their child’s care when there was little else they could do for their child.

A parent needs that little bit of control, just so that they know there is still something that they’re doing for their child, because other than that there is nothing.

(F29)

Without exception, and irrespective of their level of interactivity in the trial discussion, parents felt that the decision on trial entry was theirs, they felt happy with the decision that they had made and they were clear that they did not feel pressurised by practitioners to consent to the trial.

Responding to the young person’s needs

Parents’ impressions of the trial discussion and the practitioners themselves were also influenced by efforts made by the trial staff to address the needs and preferences of their child. While the actual steps or gestures that practitioners took to do this varied widely, it was the effort and appropriateness of the action in the light of their child’s needs that parents valued. For example, parents of children who were very young, or who had behavioural or developmental difficulties, often found it hard to include their child in the trial discussion in a meaningful way. For many of these parents it was the efforts made by the trial team to engage the child in play or conversation so that the parent was able to concentrate on his or her conversation with the practitioner that they valued.

Yeah, he was kept occupied while I was getting, you know, they were asking me questions and, you know, he just loved it. He took to [the nurse] right away.

(F6)

The nurse, she’s, like she actually even asked on the phone as well, before we went through, ‘What kind of interests has [your son]?’ as well. So I thought it was really nice because as soon as we went in she came up and she introduced herself to[my son] […] So it made it easier because that way [my son]’s not like panicking, like ‘Who’s this person?’

(F15)

By contrast, for parents of older children, it was the efforts practitioners made to involve their child in the discussion and ask for their thoughts and views that parents valued.

They didn’t approach us, they actually asked [my daughter], which I thought was brilliant. And I think she was treated like a person instead of a, a thing […] she saw that as well […] you know, ‘they’re talking to me, they’re not talking to you two. They’re asking me’, […] that’s important, I think.

(F37)

Young people’s experiences of the trial approach

The sample of young people varied considerably in age and developmental level and, as a result, so did the depth of understanding and involvement that they had in the recruitment process. Although we encouraged young people to be interviewed individually, eight of the families preferred (sometimes for pragmatic reasons if the interviews were being conducted in the hospital) to hold the interview jointly between the RECRUIT interviewer, parent and young person. In these family interviews the parents’ views often dominated. Many of the young people said little about the process of considering trial entry. It is difficult to interpret what this means but it could indicate that these young people had not spent much time thinking about the trial or had found it difficult to engage with the subject of trial recruitment.

All of the young people included in this analysis were aware that they were taking part in a trial, knew the name of the trial and had some understanding of what it involved for them, although particularly for younger children, their understanding was often quite limited ‘researching about asthma […] and see how you catch it and stop it’ (F54, 8–10 years). Specific discussions with practitioners were less salient for them than for parents, particularly where a familiar practitioner was the first person to discuss the trial with them. In these situations the distinction between normal clinical care and trial participation may have been difficult for young people to discern, indeed this could be challenging for parents. Sometimes young people were confused about elements of the trial. Where a family was taking part in more than one piece of research, some of the young people’s comments, which might be interpreted as misunderstandings, could in fact be accurate descriptions of another study. Many of the young people in one trial were also taking part in a mainly questionnaire-based study to gather information about their medical conditions, and it is possible that there may have been some blurring between the two: ‘I just thought it’ll help people later on […] or find out what they’ve got’ (F13, 15–16 years).

Those young people who did have a clear recollection of the discussion were more likely to reflect on the content of what they were told rather than the social interaction. These were often delivered as rather factual descriptions of the study:

Got to take another tablet like you don’t know which one it is yet, only like the computer knows and it’s to see in a year’s time if it’s helped you get better and see if other people can take it or not.

(F12, 11–14 years)

They basically said that some people would get the real thing and others needed to get the placebo.

(F14, 11–14 years)

They’re trying to make a new drug about asthma and they don’t know if it works or until they’ve tried it on people […] so they’re like testing it.

(F48, 8–10 years)

Young people were often able to give very accurate descriptions of the practical requirements of the trial, although they sometimes viewed their participation in the trial as serving their individual needs rather than the need for research evidence.

To help me get to sleep

(F17, 8–10 years*)

(*Children in this trial had some degree of developmental delay, which may affect their understanding.)

What they’re trying to do they’re giving you inhalers that they’ve already given to other people […] and they’re giving you them to see if it’s OK for you.

(F57, 11–14 years)

Some young people did not tell us anything about their experience of the trial discussion; several others described the trial discussion as a ‘normal’ conversation (F13, F14 and F60). However, two young people described how they had concerns prior to the discussion which the discussions with the trial team had allayed.

I was quite frightened at first because I thoughts I’d have to do tests.

(F57, 11–14 years)

[and] I felt comfortable because they [the trial team] were understanding.

(F57, 11–14 years)

Apprehensive really […] because it was like un-treaded waters, you know, you don’t actually know what’s gonna happen, but the way that [the trial team] dealt with it, I thought was really good actually […] And I felt with the people that were running that they were really like, they were nice, and like at any point I could just ask them whatever or just walk out if I didn’t agree with something which I thought was really good.

(F58, 11–14 years)

Generally, the young people felt that they had been included and spoken to during the trial discussions. One boy remarked on how this differed from his usual experience of doctors’ appointments and another commented on how this was something that he valued:

Normally like when I go to the doctor’s it’s all, they always make my mum talk and not me […] but this time I talked and not my mum.

(F48, 8–10 years)

Very important for me, that I felt […] like I was important to what was going on.

(F58, 11–14 years)

Two girls (F14 and F55) explained how, while they felt involved and able to take part in the discussion, they preferred to be quiet because they felt awkward talking to people.

I usually just sit there quietly and just listen to them. If they ask me anything then I just talk I suppose and then I go back to being very quiet again.

(F14, 11–14 years)

Young people told us that they felt able to ask questions but, like their parents, often did not feel the need to:

I was able to ask questions but I didn’t ask any because they were explaining it already […] so I didn’t need to ask any questions.

(F51, 8–10 years)

Sometimes the young people gave slightly contradictory accounts that made it unclear whether or not they were happy with the way that they had been approached, for example: ‘The doctors were talking to my mum and dad and about every five minutes they’d just go, is that OK with you? So I was, I was kind, I was a bit bored eventually’, but later on in the interview this young person said ‘The people who were doing it were really nice and they explained it well’ (F57, 11–14 years).

One young person simply replied ‘no’ when asked if people had spoken to her during the discussion but also stated ‘I weren’t worried and I was able to ask questions so that made me less worried as well’ (F26, 8–10 years).

Therefore, it was sometimes hard to gauge how the young people felt about the trial discussion and whether they were as involved as they would have liked to be. However, no one told us that they felt excluded from the conversation or unable to contribute and ask questions.

Only one young person discussed the timing of the trial approach, describing how the trial discussion was held at the end of a consultation during which he had received a worse than expected diagnosis. Reflecting the views of some parents in similar situations, the young man commented ‘that was the least, the last thing on our mind’. Later in the interview he reiterated ‘maybe on another day would have been better […] it was a bit too much to take in at the time’ (F35, 15–16 years). Another described how she had found the first trial discussion ‘a bit overwhelming at first’ but that follow-up conversations had made things ‘more clear’ (F42, 15–16 years).

Practitioners’ perspectives on trial recruitment

Like young people, practitioners spoke more about the content of trial discussions and less about their experience of the process as a social encounter than parents. They were particularly concerned about ensuring that parents understood the trial and described how the amount and complexity of information, particularly written information, they had to give parents could undermine this objective and could lead to a situation where ‘we bamboozle […] families with information’ (P7).

It’s taken a number of years before people are getting towards striking a right balance between providing crucial information, but not overwhelming […] the parents, patients with information, so they can’t sometimes see the wood for the trees.

(P15)

Acknowledging the near infinite amount of information required for ‘informed consent’, one consultant questioned whether, even if parents did read the leaflets, this would be ‘enough’.

To really give informed consent just how much would you have to do to be properly informed? Would you have to go to medical school and learn all about these treatments and to make informed decisions? Or is just reading the information leaflet enough?

(P18)

Some practitioners spoke of their concern when families were eager to agree to the trial, as they felt it their duty to ensure that families achieved a certain level of understanding. They remarked how they felt ‘happier’ (P6) when families had ‘got questions because you feel like they’re wanting to be fully informed themselves’ (P6). They also commented on how in the absence of such feedback ‘it was hard to know whether or not he truly understood what he was consenting to’ (P28).

The families I worry about […] are the families that just say, ‘Yeah don’t … yeah that’s fine […] I don’t need to read the information sheet. I’m happy, whatever you say’ […] and just really don’t want to question you about it. And, um, those are the ones where I might […] go over it a little bit more than perhaps they want me to but I’m just trying to check they have absolutely […] understood.

(P5)

Occasionally, practitioners remarked on discussions where they had annoyed or deterred a parent by continuing to explain the trial after the parent had said they were happy for their child to enter the trial: ‘the mere fact that you insist on talking about things will, will put them off […] the fact that they’ve said “yes I want to be part of the study” and you somehow want to argue with them’ (P1), ‘he seemed to be getting more, you know, more annoyed with me the more I was talking’ (P28), a view reinforced by one of the parents who told us ‘and I actually cut her short. I said “please don’t go on about it. Just do it. Just do it quickly” ’ (F57). This posed a dilemma for practitioners in ensuring parents understood what they are consenting to, while also ensuring that the parent felt listened to: ‘sometimes […] they’re not bothered about all that, but I feel we have to tell them’ (P26).

Other practitioners emphasised how parents’ understanding was something that was achieved over time and might require several discussions. Some questioned whether informed consent was achievable, particularly when the child’s condition was critical. They referred to how some parents could make a decision that they (the parents) were comfortable with based on their general disposition towards research and on only the most essential information about the trial. They regarded such families’ decisions not to seek detailed information about the trial as an appropriate form of autonomy in a stressful situation.

If a family wants to exercise its autonomy by saying yes this is a good idea, don’t really mind about the details just let me sign it […] then I’m quite happy with that.

(P1)

This concept about patient has to understand, make a rational decision. That’s true but at the same time there are patients who don’t want to go through all these things. ‘I’m perfectly happy with my decision – get on with it. I don’t want all this paper’. So we have to respect that view as well.

(P14)

Based on an understanding that the role of ethics committees and regulatory agencies is to protect the public from harmful medical research, and therefore the safety of families is protected whatever their level of understanding, some practitioners were very comfortable with parents determining how much information they wished to receive.

There are some that are very obviously want to know very little, and they’ll say, ‘Yes doc, go ahead, let’s do it.’ And others will ask questions. And if they ask questions I allow the time to answer them. But I don’t think it’s the same for every patient at all. I don’t tailor; I go by what those families want.

(P30)

A number of practitioners made a clear distinction between the ‘required’ content of the trial discussion conveyed in programmes such as Good Clinical Practice (GCP) training and their own particular approach.

Oh GCP, but that […] doesn’t teach you how to talk to people. It just tells you what the rules are really. And knowing what the rules are doesn’t mean that you follow them and it doesn’t mean that you are any good at explaining to people what the study’s about.

(P28)

These practitioners emphasised the need to be adaptable to the needs of individual parents.

Implies that there’s a right and a wrong way of doing it and I’m not sure that there is, except to be sensitive to different people having different needs at different times and to listen, which is part of communication anyway.

(P11)

Practitioners’ comfort and discomfort with approaching families

Practitioners described different levels and sources of difficulty in approaching families about trials. The majority did not describe approaching families as something that they found personally difficult, but many nevertheless believed that being approached about a trial could exacerbate the emotional impact of the child’s illness: ‘these are very, very sick kids […] you’re going up to them and this is yet another consideration for them; whether they want their child to go onto a research project’ (P2). Such concerns were particularly prominent in the rheumatology and neonatal trial, where the children were often severely or critically ill. Other practitioners expressed a strong sense of personal disquiet or anxiety about approaching families about trials: ‘each parent is different and causes me great anxiety’ (P16), ‘I will go and approach them but I feel, I feel very uncomfortable doing it every single time’ (P18). The primary source of these practitioners’ discomfort was the intensity of families’ fears and distress. This led some practitioners to ask searching questions about the morality of approaching such families: ‘this family’s at a terrible time and really is it right to be asking them to do this?’ (P19). Several research nurses expressed a lack of confidence when working on trials outside of their specialty, and some practitioners spoke in strong terms of a range of other difficulties, such as the pressure to reach recruitment targets (P26), feeling ‘like a salesman’ (P19), discomfort with children’s medication being selected at random (P31) and concerns that families were vulnerable and therefore liable to be unduly influenced by practitioners (P18). A few practitioners described how their belief in the importance of research helped them to overcome their own discomfort.

Much more stressful for the family and much more stressful for you […] it’s only because you believe that intervention is critically important to investigate that you feel that you can kind of carry on.

(P12)

Occasionally, however, practitioners echoed the sentiment of the parent interviews saying that, on the whole, parents did not object to being approached about research:

The more you recruit people […] you feel less apprehensive yourself about asking them and […] you realise that actually asking them and them saying no, you haven’t upset them. You actually […] haven’t changed anything.

(P28)

Although the trial approach was personally difficult for some practitioners, none commented that this prevented them from approaching families. Indeed, a number of practitioners, whether they felt personal discomfort or not, described a strong sense of duty to the research and a sense that all families had the right to be informed about relevant studies: ‘every child I feel that has an illness should have the option to opt into research […] and we owe it to them and the future generations to do that’ (P24). ‘And it’s taking that choice away from them if it’s not mentioned to them’ (P6). ‘Gate-keeping’, which prevented an approach being made, was sometimes viewed as unhelpful, particularly when coming from professionals outside of the trial team: ‘frustrating if the other people don’t understand what the trial’s about but they’re just doing it from sort of general protectiveness’ (P1).

When practitioners told us about their decisions not to approach families who were eligible for a study, they described their reasons in terms of the families’ difficulties with comprehension or literacy: ‘you’re obliged ethically to make a judgement as to whether […] they can make an informed decision themselves’ (P15); understanding English; compliance; and their social situation such as marital problems (P8) or the involvement of social services (P12). Hence, practitioners emphasised how practical hurdles were the reason that they sometimes avoided approaching some families, rather than their own discomfort.

The design of the POP trial in particular allowed practitioners to select a time to conduct the approach in a way that was not possible in the other trials. As a result, rather than choosing not to approach a family at all, practitioners in this trial could titrate the approach: ‘I mightn’t necessarily give them an information sheet then, but I would just put the seed in their head that there is something going on’ (P20).

Parents

Most parents were mildly positive, equivocal or neutral about the PILs, particularly when talking about them in general or global terms. Their comments, or in some cases lack of comment, implied that while the leaflets were ‘alright’, ‘OK’, ‘fine’, ‘useful’, ‘good’, they viewed them as rather unremarkable documents and had not given them much thought after the consent meeting.

I must have thought it was alright because I don’t remember having any thoughts about it.

(F11)

There is a lot of information on it. Yeah. But it was well worth reading.

(F18)

Several others commented positively on the format of the PILs – the question-and-answer format was particularly appreciated in allowing parents to scan the leaflets and select the most relevant sections to focus upon. The thoroughness of the leaflets and the presentation of the advantages and disadvantages of trial participation and the use of plain English were also commented upon favourably.

It seemed to answer questions for you, while you were going through it as well. So it was good the way that it, the way that the parents one was written out.

(F15)

However, parents remarked that the PILs were ‘a lot to read’, ‘wordy’, ‘intense’ and ‘overwhelming’. One parent commented: ‘It looks like half a forest’ (F54). Fourteen out of 59 parents specifically stated that they personally found the PIL too long or complicated, and a further four commented that while they personally were happy with the PIL, they thought it might be too much for others.

There is a lot of written information to go through […] so it’s a bit overwhelming, to try to take everything all in.

(F4)

It was a big document to read. I mean I can’t remember how many pages it was but I can remember thinking ‘oh my goodness’.

(F8)

One parent who suggested ‘don’t blind them with science’ told us that what she wanted from the PIL was to know that there was no risk, whether the trial medication would be beneficial, how long the trial was going to take and that it was voluntary: ‘I don’t want to know that there’s a β-agonist’ (F54).

Nevertheless, a few parents pointed to information that was absent from the PILs that they believed to be important, such as the licensing of the trial medication (F33), how to take trial medication (F16), urine samples (F25), use of non-trial medication (F59) and eligibility criteria (F5).

Despite these problems, parents emphasised how valuable the PILs had been in enabling them to reflect on the trial in their own time and space. Parents valued the opportunity to go over the details of the trial in the calm and quiet of their own home, particularly when their child’s condition was serious or if he or she had been noisy or demanding during the trial discussion.

I went home and I read it through […] that’s what I like to do. Come home, then read through properly and, you know. Because, like, I’m better here in my own house where I can relax and, you know, not worry.

(F6)

They described how leaflets allowed them to ‘sit down and read’, ‘relax’, ‘go over everything properly’, ‘read over it again’ and ‘go back to’.

If it wasn’t for […] the information sheets […] I’d probably forgotten a lot of what was said, you know. So it was good to have them to refer back to.

(F12)

Several mentioned reading the leaflet and then making their decision about the trial, or cited a detail from the leaflet as being important in their decision. In this way, we theorise that the PILs were important in providing parents with a sense that it was their own decision. Parents also described PILs as helping them to discuss the trial and share the decision with family members and friends who did not attend the consultation. The severity of the child’s condition and the parent’s emotional state may increase the importance of this function.

I spoke to [my family] about it and they’ve read the, the leaflet and me dad’s like me. ‘Well, why not try it?’ You know if, as long as it doesn’t cause her any harm, then there’s no, no problem.

(F16)

Almost without exception, parents placed greater value on the face-to-face discussion with practitioners than they did on PILs and would not consider participating in a trial without it.

You can only get so much information from a sheet, […] whereas, you know, the nurse […] you can ask […] any questions that you’ve got.

(F12)

If that just came through the door and I didn’t feel it’d got […] any personal contact, I’d just think, ‘no, I’m not doing it’.

(F11)

Parents’ suggestions for improving PILs centred on reducing the content and avoiding medical jargon because they thought ‘that would probably scare a lot of families off’ (F15). A website was suggested as a useful alternative to long PILs ‘so that they could go on to and get more information if they want to’ (F31). The emphasis was to provide sufficient information for everybody in a basic document while providing further information for those who wanted it.

More bullet points more pictures and a number to call rather than lots of information […] you just need a one sheeter really I would have thought.

(F5)

Young people

Like the parents, most young people had little to say about the PILs they were given and their comments were neutral or slightly positive, ‘the leaflet was helpful’ (F12, 11–14 years), ‘I thought it was fine’ (F17, 8–10 years), or mildly critical, ‘it was alright […] just less writing […] there were a fair lot of pages on there […] because really you don’t wanna sit there and read through a full booklet’ (F13, 15–16 years), ‘shorten it down I think’ (F60, 11–14 years). Only one young person specifically said that he felt the PIL was inappropriate for his age, ‘I felt more connected to the adult one […] I think it was a bit like aimed at younger children’ (F58, 11–14 years).

Young people also saw the face-to-face conversation as more important because ‘just talking it through with people makes it easier’ (F60, 11–14 years):

Myself, I always prefer the talking because then if you think about it, you can’t ask the leaflet a question.

(F42, 15–16 years)

Personally I thought the chat was more important […] the information, it kind of took second place really.

(F58, 11–14 years)

Separate PILs for young people may serve a valuable social function, in addition to their informational one, in that they recognise the young person as an individual who deserves to be informed and involved. As such, young people may appreciate having their own PIL, even if they do not necessarily read them. As one young person explained:

I liked the idea that you got your own because it makes you feel like a big person […] and it makes you feel more involved, it makes you feel, it doesn’t make you feel as though it’s your mum’s response, it makes you think that you’re able to make the decision yourself.

While at the same time stating:

I don’t read them but my mum does and, and she goes through them.

(F42, 15–16 years)

Parents also valued how young people were given their own leaflet, but recognised that often they would not read them. Parents attributed this to young people’s preference for verbal rather than written explanations (which young people themselves sometimes viewed as ‘work’) and that they trusted their parents to pass on essential information. Some parents acknowledged the difficulty of pitching the PILs appropriately, and they described rephrasing the leaflet for their child ‘to try and put it for [my son]’s language, so it didn’t scare [him]’ (F15, child aged ≤ 6 years).

Young people were clear that they wanted colour and pictures in their PILs, and PILs with such features received positive comment. Young people regarded PILs that did not have these features unfavourably:

It could have been more colourful, there’s nothing that would attract them […] they’d probably want to read it more if there was like more colours and stuff on it.

(F47, 15–16 years POP study, no pictures)

Good presentation […] because it’s got loads of pictures and it’s like in order.

(F51, 8–10 years, MASCOT study, pictures)

Two interviews indicated the potential for leaflets to cause distress to young people. One young person (F14, 11–14 years), prompted by her mother, agreed that she had found elements of the leaflet embarrassing, although the incident is described much more strongly by the mother in her own interview:

Is it the period bit? […] that’s a bit personal I suppose.

Do you remember your reaction the first time, you went, ‘What? I’m never going to answer that’ […]

I suppose everyone would mainly have the same reaction I would have.

You had the sheet and you weren’t feeling very good and you were going ‘why do they want to know that? That’s just embarrassing’.

One young person highlighted the unintentional impact that medical words can have in children’s leaflets: ‘It’s got like medication pills and inhaler and what is the medicinal device or procedure being tested and that word “tested” gave me a few worries’ (F57, 11–14 years).

The same young person suggested that to avoid additional distress to children when they attend hospital visits, information leaflets might carry a photograph of the investigator because ‘the children could worry about like “who is it mummy?” ’ (F57, 11–14 years). A number of parents, particularly in the MENDS trial, have identified that their children do not like to meet new people. This suggestion may go some way to alleviating that difficulty.

Practitioners

Practitioners commented that PILs were ‘not straightforward’ (P12), ‘too long’ (P2), ‘too detailed, too comprehensive, too busy’ (P3) and ‘too complex’ (P9). In total, 24/31 thought that the leaflets were too long and complex, with a further three stating that, although they were happy with the PIL for the trial participating in RECRUIT, they thought that PILs in general were too complicated.

Some practitioners regarded PILs as primarily serving the requirements of ethics committees and legal regulations for PILs to be comprehensive, rather than the needs of families for simple, accessible documents.

We try and produce pretty simple information sheets and in general the contribution by ethics committees is to make them more complicated. And I don’t think it’s helpful.

(P11)

A particular concern for practitioners was that families would find PILs containing scientific details overwhelming and threatening and may be deterred from participating in a trial.

If you do it according to the book then it is an intimidating document which doesn’t enhance patients’ autonomy and does occasionally turn them off being involved in the trial.

(P1)

It undermines them, it undermines their confidence and […] rather than empowering them it could actually make them feel very anxious and […] threatened. So I think it’s a difficult balance and I’m not overly sure we’ve got it completely right.

(P8)

In contrast with those who saw families at risk of being overwhelmed by information, one consultant commented that many of the details provided in PILs were ‘obvious’ and therefore superfluous.

It’s not necessarily too much information […] it’s making the assumption that everything has to be explained when actually a lot of it, I think, is pretty obvious anyway […] people understand the research process, I think, better than maybe we give them credit for.

(P9)

Some spoke of how leaflets and the information they provided were of value in principle, but in practice often failed to strike the right balance between providing meaningful information and being accessible for families, particularly those with learning or literacy difficulties. Practitioners sometimes implied that the PILs often went unread. Like the parents, practitioners placed greater importance on the personal discussion they had with families than on the PILs.

The face-to-face discussion is the time to make sure they really understand what’s, what’s going on […] because it’s only on that face to face interaction you can look at people and you know whether they’re getting it or not.

(P5)

Some suggested that, without discussion, families would not be willing to participate in trials or would find it more difficult to make up their minds.

Practitioners did acknowledge that PILs had a useful, though somewhat limited, role to play in the context of trial discussions with families. Some practitioners remarked on how leaflets were useful for families to prepare for discussions and support their participation in the discussion. They could be used to scaffold discussions, to emphasise certain points and to make abstract concepts more concrete. Practitioners also saw PILs as helping families remember the trial discussions or as a resource to which families could refer back, use to supplement their understanding and use to explain the trial to other members of the family.

It certainly lets them go back to it time and time and again sort of, you know, over a few days or whatever as a reference point really.

(P6)

Practitioners made suggestions for improving the PILs, which, like the parents’ suggestions, mostly focused on reducing their length and content. Practitioners were concerned about the readability of the document in general and some were also concerned that the parents they knew would find them difficult to understand. However, in making PILs more accessible, a balance had to be struck to ensure sufficient information was provided and to meet with ethical requirements.

I would prefer a simple, you know, say A4 sheet of this is a trial, this is what we’re doing, contact this person […] And then probably a more wordy document and especially for those people who ask for it.

(P14)

It is quite lengthy but then, you know it’s I suppose it’s a balance of the two isn’t it? If you, if you make it shorter, then you withdraw information.

(P4)

Parents

Parents who knew the practitioner prior to the trial approach tended to value the relationship as one that provided reassurances of safety and good care and continuity for their child. When the trial was introduced by a trusted health-care professional and then ‘handed over’ to an unknown researcher, these reassurances seemed to be extended to the new practitioner by association. Almost all of the families who had an existing relationship with the trial team were from the POP trial.

For the majority of the other families in our study, the trial team were completely unknown to them. For parents in the MENDS trial this practice was not unusual to the families because their child’s ongoing health care regularly required them to meet new professionals: ‘I deal with that many different people […] I’m not really fussed.’ (F16).

For parents in the TIPIT trial, approached within a few days of the birth of their very sick preterm baby, all of the practitioners responsible for the baby’s care were virtually unknown to the parents, so having a stranger approach them about research was not regarded as unusual: ‘I’d just meet them once, like, and then I’d see someone else and I didn’t really have a specific person to speak to anyway’ (F10). In their accounts, these parents often stressed the importance of the practitioner’s manner and their confidence in his or her expertise.

Parents were comfortable about speaking to someone whom they did not know if the approach was made in the right way: ‘I just clicked with him straight away and that was it’ (F43). In this sense, families did not show a consistent preference for being approached by someone they knew rather than by a practitioner they had only just met through the trial. Rather, they were consistently happy with whichever ‘model’ they had encountered (Box 3). Whatever the length of relationship that they had with the trial practitioner, none of the parents spontaneously told us they would have preferred something other than they had experienced in the circumstance. Only one parent acknowledged the potentially negative implication of an existing relationship with the practitioner:

In a way I think it would have been easier if I hadn’t have met her because I think I might have felt a bit more pressured into […] doing it.

(F36, declined trial on telephone, had never met practitioner face to face)

Young people

Not all young people talked about the practitioner with whom they had discussed the trial. In many cases they either did not know the practitioner or could not remember who it was. One young person when asked if he knew the practitioner said: ‘No. I know her well now though’ (F18, 8–10 years). This continuity once a young person had entered the trial and the developing relationship seemed to be more important to them than knowing the practitioner before they were approached about the trial.

We developed a very strong relationship with [the nurse] […] it’s better than like seeing different people every time and then you might, you’d probably feel more uncomfortable.

(F58, 11–14 years)

This young person described how the manner of the trial team overcame any potential discomfort at not knowing them prior to the trial discussion:

They were such nice people to be honest that it was easy really.

(F58, 11–14 years)

This contrasted with situations where there was not the same level of continuity:

You have to keep meeting new people and my, some like, some people, they might feel scared every time they go because they don’t know whether they’re meeting another person or not.

(F51, 8–10 years)

Where young people did give an opinion on whether it was important to know the practitioner before the trial approach, their views mirrored the pattern seen in the parents’ accounts. That is, they preferred whatever ‘model’ they had encountered:

If I didn’t know the doctor I would have been a bit more worrying, you know worry about it a bit more because I wouldn’t have known the person.

(F42, 15–16 years)

I think it helps if you are talking to someone you know.

(F47, 15–16 years)

Both of these young people knew the practitioner who discussed the trial with them and valued that relationship. By contrast, one young person that had not met the practitioner before the recorded trial discussion suggested that ‘Maybe it was better, maybe someone separate […] in case they might object to us not, um, taking part in the study’ (F35, 15–16 years). However, once the trial was under way, like others in the study, this young person valued the developing relationship: ‘It’s good to have someone specific that we know’ (F35, 15–16 years).

Practitioners

Perhaps not surprisingly, we found a similar pattern in the practitioners whom we interviewed. Those who had an existing relationship with a family were very happy to approach those families; those who were generally meeting families face to face for the first time found this perfectly acceptable also. Where practitioners did not know the family in advance they stressed the importance of making a good impression:

I always try and make a very good impression with the patient, particularly, but also with the parents, right from the beginning, so I think, once you’ve done that and established a good relationship, everything else that’s good leads on from that.

(P15)

Practitioners who knew the families well often felt that the relationship was important and, in particular, they stressed how this helped families trust to have confidence in them:

They know about their child, they know about their disease and they can explain the study to them in the context of their own child and, and make it meaningful as opposed to ‘would you like your child to be part of a study?’

(P21)

Indeed, some research nurses who did not know the families would introduce themselves as working in association with the clinical team in order to make the families feel comfortable: ‘they have very, very good relationships with the consultants […] that’s why we felt it was important for the consultants to approach the patient first of all to introduce it (P2)’*.

(*In these situations, although the research nurses discussed the trial with the family, consent was always taken by the consultant so the relationship to the medical team remained important.)

However, a number of practitioners felt that consent for research should be taken by someone not involved in the child’s clinical care and were concerned that families would feel obliged to take part as a result of the existing clinical relationship:

You don’t have to do it, just because he’s done this for you.

(P17)

You wouldn’t want to do it just because they trust me if they knew me […] it may be a bit of a conflict of interests kind of thing.

(P23)

I think, it is probably better for the patient, not for the studies […] you probably will get more consent if the clinician asks.

(P16)

These concerns were more commonly articulated by research nurses and neonatologists. Some practitioners spoke of the dilemma that this posed for best practice:

A good thing and a bad thing really […] I’m sure it would be much nicer for families if they, they knew me better because then they would […] perhaps be able to […] have more trust in what I say about the study […] Whereas if they don’t know you then they can make up their mind on the merits of the study […] they’re not […] putting themselves in a position where they feel they might upset a future therapeutic relationship with the consultants.

(P5)

Prioritising the child’s safety and well-being

Almost without exception, parents described how important it was for them to feel confident that the trial was safe and would not harm their child. Similarly, practitioners recognised the importance to parents of safety when considering entering their child in a trial. Parents particularly wanted reassurance that (1) the risks of side effects from the trial medication were minimal; and (2) the trial would cause no or minimal distress to their child and, notably, that it would not involve procedures that children find distressing (e.g. venepuncture):

My partner was like, ‘Is it going to harm him? Is it going to, you know, is it going to put him through pain or anything?’ You know, that was […] the only question.

(F41)

Some parents favourably contrasted the safety of the trial that they had been approached about with other types of research. Parents, particularly in MASCOT, spoke of how they were reassured by explanations from practitioners that the trial medications were routinely prescribed: ‘There wasn’t any sort of risk because it wasn’t trialling a new drug or anything’ (F53). In MENDS, parents derived similar reassurance from the fact that ‘Melatonin is something we do naturally anyway so it’s not as if […] I was giving her some sort of strong chemical’ (F5). Occasionally, parents contrasted the safety of the trials in this study with those trials that were testing new medicines and particularly those trials that had received extensive negative press coverage, notably the Northwick Park trial in 2006. More than one practitioner recognised the potential impact of media coverage and how this could raise safety as a concern for parents: ‘How safe is it? Because there’s always the sort of connotation […] are they sort of trying […] something not tried and, you know, trusted and tested’ (P13).

Some parents were very clear that they would not have entered their child in the trial if they doubted the safety of the trial medication. As this mother implied, the knowledge not only that a medicine had previously been tested in humans, but also that it had already been widely used with children, was important in parents’ decisions to take part:

I don’t think children should be used as guinea pigs where safety, their sort of health safety is an issue. But […] quite a lot of children already have these tablets […] but I would never have done it if it was testing something for the first, like it was a test, test of something for the first time. I would never have done that. I wouldn’t have risked it going wrong.

(F56)

Her perception that the trial is safe was critical in her decision. However, her comments suggest that she was unaware that a drug’s regular use in the population did not necessarily mean it was licensed to be used (for the particular indication in the particular age group). Similarly, she seemed unaware that having such a licence did not necessarily remove the need for further research.

Parents prioritised their child’s safety and well-being irrespective of whether the child went on to participate in the trial. For several parents who declined or withdrew from a trial, it was the perception of possible harm that drove their decision:

My main concern was actually taking it, he’s so stable at the moment, apart from a few hiccups which we can control. And I was really concerned that taking him off his medication would mess his asthma up and that was the main reason for not taking part.

(F55)

(*This comment suggests that the parent may have misunderstood the MASCOT trial design. On this trial children’s medication was changed, but it was not ceased altogether.)

One mother’s discovery, via an internet search done by the child’s father, that the trial drug was unlicensed for children had left her concerned about the safety of the trial and she subsequently withdrew her child from MENDS (although the licensing status of the trial medication was given in the PIL).

It just scared me when it said not to be given to children under 20 […] I didn’t understand they weren’t licensed for children. […] And that’s what I thought it was, just to see if it worked, not to actually like so then it could be licensed.

(F33)

Benefits to the child, the family and others

Most parents spoke of the potential benefits that participating in a trial might hold for their own child. For some, participation was seen as a way of gaining access to medication that they thought was otherwise unavailable. For others, participation offered hope that their child might receive a treatment during the trial that would prove to be effective:

I didn’t see why I […] could say ‘no’ to it. Because I thought, well it’s, you know, a 50/50 chance of her getting […] this additional help which she might need.

(F21)

A number of parents also told us that they perceived very real benefits to participation even if their child did not receive active trial treatment in the sense that they would get ‘additional attention’ (F60). Parents saw additional monitoring, vitamin and mineral supplements (specific to the POP trial) and appointments with a specialist as positive aspects of participation (e.g. F14 and F56).

For 4 out of 10 parents who declined a trial, benefit to their child was an important consideration, but it was the lack of definite and immediate benefit of the trial for their child that they emphasised as being significant in their decision. Some practitioners acknowledged this as potentially problematic for recruitment, ‘It’s just that parents want the best treatment’ (P15).

Parents also discussed the importance of benefit to other children and families. Most recognised that their family might not benefit personally from the trial, but for some this possible drawback was offset by the knowledge that even if their child did not benefit personally, his or her participation could make a valuable contribution:

We might make a bit of a difference somewhere along the line and even if it doesn’t help [my son] it might help someone else […] It’s just nice to think you’re, you know, doing something useful.

(F56)

You kind of want to, to help in any way, you almost feel it’s kind of your obligation as a human being to help […] not in a pressured sort of way but, but well you want to do what you can.

(F35)

For some parents, participation was an opportunity to ‘give something back somewhere along the line’ (F51). Those parents who had had preterm babies in the past or who themselves had asthma were particularly conscious that the treatment their child was receiving was a direct result of previous generations of families choosing to take part in research. These parents indicated that they wanted to reciprocate:

Agreeing to it wasn’t really a problem because, at the end of the day, the medicines that my lad’s had I know have been tested at some time or other many years ago […] he wouldn’t be around today if they hadn’t been.

(F45)

Parents’ accounts of the benefits to others were often expressed with a considerable sense of conviction, though the benefits they identified could be quite general or idealised. For example, families in the POP trial had often experienced lengthy, painful and frightening periods of illness before their child was diagnosed and treated. Some saw participation in the trial as offering a way to prevent future children suffering in the way that their child had, even though the trial itself could not specifically contribute evidence to speed the diagnosis of the condition. Parents saw their contribution to the trial as helping towards the general aim of improving medical knowledge about their child’s condition:

It was the most horrible thing I’ve ever […] lived through in my life, to be honest. So to help other people […] For somebody else to suffer that, I’d rather, as long as it wasn’t going to hurt [my son] I would do anything to stop that.

(F26)

While it was common for parents to stress that they thought participation would ‘help other kids’ (F54), their priorities lay with their own child, and benefits to others were a secondary consideration.

Firstly to, to get his asthma better and secondly because I think it was a good thing to do to try and get sort of the different varieties of the medication, the different things more researched and better used for children.

(F59)

I’d hate it to be in vain from our point of view. Yes it might help the study as a whole but from a selfish point of view I’d prefer [my son] to get something out of it.

(F56)

Indeed, parents described a combination of several factors as important in their decision. In general order of priority, this typically included securing their own child’s safety, benefit to child/family and benefit to others. However, for many parents there was also some kind of trade-off between these factors when considering trial entry:

Maybe he might get [the trial drug], maybe he mightn’t. Maybe, if he does get it, it might help him in some way and if he doesn’t get it then, you know, at least I tried to help [you] with the study.

(F9)

If it’s going to hurt them, I wouldn’t let him do it. If it’s not going to hurt him, there’s no harm in them doing it. If it helps somebody else then he does it.

(F2)

Most practitioners recognised that parents wanted to help other families and their doctors, and that this desire informed their decisions. Trials such as TIPIT, which involve extremely premature babies, present an intensely stressful and emotional environment for parents to consider trial entry, particularly given the high mortality and morbidity rate in this group. One practitioner spoke of how, even in the most intensely distressing situations, some parents might take comfort from their child’s participation in a trial: ‘I think they also found it a little bit helpful that maybe the babies were going to die but maybe all of that wasn’t in, in vain if they were helping push things forward with one aspect of care’ (P1). However, reflecting our observation from parents’ accounts that their foremost concern was their own child, another practitioner noted: ‘Their first question is “My child.” But I think when they’ve made up their mind they also say, “Yeah, and it’s going to help other people.” […] So it’s not necessarily an immediate response’ (P25).

Practicalities of participation

Many families discussed in considerable detail the simple practical difficulties and inconveniences of participating in a trial, such as school absences or the need to travel to hospital for additional appointments. Six families who declined the trial cited practical reasons, such as frequent hospital visits, although none gave practical reasons as the only reason for non-participation:

[My husband] said, ‘How many times are you going to, you know, how many times are we going to have to go to the hospital?’ And different things about school and him having time off.

(F19)

Decliners’ comments about practicalities were often tempered in ways that suggested that a practicality would be weighed differently if the trial’s benefit to the child and family was stronger. In this sense, placebo-controlled trials could fail, in parents’ minds, to outweigh the inconveniences of the trial: ‘it just seemed like a very long drawn-out process for something that wasn’t guaranteed that she was going to get the medication’ (F44).*

(*This parent declined MENDS. This trial required a 4-week run-in period during which the parent was required to keep sleep diaries and follow sleep hygiene guidelines prior to the 12-week trial period.)

Similarly, several consenting families commented that had participation placed more demands on them, they would have said ‘no’. This indicates that, like the decliners, these families had weighed practical considerations against the potential benefits of participation but, for them, the balance had fallen in favour of the trial:

If it had meant that we had to go extra times to [the hospital] again […] I, I wouldn’t, I wouldn’t, I wouldn’t have had any problems saying ‘no’. I would have apologised but I would have said no.

(F35)

It really wasn’t a big decision. It sounded very much the right thing to do […] and the inconvenience was absolutely minimal […] so it definitely was an easy decision.

(F60)

The same parent noted, ‘Had it been additional time required, you know, it certainly would have been a factor in my decision’ (F60).

Practicalities of participation were not a concern for parents considering the neonatal trial, as trial procedures were conducted alongside the baby’s routine treatment in the neonatal unit.

The majority of practitioners acknowledged that practical considerations were important to families. However, they sometimes seemed to downplay or dismiss the significance of these factors in parents’ decisions about the trial: ‘that’s probably a partial reason but it just demonstrates their reluctance to be part of the study rather than being, you know, an actual reason’ (P5).

What is important to young people when considering a trial?

Young people reported many of the same concerns and considerations as parents in deciding about the trials. Many had a clear appreciation that a trial’s purpose was to benefit future patients. Some expressed a passionate desire to help other young people or their doctors and explained that this was an important influence on their decision to take part:

I just wanted to help, just the cause, and just to see if other people could get better quicker.

(F35, 15–16 years)

I will give it a go because, because I might be helping other people right now […] I felt like, like a life saver.

(F48, 8–10 years)

Many young people, particularly in the POP trial, were unwell for long periods and some remarked that they hoped their participation would make life easier for other children in the same position:

It would benefit me and other children in the future for like if they have the same thing they can get medicine and not have to do the study but like get it straight away because I helped.

(F49, 11–14 years)

One practitioner commented on how, compared with parents, young people were motivated to enter a trial by the contribution their participation could make to the broader population: ‘they have a very good altruistic view of sort of wanting to make everything better not just themselves. Parents are often much more focused on their own child’ (P8). Another noted, ‘children generally, as long as it’s not going to hurt them more than necessary are very, very happy to take part […] it’s not like a big block for them usually’ (P12).

Some young people from the POP trial were concerned with the amount of medication that they were already taking and described how they were reluctant to increase this (e.g. F14, F12 and F20). Like parents, a number of the young people expressed concerns about the safety and side effects of medication and whether the trial would require extra injections or blood being taken. In particular, a number described the importance of reassurance that the trial did not involve ‘new medications that they’d never used before’ (F35, 15–16 years):

You have all the thoughts of like, like will there be side effects or whatever then you realise that actually there won’t be because it’s not that kind of trial is it, it’s not that kind of drug.

(F57, 11–14 years)

Some young people, many of whom already had numerous hospital appointments, mentioned the practicalities of participation. For these young people, extra visits to the hospital could deter them from participating:

Just because I would have to go to hospital more and I wouldn’t have wanted to have done that so I wouldn’t have done it.

(F13, 15–16 years)

If it would have impacted on you know, having to, say, either go to the hospital or go swimming, or go out with your friends […] then I would have maybe said it’s not worth, you know, giving up all my extra time, but it hasn’t impacted on it that was, so it’s good.

(F42, 15–16 years)

Like parents, the potential for personal benefit was important for some young people, and they also described their decisions in ways that suggested they weighed up the different aspects of the trial against each other:

I was thinking, this could be really good for me but what if it’s the placebo then, um, it’s like I’m doing it for nothing basically.

(F14, 11–14 years)

It was all new to me, the whole thing, […] at first I thought ‘oh no, I’m not going to do this’ but then I realised that it had benefits for me as well.

(F35, 15–16 years)

You just think like ‘oh […] what are we gonna have to do’ like, ‘what medicines are we gonna take’ and then obviously […] ‘what will happen as a consequence of the medicine’.

(F57, 11–14 years)

Young people’s part in decision-making

Young people’s views on their involvement in the decision varied considerably. Most described how they had been involved in the joint decision to take part in the trial ‘with the doctors and my mum and dad’ (F28, 11–14 years). These young people were content for their parents to guide them and valued their support. They also described how they were happy with the decision and their part in making it:

The nurse went out and I talked to my mum a bit and I just went with her decision and it was good so I just stuck with that.

(F48, 8–10 years)

I wanted my mum, because I like my mum being in on it so that if there’s anything I’m concerned about I can say to my mum.

(F42, 15–16 years)

It was not unusual for young people to describe how their parents ‘sort of influenced me to go ahead with it’ (F60, 11–14 years) or that the decision had really been their parents’, but the young person ‘didn’t have any objection to it’ (F35, 15–16 years).

Occasionally, they described how they themselves had initially been more positive than their parents, and emphasised the importance of reaching a decision that all parties were content with and could support:

I think at first mum was quite negative, not negative, she had loads of questions because she, I think she was worried about side effects and things and later in the interview, well I was really joint with my mum about it really, because I wasn’t going to do it if she wasn’t happy.

(F57, 11–14 years)

I wanted to do it as soon as I found out about it but, and so did daddy but mummy had her concerns […] I didn’t want to do it unless mummy was comfortable doing it.

(F49, 11–14 years)

If I said ‘yes’ but my mum and dad didn’t approve well, well I just probably would say, say ‘can we talk about it?’ because if they don’t approve I won’t be, feel confident about it will I? […] because your family and support is more or less what people need to do things.

(F53, 11–14 years)

These descriptions imply that these young people often had their own ideas about the trial but saw the decision as shared within the context of a supportive family. Indeed, of the 21 young people in this study, only one described making the decision independently. (This young person chose to participate in the RECRUIT study even though her mother declined to be interviewed.)

It was my decision […] because your mum’s not really taking part in it, is she?

(F47, 15–16 years)

The great majority of the young people we interviewed were happy with the level of involvement they had in the decision on trial entry and the decision that was made, but there were some exceptions. Two cases (Cases 6 and 7) warrant particular discussion because they highlight the complex difficulties that a few young people experienced in decision-making about the trial.

Parents’ and practitioners’ views on young people’s part in decision-making

Some parents and a few practitioners described young people’s involvement in the decision as empowering for them whichever direction the decision took and allowing young people to exercise some autonomy or ‘control’. Young people themselves never spoke of the trial decision in these terms.

Perhaps it empowers them a bit, that they are somehow, you know, taking control of their treatment by being part of the study.

(P21)

We’ve had two teenagers refuse the trial […] and that may be a sort of control issue […] ‘I can say no, I’m not going into the study’.

(P7)

I think she probably feels that she’s not had a lot of control since she became ill, […] And that’s why I think it’s so important to allow her to have control over these kind of decisions […] because there’s so much of her life that she can’t control.

(F14)

And [my daughter] was kept fully on board and communicated to directly, along with myself […] I think that was very good as well because [she] felt she had ownership in terms of whether or not to participate.

(F60)

However, one parent emphasised how her 10-year-old son was not old enough ‘to decide things like that’ and described how the team had placed too much importance on involving him in the decision:

It’s a good thing that obviously the child’s opinion is asked […] but it, it was sort of, it could have become a bit of a power thing with the, with him, with the children, […] I thought they sort of, they went on a bit much about it.

(F56)

This highlights the difficulties for practitioners in balancing the interests of both parties when seeking assent and proxy consent, particularly as the precise balance needed will undoubtedly vary from family to family. Most parents felt that it was important for their child to be involved in the decision in a way that was appropriate for them. For very young children and those with learning difficulties it was often the case that parents had made the decision, but sought their child’s assent themselves:

We explained to [my son] as well, if he doesn’t want to do it any more he can just say and it can stop at any time as well, so he understands he’s not being forced to do anything and, and he asked why he was doing it, so we explained it can help other little boys and girls […] so he thinks that’s good.

(F15)

For older children there was a clear recognition from parents that it was important for their child to be involved in the decision, and in some cases parents implied that their child should have decisional authority:

We always sort of discuss everything with her fully, because it’s not happening to me. It’s happening to her.

(F14)

I can say ‘yes’ a hundred times; if you say ‘no’, that’s the end of it […] it’s her body, it’s her life. I’m just the taxi driver.

(F42)

Other parents spoke of guiding their child’s decision – ‘we would have also persuaded her to do it’ (F60) – if they felt that the child was not too keen on participation because ‘I think it’s important’ (F51).

I think they rely on you, as an adult, to say, you know, ‘Is everything, you know, OK? You know, is there anything I really, really need to know?’

(F13)

Parents’ and practitioners’ experiences of the trial approach

One of the study’s most striking findings was the marked divergence between parents and practitioners in how they regarded the trial approach. While many practitioners viewed an approach as a burden for parents, even in the most difficult situations parents did not mind being asked about trials and they did not describe the approach as burdensome. Indeed, some viewed the trial approach as a positive or exciting opportunity.

Our findings therefore challenge the protective stance towards families that imbues some thinking in this field. Nevertheless, practitioners’ accounts illustrate vividly the complexities they experienced in recruiting to children’s trials, particularly in situations in which parents were already distressed and anxious about their child’s health. Practitioners in all specialties were concerned to avoid overburdening parents with information and strove to find a balance between providing sufficient information, while not overwhelming them. The accounts of some practitioners suggested that they found approaching families about trials to be aversive. (In this chapter we use the term ‘parent’ or ‘young people’ when referring to a specific group and ‘families’ when the comment can be more generally applied to both groups.)

Parents did not express a consistent opinion on whether it was better to be approached by the child’s regular practitioner or one who was not responsible for their child’s clinical care and so was unknown to them. Rather, they tended to emphasise the benefit of whichever ‘model’ they had encountered. However, some young people seemed to prefer interacting with practitioners whom they knew, particularly once they were participating in the trial. Parents felt it important to involve their child in the decision-making and young people concurred, but parents sometimes described trying to steer their child’s decision if they felt their child might choose unwisely. All parties valued the face-to-face discussion more highly than the PILs, and wanted shorter and less complex written information. Some parents expressed disappointment when their children were ineligible to enter a trial, which seemed to be linked to their concerns about returning to ‘pre-trial’ health care.

The ‘look’ and ‘feel’ of trial recruitment

The study’s novel design allowed us to take account of a fundamentally important, but often overlooked, complexity in research on communication: meaning arises in how people experience what is said133 and cannot simply be ‘observed’ in their dialogue. 134 That is, communication can ‘look’ and ‘feel’ very different. Previous studies that have used observational or qualitative interview data to study recruitment cannot take account of this difference. We did so in this study by simultaneously collecting and comparing observational and interview data. Previous research on the ‘look’ of trial communication has been critical of how practitioners communicate about trials and encouraged them to facilitate interactivity. 12,33,35,40,135–137 We found that parents and young people said very little in trial discussions and asked few questions. Evidence suggests that low family interactivity is common to many types of practitioner–family consultation, not just trial discussions. 96,138–140 However, the proportion of family speech relative to practitioners’ was particularly low in our study and may reflect the information-giving function of the trial discussion and the requirement for practitioners to explain the trials. This is further supported by our finding that the trial discussions in which parents and children spoke most tended to be those that required their input to establish eligibility, thereby dictating a more even balance of family versus practitioner speech.

We found that while parents and young people took little part in the trial discussions, they nevertheless felt involved and were highly satisfied about how they had been approached. Judged solely via families’ accounts of the ‘feel’ of the approach, practitioners were communicating well. However, our interviews with parents also identified several cases in which parents had important misunderstandings of the trial. Some of these could stem from the ways in which practitioners communicated and particularly their tendency to use closed rather than open questions in discussing the trial with parents. This often meant that parents’ views about the trial were not explored before practitioners sought their decisions about trial entry.

Families who consent, withdraw or decline

RECRUIT is also one of the few qualitative studies to have compared the views of families who consented to the trial versus those who declined or withdrew. Regardless of whether or not they consented, the factors that influenced parents’ decisions on trial entry were the child’s safety and well-being; potential benefits to the child and family; potential benefits to others; and the practicality of participation. Of these, parents’ paramount consideration was their perception of the trial’s safety. However, the interpretation of all these considerations differed between those who consented and those who declined; for example, while the majority of parents evaluated the trials as ‘safe’, two parents who declined and one who withdrew did so for reasons of ‘safety’. How these factors are evaluated by parents depends not just on the trial itself and how it is presented, but also on individual parents’ previous experiences and beliefs. Parents were clear that they did not feel pressurised by the trial team to participate, but a number described how their personal values made them reluctant to decline, and several parents who did decline described a passing sense of discomfort at the time they made their decision.

These findings advance our understanding of how parents and young people experience trial recruitment and the factors that influence their decisions. Later in this chapter we will discuss the significance of these findings with regard to their implications for enhancing recruitment and its conduct. However, first we will consider the study’s strengths and limitations.

Transferability of findings

Besides its novel multiperspective methods, one of RECRUIT’s key strengths was its scale and scope. We interviewed 60 families who had been approached about one of four trials, from four different paediatric specialties. Eleven different trial teams across seven hospitals recruited the families and took part in interviews themselves. The diversity of the research participants, the children’s medical situations and the trials means our findings have transferability to a broad range of trials that recruit children. The selection of four different trials in contrasting specialties has enabled us to identify how certain types of trials give rise to particular challenges. For example, the complexities for practitioners who recruit to trials of treatments for patients with recently diagnosed serious/critical illness versus those recruiting to trials of treatments for patients with chronic illness, or how trials that use letters as the first step of the approach are likely to have recruitment problems linked to the value parents place on the face-to-face approach. Despite the diversity of the trials included in RECRUIT, it is important to note that all were placebo-controlled trials; were perceived to be ‘low risk’; were largely conducted in hospital rather than community settings; and investigated the efficacy of treatments that were add-ons to the child’s standard clinical care rather than trialling protocols that constituted the core of the child’s treatment.

Study procedures and implementation

Procedurally the study worked well though it was not free of challenges, complexities and delays, as we describe earlier (see Chapter 2, Methods). One aspect of the study’s procedure warrants particular discussion. Trial practitioners sought verbal consent to record the trial discussion and to pass on families’ details to the RECRUIT team. The RECRUIT team later sought informed consent, and this consent was a prerequisite for the trial teams to release the audio-recordings to the RECRUIT team. Despite our initial concerns about the acceptability to families of the audio-recordings and this consent process, most (94%) gave permission for the trial discussions to be recorded. While it could be argued that families might have found it difficult to decline the recordings, 30% of those with recorded trial discussions later declined RECRUIT, indicating that families were able to exercise their autonomy in deciding whether or not to participate. When we asked parents for their opinions about recording and consent procedure for the trial discussions, without exception all reported that they had found these acceptable. Previous studies in the UK have reported difficulty in obtaining such audio-recordings141–143 and we noted reluctance among some practitioners to record trial discussions. This is a potential source of bias in the sampling of trial discussions, as some families may have been perceived as ‘easier’ to approach about the audio-recordings than others.

Sampling of participants

Despite trying several different routes to reach our quota of families who declined a trial (described in Chapter 2, Methods: see Changes to protocol and Other clarifications and changes to the methodology, item 3), we recruited fewer decliners than anticipated and most of those we did recruit were from the MENDS trial (this reflects the efforts of the trial team to assist us in sampling such families and is not necessarily a reflection of the recruitment rate to the trial itself). We acknowledge that this is a limitation of the study. However, as we will suggest in Recommendations for research, below, we believe the recruitment of such families to be a unique methodological challenge, worthy of research in its own right. Nevertheless, as well as the 10 decliners, we also accessed two groups that we did not anticipate sampling at the study outset: families who had withdrawn from a trial and those who were ineligible. The experiences of these groups have previously been little investigated and their accounts provided important insights into the different trajectories families experience after the trial approach. If trial conduct is to be improved from the perspective of all approached families, it is important to investigate their experiences regardless of their trajectory through the trial. Given the divergences that we found between parents and practitioners and the under-representation of decliners in our sample, an important question is how far families’ positive views of the trial approach and the trial itself were a reflection of the limitations of our sampling? This is difficult to resolve. However, it is worth noting that we identified few differences between those who joined and remained in the trials and those who did not. A further question is whether parents felt reticent about directly criticising a practitioner for fear that the relationship or their child’s clinical care may be affected. However, we were careful to reassure families of our independence from the trial teams, and a reluctance to criticise might predict neutral or mildly positive accounts rather than the highly positive ones that parents often gave. Mirroring other research on children’s health, there were few fathers in our sample.

Of the young people we interviewed, most (60%) came from the POP trial. Relatively few spoke in detail about their experiences of being approached about the trials. Although we tried to interview young people separately from their parents, 8 out of 21 opted to be interviewed jointly with their parent. Parents often interjected on behalf of the young people; sometimes this was because young people looked to them to do so. It is conceivable that the young people’s interviews might have taken a different direction had they been interviewed alone. However, it is difficult to see how this could be resolved: some young people may be reticent about speaking to a researcher who was a stranger to them. Without the option to be interviewed in the presence of their parent, they may not have participated at all.

Parents

Young people

Practitioners

Mentoring for practitioners

Some practitioners described the trial approach in ways that suggested that they found it aversive, while many were concerned that the approach was burdensome for families. Ongoing ‘moral support’ or mentoring for recruiting practitioners, alongside training in the recruitment process and informed consent, would allow practitioners to reflect openly on the emotional and ethical aspects of recruitment. Having opportunities for practitioners to informally discuss their concerns and get advice and feedback on practice may be particularly beneficial for less experienced practitioners and those working in specialties in which families are under considerable emotional strain. This support could potentially be built into existing mentoring arrangements, or developed with the help of LRNs. Dissemination of the RECRUIT study findings will have an important part to play in this process, for example reflection on the finding that parents were generally predisposed to help with research if they felt able to may ease the discomfort that some practitioners experience in approaching families.

Practitioner training

Practitioner training should reflect how trial recruitment is a social process, as well as a procedural and legal one. While previous research has addressed clarity in trial discussions, the importance of the experience or ‘feel’ of the trial approach to the different parties has largely been overlooked. Our findings indicate the social and emotional complexity of the trial approach and how practitioners have to negotiate several tensions including (1) giving ‘enough’ information without overwhelming families; (2) attending to the social norms of the encounter while ensuring clarity and understanding of the trial; and (3) balancing the needs of parent and young person. Given the considerable importance that families in this study placed on the ‘feel’ of the trial discussion relative to its informational content, it is important to consider the social and emotional dynamics of the trial discussion in designing recruitment training, and not focus exclusively on the procedural and informational aspects of informed consent.

Participant information leaflets

Both practitioners and parents were dissatisfied with the current PILs, viewing them as too lengthy and complicated. Practitioners attributed these flaws to the need to follow what they perceived as stringent guidelines and directions from RECs on the design and content of PILs. These findings add to the growing body of literature suggesting that regulatory guidelines may be at odds with the requirements of families and practitioners, and hinder rather than facilitate families’ understanding of trials. 167,168 A review of the current guidelines on PILs,169 taking into account parents’, young people’s and practitioners’ perspectives, may enhance the value and usefulness of these documents for all parties.

Clarity in the trial discussion

In the trial discussions, practitioners rarely asked parents open questions. We identified parental misunderstandings, some of which may have been avoided had practitioners used open questions to elicit families’ views and understanding of the trial before seeking their trial entry decisions. However, as we note below, to reflect the social dynamics of family–practitioner interactions, such questioning needs to be conversational and conducted in a way with which families and practitioners are comfortable.

Establishing what constitutes normal clinical care at the start of the discussion may also help parents to understand what procedures and treatments are part of the trial and thereby help them to distinguish between routine clinical care and care that is given as part of a trial. A policy of continuous consent may help to maintain this distinction. Many parents choose to enter a trial in the hope that it will benefit their child. Our analysis showed that some parents saw the trial medication as offering a guaranteed benefit. For clarity, it is important that practitioners describe the treatment arms in a neutral fashion and stress that the purpose of the trial is to assess the efficacy of the trial medication.

To help young people in the trial discussion, practitioners may consider asking parents’ advice on how best to approach them. This could involve offering young people the chance to discuss the trial separately from their parents, if this is acceptable to all parties. Practitioners should also be aware that young people might find it difficult to express their views directly and may need additional support.

Parents’ discomfort in saying ‘no’ to research

Several parents who consented to the trial expressed discomfort in saying ‘no’ to research. Many of the reasons parents gave suggested a personal sense of ‘moral duty’. For example, they described an obligation to medicine, to the hospital and to the practitioners. They felt that non-participation would let down the trial team or hinder the advancement of medical knowledge. Five of the parents who declined described a passing sense of ‘guilt’ at their decision not to take part. All traced their unease to recognition that the trial was important and a wish to help.

Mirroring parents, several practitioners were conscious of the potential difficulty for parents in declining a trial. While parents were clear that they did not feel pressurised to consent by practitioners, these data raise the question of how far practitioners should go to facilitate parents in saying ‘no’ to research. For some families saying ‘no’ to research may be difficult without ‘permission’ from the practitioner. However, such facilitation could inadvertently send the message that the trial is not important. Moreover, how far can practitioners be responsible for parents’ personal beliefs and values that are the source of such discomfort and which, in this study at least, were transient for those who did decline?

Such tensions indicate caution in prescribing how practitioners should manage these situations and point to the value of enabling practitioners to respond according to their judgement of each family’s individual situation. When parents do decline, discomfort could perhaps be ameliorated if practitioners endorsed parents’ decisions, for example by acknowledging that, above all else, it is important that families feel able to make a decision that they are comfortable with.

Trial designs that make participation easier

Parents and some young people in this study described the importance of the practical requirements of the trial in terms of the disruption associated with extra trips to hospital and absences from school or employment. Some parents cited such practicalities as the reason why they had declined the trial, while others stated that if the trial placed greater demands upon them, they would have declined. The practical requirements of a trial could also potentially affect retention (although not investigated in this study). Practicalities are therefore important to consider at the trial design stage, in patient and public involvement consultation with families. Working with families at the trial design stage to arrange the schedule of visits to the trial site, providing staffing for home or school visits, and designing trials with built-in flexibility, in terms of both out-of-hours appointments and the time-frame in which appointments must happen, could allow more parents to say ‘yes’. It is also important to discuss practicalities with families at the time of the trial approach: practitioners in this study often spent more time explaining the trial design and rationale than discussing its practicalities, which could inadvertently send a message to families that such factors are an afterthought.

Aiding families’ understanding

Although the majority of families in this study had a working understanding of issues such as randomisation and placebos, the use of simple educational aids embedded in the trial discussion, such as mock trial medications and family-friendly flow charts, might help families to visualise the different trial stages and arms of the trials. The use of such aids may help practitioners craft explanations that help avoid misunderstandings and may be particularly helpful when explaining trials to children and young people.

Public education about research

Most parents in this study were positively orientated towards medical research in general. Nonetheless, several expressed initial reservations about medical research, which they linked to the negative connotations that medical research had for them, for example referring to ‘white coats’ and animal experimentation. Such stereotyped views suggest a need for greater public awareness and education to help transform beliefs about medical research in general. Public education about clinical trials would also be helpful so that when families are approached about a particular trial they already have some basic research literacy. This would reduce the amount of effort involved in deciding on trial entry at what is sometimes a very difficult point in families’ lives. Such education might also help to create a culture in which people expect to be asked to participate in research. If the concept of research and trials was less alien to families, this would also ease the burden of explanation that currently falls to trial practitioners, allowing them to focus on the specifics of the trial at hand.

Background and project justification

Forthcoming policy developments will increase the number of children’s RCTs initiated, but children’s triallists face considerable challenges in recruiting to RCTs. Despite these difficulties, most research on recruitment has concentrated on adult trials, leaving those working on children’s trials with little evidence to inform their recruitment strategies. Many RCTs recruit too few child participants, which can mean that the answers provided by the trials are unclear or misleading. There are also distinctive ethical, regulatory, pragmatic and psychosocial considerations surrounding children’s trials. The recruitment of children to trials therefore merits study in its own right. By informing strategies to improve recruitment and its conduct, this study will produce evidence to underpin the new policy developments for children’s medicines. These policies will significantly increase the resource invested in paediatric RCTs. By assisting children’s triallists with one of the most difficult aspects of their work, this study will help to ensure these long-awaited resources for children’s health are used to best effect.

Planned investigation

Research methods

Project timetable and milestones

This is a 2-year study. By the end of month 2, the investigators will have liaised with the different RCT sites and prepared and piloted the prompt guides. By end of month 20, we will have completed and transcribed the interviews and, in line with the constant comparative method, the data analysis will be well under way. On average, we expect to recruit two professionals and six to eight parents and children per month during months 3–20, with some concentration of this in the first 12 months of data collection. By the end of month 22, data analysis will be complete. Final writing-up will be in months 23 and 24.

Expertise

The study team is multidisciplinary, including health psychology, academic and clinical paediatrics, medical statistics, and clinical trial design and conduct. Over the last 5 years, BY has authored or co-authored 23 peer-reviewed publications, most of which are directly relevant to psychosocial and communication processes in child health or qualitative methods (e.g. Dixon-Woodset al. 2001; Younget al. 2002a,b, 2003; 2006). Several of these appear in major international journals including, the BMJ, The Lancet and SocialScience & Medicine. BY has also produced numerous other research and scholarship outputs and brings expertise in qualitative methods to the study team. Her recent grant support, all of which has been secured to conduct projects that use qualitative methods, is testament to this. Currently, she is PI on an Economic and Social Research Council (ESRC) study of quality of life in disabled children and a recently awarded multicentre Cancer Research UK (CRUK) study of communication processes in childhood leukaemia. The latter project will employ very similar methods to current study, but involves a different study team, so will add considerable value to this study through cross-fertilisation at methodological and other levels. BY is also a co-investigator on an ERSC study of tumour tissue donation in childhood cancer, which is leading to important new findings on children’s research participation in specialised research intense settings. PRW and RLS have track records of world-class standing in paediatric medicine (RLS), multicentre RCT design, implementation and analysis (PRW and RLS), and collaborations and publications commensurate with this; since 2001 RLS has produced 27 peer-reviewed publications in major international journals, plus numerous Cochrane Reviews, editorial-reviewed papers, and a clutch of highly influential editorials of close relevance to this study in journals such as The Lancet and the BMJ; in the same period, PRW has published more than 30 peer-reviewed papers in high-impact journals, alongside other key outputs including, numerous Cochrane reviews and influential writings of RCT methodology. PRW has provided steering committee support to several international RCTs, while RLS has particular expertise in children’s RCTs, including extensive experience in recruiting children to trials. PRW and RLS have a strong portfolio of research council and other major grants to support clinical and methodological investigations relevant to children’s health, including RCT-related work. Taken together, the value of the current and previous research income secured by PRW and RLS is in excess of £20M. HH has co-authored several papers in high-impact journals, including a report of an RCT, which appeared in the New England Journal of Medicine. She contributes in-depth knowledge and experience of the co-ordination and management of multicentre clinical trials to the study team. Importantly, HH’s pivotal contribution to the study brings no directly allocated or incurred costs owing to the nature of the funding for her post.

Service users

In the context of this study, service users are the children and families who may be approached to participate in trials. Consultation with both of these groups will be assisted by the UKMCRN Consumer Liaison Officer and occur throughout the study, but will particularly focus on the study aims and design before its commencement, and on the appropriateness of the study recommendations towards the end. The inclusion of parent representatives on the steering group will provide further opportunities to consult with parents. Another key interest group are triallists and trial recruiters. Our regular liaison with the trial sites as the study is ongoing, involvement of PIs in the steering group, and consultation with the wider body of triallists through the UKMCRN regarding the recommendations, will ensure representation of this group. Ethics experts are an important group too. The steering group members with ethics expertise will provide representation of the wider ethics community and it is anticipated that these members will direct the study group towards any further consultation activities, as befits the ethical implications of the study.

References

Prioritisation Group

1. Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

2. Professor Imti Choonara, Professor in Child Health, Academic Division of Child Health, University of Nottingham

   Chair – Pharmaceuticals Panel

3. Dr Bob Coates, Consultant Advisor – Disease Prevention Panel

4. Dr Andrew Cook, Consultant Advisor – Intervention Procedures Panel

5. Dr Peter Davidson, Director of NETSCC, Health Technology Assessment

6. Dr Nick Hicks, Consultant Adviser – Diagnostic Technologies and Screening Panel, Consultant Advisor–Psychological and Community Therapies Panel

7. Ms Susan Hird, Consultant Advisor, External Devices and Physical Therapies Panel

8. Professor Sallie Lamb, Director, Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick

   Chair – HTA Clinical Evaluation and Trials Board

9. Professor Jonathan Michaels, Professor of Vascular Surgery, Sheffield Vascular Institute, University of Sheffield

   Chair – Interventional Procedures Panel

10. Professor Ruairidh Milne, Director – External Relations

11. Dr John Pounsford, Consultant Physician, Directorate of Medical Services, North Bristol NHS Trust

    Chair – External Devices and Physical Therapies Panel

12. Dr Vaughan Thomas, Consultant Advisor – Pharmaceuticals Panel, Clinical

    Lead – Clinical Evaluation Trials Prioritisation Group

13. Professor Margaret Thorogood, Professor of Epidemiology, Health Sciences Research Institute, University of Warwick

    Chair – Disease Prevention Panel

14. Professor Lindsay Turnbull, Professor of Radiology, Centre for the MR Investigations, University of Hull

    Chair – Diagnostic Technologies and Screening Panel

15. Professor Scott Weich, Professor of Psychiatry, Health Sciences Research Institute, University of Warwick

    Chair – Psychological and Community Therapies Panel

16. Professor Hywel Williams, Director of Nottingham Clinical Trials Unit, Centre of Evidence-Based Dermatology, University of Nottingham

    Chair – HTA Commissioning Board

    Deputy HTA Programme Director

HTA Commissioning Board

1. Professor of Dermato-Epidemiology, Centre of Evidence-Based Dermatology, University of Nottingham

2. Professor of General Practice, Department of Primary Health Care, University of Oxford Programme Director,

3. Professor of Clinical Pharmacology, Director, NIHR HTA programme, University of Liverpool

1. Professor Ann Ashburn, Professor of Rehabilitation and Head of Research, Southampton General Hospital

2. Professor Deborah Ashby, Professor of Medical Statistics and Clinical Trials, Queen Mary, Department of Epidemiology and Public Health, Imperial College London

3. Professor Peter Brocklehurst, Director, National Perinatal Epidemiology Unit, University of Oxford

4. Professor John Cairns, Professor of Health Economics, London School of Hygiene and Tropical Medicine

5. Professor Peter Croft, Director of Primary Care Sciences Research Centre, Keele University

6. Professor Jenny Donovan, Professor of Social Medicine, University of Bristol

7. Professor Jonathan Green, Professor and Acting Head of Department, Child and Adolescent Psychiatry, University of Manchester Medical School

8. Professor John W Gregory, Professor in Paediatric Endocrinology, Department of Child Health, Wales School of Medicine, Cardiff University

9. Professor Steve Halligan, Professor of Gastrointestinal Radiology, University College Hospital, London

10. Professor Freddie Hamdy, Professor of Urology, Head of Nuffield Department of Surgery, University of Oxford

11. Professor Allan House, Professor of Liaison Psychiatry, University of Leeds

12. Dr Martin J Landray, Reader in Epidemiology, Honorary Consultant Physician, Clinical Trial Service Unit, University of Oxford

13. Professor Stephen Morris, Professor of Health Economics, University College London, Research Department of Epidemiology and Public Health, University College London

14. Professor E Andrea Nelson, Professor of Wound Healing and Director of Research, School of Healthcare, University of Leeds

15. Professor John David Norris, Chair in Clinical Trials and Biostatistics, Robertson Centre for Biostatistics, University of Glasgow

16. Dr Rafael Perera, Lecturer in Medical Statisitics, Department of Primary Health Care, University of Oxford

17. Professor James Raftery, Chair of NETSCC and Director of the Wessex Institute, University of Southampton

18. Professor Barney Reeves, Professorial Research Fellow in Health Services Research, Department of Clinical Science, University of Bristol

19. Professor Martin Underwood, Warwick Medical School, University of Warwick

20. Professor Marion Walker, Professor in Stroke Rehabilitation, Associate Director UK Stroke Research Network, University of Nottingham

21. Dr Duncan Young, Senior Clinical Lecturer and Consultant, Nuffield Department of Anaesthetics, University of Oxford

22. Professor Stephen Morris, Professor of Health Economics, University College London, Research Department of Epidemiology and Public Health, University College London

23. Professor E Andrea Nelson, Professor of Wound Healing and Director of Research, School of Healthcare, University of Leeds

24. Professor John David Norris Chair in Clinical Trials and Biostatistics, Robertson Centre for Biostatistics, University of Glasgow

25. Dr Rafael Perera, Lecturer in Medical Statisitics, Department of Primary Health Care, University of Oxford

26. Professor James Raftery, Chair of NETSCC and Director of the Wessex Institute, University of Southampton

27. Professor Barney Reeves, Professorial Research Fellow in Health Services Research, Department of Clinical Science, University of Bristol

28. Professor Martin Underwood, Warwick Medical School, University of Warwick

29. Professor Marion Walker, Professor in Stroke Rehabilitation, Associate Director UK Stroke Research Network, University of Nottingham

30. Dr Duncan Young, Senior Clinical Lecturer and Consultant, Nuffield Department of Anaesthetics, University of Oxford

1. Dr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council

HTA Clinical Evaluation and Trials Board

1. Director, Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick and Professor of Rehabilitation, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, University of Oxford

2. Professor of the Psychology of Health Care, Leeds Institute of Health Sciences, University of Leeds

3. Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

1. Professor Keith Abrams, Professor of Medical Statistics, Department of Health Sciences, University of Leicester

2. Professor Martin Bland, Professor of Health Statistics, Department of Health Sciences, University of York

3. Professor Jane Blazeby, Professor of Surgery and Consultant Upper GI Surgeon, Department of Social Medicine, University of Bristol

4. Professor Julia M Brown, Director, Clinical Trials Research Unit, University of Leeds

5. Professor Alistair Burns, Professor of Old Age Psychiatry, Psychiatry Research Group, School of Community-Based Medicine, The University of Manchester & National Clinical Director for Dementia, Department of Health

6. Dr Jennifer Burr, Director, Centre for Healthcare Randomised trials (CHART), University of Aberdeen

7. Professor Linda Davies, Professor of Health Economics, Health Sciences Research Group, University of Manchester

8. Professor Simon Gilbody, Prof of Psych Medicine and Health Services Research, Department of Health Sciences, University of York

9. Professor Steven Goodacre, Professor and Consultant in Emergency Medicine, School of Health and Related Research, University of Sheffield

10. Professor Dyfrig Hughes, Professor of Pharmacoeconomics, Centre for Economics and Policy in Health, Institute of Medical and Social Care Research, Bangor University

11. Professor Paul Jones, Professor of Respiratory Medicine, Department of Cardiac and Vascular Science, St George‘s Hospital Medical School, University of London

12. Professor Khalid Khan, Professor of Women’s Health and Clinical Epidemiology, Barts and the London School of Medicine, Queen Mary, University of London

13. Professor Richard J McManus, Professor of Primary Care Cardiovascular Research, Primary Care Clinical Sciences Building, University of Birmingham

14. Professor Helen Rodgers, Professor of Stroke Care, Institute for Ageing and Health, Newcastle University

15. Professor Ken Stein, Professor of Public Health, Peninsula Technology Assessment Group, Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth

16. Professor Jonathan Sterne, Professor of Medical Statistics and Epidemiology, Department of Social Medicine, University of Bristol

17. Mr Andy Vail, Senior Lecturer, Health Sciences Research Group, University of Manchester

18. Professor Clare Wilkinson, Professor of General Practice and Director of Research North Wales Clinical School, Department of Primary Care and Public Health, Cardiff University

19. Dr Ian B Wilkinson, Senior Lecturer and Honorary Consultant, Clinical Pharmacology Unit, Department of Medicine, University of Cambridge

1. Ms Kate Law, Director of Clinical Trials, Cancer Research UK

2. Dr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council

Diagnostic Technologies and Screening Panel

1. Scientific Director of the Centre for Magnetic Resonance Investigations and YCR Professor of Radiology, Hull Royal Infirmary

2. Professor Judith E Adams, Consultant Radiologist, Manchester Royal Infirmary, Central Manchester & Manchester Children’s University Hospitals NHS Trust, and Professor of Diagnostic Radiology, University of Manchester

3. Mr Angus S Arunkalaivanan, Honorary Senior Lecturer, University of Birmingham and Consultant Urogynaecologist and Obstetrician, City Hospital, Birmingham

4. Dr Stephanie Dancer, Consultant Microbiologist, Hairmyres Hospital, East Kilbride

5. Dr Diane Eccles, Professor of Cancer Genetics, Wessex Clinical Genetics Service, Princess Anne Hospital

6. Dr Trevor Friedman, Consultant Liason Psychiatrist, Brandon Unit, Leicester General Hospital

7. Dr Ron Gray, Consultant, National Perinatal Epidemiology Unit, Institute of Health Sciences, University of Oxford

8. Professor Paul D Griffiths, Professor of Radiology, Academic Unit of Radiology, University of Sheffield

9. Mr Martin Hooper, Public contributor

10. Professor Anthony Robert Kendrick, Associate Dean for Clinical Research and Professor of Primary Medical Care, University of Southampton

11. Dr Anne Mackie, Director of Programmes, UK National Screening Committee, London

12. Mr David Mathew, Public contributor

13. Dr Michael Millar, Consultant Senior Lecturer in Microbiology, Department of Pathology & Microbiology, Barts and The London NHS Trust, Royal London Hospital

14. Mrs Una Rennard, Public contributor

15. Dr Stuart Smellie, Consultant in Clinical Pathology, Bishop Auckland General Hospital

16. Ms Jane Smith, Consultant Ultrasound Practitioner, Leeds Teaching Hospital NHS Trust, Leeds

17. Dr Allison Streetly, Programme Director, NHS Sickle Cell and Thalassaemia Screening Programme, King’s College School of Medicine

18. Dr Alan J Williams, Consultant Physician, General and Respiratory Medicine, The Royal Bournemouth Hospital

1. Dr Tim Elliott, Team Leader, Cancer Screening, Department of Health

2. Dr Catherine Moody, Programme Manager, Medical Research Council

3. Professor Julietta Patrick, Director, NHS Cancer Screening Programme, Sheffield

4. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

5. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

6. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Disease Prevention Panel

1. Professor of Epidemiology, University of Warwick Medical School, Coventry

2. Dr Robert Cook, Clinical Programmes Director, Bazian Ltd, London

3. Dr Colin Greaves, Senior Research Fellow, Peninsula Medical School (Primary Care)

4. Mr Michael Head, Public contributor

5. Professor Cathy Jackson, Professor of Primary Care Medicine, Bute Medical School, University of St Andrews

6. Dr Russell Jago, Senior Lecturer in Exercise, Nutrition and Health, Centre for Sport, Exercise and Health, University of Bristol

7. Dr Julie Mytton, Consultant in Child Public Health, NHS Bristol

8. Professor Irwin Nazareth, Professor of Primary Care and Director, Department of Primary Care and Population Sciences, University College London

9. Dr Richard Richards, Assistant Director of Public Health, Derbyshire Country Primary Care Trust

10. Professor Ian Roberts, Professor of Epidemiology and Public Health, London School of Hygiene & Tropical Medicine

11. Dr Kenneth Robertson, Consultant Paediatrician, Royal Hospital for Sick Children, Glasgow

12. Dr Catherine Swann, Associate Director, Centre for Public Health Excellence, NICE

13. Professor Carol Tannahill, Glasgow Centre for Population Health

14. Mrs Jean Thurston, Public contributor

15. Professor David Weller, Head, School of Clinical Science and Community Health, University of Edinburgh

1. Ms Christine McGuire, Research & Development, Department of Health

2. Dr Kay Pattison Senior NIHR Programme Manager, Department of Health

3. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

External Devices and Physical Therapies Panel

1. Consultant Physician North Bristol NHS Trust

2. Reader in Wound Healing and Director of Research, University of Leeds

3. Professor Bipin Bhakta, Charterhouse Professor in Rehabilitation Medicine, University of Leeds

4. Mrs Penny Calder, Public contributor

5. Dr Dawn Carnes, Senior Research Fellow, Barts and the London School of Medicine and Dentistry

6. Dr Emma Clark, Clinician Scientist Fellow & Cons. Rheumatologist, University of Bristol

7. Mrs Anthea De Barton-Watson, Public contributor

8. Professor Nadine Foster, Professor of Musculoskeletal Health in Primary Care Arthritis Research, Keele University

9. Dr Shaheen Hamdy, Clinical Senior Lecturer and Consultant Physician, University of Manchester

10. Professor Christine Norton, Professor of Clinical Nursing Innovation, Bucks New University and Imperial College Healthcare NHS Trust

11. Dr Lorraine Pinnigton, Associate Professor in Rehabilitation, University of Nottingham

12. Dr Kate Radford, Senior Lecturer (Research), University of Central Lancashire

13. Mr Jim Reece, Public contributor

14. Professor Maria Stokes, Professor of Neuromusculoskeletal Rehabilitation, University of Southampton

15. Dr Pippa Tyrrell, Senior Lecturer/Consultant, Salford Royal Foundation Hospitals’ Trust and University of Manchester

16. Dr Sarah Tyson, Senior Research Fellow & Associate Head of School, University of Salford

17. Dr Nefyn Williams, Clinical Senior Lecturer, Cardiff University

1. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

2. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

3. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Interventional Procedures Panel

1. Professor of Vascular Surgery, University of Sheffield

2. Consultant Colorectal Surgeon, Bristol Royal Infirmary

3. Mrs Isabel Boyer, Public contributor

4. Mr David P Britt, Public contributor

5. Mr Sankaran ChandraSekharan, Consultant Surgeon, Breast Surgery, Colchester Hospital University NHS Foundation Trust

6. Professor Nicholas Clarke, Consultant Orthopaedic Surgeon, Southampton University Hospitals NHS Trust

7. Ms Leonie Cooke, Public contributor

8. Mr Seamus Eckford, Consultant in Obstetrics & Gynaecology, North Devon District Hospital

9. Professor David Taggart, Consultant Cardiothoracic Surgeon, John Radcliffe Hospital

10. Professor Sam Eljamel, Consultant Neurosurgeon, Ninewells Hospital and Medical School, Dundee

11. Dr Adele Fielding, Senior Lecturer and Honorary Consultant in Haematology, University College London Medical School

12. Dr Matthew Hatton, Consultant in Clinical Oncology, Sheffield Teaching Hospital Foundation Trust

13. Dr John Holden, General Practitioner, Garswood Surgery, Wigan

14. Professor Nicholas James, Professor of Clinical Oncology, School of Cancer Sciences, University of Birmingham

15. Dr Fiona Lecky, Senior Lecturer/Honorary Consultant in Emergency Medicine, University of Manchester/Salford Royal Hospitals NHS Foundation Trust

16. Dr Nadim Malik, Consultant Cardiologist/ Honorary Lecturer, University of Manchester

17. Mr Hisham Mehanna, Consultant & Honorary Associate Professor, University Hospitals Coventry & Warwickshire NHS Trust

18. Dr Jane Montgomery, Consultant in Anaesthetics and Critical Care, South Devon Healthcare NHS Foundation Trust

19. Professor Jon Moss, Consultant Interventional Radiologist, North Glasgow Hospitals University NHS Trust

20. Dr Simon Padley, Consultant Radiologist, Chelsea & Westminster Hospital

21. Dr Ashish Paul, Medical Director, Bedfordshire PCT

22. Dr Sarah Purdy, Consultant Senior Lecturer, University of Bristol

23. Professor Yit Chiun Yang, Consultant Ophthalmologist, Royal Wolverhampton Hospitals NHS Trust

1. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

2. Dr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council

3. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

4. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Pharmaceuticals Panel

1. Professor in Child Health, University of Nottingham

2. Senior Lecturer in Clinical Pharmacology, University of East Anglia

3. Dr Martin Ashton-Key, Medical Advisor, National Commissioning Group, NHS London

4. Mr John Chapman, Public contributor

5. Dr Peter Elton, Director of Public Health, Bury Primary Care Trust

6. Dr Peter Elton, Director of Public Health, Bury Primary Care Trust

7. Dr Ben Goldacre, Research Fellow, Division of Psychological Medicine and Psychiatry, King’s College London

8. Dr James Gray, Consultant Microbiologist, Department of Microbiology, Birmingham Children’s Hospital NHS Foundation Trust

9. Ms Kylie Gyertson, Oncology and Haematology Clinical Trials Manager, Guy’s and St Thomas’ NHS Foundation Trust London

10. Dr Jurjees Hasan, Consultant in Medical Oncology, The Christie, Manchester

11. Dr Carl Heneghan Deputy Director Centre for Evidence-Based Medicine and Clinical Lecturer, Department of Primary Health Care, University of Oxford

12. Dr Dyfrig Hughes, Reader in Pharmacoeconomics and Deputy Director, Centre for Economics and Policy in Health, IMSCaR, Bangor University

13. Dr Maria Kouimtzi, Pharmacy and Informatics Director, Global Clinical Solutions, Wiley-Blackwell

14. Professor Femi Oyebode, Consultant Psychiatrist and Head of Department, University of Birmingham

15. Dr Andrew Prentice, Senior Lecturer and Consultant Obstetrician and Gynaecologist, The Rosie Hospital, University of Cambridge

16. Ms Amanda Roberts, Public contributor

17. Dr Martin Shelly, General Practitioner, Silver Lane Surgery, Leeds

18. Dr Gillian Shepherd, Director, Health and Clinical Excellence, Merck Serono Ltd

19. Mrs Katrina Simister, Assistant Director New Medicines, National Prescribing Centre, Liverpool

20. Professor Donald Singer Professor of Clinical Pharmacology and Therapeutics, Clinical Sciences Research Institute, CSB, University of Warwick Medical School

21. Mr David Symes, Public contributor

22. Dr Arnold Zermansky, General Practitioner, Senior Research Fellow, Pharmacy Practice and Medicines Management Group, Leeds University

1. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

2. Mr Simon Reeve, Head of Clinical and Cost-Effectiveness, Medicines, Pharmacy and Industry Group, Department of Health

3. Dr Heike Weber, Programme Manager, Medical Research Council

4. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

5. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Psychological and Community Therapies Panel

1. Professor of Psychiatry, University of Warwick, Coventry

2. Consultant & University Lecturer in Psychiatry, University of Cambridge

3. Professor Jane Barlow, Professor of Public Health in the Early Years, Health Sciences Research Institute, Warwick Medical School

4. Dr Sabyasachi Bhaumik, Consultant Psychiatrist, Leicestershire Partnership NHS Trust

5. Mrs Val Carlill, Public contributor

6. Dr Steve Cunningham, Consultant Respiratory Paediatrician, Lothian Health Board

7. Dr Anne Hesketh, Senior Clinical Lecturer in Speech and Language Therapy, University of Manchester

8. Dr Peter Langdon, Senior Clinical Lecturer, School of Medicine, Health Policy and Practice, University of East Anglia

9. Dr Yann Lefeuvre, GP Partner, Burrage Road Surgery, London

10. Dr Jeremy J Murphy, Consultant Physician and Cardiologist, County Durham and Darlington Foundation Trust

11. Dr Richard Neal, Clinical Senior Lecturer in General Practice, Cardiff University

12. Mr John Needham, Public contributor

13. Ms Mary Nettle, Mental Health User Consultant

14. Professor John Potter, Professor of Ageing and Stroke Medicine, University of East Anglia

15. Dr Greta Rait, Senior Clinical Lecturer and General Practitioner, University College London

16. Dr Paul Ramchandani, Senior Research Fellow/Cons. Child Psychiatrist, University of Oxford

17. Dr Karen Roberts, Nurse/Consultant, Dunston Hill Hospital, Tyne and Wear

18. Dr Karim Saad, Consultant in Old Age Psychiatry, Coventry and Warwickshire Partnership Trust

19. Dr Lesley Stockton, Lecturer, School of Health Sciences, University of Liverpool

20. Dr Simon Wright, GP Partner, Walkden Medical Centre, Manchester

1. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

2. Dr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council

3. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

4. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Expert Advisory Network

1. Professor Douglas Altman, Professor of Statistics in Medicine, Centre for Statistics in Medicine, University of Oxford

2. Professor John Bond, Professor of Social Gerontology & Health Services Research, University of Newcastle upon Tyne

3. Professor Andrew Bradbury, Professor of Vascular Surgery, Solihull Hospital, Birmingham

4. Mr Shaun Brogan, Chief Executive, Ridgeway Primary Care Group, Aylesbury

5. Mrs Stella Burnside OBE, Chief Executive, Regulation and Improvement Authority, Belfast

6. Ms Tracy Bury, Project Manager, World Confederation of Physical Therapy, London

7. Professor Iain T Cameron, Professor of Obstetrics and Gynaecology and Head of the School of Medicine, University of Southampton

8. Professor Bruce Campbell, Consultant Vascular & General Surgeon, Royal Devon & Exeter Hospital, Wonford

9. Dr Christine Clark, Medical Writer and Consultant Pharmacist, Rossendale

10. Professor Collette Clifford, Professor of Nursing and Head of Research, The Medical School, University of Birmingham

11. Professor Barry Cookson, Director, Laboratory of Hospital Infection, Public Health Laboratory Service, London

12. Dr Carl Counsell, Clinical Senior Lecturer in Neurology, University of Aberdeen

13. Professor Howard Cuckle, Professor of Reproductive Epidemiology, Department of Paediatrics, Obstetrics & Gynaecology, University of Leeds

14. Professor Carol Dezateux, Professor of Paediatric Epidemiology, Institute of Child Health, London

15. Mr John Dunning, Consultant Cardiothoracic Surgeon, Papworth Hospital NHS Trust, Cambridge

16. Mr Jonothan Earnshaw, Consultant Vascular Surgeon, Gloucestershire Royal Hospital, Gloucester

17. Professor Martin Eccles, Professor of Clinical Effectiveness, Centre for Health Services Research, University of Newcastle upon Tyne

18. Professor Pam Enderby, Dean of Faculty of Medicine, Institute of General Practice and Primary Care, University of Sheffield

19. Professor Gene Feder, Professor of Primary Care Research & Development, Centre for Health Sciences, Barts and The London School of Medicine and Dentistry

20. Mr Leonard R Fenwick, Chief Executive, Freeman Hospital, Newcastle upon Tyne

21. Mrs Gillian Fletcher, Antenatal Teacher and Tutor and President, National Childbirth Trust, Henfield

22. Professor Jayne Franklyn, Professor of Medicine, University of Birmingham

23. Mr Tam Fry, Honorary Chairman, Child Growth Foundation, London

24. Professor Fiona Gilbert, Consultant Radiologist and NCRN Member, University of Aberdeen

25. Professor Paul Gregg, Professor of Orthopaedic Surgical Science, South Tees Hospital NHS Trust

26. Bec Hanley, Co-director, TwoCan Associates, West Sussex

27. Dr Maryann L Hardy, Senior Lecturer, University of Bradford

28. Mrs Sharon Hart, Healthcare Management Consultant, Reading

29. Professor Robert E Hawkins, CRC Professor and Director of Medical Oncology, Christie CRC Research Centre, Christie Hospital NHS Trust, Manchester

30. Professor Richard Hobbs, Head of Department of Primary Care & General Practice, University of Birmingham

31. Professor Alan Horwich, Dean and Section Chairman, The Institute of Cancer Research, London

32. Professor Allen Hutchinson, Director of Public Health and Deputy Dean of ScHARR, University of Sheffield

33. Professor Peter Jones, Professor of Psychiatry, University of Cambridge, Cambridge

34. Professor Stan Kaye, Cancer Research UK Professor of Medical Oncology, Royal Marsden Hospital and Institute of Cancer Research, Surrey

35. Dr Duncan Keeley, General Practitioner (Dr Burch & Ptnrs), The Health Centre, Thame

36. Dr Donna Lamping, Research Degrees Programme Director and Reader in Psychology, Health Services Research Unit, London School of Hygiene and Tropical Medicine, London

37. Professor James Lindesay, Professor of Psychiatry for the Elderly, University of Leicester

38. Professor Julian Little, Professor of Human Genome Epidemiology, University of Ottawa

39. Professor Alistaire McGuire, Professor of Health Economics, London School of Economics

40. Professor Neill McIntosh, Edward Clark Professor of Child Life and Health, University of Edinburgh

41. Professor Rajan Madhok, Consultant in Public Health, South Manchester Primary Care Trust

42. Professor Sir Alexander Markham, Director, Molecular Medicine Unit, St James’s University Hospital, Leeds

43. Dr Peter Moore, Freelance Science Writer, Ashtead

44. Dr Andrew Mortimore, Public Health Director, Southampton City Primary Care Trust

45. Dr Sue Moss, Associate Director, Cancer Screening Evaluation Unit, Institute of Cancer Research, Sutton

46. Professor Miranda Mugford, Professor of Health Economics and Group Co-ordinator, University of East Anglia

47. Professor Jim Neilson, Head of School of Reproductive & Developmental Medicine and Professor of Obstetrics and Gynaecology, University of Liverpool

48. Mrs Julietta Patnick, Director, NHS Cancer Screening Programmes, Sheffield

49. Professor Robert Peveler, Professor of Liaison Psychiatry, Royal South Hants Hospital, Southampton

50. Professor Chris Price, Director of Clinical Research, Bayer Diagnostics Europe, Stoke Poges

51. Professor William Rosenberg, Professor of Hepatology and Consultant Physician, University of Southampton

52. Professor Peter Sandercock, Professor of Medical Neurology, Department of Clinical Neurosciences, University of Edinburgh

53. Dr Philip Shackley, Senior Lecturer in Health Economics, Sheffield Vascular Institute, University of Sheffield

54. Dr Eamonn Sheridan, Consultant in Clinical Genetics, St James’s University Hospital, Leeds

55. Dr Margaret Somerville, Director of Public Health Learning, Peninsula Medical School, University of Plymouth

56. Professor Sarah Stewart-Brown, Professor of Public Health, Division of Health in the Community, University of Warwick, Coventry

57. Dr Nick Summerton, GP Appraiser and Codirector, Research Network, Yorkshire Clinical Consultant, Primary Care and Public Health, University of Oxford

58. Professor Ala Szczepura, Professor of Health Service Research, Centre for Health Services Studies, University of Warwick, Coventry

59. Dr Ross Taylor, Senior Lecturer, University of Aberdeen

60. Dr Richard Tiner, Medical Director, Medical Department, Association of the British Pharmaceutical Industry

61. Mrs Joan Webster, Consumer Member, Southern Derbyshire Community Health Council

62. Professor Martin Whittle, Clinical Co-director, National Co-ordinating Centre for Women’s and Children’s Health, Lymington