The acceptability and feasibility of a randomised controlled trial of serial prophylactic exchange blood transfusion (SPEBT) versus usual care in pregnant women with SCD. A qualitative study with recommendations for recruitment strategies for a future definitive trial

The acceptability and feasibility of a randomised controlled trial of serial prophylactic exchange blood transfusion (SPEBT) versus usual care in pregnant women with SCD. 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A qualitative study with recommendations for recruitment strategies for a future definitive trial Laura L Oakley, Clare McDemott, Vicky Robinson, Jeannine Joseph, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6577176/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 18 You are reading this latest preprint version Abstract Background: Pregnancy in women living with sickle cell disease (SCD) is associated with increased risk of morbidity and mortality for mother and baby. Outside of pregnancy, serial prophylactic exchange blood transfusion (SPEBT) has proven efficacy as a treatment for acute SCD complications, however, there is inadequate evidence for the safety and benefit for SCD during pregnancy. Aim: To explore health professionals and women’s view on the acceptability and feasibility of a randomised control trial of SPEBT versus usual care in pregnant women with SCD. Methods: Semi-structured telephone interviews were conducted with TAPS2 trial participants, trial decliners and clinical staff working on the TAPS2 trial. Interviews were analysed using reflexive thematic analysis . Results: We interviewed 19 trial participants, 12 trial decliners and 15 clinical staff. Three overarching themes were identified; (1) factors affecting patient decisions on participation; (2) experiences of the TAPS2 trial; and (3) recommendation for a future RCT. (1) Motivations for participation included hope that SPEBT would lead to a healthier pregnancy, and/or help other women with SCD. Factors deterring women from participating included concerns about SPEBT, e.g. perceived risk of infections, side effects, or transfusion reactions. (2) Participants allocated to SPEBT recounted health benefits as well as ‘expected’ side effects. The time and cost involved in attending transfusion sessions had been difficult for some patients. For staff at some sites, pressures on local apheresis capacity made delivering the intervention challenging. (3) Participants offered suggestions to improve recruitment and delivery for a definitive trial. Recommendations included: providing accessible, evidenced-based patient education to patients, partners and families to enable informed decision-making. There was strong support for including an observational arm in any future trial to enable patients unwilling, or unable, to be randomised to take part. Conclusion: Addressing pregnant SCD women’s treatment concerns and preferences is key to maximising recruitment/retention in future trials. Addressing information gaps or misinformation through accessible patient education is needed. Including an observational study arm as part of a future definitive RCT, along with other highlighted strategies, will ensure that the evidence base and understanding of clinical outcomes in pregnant women with SCD is maximised for future research. Trial registration : NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19) Sickle cell disease pregnancy serial prophylactic exchange blood transfusions qualitative feasibility trial recruitment barriers patient decision-making treatment preferences Figures Figure 1 BACKGROUND Sickle cell disease (SCD) is the most common inherited disease worldwide, characterised by anaemia, intermittent painful vaso-occlusive crisis (commonly known as ‘crises’) and chronic complications including chronic lung disease, sickle renal disease, stroke and pulmonary hypertension.[ 1 ] In SCD, abnormal haemoglobin (‘sickle’ Hb) in red blood cells makes them becomes hard and sticky, in the shape of a ‘sickle’ and unable to properly carry oxygen around the blood. This causes the associated symptoms. In high income and some middle-income countries, the majority of children born with SCD will survive to adulthood,[ 2 ] and have a good expectation of having their own families. In the UK, approximately 110 pregnancies occur annually in women living with SCD.[ 3 ] Pregnancy in women living with SCD is high risk, associated with increased risk of perinatal and maternal morbidity and mortality.[ 4 – 8 ] Pregnancy also exacerbates SCD-related complications such as anaemia, painful crisis, pulmonary complications, and infection.[ 3 , 8 ] There are very limited treatment options for pregnant women with SCD. In the UK, standard care only consists of blood transfusion when clinically indicated.[ 4 , 9 ] Available current disease-modifying treatments during pregnancy are not recommended.[ 10 ] When blood transfusions are clinically required, they can be given as a simple top-up transfusion, which, whilst improving oxygen carriage around the body, can potentially cause hyperviscosity and iron overload. Alternatively, pregnant women living with SCD can be offered exchange blood transfusion where their own red blood cells (RBC) are removed and replaced with healthy RBC from donors. Exchange transfusions can be done either manually or automatically, using a machine. Where transfusions need to be done on a long-term basis, automated serial prophylactic exchange blood transfusion (SPEBT) is the preferred approach. Exchange blood transfusion are more effective in reducing the percentage of sickle Hb than top up transfusions, and therefore better at reducing the risk of acute SCD complications.[ 11 , 12 ] Outside of pregnancy, serial prophylactic exchange blood transfusion (SPEBT) has proven efficacy as a treatment for acute SCD complications, and for the prevention of pain, acute chest syndrome and strokes in people with SCD. However, there is inadequate evidence for the safety and benefit of SPEBT for SCD during pregnancy.[ 13 ] There have been repeated calls for a definitive randomised controlled trial (RCT) to establish the effectiveness of SPEBT in pregnancy.[ 13 , 14 ] We conducted a multi-centre randomised feasibility trial of SPEBT versus usual care in pregnant women with SCD (TAPS2) to assess the feasibility and acceptability of conducting a definitive RCT of SPEBT in pregnancy. The protocol, analysis plan and feasibility RCT findings have previously been published. [ 15 – 17 ] In TAPS2, participants were randomised to either SPEBT or usual care; with maternal and neonatal outcomes recorded up to 4 weeks post-partum. In summary, 35 participants were recruited (39.8% of those eligible); 18 participants were randomised to intervention, and 17 to usual care, with 100% follow up data achieved. The results confirmed it was feasible to perform a definitive RCT, with satisfactory rates of recruitment and retention. Although not powered to compare outcomes, positive trends in some maternal, infant and postnatal outcomes were identified in the intervention arm. There is increasing recognition of the importance of conducting qualitative research alongside feasibility trials.[ 18 ] We therefore conducted a qualitative study embedded within TAPS2. The primary aim of this qualitative study was to inform the design for a future definitive trial. METHODS An embedded qualitative study was conducted within the multi-centre feasibility RCT assessing SPEBT versus usual care in pregnant women with SCD. Study setting and participant recruitment Participants for the qualitative study were recruited from the same seven NHS hospitals in the UK recruiting patients for the feasibility RCT.[ 17 ] We invited three groups of participants involved in the TAPS2 feasibility RCT to participate in the qualitative study: trial participants, women who were eligible for the trial but declined to participate (‘decliners’), and clinicians and research staff involved in delivering the trial. All potential participants were provided with an information sheet and a consent form and the opportunity to ask questions. Trial participants and clinical/research staff who provided written informed consent were purposively sampled to ensure a maximum variation sample across key characteristics (Box 1). We aimed to interview all the decliners who provided informed written consent. Trial participants Staff participants • Study site • Treatment allocation: intervention/usual care • Trial status: completers/drop outs • Pregnancy number: 0/≥1 • SCD genotype: SS/SC/other • Disease severity: SCD-related hospital admission in last year yes/no • History of transfusion • Study site • Staff role: clinical role (consultant obstetrician, consultant haematologist)/staff involved in recruitment (research midwife, sickle cell nurse research practitioner) Box 1: Sampling characteristics Data collection Semi-structured interviews were conducted by telephone (LO and SB) with study participants. Face-to-face interviews were not feasible due to the ongoing Covid pandemic. Informed consent was re-sought verbally prior to the interviews commencing. All interviews were recorded using an encrypted audio recording device. Interviews with trial participants were conducted at 6–8 weeks post-partum; interviews with decliners were conducted within eight weeks of providing consent; and interviews with trial staff were conducted near the end of, or after, the recruitment phase ended at their site, ensuring participants had adequate time for reflection. Separate interview topic guides were developed for each participant group by SB and LO, with input from patient contributors and clinicians. Initial interviews for each group were used to pilot and refine the wording of the questions. Consistent with an inductive qualitative approach, new topics arising during interviews were added to the topic guide. Interviews explored the following topics, dependant on the participant group as shown in Box 2. Participant group/ Topic questions Trial Participants Decliners Staff Views on the Acceptability of the trial intervention ✓ ✓ ✓ Experiences of trial recruitment processes ✓ ✓ ✓ Reasons for declining participation N/A ✓ N/A Experiences of taking part in the trial including randomisation and study conduct ✓ N/A ✓ Experiences of receiving the trial intervention ✓ (Only trial participants randomised to SPEBT) N/A N/A Experience of delivering the trial intervention N/A N/A ✓ (relevant clinical staff only) Views on future research including recommendations for improving recruitment ✓ ✓ ✓ Box 2: Topic questions per participant group The final topic guides are included as supplementary material [Additional file 1, trial participants; Additional file 2, decliners; and Additional file 3, staff]. Given the study aims, the proposed sample sizes were not aimed to achieve data saturation, rather to elicit a diversity of views through the use of maximum variation sampling approach for staff and trial participants. We aimed to interview 15–25 trial participants; 5–15 decliners; and 15–20 trial staff (two to three staff considered ‘key informants’ in each study site). The study was conducted by three female post-doctoral researchers (SB, LO and CM) with > 10 years research experience, based in medical research departments in two UK universities. SB and LO conducted the interviews, CM led the data analysis with input from SB and LO. All were involved in the write-up. None of the patients were known to the researchers before this study. Some staff interviewees were known to SB and LO prior to interview from earlier stages in the TAPS2 trial, but none were known to CM. Analysis Trial participant and staff interviews were transcribed verbatim, and anonymised transcripts uploaded onto NVivo version 13 for data management and coding (LO, SB and CM). These interviews were analysed by CM using reflexive thematic analysis,[ 19 ] using the constant comparison approach to compare data within and across individual interviews to identify themes and subthemes. Trial participant interviews were analysed for themes and subthemes, with additional subgroup analyses to identify any different patterns emerging, including intervention vs control; trial completers vs patients who withdrew; different illness severity levels; different SCD genotypes; patients with and without prior experience of transfusion; previous pregnancy history and across different trial sites. Staff interviews were analysed for themes and subthemes. A site-by-site analysis was then carried using the mixed-methods matrix approach. [ 18 , 20 ]This enabled us to synthesise the quantitative screening/recruitment data, with the qualitative data from each site. Decliner interviews were not transcribed nor formally analysed. Rather, data was extracted (SB) through repeated listening of the audio files and summarised in tables to report their reasons for declining, suggestions to improve recruitment and study design for the definitive trial. Illustrative anonymised key quotes were transcribed verbatim by SB. No subgroup analysis was conducted due to limited sample size and data. Findings across the three participant groups were then mapped onto key themes and sub-themes. Standard methods were employed to ensure rigour (e.g. through the use of audit trail, reflexive diaries, double coding and deviant case analysis). Illustrative anonymised quotes are reported to support themes and subthemes for the data corpus. RESULTS Participant characteristics Figure 1 reports the study flow of participant recruitment. All but one (n = 34) trial participants consented to be contacted for interview. To ensure balance in sampling characteristics, after completing 14 interviews we reviewed participant characteristics and thereafter prioritised interviewing participants with underrepresented characteristics. Eighteen interviews were conducted by telephone (11 participants allocated to intervention, and seven to usual care) with one interview by email, at the participant’s request. Interviews were completed between May 2020 and August 2022, and the mean duration of telephone interviews was 22 minutes (range: 10– 64 minutes). Twenty-four decliners consented to the qualitative study, of which 12 were interviewed from four study sites. Interviews completed between May 2020 and October 2022. The mean interview duration for decliner interviews was 12 minutes (range: 5–22 minutes). For staff interviews, we screened all 30 eligible staff and identified 17 priority interviews based on capturing a range of staff characteristics. Fifteen staff interviews were completed across all seven study sites. Staff interviews took place between July 2022 and November 2022. The mean interview duration was 29 minutes (range: 16–51 minutes). In total, we conducted 46 interviews, with our recruitment target met for all three participant groups. Full details of participant recruitment are presented in Fig. 1. We achieved a maximum variation sample for key characteristics for the trial participants (Table 1), and staff interviews (Table 2) as planned, within the trial constraints. Table 1 Sampling characteristics for trial participants (N = 19) Characteristic N Treatment allocation Intervention Usual care 11 8 Trial status Completer Drop out 16 3 Study site* 1 2 3 4 5 6 7 6 2 5 0 5 1 0 Pregnancy number 0 > = 1 10 9 Hospital admission in the year prior to pregnancy Yes No 6 13 Crises in the year prior to pregnancy Yes No 11 8 Genotype HbSS 1 HbSC 2 Other 10 8 1 Self-reported transfusion history at RCT enrolment None Top-up only Exchange only Top-up and exchange Not known 9 4 1 4 1 *Participants recruited to RCT by study site:1 (n = 11), 2 (n = 1), 3 (n = 7), 4 (n = 7), 5 (n = 7), 6 (n = 2), 7 (n = 0) 1 HbSS = homozygous sickle cell 2 HBSc = Haemoglobin Sickle C disease Table 2 Sampling characteristics for staff (N = 15) Characteristic N Staff Role Consultant obstetrician Consultant haematologist Research Midwife Research Nurse Clinical Research Practitioner 3 4 5 1 2 Study site 1 2 3 4 5 6 7 3 2 2 2 2 2 2 Findings The finding reports the combined data from the interviews with 19 trial participants, 12 decliners and 15 staff participants. We identified three overarching themes: (1) Factors affecting patient decisions on taking part in the trial; (2) experiences of the TAPS2 trial; (3) recommendation for a future RCT. Each theme incorporated several subthemes summarised in Table 3. For Themes 1 and 3, we considered data from trial participants, decliners and staff, using these three datasets to explore and illuminate the issues, providing triangulation of findings. Theme 2 related to trial participants and staff only. Illustrative verbatim quotations from the interviews are reported in the text. TABLE 3: KEY FINDINGS Key findings Trial participants Decliners Staff Theme 1. Factors affecting patient decision-making on trial participation Positive motivations for trial participation Hope of benefit to their own health ✓ Decliners wanted to help others with SCD but not to receive transfusions Staff reported hearing these motivations from patients Benefit to the pregnancy and their baby’s health ✓ As above As above Wish to support research for the benefit for others with SCD ✓ As above As above Concerns about SPEBT Risk of Infection ✓ ✓ Staff reported that patients expressed these concerns about transfusions. Risk of being given the wrong blood ✓ ✓ As above Other adverse reactions ✓ ✓ As above Concern that SPEBT could trigger sickle crises ✓ ✓ As above Fear of SPEBT causing problems in current pregnancy if not needed in previous pregnancy ✓ ✓ As above Concerns about cannulation ✓ ✓ As above Cultural stigma around receiving blood X X Cultural stigma was mentioned by one clinician but not by any patients Perceptions of the benefit or relevance of SPEBT to participants Benefits to mother ✓ Decliners felt that either their SCD was too mild to need SPEBT, or it was not worth the risks ✓ Benefit to baby ✓ As above ✓ Reduction in sickle crises ✓ As above ✓ - Weighing up risk vs benefits of SCD Severity of SCD affects perceptions of risk vs benefits ✓ As above ✓ Women with milder SCD less likely to view SPEBT as relevant or beneficial to themselves ✓ As above ✓ Partner or family influence on perceptions of transfusions Influence of family in patient’s decision to take part (or not) ✓ ✓ ✓ Role of partner in decision ✓ ✓ ✓ Importance of a good patient-clinician relationship ✓ ✓ ✓ Some women of colour might feel less trusting of a white healthcare professional X X Reported by one clinician Trial Burden Time, cost and effort of travel, arranging childcare or time off work ✓ ✓ ✓ Participation could place an additional burden on women already coping with pressures of SCD, work and/or caring for other children. ✓ ✓ ✓ Theme 2. Experiences of trial -Recruitment process- patient’s experiences No significant concerns were highlighted by patients regarding their experience of the recruitment process ✓ ✓ These findings concurred with staff reports of feedback from patients to them Recruitment materials appeared generally acceptable to patients, although one participant suggested including more pictures and visual aids to improve readability ✓ ✓ As above Recruitment process - staff experiences Recruiting staff reported challenges in identifying eligible women and completing all entry criteria early enough in pregnancy to enrol the patient into the trial before six weeks gestation (the recruitment cut off point). N/R N/R ✓ At some sites with linguistically diverse populations, need for translation had presented difficulties N/R N/R ✓ Outcome measures – patient reported outcome measures Questionnaires appeared generally acceptable to all trial participants ✓ N/R Research staff confirmed general acceptability of questionnaires to patients Trial participants suggested including additional outcomes focussing on impact of SCD on employment, and mothers’ perceptions of how pregnancy was going ✓ As above As above Control group experiences Trial participation was acceptable and not burdensome ✓ N/R ✓ Participants experiences of SPEBT during the trial - Positive experiences of SPEBT . Benefits included more energy, less pain, reduction or stopping of crisis for some women, fewer hospitalisations, a sense of ‘feeling better in myself’ or an overall sense the current pregnancy was going better than previous pregnancies ✓ N/R ✓ - Negative experiences of SPEBT Side effects (dizziness, pins and needles, headaches and one report of citrate toxicity) ✓ N/R ✓ Issues with cannulation ✓ N/R ✓ Effort/cost of attending appointments. ✓ N/R ✓ Reasons for patients withdrawing from trial All three patients who withdrew had hoped to be allocated to usual care but had been randomised to SPEBT ✓ N/R Reasons for withdrawals not mentioned in staff interviews One began transfusions but withdrew from the trial after difficulties in cannulation ✓ N/R As above Theme 3. Improving recruitment and trial experiences for future trials Improving trial recruitment- recommendations Raising awareness of: § the effects of pregnancy on SCD § potential benefits of SPEBT § the TAPS2 trial findings ✓ ✓ ✓ N/R ✓ ✓ ✓ Raising awareness through social media, internet websites and posters in hospitals ✓ N/R ✓ Recruitment information needs to be: § easy to understand, e.g. using visuals/ videos to increase accessibility § accessible to partners & family § available earlier in pregnancy if possible ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ Value of video peer testimonies ✓ N/R ✓ Staff recommended raising wider awareness among clinical colleagues through existing clinical networks N/R N/R ✓ Improving trial experiences and conduct – key recommendations Support with childcare and travel costs to attend trial appointments ✓ N/R ✓ Providing pre-transfusion advice to patients on how to reduce issues with venous access ✓ N/R N/R Adding outcome measures on impact on employment, and on how the mother herself felt that the pregnancy was going. ✓ N/R X Ensuring adequate apheresis capacity, for example through additional funding or ringfencing resources. N/R N/R ✓ Future study design Clear support from all interviewees to include an observational study arm to the design of a future trial for women who do not want to be randomised, or ineligible for the trial. ✓ ✓ ✓ √ indicates finding supported by data from this interviewee group X indicates that issue was not mentioned by this interviewee group N/R : Question/s were not relevant to participant group so no response is recorded SCD : Sickle cell disease SPEBT : Serial prophylactic exchange blood transfusion TAPS2 : The ‘ T ransfusion A ntenatally in P regnant Women with S ickle Cell Disease study’: See reference 15: Prophylactic exchange transfusion in sickle cell disease pregnancy: a TAPS2 feasibility randomized controlled trial Theme 1. Factors affecting patient decision-making on trial participation Positive motivations for trial participation Trial participants were motivated to take part in the trial for three reasons; hope of benefit to their own health, benefit to their pregnancy and their baby’s health, or wish to support research to benefit others with SCD. Just because all the pros that were explained to me and obviously it would help the baby out, so I just wanted to do what was best, just to help my baby and myself… And just get through the pregnancy easier. (Trial participant 3, intervention arm, completer ) Taking part in the trial was also seen to offer health benefits either directly, through receiving transfusions, or from additional clinical time and attention. Staff concurred that a desire to help others with SCD was a key factor for many women in their decision to participate. Both patients and staff perceived SCD as an under-researched and neglected condition. Within this context, the trial could increase public awareness of SCD as well as potentially finding better treatments for SCD during pregnancy. So, I know there is little research about this whole issue, sorry, I know there is not enough support for people like that, so I thought the research might, you know, enable help the government either to put in more like, you know, support and everything to lots of people, especially when you get to the hospital and you are in crisis or something and you have no support, because people around don't really understand or know what to do with you. (Trial participant 12, control arm, completer) Views on blood transfusions Patients’ views on blood transfusions emerged as a key determinant in whether they chose to take part in the trial. Among the trial participants interviewed, four expressed a preference to be allocated to SPEBT, four preferred usual care and the remainder expressed no preference or were uncertain. Preference for SPEBT At the time I was hoping that I had luck and the computer would have chosen me to have the [blood] exchanges because I just couldn't, I just couldn't imagine going through the pregnancy with many more crises which I thought in turn would affect how the baby grew. (Trial participant 2, intervention arm, completer) No preference I did not mind which group I was assigned to because being a part of the study I was still being monitored closely during my pregnancy and I felt assured that whichever group I ended up in that I would be receiving the best needed treatment. It was never a concern that I would end up in a group and not get the needed transfusions or care I needed. (Trial participant 18, control group, completer) Preference for usual care I definitely preferred not to be in the transfusion group because I just thought it was slightly less onerous. (Trial participant 10, intervention arm, drop out) Staff interviewees also perceived that the main barrier to recruitment had been patient reluctance to receive transfusions, and the importance of this concern was supported by triangulation of evidence from staff, trial participant, and decliner data. For those patients reluctant to receive transfusions, perceptions that SPEBT might involve risk of harm was a common concern. Concerns about SPEBT Concerns about harm from transfusions centred on risk of infection (either through the cannulation site or through contaminated blood), risk of being given the wrong blood, or other adverse reactions. I was more worried you know like in the past it has been in the news that people are being given...the wrong blood…And infected blood and things like that… (Trial participant 9, intervention arm, completer) Whether [transfusion] would be safe for me and my baby as well or not.. I was worried about the infections and all like that. (Trial participant 15, intervention arm, dropped out of trial immediately after randomisation) One woman who declined the trial expressed concerns that SPEBT could trigger a sickle crisis. I don’t have too many crisis, twice or three times [ a year], so take old blood out and put new blood …. maybe that is going to cause some crises (Decliner, Participant 10) Staff also reported that risk from transfusion, especially blood safety, was a concern for many patients. Several clinicians observed that where patients had a cultural background and/or personal experiences in other countries where HIV rates were high, this could heighten awareness of the risks of infected blood. If you have an Afro Caribbean background, it’s like, is it safe? Has the blood been screened? Could you get an infection from HIV?… Some of them might be wary about it. Like gosh, people with a sickle cell from an Afro Caribbean background, like basically they are needing that reassurance. (Research Midwife, Staff interview 8) Some women expressed more general fears that starting a new intervention could adversely affect their pregnancy. One participant, who had three previous failed pregnancies, explained that she did not want additional interventions which she could later regret if she lost this baby. It was interesting to note that for this participant, the decision to avoid SPEBT was perceived as a safer choice, despite past pregnancies having ended in miscarriage. One of the reasons I decided to not take part as I didn't know if it has any risks or adverse effects based on some of the challenges, I have had in trying to get pregnant... this is my fourth pregnancy and I don't have a child yet... I had miscarriages and a termination too and this is an IVF... since everything is going on well, I don't want to have regrets…. this one looks like it’s going well so why don't we let it be.. and not do external stuff that might affect it (Decliner, interview 1) Where women had already experienced a successful pregnancy, their reluctance to receive transfusions was linked to fear of causing new problems and less successful outcomes for their current pregnancy. Clinicians had observed similar concerns among patients. It's such a big thing. They may never have had a transfusion before, had children before and not needed one so they couldn't understand why it was a good idea to do it. (Research Midwife, Staff interview 1) Some participants who had not had blood transfusion before were apprehensive about the transfusion procedure, particularly cannulation. Concerns about cannulation I cannot remember what they said about the veins, like it can get injured or something like that. I cannot remember. So I was kind of scared about that. (Trial participant 9, intervention arm, completer) Having a femoral line (a cannula for transfusion inserted into the femoral vein in the thigh) was a particular concern for some women. Well it was going through the vein, but it was going like near my groin, so if I was just a bit worried about that because obviously it's going in [there] like. (Trial participant 19, intervention arm, completer) Clinicians also reflected on patient concerns about transfusions, acknowledging that this was a complex issue due to the interplay between actual, current clinical risks, and myths or misapprehensions (e.g. based on times in the past when blood safety procedures had been less rigorous). One clinician, a haematologist, also reflected on the paradoxical nature of recruiting patients for regular SPEBT as part of a trial, when they routinely advised patients to be wary of unnecessary transfusions. I mean we spend a lot of time as haematologists saying "don't let those other doctors transfuse you if you don't need it". You know, "don't have an unnecessary transfusion, transfusions can be risky if they're not matched properly" and then we're saying "alright we want you to have a transfusion as part of this trial...‘You're fine, the baby's fine, we're not doing it to save your life, it kind of is a bit against a lot of the messages we give patients.’ (Consultant Haematologist, Staff interview 6) All clinicians reflected on the complexity for their patients in balancing the potential risks and benefits from SPEBT, and the importance of supporting women in making their own choice on what was best for themselves and their baby. However, the key role of patient education emerged as an important finding within clinician interviews, from observing how patient concerns could be exacerbated by out-dated information or myths about transfusion safety. This issue is discussed in detail in Theme 3. Feedback on improving recruitment. For patients trying to weigh up the risks vs benefits of SPEBT for their pregnancy, possible benefits from SPEBT presented the other side of the risk-benefit equation. Perceptions of the benefit or relevance of SPEBT to participants Perceptions of benefit from transfusions tended to relate to a participant’s perception of the severity of their SCD. Some women with a history of frequent and painful sickle crises explained that they specifically wanted transfusions to reduce the number of crises they might experience during their pregnancy. In contrast, several of the women with milder SCD saw no potential benefits from SPEBT since they were feeling well without transfusions. These included women with mild SCD experiencing their first pregnancy, as well as women who had previously had successful pregnancies without requiring transfusions. I have 2 kids and did not need any transfusions and I did not want to risk it this time. (Decliner, interview 3) The value of blood transfusions as a resource was commented on by several women with mild SCD who declined participation, expressing concerns that if they received transfusions this would waste blood which could be used for patients who were more severely affected. Blood is very valuable and to someone like me, even though it’s a trial, someone who is probably symptomatic and it could make a difference in their pregnancy, it would be better off for them because I don’t feel like I am a good candidate. (Decliner, interview 12) Staff interviewees also reflected on the difficulties of asking patients with mild SCD to receive SPEBT for the trial. The ones that didn't want to take part either have had a completely normal life and didn't feel that they were sick enough to require intervention anyway, so that was one group that just said, well, you know, my sickle's not a big deal, I'm well, I've got no medical problems, I don't think I want to start having intervention if I don't need it. (Consultant Obstetrician, Staff interview 11) Partner or family influence on perceptions of transfusions Partners and family (including parents and siblings, aunts, and grandparents) could have a major influence on patients’ perceptions of transfusions and decision on whether to join the trial. I come from quite a medical family anyway, I had conversations with my husband, my dad, my mum, my sister and we all had a family conversation about things and the risks. (Trial participant 2, intervention arm, completer) In the staff interviews, recruiters, especially nurses and midwives, discussed ways in which they had been aware that family interactions affected patients’ decisions. Family members could either influence the decision towards or against participation. A couple of times, because I had somebody who came who would have been an ideal candidate… she came with an aunt who said no I don't think you should because we have always had someone with sickle in the family and nobody gets blood and they are fine and equally then I had somebody who came with another family member who said that this is for your benefit, this is for your good and if it makes you better and healthier, then you should have a go with it, just listen to what the doctor is saying to you. (Consultant Obstetrician, Staff interview 13) Staff also reflected on the role of the patient’s partner in decision making; and the difficulty of addressing partner concerns fully when all information about the trial was relayed second-hand via the patient themselves. As one haematologist described, family concerns were especially understandable where there was a known case of fatal complications following transfusion, leading to fears that this could happen again. There are people in the community who have died because of blood transfusions, their reaction to blood and that is in the psyche of the patient population so there is a little bit of nervousness about transfusion which is completely understandable. (Consultant Haematologist, Staff interview 6) Staff also discussed the importance of a good patient-clinician relationship to enable patients to discuss their feelings and concerns. They highlighted the importance of taking time with patients to explain, reassure and educate patients about SCD during pregnancy to empower patients to understand their condition better and make informed decisions. Building rapport and trust was considered essential to this process to reassure the patients that their clinician genuinely wanted the best for them and their baby, rather than simply wanting them to recruit them into the trial. I think you have to get a rapport with when you are trying to recruit, so they trust you. You don't want them to feel like you are using them just for research purposes, that you care about them. (Research Midwife, Staff interview 8) Several clinicians also reflected on ways in which patients’ past experiences might lead to mistrust of clinicians, for example from times where women had felt their condition had been dismissed in the past by clinicians. A lot of [patients] think that this something they have to spend their lives suffering with and because they have been dismissed throughout their life, they don't trust health care workers. (Consultant Obstetrician, Staff interview 13) Issues of race were only briefly mentioned by staff interviewees, and not directly mentioned at all by trial participants or decliners. However, one midwife acknowledged the possibility that some women of colour might feel less trusting of a white health professional than if the recruiting member of staff was themselves a person of colour. From what they told me, things like they didn't have time, they perhaps didn't understand it as much, they didn't like the idea of a blood transfusion, the risks associated with that, partners didn't want, or family members, didn't want them to participate, that came back a few times. But then things they didn't tell me, I do wonder whether the colour of my skin was an issue because I don't have black or brown skin and I just wonder whether that might have been a barrier, but I never asked that question. (Research Midwife, Staff interview 7) Trial burden The practical requirements of participating in the trial were highlighted as an important consideration by trial participants, decliners and staff. These included the time, cost and effort of travel to attend the appointments, especially where it was necessary to arrange childcare or time off work. I would have to come to the hospital more often... if I were sick I would obviously have to come, but I would rather not have to come to hospital where I already have a child, so I would need to look for childcare for the whole day, for the whole process. (Decliner, interview 2) Clinicians reflected that participation could place an additional burden on women who were already coping with the physical and emotional challenges of living with SCD, often combined with pressures of work and/or caring for their other children. It's quite a difficult population to sell another treatment to as they have to endure as much as they do. (Research Midwife, Staff interview 1) Despite the challenges involved, the TAPS2 trial did successfully recruit, and the next theme focuses on the experiences of participation. Theme 2. Experiences of trial Recruitment process None of the trial participants highlighted significant issues regarding their experience of the recruitment process. Recruitment materials appeared generally acceptable to patients, although one participant suggested including more pictures and visual aids to improve readability. Recruiting staff had experienced a range of challenges, including identifying eligible women and completing all entry criteria early enough in pregnancy to enrol the patient into the trial before 18 weeks gestation (the recruitment cut off point). This had been particularly problematic for ‘out of area’ patients if additional patient notes needed to be obtained from their referring clinician. Some recruiting staff worked at hospitals where not all patients could speak English. The need for translation had presented difficulties, since getting family members to translate could lead to uncertainty about whether the translating family member might be influencing a patient’s decision on whether or not to participate. Providing professional translators was not feasible at sites where many different languages could be involved. You've got 200 languages spoken, and women with sickle cell are of African heritage and Caribbean and we have had that so it would take a lot of resource. (Research Midwife, Staff interview 1) Trial questionnaires None of the participants appeared to consider the trial questionnaires difficult to complete. There were a few requests for additional questions to add for any future trial, and these are discussed in Theme 3: Improving recruitment and trial experiences for future trials. Control group experiences For the control group, completion of questionnaires was the only trial procedure extra to their routine clinical care. None felt that participating in the trial had been burdensome. This was in contrast to several participants in the intervention arm who highlighted the time, effort and cost involved in attending for transfusions. Participants experiences of SPEBT during the trial Positive experiences of SPEBT Positive benefits from SPEBT reported by trial participants included; more energy, less SCD-related pain, reduction or stopping of crisis for some women, fewer hospitalisations, a sense of ‘feeling better in myself’ or an overall sense the current pregnancy was going better than previous pregnancies. Because every time I was in the intervention and then we had the results, all my values were really good. …I was feeling good, I didn't have any crises and I wasn't feeling that tired…. so between me and doctors we said, we saw that was working, I didn't have any issues in my pregnancy, so yeah, we saw it was working. (Trial participant 7 intervention arm, completer) Several women reported that improvement in their energy levels following SPEBT had been noticed by their partner. Yes, my husband would always say coming up to the next one that was due, he noticed that I was getting a bit tired and just a bit, you know, stayed in bed a bit more and then said he'd noticed that after a few days after the transfusion, I would perk up again and have a bit more energy and work wise and doing the school run so he could see a pattern. (Trial participant 20, intervention arm, completer) In the staff interviews, clinicians also described seeing health benefits in patients following transfusion. I think definitely in the patients who have lots of admissions to hospital, I've definitely seen, you know, women have good outcomes following, you know, outpatients have said compared to previous pregnancies when they've had the intervention arm, there's a second pregnancy they've been you know, that much better and flown through the pregnancy and they've not had any of the crises, and did not need any emergency transfusions, so I think definitely it does help prevent a lot of those crises and things. (Consultant Haematologist, Staff interview 12) Whilst the interviews highlighted many positive experiences of SPEBT, participants also reported negatives included side effects, issues with cannulation, and the effort/cost of attending appointments. Negative experiences of transfusion Side-effects All side effects mentioned in the interviews by trial participants or staff were within the range of common, anticipated side effects from SPEBT including dizziness, pins and needles and headaches. One participant explained how she had a reaction and felt dizzy and very unwell which was treated with calcium. Staff also recounted examples of negative reactions from transfusions including citrate toxicity. The only side effects we have had were one of the ladies got the toxicity from the citrate, but that is the normal side effect from the transfusion. (Research Nurse, Staff interview 4) Cannulation Cannulation had been painful for some patients, either during the procedure or from painful bruising at the cannulation site afterwards. One trial participant explained the pain from the cannulation made them initially consider leaving the trial, though they had persevered and completed the trial. Cannulas, … it was a new experience for me because I never experienced that…Because it was very painful, I could not bend my hand. And I was beginning to have terrible pain. Because the Nurse insisted like that was the only place she could place it. So it got too much. (Trial participant 9, intervention arm, completer) One participant withdrew from the trial after multiple attempts to put in a line which she had found painful and distressing. For many women, attending transfusion sessions could involve complex plans to arrange care for other children, and/or take time off work, and travel to the outpatient department. It was juggling having a two year old, obviously being pregnant, working and having to fit this in amongst appointments and I had midwife appointments anyway I found [it] hard and then obviously... it was on the Thursday so Thursday was my only day off during the week, which meant I had to then plan child care which I had to pay for because we don't live next to family and on top of paying for child care which was 60/70 pounds a day I then had to obviously pay for my transport to get into London, and my lunch in London. (Trial participant 2, intervention arm, completer) Reasons for patients withdrawing from trial Of the trial participants interviewed, three had withdrawn from the trial before completing. All three had hoped to be allocated to usual care but had been randomised to SPEBT. Two women withdrew before starting SPEBT when they found out they had been allocated to the intervention arm. Another had no strong preference for which trial arm she was allocated, but withdrew from the trial due to experiencing cannulation difficulties; she had multiple unsuccessful cannulations attempts which she found painful and distressing. This time, 20 needles did not work, I was so, it was, at that time I felt like I don't want to go for it, like…I can't tolerate this anymore. I have got bruises and it was so horrible and I had to take some paracetamol for a week. (Trial participant 28, intervention arm, dropped out of trial) Theme 3. Improving recruitment and trial experiences for future trials Trial participants, decliners and staff interviewees were asked for suggestions on improving any future trial of SPEBT. Findings provided two subthemes: recommendations on improving recruitment, and recommendations on improving the experience and/or delivery of the trial itself. Improving trial recruitment To improve recruitment, participants suggested raising general awareness of SPEBT and the clinical trial through increased activity on social media, NHS and charity websites and posters within participating Trusts. This could potentially enable women referred into SCD specialist centres to become aware of the trial, even before being approached by a recruiting clinician. I've been thinking about this and it can be quite intimidating...women have told me this...when they're approached by a health care professional, so would a half-way house be just giving them some information on social media, targeted stuff, things like on posters, first they'll get an idea when they see it around...on Twitter, on Instagram, whatever else they're looking at...TikTok... just to build awareness rather than trying to recruit, that awareness first of all because so many times that I approached women and they had no idea at all a) that we did research, "what, are you allowed to do that on pregnant women?" and then also sickle cell disease as well, so I think building an awareness I think would be a good thing to do. (Research Midwife, Staff interview 7) Staff also recommended raising wider awareness among clinical colleagues through existing clinical networks, such as regional Haemoglobinopathy Coordinating Centres (HCC). All staff interviewees, as well as many trial participants, considered providing high quality, easily understandable information was crucial to support patient’s decision making when assessing the risks and benefits of SPEBT. They suggested including information about: the increased risk of SCD complications during pregnancy; explaining SPEBT including the procedure involved; blood safety and side effects; as well as the potential clinical benefits of SPEBT to pregnant women and their babies. Participants agreed the format of delivering this information was important, particularly highlighting the value of video peer testimonies from patients about their own experiences of transfusion during pregnancy. Hopefully the more the message gets out there and we get involved with user groups. ...I have noticed that people with sickle cell tend to be quite active on social media so anything we can do in that way would be helpful. But yes, I think when we have someone with sickle cell talking [in a video] about it, it is more powerful than somebody like me, because I'm like, for want of a better a term, I'm like from an authoritarian side of things really. Telling them what is all about when I can never know but it is coming across from someone who does know what they are talking about. (Research Midwife, Staff interview 1). Making information openly and easily accessible (e.g. through social media or websites) could enable it to be accessed by partners and families, who can influence patients’ decisions. Making the information accessible to a multi linguistic population through the use of lay language, pictures and videos could also maximise accessibility. I think that (using videos] could be helpful because people learn in different ways, sometimes when there's a lot of information on paper, it can be overwhelming and sometimes just having it broken down visually can be helpful for people that need that, as well (Decliner Participant 11) Several staff suggested that online patient information sessions could incorporate a range of information likely to be of topical interest to patients, as well as information on the trial itself. Improving trial experiences Key recommendations from trial participants to improve any future trial included the need to provide clearer pre-transfusion advice to patients on how to reduce issues with venous access, particularly the need to drink plenty of fluids before the procedure. So I think going forward if they just mention make sure when you come for the appointments give yourself enough time to have a good breakfast, drink lots of fluids because that will really help in terms of being able to get your blood vessels and things... because I was like, ‘Oh OK’. (Trial participant 2, intervention arm, completer) Several trial participants who had to juggle childcare commitments and/or long journeys to the hospital suggested that support with childcare and travel costs would be welcomed in a future trial. Staff interviewees also suggested that helping trial participants with travel expenses would help mitigate trial burden and allow more women to take part. Most participants were happy with the proposed choice of trial outcomes, but several participants suggested the use of additional patient reported outcome measures such as the impact of SCD on a patient’s occupation (e.g. employment or homecare tasks), their experience of transfusion reactions, and the woman’s own perception about how the pregnancy was going. The main recommendation which emerged from staff interviews for any future trial was to find ways to ensure adequate apheresis capacity, for example through additional funding or ringfencing resources. Whilst provision of SPEBT for trial patients had not been an issue at some sites, at others it had felt a major struggle. If there was a big study you would have to look at the funding better, because we've really struggled in terms of staffing over here. We don't have sickle midwives, we don't have a decent size apheresis team, you know, every exchange we've done as part of TAPS2 we've had to scrabble about and beg for people to put lines in, and beg for apheresis to do it, so if we were to take part it would need to be much better funded. (Obstetric Consultant, Staff interview 11). Future study design Shortly after interviews started, the topic guides for participants and decliners were revised to add a question about whether the interviewee would have been willing to take part in a future observational study. This approach would aim to capture outcome data from pregnant women with SCD who did not want to be randomised but were willing to have their data included in research. Among those who were asked about this, there was strong support from trial participants and decliners for this idea. Eleven of the 12 decliners said that they would have participated in the trial if an observational arm was included. I would have happily taken part in the [observational study] and if you had things like questionnaires and focus groups, I would happily be a part in it, but anything that kind of is intrusive, then I wouldn't do it. (Decliner, interview 9) All staff interviewees supported including an observational arm to the trial, with many pointing out this this could capture valuable outcome data from patients which would otherwise be missed. Additionally, this would ensure clinical outcomes could be recorded for the increasing number of women already receiving SPEBT who would be excluded from a future trial, but whose data could contribute to our understanding of how best this intervention can be used to improve the health of women with SCD in pregnancy. DISCUSSION This qualitative study explored the views of trial participants, decliners and staff on the feasibility and acceptability of a RCT to assess SPEBT versus usual care in pregnant women with SCD. Whilst SPEBT is increasingly used for women with SCD during pregnancy in clinical practice, recommendations about the use of SPEBT in this population have not yet been incorporated within clinical guidelines due to the paucity of evidence. This study provides the first qualitative report on participant experiences within a feasibility RCT of SPEBT during pregnancy. Key findings and interpretation in the context of existing research The target population for the TAPS2 trial represents a unique group of individuals who must manage multiple identities: they are pregnant women; living with a potentially life-threatening chronic condition; and (as in the UK SCD largely affects those from Black African and Black Caribbean backgrounds), they are part of a minority ethnic group. A recognition of these intersecting identities is essential when interpreting the findings from our study. Data from all interview groups agreed that the main factor determining patients’ willingness to participate in the trial was based on their treatment views and preferences, especially whether potential participants felt the likely benefits of receiving SPEBT outweighed the perceived risks. As pregnant women, potential participants in the TAPS2 trial had to consider the risk/benefit balance to their baby as well as for themselves. Other studies in pregnant women generally show that the primary determinant for agreeing to participate in research is the potential benefit to the health of their baby,[ 21 – 23 ] a finding echoed in our study. Benefit to the woman’s own health and also altruism were secondary motivations mentioned by the participants we interviewed, consistent with a survey investigating the willingness of pregnant women to participate in clinical trials.[ 23 ] As a patient group who are well-informed about their own condition, we found that in general both decliners and trial participants understood the importance of research and were positive about opportunities to be involved. This was reflected in the willingness of many decliners to take part in our qualitative sub-study: it was the invasive nature of the intervention in TAPS2 which they were less sure about. Our finding that both decliners and trial participants made an informed and careful decision about participation, is also supported by a similar finding from a study of non-pregnant people with SCD invited to take part in high-risk clinical research.[ 24 ] Potential participants in the TAPS2 trial were concerned about risk of infection, ‘getting the wrong blood’ or having side effects. A few believed that SPEBT could lead to sickle crises or adversely affect their pregnancy. Previous literature has reported participants decline participation if the intervention is unacceptable.[ 25 ] Set against these risks, many patients hoped that SPEBT could lead to a healthier pregnancy and baby. This is consistent with other literature identifying positive attitudes and belief in treatment benefits as facilitators for recruitment.[ 26 ] Many women with mild or asymptomatic SCD questioned the relevance of SPEBT to their situation, especially if they had previous successful pregnancies without needing transfusions. Among women with more severe SCD, motivation to receive SPEBT appeared higher. The finding that patients with SCD evaluate the risk and potential benefits in light of their SCD experiences has been previously reported in people with SCD considering participating in clinical research who were not pregnant.[ 24 ] All participant groups in our study noted that partner or family views were important to some women in their decision making. Negative experiences of transfusion among relatives or the wider community were also cited as influencing decisions about participation. In a study of reasons for participation in a clinical trial targeting women at a high risk of pre-eclampsia, pregnant women identified that whilst views of significant others was important, it did not influence their decision.[ 27 ] Our finding that partner or family views were given greater weight in decision making may reflect both the higher-risk nature of the intervention in TAPS2 and also the fact there is considerable lived experience of SCD amongst families and communities due to the high concentration of individuals with SCD within certain groups. Experiences of trial participation appeared generally positive and acceptable to most patients. Participants allocated to the intervention reported benefits included increased energy, fewer SCD crises, and fewer hospitalisations. No unexpected side effects were reported, and all side effects/reactions appeared to have been treated and/or resolved. With the exception of one patient who withdrew after problems with cannulation, participants in the intervention group generally perceived the intervention as acceptable. Several participants highlighted the cost and effort involved in attending for SPEBT (e.g. travel, childcare), with individual-level barriers such as these commonly cited as reasons for pregnant women not to participate in clinical research trials.[ 25 , 28 ] Among participants allocated to the control group, all reported that taking part in the trial had been acceptable. Trial burden was perceived as minimal, with trial questionnaires and assessments having been completed at routine care appointments for their pregnancy. Feedback from staff interviewees highlighted difficulties in recruitment caused by the Covid pandemic, with the need to ensure that patients entered the trial before the 18-week entry threshold made more challenging by Covid-related disruptions to healthcare systems and processes. Ensuring timely recruitment was especially difficult if the patient was unsure about participation and needed time to consider their options. A recent mixed-methods study concluded that the pandemic exacerbated negative experiences of healthcare experienced by people living with SCD in the UK.[ 29 ] Although Covid-19 was not explicitly cited by women in our study as a key influencing factor in participation, it may have adversely impacted recruitment to the main TAPS2 trial (and this study) given the incongruence between advice to ‘shield’ yet being invited to participate in a trial potentially requiring additional lengthy hospital visits. The capacity to provide a well-staffed apheresis service was a key concern among staff, with some staff reporting having to repeatedly chase the service themselves to ensure women allocated to the intervention were offered SPEBT in a timely manner. This finding was reflected by a recent qualitative study of health care professionals in two UK haematology units, which highlighted the complexity of managing transfusions within an already overwhelmed service.[ 30 ] SCD has been described as one of the most ‘racialized’ medical conditions,[ 31 , 32 ] and numerous studies have described the stigma and bias experienced by individuals living with SCD in the UK and other HIC.[ 29 , 33 , 34 ] Many individuals with SCD experience a lack of timely and appropriate care (particularly in emergency contexts),[ 35 ] and their own often ‘expert’ understanding of their own condition[ 36 ] contrasts with poor knowledge about SCD among many healthcare professionals. Whilst research in the US has identified distrust of the medical community as a barrier to participation in clinical trials,[ 37 ] the evidence base for the UK is less clear.[ 38 ] In our study only staff explicitly raised this as a potential barrier; however, patient participants may have been unwilling to disclose these sensitive concerns to us during interviews. Clinicians reflected the importance of establishing rapport and trust with their patients in order to support decision making around trial participation. Some trial participants also alluded to good relationships with their clinical team, evidenced by supportive discussions around whether to participate in the trial, and then later on efforts to minimise the impact of trial participation for example by combining hospital visits where possible. Recommendations for future studies Based on our findings, future RCTS of SPEBT in this study population should include recruitment strategies to address concerns from all ‘groups’ of pregnant women with SCD: those with mild disease, those with severe disease, those with ‘good’ relationships with their clinical team, and those who have previously had negative experiences within the healthcare system. This includes approaches to address how patients make decisions and factors that influence them including how they evaluate the risk/benefit of SPEBT. We propose three complementary strategies to support future studies of this intervention in this population. - Patient Education Firstly, for all patients: patient education may reduce the barriers to recruiting especially for the many patients who were unwilling to take part; those with ‘mild’ SCD, those with previously successful pregnancies, those unaware of the increased risks of complications during pregnancy, those with no prior transfusion history and those with concerns about the risks of the intervention, including their significant others. Recommendations on patient education are summarised in Box 2. - Study design Secondly, through adapting the study design or including strategies to accommodate those with a strong treatment preference. This could be achieved by including an observational arm in a future definitive RCT, or a patient preference RCT design. This option would enable the inclusion of patients who are not willing to be randomised, as well as those currently excluded from the trial e.g. those already receiving SPEBT. Women with SCD in pregnancy are a small patient population and assessing clinical outcomes for this whole patient cohort will inform the overall evidence base of usual care (including SPEBT) during pregnancy. Our data showed that the majority of decliners would have participated in an observational study if the option was provided, and those who randomised to SPEBT but withdrew from the trial because they had not wanted transfusions. - Additional support for specific patients In addition, strategies should be particularly considered when recruiting the following patients: Those patients who mistrust the intervention and/or clinicians: those who are referred in to specialist centres; and those who have had negative transfusions or medical experiences in the past. Clinicians need to take the time with these patients to build rapport and develop a trusting relationship this will enable these patients to safely disclose and discuss their concerns. Strategies to reduce the risk of drop outs which could bias the trial outcomes. For example, for recruiters to discuss and understand the strength of patient treatment preferences in those willing to be randomised so they can communicate the potential implications to patients. Strategies to support participants to cover the costs associated with trial participation, in particular, for those in the intervention group – which would ensure this research is inclusive. Box 2. Recommendations on patient education strategies to address barriers to recruitment and support patient decision-making Content of patient education: Information needs to be balanced and focussed on issues of most concern to patients, as well as addressing common myths or misunderstandings about transfusions. Participants recommended the use of videoed peer testimonies from patients who have received SPEBT during pregnancy to explain the treatment procedure, their experiences and benefits and side effects, which will also allay cultural mistrust. Information needs to include the increased risk of SCD complications during pregnancy, as well as the potential benefits of transfusion, along with information about the safety and risks of blood transfusions from trusted sources. Inclusion of videos and information from trusted clinicians, to address those patients with mild SCD who are concerned about the risks and see no benefit from receiving transfusion. Some staff recommended inviting women to come and visit the day unit and talk to other women having transfusions. To make patients aware of the trial, earlier in pregnancy or ideally even before they became pregnant through more posters in hospital clinics, online information including websites and social media, patient support organisations. Delivery of patient education Online information and social media offer a means of getting information to patients not yet recruited, as well as to partners and families who may contribute to the patient’s decision. Information needs to be inclusive to recruit from a diverse population e.g. translated or use of pictures/videos to ensure potential participants with limited English or their partners or families are not excluded. To make patients aware of the trial, earlier in pregnancy or ideally even before they became pregnant through posters in hospital clinics and online information including websites and social media, patient support organisations. Strengths and limitations Our study achieved the planned sample size and through purposive sampling, ensured a wide range of experiences and perspectives were sought. We achieved coherent findings, including a depth understanding of the barriers to participation in this study population, drawn from interviews with trial participant, staff and decliners, providing a breadth of perspective. A key limitation to this study was the brevity of some of the interviews, especially those with decliners. Nevertheless, though relatively brief, these interviews provided valuable first-hand insights on why some patients chose not to take part. Whilst many staff interviewees reflected on the issue of patient-clinician trust, this issue was not talked about by trial participants or decliners. It is possible that conducting interviews by phone, and by white interviewers, may have made it harder for women of colour to feel able to share their feelings on these sensitive issues. CONCLUSION Recognising and addressing the unique concerns and treatment preferences of pregnant women living with Sickle Cell Disease (SCD) through empathetic, participant-centred recruitment and design strategies is essential for maximising recruitment in future trials. We identified that participants treatment preferences and evaluation of the risk-benefits of the intervention played a key role in their decisions to take part in this feasibility trial. These factors need to be considered to avoid unnecessary ‘drop outs’ in the main trial or potentially biasing the future trial sample. Including an observational study arm as part of a future definitive RCT, along with other strategies, would maximise the evidence base and understanding of clinical outcomes in pregnant women with SCD. Abbreviations RCT Randomised control trial SCD Sickle cell disease SPEBT Serial prophylactic exchange blood transfusion TAPS2 The T ransfusion A ntenatally in P regnant Women with S ickle Cell Disease study Completers Patients who joined the TAPS2 study and completed participation Decliners Patients who were invited into the trial but declined to participate Declarations ETHICAL APPROVAL AND CONSENT TO PARTICIPATE The study received NHS ethics approval on 28 March 2019 from the London–Surrey Borders Research Ethics Committee (REC reference 18/LO/2070). Written informed consent was obtained from all participants including consent to their anonymised verbatim quotes being included in publications, with verbal re-consent obtained at the start of the interviews. CONSENT FOR PUBLICATION Not applicable AVAILABILITY OF DATA AND MATERIALS. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. COMPETING INTERESTS The authors declare that they have no competing interests. FUNDING This manuscript presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0317-20024). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funder had no role in the design of the study, in the writing of the protocol, or the decision to submit for publication. AUTHORS CONTRIBUTIONS SB led the study, overseeing the design, ethical approval and conduct of the study. SB prepared all study materials, collected study data, led the analysis of decliner interviews, contributed to the analysis of other interviews, and co-led the interpretation of data. LO contributed to the study design, ethical approvals, study materials, study conduct, collected study data, and contributed to data analysis and interpretation. CMcD conducted the analysis of the trial and staff interviews, led the combined analysis, and co-led interpretation of data. VR led ethical approval as part of approvals for the feasibility trial, facilitated participant recruitment, and contributed to data interpretation. JJ contributed to study materials, data interpretation and the plain English summary. EO was chief investigator of the feasibility RCT and led the funding application, and contributed to ethical approval and data interpretation. SB drafted the initial manuscript and with significant input from CMcD and LO. All authors read, reviewed and approved the final manuscript. ACKNOWLEDGEMENTS We want to acknowledge and thank all of the study participants who agreed, and gave up their time, to take part in this study. Many thanks to all those involved at our participating study sites, who recruited trial participants as well as the ‘trial decliners’ into the study. 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Sekhon M, Cartwright M, Lawes-Wickwar S, McBain H, Ezra D, Newman S, Francis JJ: Does prospective acceptability of an intervention influence refusal to participate in a randomised controlled trial? An interview study . Contemporary Clinical Trials Communications 2021, 21 :100698. Haywood C, Lanzkron S, Diener-West M, Haythornthwaite J, Strouse JJ, Bediako S, Onojobi G, Beach MC: Attitudes toward clinical trials among patients with sickle cell disease . Clinical Trials 2014, 11 (3):275-283. Nikčević AV, Dodd Z, Prior J, O'Gorman N, Poon LC, Nicolaides KH: Reasons for accepting or declining participation in the ASPRE trial: A qualitative study with women at high risk of preterm pre‐eclampsia . Prenatal Diagnosis 2019, 39 (12):1127-1135. Frew PM, Saint-Victor DS, Isaacs MB, Kim S, Swamy GK, Sheffield JS, Edwards KM, Villafana T, Kamagate O, Ault K: Recruitment and Retention of Pregnant Women Into Clinical Research Trials: An Overview of Challenges, Facilitators, and Best Practices . Clinical Infectious Diseases 2014, 59 (suppl_7):S400-S407. Berghs MJ, Horne F, Yates S, Graham S, Kemp R, Webster A, Howson C: Black sickle cell patients’ lives matter: healthcare, long-term shielding and psychological distress during a racialised pandemic in England – a mixed-methods study . BMJ Open 2022, 12 (9):e057141. Volkmer B, Lorencatto F, Stanworth SJ, Hirani SP, Francis JJ: Blood transfusion in haematology: A qualitative exploration of patients’ and healthcare professionals’ perceptions . British Journal of Health Psychology 2022, 27 (4):1241-1274. Bediako SM, Moffitt KR: Race and social attitudes about sickle cell disease . Ethnicity & Health 2011, 16 (4-5):423-429. Power-Hays A, McGann Patrick T: When Actions Speak Louder Than Words — Racism and Sickle Cell Disease . New England Journal of Medicine 2020, 383 (20):1902-1903. Wu JK, McVay K, Mahoney KM, Sayani FA, Roe AH, Cebert M: Experiences with healthcare navigation and bias among adult women with sickle cell disease: a qualitative study . Quality of Life Research 2024. Bulgin D, Tanabe P, Jenerette C: Stigma of Sickle Cell Disease: A Systematic Review . Issues in Mental Health Nursing 2018, 39 (8):675-686. All-Party Parliamentary Group on Sickle Cell and Thalassaemia (SCTAPPG): No One's Listening: An inquiry into the avoidable deaths and failures of care for sickle cell patients in secondary care . In . ; 2021. National Institute for Health and Care Excellence (NICE): Sickle cell disease: managing acute painful episodes in hospital (CG143) . In: Clinical guideline. London: NICE; 2012. Corbie-Smith G, Thomas SB, Williams MV, Moody-Ayers S: Attitudes and beliefs of african americans toward participation in medical research . Journal of General Internal Medicine 1999, 14 (9):537-546. Smart A, Harrison E: The under-representation of minority ethnic groups in UK medical research . Ethnicity & Health 2017, 22 (1):65-82. Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.FINALInterviewguidefortrialparticipants.docx Additional file 1: PDF - Final topic guide for trial participants Additionalfile2.FINALInterviewguidefordecliners.docx Additional file 2: PDF - Final topic guide for participants declining the trial (‘decliners’) Additionalfile3.FINALInterviewguideforstaffparticipants.docx Additional file 3 : PDF – Final topic guide for staff participants. 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Final topic guide for trial participants\u003c/p\u003e","description":"","filename":"Additionalfile1.FINALInterviewguidefortrialparticipants.docx","url":"https://assets-eu.researchsquare.com/files/rs-6577176/v1/15e493419bc7d63bf76da746.docx"},{"id":83892546,"identity":"4700f6bf-492e-4c8b-99e8-e0f52fc42b4d","added_by":"auto","created_at":"2025-06-04 08:21:00","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":21761,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 2: PDF - Final topic guide for participants declining the trial (‘decliners’)\u003c/p\u003e","description":"","filename":"Additionalfile2.FINALInterviewguidefordecliners.docx","url":"https://assets-eu.researchsquare.com/files/rs-6577176/v1/4679e6804b615463b72fdda2.docx"},{"id":83892548,"identity":"3da9433f-8694-4519-9cfd-4e3cc7e5e884","added_by":"auto","created_at":"2025-06-04 08:21:00","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":24124,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 3 : PDF – Final topic \u0026nbsp;guide for staff participants.\u003c/p\u003e","description":"","filename":"Additionalfile3.FINALInterviewguideforstaffparticipants.docx","url":"https://assets-eu.researchsquare.com/files/rs-6577176/v1/4b43e9d25fd10cd72688702e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The acceptability and feasibility of a randomised controlled trial of serial prophylactic exchange blood transfusion (SPEBT) versus usual care in pregnant women with SCD. A qualitative study with recommendations for recruitment strategies for a future definitive trial","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eSickle cell disease (SCD) is the most common inherited disease worldwide, characterised by anaemia, intermittent painful vaso-occlusive crisis (commonly known as \u0026lsquo;crises\u0026rsquo;) and chronic complications including chronic lung disease, sickle renal disease, stroke and pulmonary hypertension.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] In SCD, abnormal haemoglobin (\u0026lsquo;sickle\u0026rsquo; Hb) in red blood cells makes them becomes hard and sticky, in the shape of a \u0026lsquo;sickle\u0026rsquo; and unable to properly carry oxygen around the blood. This causes the associated symptoms.\u003c/p\u003e \u003cp\u003eIn high income and some middle-income countries, the majority of children born with SCD will survive to adulthood,[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and have a good expectation of having their own families. In the UK, approximately 110 pregnancies occur annually in women living with SCD.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Pregnancy in women living with SCD is high risk, associated with increased risk of perinatal and maternal morbidity and mortality.[\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Pregnancy also exacerbates SCD-related complications such as anaemia, painful crisis, pulmonary complications, and infection.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThere are very limited treatment options for pregnant women with SCD. In the UK, standard care only consists of blood transfusion when clinically indicated.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Available current disease-modifying treatments during pregnancy are not recommended.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] When blood transfusions are clinically required, they can be given as a simple top-up transfusion, which, whilst improving oxygen carriage around the body, can potentially cause hyperviscosity and iron overload. Alternatively, pregnant women living with SCD can be offered exchange blood transfusion where their own red blood cells (RBC) are removed and replaced with healthy RBC from donors. Exchange transfusions can be done either manually or automatically, using a machine. Where transfusions need to be done on a long-term basis, automated serial prophylactic exchange blood transfusion (SPEBT) is the preferred approach. Exchange blood transfusion are more effective in reducing the percentage of sickle Hb than top up transfusions, and therefore better at reducing the risk of acute SCD complications.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOutside of pregnancy, serial prophylactic exchange blood transfusion (SPEBT) has proven efficacy as a treatment for acute SCD complications, and for the prevention of pain, acute chest syndrome and strokes in people with SCD. However, there is inadequate evidence for the safety and benefit of SPEBT for SCD during pregnancy.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] There have been repeated calls for a definitive randomised controlled trial (RCT) to establish the effectiveness of SPEBT in pregnancy.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eWe conducted a multi-centre randomised feasibility trial of SPEBT versus usual care in pregnant women with SCD (TAPS2) to assess the feasibility and acceptability of conducting a definitive RCT of SPEBT in pregnancy. The protocol, analysis plan and feasibility RCT findings have previously been published. [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] In TAPS2, participants were randomised to either SPEBT or usual care; with maternal and neonatal outcomes recorded up to 4 weeks post-partum. In summary, 35 participants were recruited (39.8% of those eligible); 18 participants were randomised to intervention, and 17 to usual care, with 100% follow up data achieved. The results confirmed it was feasible to perform a definitive RCT, with satisfactory rates of recruitment and retention. Although not powered to compare outcomes, positive trends in some maternal, infant and postnatal outcomes were identified in the intervention arm.\u003c/p\u003e \u003cp\u003eThere is increasing recognition of the importance of conducting qualitative research alongside feasibility trials.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] We therefore conducted a qualitative study embedded within TAPS2. The primary aim of this qualitative study was to inform the design for a future definitive trial.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eAn embedded qualitative study was conducted within the multi-centre feasibility RCT assessing SPEBT versus usual care in pregnant women with SCD.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting and participant recruitment\u003c/h2\u003e \u003cp\u003eParticipants for the qualitative study were recruited from the same seven NHS hospitals in the UK recruiting patients for the feasibility RCT.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] We invited three groups of participants involved in the TAPS2 feasibility RCT to participate in the qualitative study: trial participants, women who were eligible for the trial but declined to participate (\u0026lsquo;decliners\u0026rsquo;), and clinicians and research staff involved in delivering the trial. All potential participants were provided with an information sheet and a consent form and the opportunity to ask questions.\u003c/p\u003e \u003cp\u003eTrial participants and clinical/research staff who provided written informed consent were purposively sampled to ensure a maximum variation sample across key characteristics (Box 1). We aimed to interview all the decliners who provided informed written consent.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrial participants\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStaff participants\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Study site\u003c/p\u003e \u003cp\u003e\u0026bull; Treatment allocation: intervention/usual care\u003c/p\u003e \u003cp\u003e\u0026bull; Trial status: completers/drop outs\u003c/p\u003e \u003cp\u003e\u0026bull; Pregnancy number: 0/\u0026ge;1\u003c/p\u003e \u003cp\u003e\u0026bull; SCD genotype: SS/SC/other\u003c/p\u003e \u003cp\u003e\u0026bull; Disease severity: SCD-related hospital admission in last year yes/no\u003c/p\u003e \u003cp\u003e\u0026bull; History of transfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026bull; Study site\u003c/p\u003e \u003cp\u003e\u0026bull; Staff role: clinical role (consultant obstetrician, consultant haematologist)/staff involved in recruitment (research midwife, sickle cell nurse research practitioner)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eBox 1: Sampling characteristics\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003e Semi-structured interviews were conducted by telephone (LO and SB) with study participants. Face-to-face interviews were not feasible due to the ongoing Covid pandemic. Informed consent was re-sought verbally prior to the interviews commencing. All interviews were recorded using an encrypted audio recording device.\u003c/p\u003e \u003cp\u003eInterviews with trial participants were conducted at 6\u0026ndash;8 weeks post-partum; interviews with decliners were conducted within eight weeks of providing consent; and interviews with trial staff were conducted near the end of, or after, the recruitment phase ended at their site, ensuring participants had adequate time for reflection.\u003c/p\u003e \u003cp\u003eSeparate interview topic guides were developed for each participant group by SB and LO, with input from patient contributors and clinicians. Initial interviews for each group were used to pilot and refine the wording of the questions. Consistent with an inductive qualitative approach, new topics arising during interviews were added to the topic guide. Interviews explored the following topics, dependant on the participant group as shown in Box 2.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParticipant group/\u003c/p\u003e \u003cp\u003eTopic questions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTrial Participants\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDecliners\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStaff\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eViews on the Acceptability of the trial intervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExperiences of trial recruitment processes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReasons for declining participation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExperiences of taking part in the trial including randomisation and study conduct\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExperiences of receiving the trial intervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e✓ (Only trial participants randomised to SPEBT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExperience of delivering the trial intervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e✓ (relevant clinical staff only)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eViews on future research including recommendations for improving recruitment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e✓\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eBox 2: Topic questions per participant group\u003c/h3\u003e\n\u003cp\u003eThe final topic guides are included as supplementary material [Additional file 1, trial participants; Additional file 2, decliners; and Additional file 3, staff].\u003c/p\u003e \u003cp\u003eGiven the study aims, the proposed sample sizes were not aimed to achieve data saturation, rather to elicit a diversity of views through the use of maximum variation sampling approach for staff and trial participants. We aimed to interview 15\u0026ndash;25 trial participants; 5\u0026ndash;15 decliners; and 15\u0026ndash;20 trial staff (two to three staff considered \u0026lsquo;key informants\u0026rsquo; in each study site).\u003c/p\u003e \u003cp\u003eThe study was conducted by three female post-doctoral researchers (SB, LO and CM) with \u0026gt;\u0026thinsp;10 years research experience, based in medical research departments in two UK universities. SB and LO conducted the interviews, CM led the data analysis with input from SB and LO. All were involved in the write-up. None of the patients were known to the researchers before this study. Some staff interviewees were known to SB and LO prior to interview from earlier stages in the TAPS2 trial, but none were known to CM.\u003c/p\u003e\n\u003ch3\u003eAnalysis\u003c/h3\u003e\n\u003cp\u003e Trial participant and staff interviews were transcribed verbatim, and anonymised transcripts uploaded onto NVivo version 13 for data management and coding (LO, SB and CM). These interviews were analysed by CM using reflexive thematic analysis,[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] using the constant comparison approach to compare data within and across individual interviews to identify themes and subthemes.\u003c/p\u003e \u003cp\u003eTrial participant interviews were analysed for themes and subthemes, with additional subgroup analyses to identify any different patterns emerging, including intervention vs control; trial completers vs patients who withdrew; different illness severity levels; different SCD genotypes; patients with and without prior experience of transfusion; previous pregnancy history and across different trial sites.\u003c/p\u003e \u003cp\u003eStaff interviews were analysed for themes and subthemes. A site-by-site analysis was then carried using the mixed-methods matrix approach. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]This enabled us to synthesise the quantitative screening/recruitment data, with the qualitative data from each site.\u003c/p\u003e \u003cp\u003eDecliner interviews were not transcribed nor formally analysed. Rather, data was extracted (SB) through repeated listening of the audio files and summarised in tables to report their reasons for declining, suggestions to improve recruitment and study design for the definitive trial. Illustrative anonymised key quotes were transcribed verbatim by SB. No subgroup analysis was conducted due to limited sample size and data.\u003c/p\u003e \u003cp\u003eFindings across the three participant groups were then mapped onto key themes and sub-themes. Standard methods were employed to ensure rigour (e.g. through the use of audit trail, reflexive diaries, double coding and deviant case analysis). Illustrative anonymised quotes are reported to support themes and subthemes for the data corpus.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eParticipant characteristics\u003c/h2\u003e \u003cp\u003eFigure 1 reports the study flow of participant recruitment.\u003c/p\u003e \u003cp\u003e All but one (n\u0026thinsp;=\u0026thinsp;34) trial participants consented to be contacted for interview. To ensure balance in sampling characteristics, after completing 14 interviews we reviewed participant characteristics and thereafter prioritised interviewing participants with underrepresented characteristics. Eighteen interviews were conducted by telephone (11 participants allocated to intervention, and seven to usual care) with one interview by email, at the participant\u0026rsquo;s request. Interviews were completed between May 2020 and August 2022, and the mean duration of telephone interviews was 22 minutes (range: 10\u0026ndash; 64 minutes).\u003c/p\u003e \u003cp\u003eTwenty-four decliners consented to the qualitative study, of which 12 were interviewed from four study sites. Interviews completed between May 2020 and October 2022. The mean interview duration for decliner interviews was 12 minutes (range: 5\u0026ndash;22 minutes).\u003c/p\u003e \u003cp\u003eFor staff interviews, we screened all 30 eligible staff and identified 17 priority interviews based on capturing a range of staff characteristics. Fifteen staff interviews were completed across all seven study sites. Staff interviews took place between July 2022 and November 2022. The mean interview duration was 29 minutes (range: 16\u0026ndash;51 minutes).\u003c/p\u003e \u003cp\u003eIn total, we conducted 46 interviews, with our recruitment target met for all three participant groups. Full details of participant recruitment are presented in Fig.\u0026nbsp;1. We achieved a maximum variation sample for key characteristics for the trial participants (Table\u0026nbsp;1), and staff interviews (Table\u0026nbsp;2) as planned, within the trial constraints.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e\u003c Insert Tables 1 and 2 here\u003e\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSampling characteristics for trial participants (N\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment allocation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003cp\u003eUsual care\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTrial status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCompleter\u003c/p\u003e \u003cp\u003eDrop out\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStudy site*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePregnancy number\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHospital admission in the year prior to pregnancy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCrises in the year prior to pregnancy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGenotype\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHbSS\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHbSC\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSelf-reported transfusion history at RCT enrolment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003cp\u003eTop-up only\u003c/p\u003e \u003cp\u003eExchange only\u003c/p\u003e \u003cp\u003eTop-up and exchange\u003c/p\u003e \u003cp\u003eNot known\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Participants recruited to RCT by study site:1 (n\u0026thinsp;=\u0026thinsp;11), 2 (n\u0026thinsp;=\u0026thinsp;1), 3 (n\u0026thinsp;=\u0026thinsp;7), 4 (n\u0026thinsp;=\u0026thinsp;7), 5 (n\u0026thinsp;=\u0026thinsp;7), 6 (n\u0026thinsp;=\u0026thinsp;2), 7 (n\u0026thinsp;=\u0026thinsp;0)\u003c/p\u003e \u003cp\u003e \u003csup\u003e1\u003c/sup\u003e HbSS\u0026thinsp;=\u0026thinsp;homozygous sickle cell\u003c/p\u003e \u003cp\u003e \u003csup\u003e2\u003c/sup\u003e HBSc\u0026thinsp;=\u0026thinsp;Haemoglobin Sickle C disease\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSampling characteristics for staff (N\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStaff Role\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConsultant obstetrician\u003c/p\u003e \u003cp\u003eConsultant haematologist\u003c/p\u003e \u003cp\u003eResearch Midwife\u003c/p\u003e \u003cp\u003eResearch Nurse\u003c/p\u003e \u003cp\u003eClinical Research Practitioner\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStudy site\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eFindings\u003c/h2\u003e \u003cp\u003eThe finding reports the combined data from the interviews with 19 trial participants, 12 decliners and 15 staff participants.\u003c/p\u003e \u003cp\u003eWe identified three overarching themes: (1) Factors affecting patient decisions on taking part in the trial; (2) experiences of the TAPS2 trial; (3) recommendation for a future RCT. Each theme incorporated several subthemes summarised in Table\u0026nbsp;3. For Themes 1 and 3, we considered data from trial participants, decliners and staff, using these three datasets to explore and illuminate the issues, providing triangulation of findings. Theme 2 related to trial participants and staff only. Illustrative verbatim quotations from the interviews are reported in the text.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTABLE 3: KEY FINDINGS\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKey findings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTrial participants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDecliners\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStaff\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTheme 1. Factors affecting patient decision-making on trial participation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive motivations for trial participation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eHope of benefit to their own health\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eDecliners wanted to help others with SCD but not to receive transfusions\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eStaff reported hearing these motivations from patients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eBenefit to the pregnancy and their baby\u0026rsquo;s health\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eWish to support research for the benefit for others with SCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConcerns about\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSPEBT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eRisk of Infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Staff reported that patients expressed these concerns about transfusions.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eRisk of being given the wrong blood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eOther adverse reactions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eConcern that SPEBT could trigger sickle crises\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eFear of SPEBT causing problems in current pregnancy if not needed in previous pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eConcerns about cannulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eCultural stigma around receiving blood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003eX\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eCultural stigma was mentioned by one clinician but not by any patients\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerceptions of the benefit or relevance of SPEBT to participants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eBenefits to mother\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eDecliners felt that either their SCD was too mild to need SPEBT, or it was not worth the risks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eBenefit to baby\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eReduction in sickle crises\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e- Weighing up risk vs benefits of SCD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eSeverity of SCD affects perceptions of risk vs benefits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eWomen with milder SCD less likely to view SPEBT as relevant or beneficial to themselves\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePartner or family influence on perceptions of transfusions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eInfluence of family in patient\u0026rsquo;s decision to take part (or not)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eRole of partner in decision\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eImportance of a good patient-clinician relationship\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eSome women of colour might feel less trusting of a white healthcare professional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eReported by one clinician\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTrial Burden\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eTime, cost and effort of travel, arranging childcare or time off work\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eParticipation could place an additional burden on women already coping with pressures of SCD, work and/or caring for other children.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTheme 2. Experiences of trial\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Recruitment process- patient\u0026rsquo;s experiences\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eNo significant concerns were highlighted by patients regarding their experience of the recruitment process\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eThese findings concurred with staff reports of feedback from patients to them\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eRecruitment materials appeared generally acceptable to patients, although one participant suggested including more pictures and visual aids to improve readability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRecruitment process - staff experiences\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eRecruiting staff reported challenges in identifying eligible women and completing all entry criteria early enough in pregnancy to enrol the patient into the trial before six weeks gestation (the recruitment cut off point).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eAt some sites with linguistically diverse populations, need for translation had presented difficulties\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome measures \u0026ndash; patient reported outcome measures\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eQuestionnaires appeared generally acceptable to all trial participants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eResearch staff confirmed general acceptability of questionnaires to patients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eTrial participants suggested including additional outcomes focussing on impact of SCD on employment, and mothers\u0026rsquo; perceptions of how pregnancy was going\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group experiences\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eTrial participation was acceptable and not burdensome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParticipants experiences of SPEBT during the trial\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e- \u003cem\u003ePositive experiences of SPEBT\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cem\u003e.\u0026nbsp;\u003c/em\u003e Benefits included more energy, less pain, reduction or stopping of crisis for some women, fewer hospitalisations, a sense of \u0026lsquo;feeling better in myself\u0026rsquo; or an overall sense the current pregnancy was going better than previous pregnancies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e- Negative experiences of SPEBT\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eSide effects (dizziness, pins and needles, headaches and one report of citrate toxicity)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eIssues with cannulation\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eEffort/cost of attending appointments.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReasons for patients withdrawing from trial\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eAll three patients who withdrew had hoped to be allocated to usual care but had been randomised to SPEBT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eReasons for withdrawals not mentioned in staff interviews\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eOne began transfusions but withdrew from the trial after difficulties in cannulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cem\u003eAs above\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTheme 3. Improving recruitment and trial experiences for future trials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImproving trial recruitment- recommendations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eRaising awareness of:\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e\u0026sect; \u0026nbsp;the effects of pregnancy on SCD\u003c/li\u003e\n \u003cli\u003e\u0026sect; \u0026nbsp;potential benefits of SPEBT\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026sect; \u0026nbsp;the TAPS2 trial findings\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eRaising awareness through social media, internet websites and posters in hospitals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eRecruitment information needs to be:\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e\u0026sect; \u0026nbsp;easy to understand, e.g. using visuals/ videos to increase accessibility\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026sect; \u0026nbsp;accessible to partners \u0026amp; family\u003c/li\u003e\n \u003cli\u003e\u0026sect; \u0026nbsp;available earlier in pregnancy if possible\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cs\u003e\u0026nbsp;\u003c/s\u003e\u003c/p\u003e\n \u003cp\u003e\u003cs\u003e\u0026nbsp;\u003c/s\u003e\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u003cs\u003e\u0026nbsp;\u003c/s\u003e\u003c/p\u003e\n \u003cp\u003e\u003cs\u003e\u0026nbsp;\u003c/s\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eValue of video peer testimonies\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eStaff recommended raising wider awareness among clinical colleagues through existing clinical networks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImproving trial experiences and conduct \u0026ndash; key recommendations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eSupport with childcare and travel costs to attend trial appointments\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eProviding pre-transfusion advice to patients on how to reduce issues with venous access\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eAdding outcome measures on impact on employment, and on how the mother herself felt that the pregnancy was going.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eEnsuring adequate apheresis capacity, for example through additional funding or ringfencing resources.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eN/R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFuture study design\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eClear support from all interviewees to include an observational study arm to the design of a future trial for women who do not want to be randomised, or ineligible for the trial.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e✓\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026radic;\u0026nbsp;\u003c/strong\u003eindicates finding supported by data from this interviewee group\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eX\u0026nbsp;\u003c/strong\u003eindicates that issue was not mentioned by this interviewee group\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN/R\u003c/strong\u003e: Question/s were not relevant to participant group so no response is recorded\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCD\u003c/strong\u003e: Sickle cell disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSPEBT\u003c/strong\u003e: Serial prophylactic exchange blood transfusion\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTAPS2\u003c/strong\u003e: The \u0026lsquo;\u003cstrong\u003eT\u003c/strong\u003eransfusion \u003cstrong\u003eA\u003c/strong\u003entenatally in \u003cstrong\u003eP\u003c/strong\u003eregnant Women with \u003cstrong\u003eS\u003c/strong\u003eickle Cell Disease study\u0026rsquo;: See reference 15: \u003cem\u003eProphylactic exchange transfusion in sickle cell disease pregnancy: a TAPS2 feasibility randomized controlled trial\u0026nbsp;\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u0026lt;Insert Table\u0026nbsp;3 here\u0026gt;\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eTheme 1. Factors affecting patient decision-making on trial participation\u003c/h2\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003ePositive motivations for trial participation\u003c/h2\u003e \u003cp\u003eTrial participants were motivated to take part in the trial for three reasons; hope of benefit to their own health, benefit to their pregnancy and their baby\u0026rsquo;s health, or wish to support research to benefit others with SCD.\u003c/p\u003e \u003cp\u003e \u003cem\u003eJust because all the pros that were explained to me and obviously it would help the baby out, so I just wanted to do what was best, just to help my baby and myself\u0026hellip; And just get through the pregnancy easier. (Trial participant 3, intervention arm, completer\u003c/em\u003e)\u003c/p\u003e \u003cp\u003eTaking part in the trial was also seen to offer health benefits either directly, through receiving transfusions, or from additional clinical time and attention.\u003c/p\u003e \u003cp\u003eStaff concurred that a desire to help others with SCD was a key factor for many women in their decision to participate. Both patients and staff perceived SCD as an under-researched and neglected condition. Within this context, the trial could increase public awareness of SCD as well as potentially finding better treatments for SCD during pregnancy.\u003c/p\u003e \u003cp\u003e \u003cem\u003eSo, I know there is little research about this whole issue, sorry, I know there is not enough support for people like that, so I thought the research might, you know, enable help the government either to put in more like, you know, support and everything to lots of people, especially when you get to the hospital and you are in crisis or something and you have no support, because people around don't really understand or know what to do with you. (Trial participant 12, control arm, completer)\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eViews on blood transfusions\u003c/h2\u003e \u003cp\u003ePatients\u0026rsquo; views on blood transfusions emerged as a key determinant in whether they chose to take part in the trial. Among the trial participants interviewed, four expressed a preference to be allocated to SPEBT, four preferred usual care and the remainder expressed no preference or were uncertain.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePreference for SPEBT\u003c/h2\u003e \u003cp\u003e \u003cem\u003eAt the time I was hoping that I had luck and the computer would have chosen me to have the [blood] exchanges because I just couldn't, I just couldn't imagine going through the pregnancy with many more crises which I thought in turn would affect how the baby grew. (Trial participant 2, intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eNo preference\u003c/h2\u003e \u003cp\u003e \u003cem\u003eI did not mind which group I was assigned to because being a part of the study I was still being monitored closely during my pregnancy and I felt assured that whichever group I ended up in that I would be receiving the best needed treatment. It was never a concern that I would end up in a group and not get the needed transfusions or care I needed. (Trial participant 18, control group, completer)\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003ePreference for usual care\u003c/h2\u003e \u003cp\u003e \u003cem\u003eI definitely preferred not to be in the transfusion group because I just thought it was slightly less onerous. (Trial participant 10, intervention arm, drop out)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eStaff interviewees also perceived that the main barrier to recruitment had been patient reluctance to receive transfusions, and the importance of this concern was supported by triangulation of evidence from staff, trial participant, and decliner data. For those patients reluctant to receive transfusions, perceptions that SPEBT might involve risk of harm was a common concern.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eConcerns about SPEBT\u003c/h2\u003e \u003cp\u003eConcerns about harm from transfusions centred on risk of infection (either through the cannulation site or through contaminated blood), risk of being given the wrong blood, or other adverse reactions.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI was more worried you know like in the past it has been in the news that people are being given...the wrong blood\u0026hellip;And infected blood and things like that\u0026hellip; (Trial participant 9, intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eWhether [transfusion] would be safe for me and my baby as well or not.. I was worried about the infections and all like that. (Trial participant 15, intervention arm, dropped out of trial immediately after randomisation)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eOne woman who declined the trial expressed concerns that SPEBT could trigger a sickle crisis.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI don\u0026rsquo;t have too many crisis, twice or three times [ a year], so take old blood out and put new blood \u0026hellip;. maybe that is going to cause some crises (Decliner, Participant 10)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eStaff also reported that risk from transfusion, especially blood safety, was a concern for many patients. Several clinicians observed that where patients had a cultural background and/or personal experiences in other countries where HIV rates were high, this could heighten awareness of the risks of infected blood.\u003c/p\u003e \u003cp\u003e \u003cem\u003eIf you have an Afro Caribbean background, it\u0026rsquo;s like, is it safe? Has the blood been screened? Could you get an infection from HIV?\u0026hellip; Some of them might be wary about it. Like gosh, people with a sickle cell from an Afro Caribbean background, like basically they are needing that reassurance. (Research Midwife, Staff interview 8)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eSome women expressed more general fears that starting a new intervention could adversely affect their pregnancy. One participant, who had three previous failed pregnancies, explained that she did not want additional interventions which she could later regret if she lost this baby. It was interesting to note that for this participant, the decision to avoid SPEBT was perceived as a safer choice, despite past pregnancies having ended in miscarriage.\u003c/p\u003e \u003cp\u003e \u003cem\u003eOne of the reasons I decided to not take part as I didn't know if it has any risks or adverse effects based on some of the challenges, I have had in trying to get pregnant... this is my fourth pregnancy and I don't have a child yet... I had miscarriages and a termination too and this is an IVF... since everything is going on well, I don't want to have regrets\u0026hellip;. this one looks like it\u0026rsquo;s going well so why don't we let it be.. and not do external stuff that might affect it (Decliner, interview 1)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eWhere women had already experienced a successful pregnancy, their reluctance to receive transfusions was linked to fear of causing new problems and less successful outcomes for their current pregnancy.\u003c/p\u003e \u003cp\u003eClinicians had observed similar concerns among patients.\u003c/p\u003e \u003cp\u003e \u003cem\u003eIt's such a big thing. They may never have had a transfusion before, had children before and not needed one so they couldn't understand why it was a good idea to do it. (Research Midwife, Staff interview 1)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eSome participants who had not had blood transfusion before were apprehensive about the transfusion procedure, particularly cannulation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eConcerns about cannulation\u003c/h2\u003e \u003cp\u003e \u003cem\u003eI cannot remember what they said about the veins, like it can get injured or something like that. I cannot remember. So I was kind of scared about that. (Trial participant 9, intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eHaving a femoral line (a cannula for transfusion inserted into the femoral vein in the thigh) was a particular concern for some women.\u003c/p\u003e \u003cp\u003e \u003cem\u003eWell it was going through the vein, but it was going like near my groin, so if I was just a bit worried about that because obviously it's going in [there] like. (Trial participant 19, intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eClinicians also reflected on patient concerns about transfusions, acknowledging that this was a complex issue due to the interplay between actual, current clinical risks, and myths or misapprehensions (e.g. based on times in the past when blood safety procedures had been less rigorous).\u003c/p\u003e \u003cp\u003eOne clinician, a haematologist, also reflected on the paradoxical nature of recruiting patients for regular SPEBT as part of a trial, when they routinely advised patients to be wary of unnecessary transfusions.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI mean we spend a lot of time as haematologists saying \"don't let those other doctors transfuse you if you don't need it\". You know, \"don't have an unnecessary transfusion, transfusions can be risky if they're not matched properly\" and then we're saying \"alright we want you to have a transfusion as part of this trial...\u0026lsquo;You're fine, the baby's fine, we're not doing it to save your life, it kind of is a bit against a lot of the messages we give patients.\u0026rsquo; (Consultant Haematologist, Staff interview 6)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eAll clinicians reflected on the complexity for their patients in balancing the potential risks and benefits from SPEBT, and the importance of supporting women in making their own choice on what was best for themselves and their baby. However, the key role of patient education emerged as an important finding within clinician interviews, from observing how patient concerns could be exacerbated by out-dated information or myths about transfusion safety. This issue is discussed in detail in \u003cem\u003eTheme 3. Feedback on improving recruitment.\u003c/em\u003e\u003c/p\u003e \u003cp\u003eFor patients trying to weigh up the risks vs benefits of SPEBT for their pregnancy, possible benefits from SPEBT presented the other side of the risk-benefit equation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003ePerceptions of the benefit or relevance of SPEBT to participants\u003c/h2\u003e \u003cp\u003ePerceptions of benefit from transfusions tended to relate to a participant\u0026rsquo;s perception of the severity of their SCD. Some women with a history of frequent and painful sickle crises explained that they specifically wanted transfusions to reduce the number of crises they might experience during their pregnancy.\u003c/p\u003e \u003cp\u003eIn contrast, several of the women with milder SCD saw no potential benefits from SPEBT since they were feeling well without transfusions. These included women with mild SCD experiencing their first pregnancy, as well as women who had previously had successful pregnancies without requiring transfusions.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI have 2 kids and did not need any transfusions and I did not want to risk it this time. (Decliner, interview 3)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe value of blood transfusions as a resource was commented on by several women with mild SCD who declined participation, expressing concerns that if they received transfusions this would waste blood which could be used for patients who were more severely affected.\u003c/p\u003e \u003cp\u003e \u003cem\u003eBlood is very valuable and to someone like me, even though it\u0026rsquo;s a trial, someone who is probably symptomatic and it could make a difference in their pregnancy, it would be better off for them because I don\u0026rsquo;t feel like I am a good candidate. (Decliner, interview 12)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eStaff interviewees also reflected on the difficulties of asking patients with mild SCD to receive SPEBT for the trial.\u003c/p\u003e \u003cp\u003e \u003cem\u003eThe ones that didn't want to take part either have had a completely normal life and didn't feel that they were sick enough to require intervention anyway, so that was one group that just said, well, you know, my sickle's not a big deal, I'm well, I've got no medical problems, I don't think I want to start having intervention if I don't need it. (Consultant Obstetrician, Staff interview 11)\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003ePartner or family influence on perceptions of transfusions\u003c/h2\u003e \u003cp\u003ePartners and family (including parents and siblings, aunts, and grandparents) could have a major influence on patients\u0026rsquo; perceptions of transfusions and decision on whether to join the trial.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI come from quite a medical family anyway, I had conversations with my husband, my dad, my mum, my sister and we all had a family conversation about things and the risks. (Trial participant 2, intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eIn the staff interviews, recruiters, especially nurses and midwives, discussed ways in which they had been aware that family interactions affected patients\u0026rsquo; decisions. Family members could either influence the decision towards or against participation.\u003c/p\u003e \u003cp\u003e \u003cem\u003eA couple of times, because I had somebody who came who would have been an ideal candidate\u0026hellip; she came with an aunt who said no I don't think you should because we have always had someone with sickle in the family and nobody gets blood and they are fine and equally then I had somebody who came with another family member who said that this is for your benefit, this is for your good and if it makes you better and healthier, then you should have a go with it, just listen to what the doctor is saying to you. (Consultant Obstetrician, Staff interview 13)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eStaff also reflected on the role of the patient\u0026rsquo;s partner in decision making; and the difficulty of addressing partner concerns fully when all information about the trial was relayed second-hand via the patient themselves. As one haematologist described, family concerns were especially understandable where there was a known case of fatal complications following transfusion, leading to fears that this could happen again.\u003c/p\u003e \u003cp\u003e \u003cem\u003eThere are people in the community who have died because of blood transfusions, their reaction to blood and that is in the psyche of the patient population so there is a little bit of nervousness about transfusion which is completely understandable. (Consultant Haematologist, Staff interview 6)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eStaff also discussed the importance of a good patient-clinician relationship to enable patients to discuss their feelings and concerns. They highlighted the importance of taking time with patients to explain, reassure and educate patients about SCD during pregnancy to empower patients to understand their condition better and make informed decisions. Building rapport and trust was considered essential to this process to reassure the patients that their clinician genuinely wanted the best for them and their baby, rather than simply wanting them to recruit them into the trial.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI think you have to get a rapport with when you are trying to recruit, so they trust you. You don't want them to feel like you are using them just for research purposes, that you care about them. (Research Midwife, Staff interview 8)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eSeveral clinicians also reflected on ways in which patients\u0026rsquo; past experiences might lead to mistrust of clinicians, for example from times where women had felt their condition had been dismissed in the past by clinicians.\u003c/p\u003e \u003cp\u003e \u003cem\u003eA lot of [patients] think that this something they have to spend their lives suffering with and because they have been dismissed throughout their life, they don't trust health care workers. (Consultant Obstetrician, Staff interview 13)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eIssues of race were only briefly mentioned by staff interviewees, and not directly mentioned at all by trial participants or decliners. However, one midwife acknowledged the possibility that some women of colour might feel less trusting of a white health professional than if the recruiting member of staff was themselves a person of colour.\u003c/p\u003e \u003cp\u003e \u003cem\u003eFrom what they told me, things like they didn't have time, they perhaps didn't understand it as much, they didn't like the idea of a blood transfusion, the risks associated with that, partners didn't want, or family members, didn't want them to participate, that came back a few times. But then things they didn't tell me, I do wonder whether the colour of my skin was an issue because I don't have black or brown skin and I just wonder whether that might have been a barrier, but I never asked that question. (Research Midwife, Staff interview 7)\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eTrial burden\u003c/h2\u003e \u003cp\u003eThe practical requirements of participating in the trial were highlighted as an important consideration by trial participants, decliners and staff. These included the time, cost and effort of travel to attend the appointments, especially where it was necessary to arrange childcare or time off work.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI would have to come to the hospital more often... if I were sick I would obviously have to come, but I would rather not have to come to hospital where I already have a child, so I would need to look for childcare for the whole day, for the whole process. (Decliner, interview 2)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eClinicians reflected that participation could place an additional burden on women who were already coping with the physical and emotional challenges of living with SCD, often combined with pressures of work and/or caring for their other children.\u003c/p\u003e \u003cp\u003e \u003cem\u003eIt's quite a difficult population to sell another treatment to as they have to endure as much as they do. (Research Midwife, Staff interview 1)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eDespite the challenges involved, the TAPS2 trial did successfully recruit, and the next theme focuses on the experiences of participation.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eTheme 2. Experiences of trial\u003c/h2\u003e \u003cdiv id=\"Sec24\" class=\"Section4\"\u003e \u003ch2\u003eRecruitment process\u003c/h2\u003e \u003cp\u003eNone of the trial participants highlighted significant issues regarding their experience of the recruitment process. Recruitment materials appeared generally acceptable to patients, although one participant suggested including more pictures and visual aids to improve readability.\u003c/p\u003e \u003cp\u003eRecruiting staff had experienced a range of challenges, including identifying eligible women and completing all entry criteria early enough in pregnancy to enrol the patient into the trial before 18 weeks gestation (the recruitment cut off point). This had been particularly problematic for \u0026lsquo;out of area\u0026rsquo; patients if additional patient notes needed to be obtained from their referring clinician.\u003c/p\u003e \u003cp\u003eSome recruiting staff worked at hospitals where not all patients could speak English. The need for translation had presented difficulties, since getting family members to translate could lead to uncertainty about whether the translating family member might be influencing a patient\u0026rsquo;s decision on whether or not to participate. Providing professional translators was not feasible at sites where many different languages could be involved.\u003c/p\u003e \u003cp\u003e \u003cem\u003eYou've got 200 languages spoken, and women with sickle cell are of African heritage and Caribbean and we have had that so it would take a lot of resource. (Research Midwife, Staff interview 1)\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eTrial questionnaires\u003c/h2\u003e \u003cp\u003eNone of the participants appeared to consider the trial questionnaires difficult to complete. There were a few requests for additional questions to add for any future trial, and these are discussed in \u003cem\u003eTheme 3: Improving recruitment and trial experiences for future trials.\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eControl group experiences\u003c/h2\u003e \u003cp\u003eFor the control group, completion of questionnaires was the only trial procedure extra to their routine clinical care. None felt that participating in the trial had been burdensome. This was in contrast to several participants in the intervention arm who highlighted the time, effort and cost involved in attending for transfusions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003eParticipants experiences of SPEBT during the trial\u003c/h2\u003e \u003cdiv id=\"Sec28\" class=\"Section4\"\u003e \u003ch2\u003ePositive experiences of SPEBT\u003c/h2\u003e \u003cp\u003ePositive benefits from SPEBT reported by trial participants included; more energy, less SCD-related pain, reduction or stopping of crisis for some women, fewer hospitalisations, a sense of \u0026lsquo;feeling better in myself\u0026rsquo; or an overall sense the current pregnancy was going better than previous pregnancies.\u003c/p\u003e \u003cp\u003e \u003cem\u003eBecause every time I was in the intervention and then we had the results, all my values were really good. \u0026hellip;I was feeling good, I didn't have any crises and I wasn't feeling that tired\u0026hellip;. so between me and doctors we said, we saw that was working, I didn't have any issues in my pregnancy, so yeah, we saw it was working. (Trial participant 7 intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eSeveral women reported that improvement in their energy levels following SPEBT had been noticed by their partner.\u003c/p\u003e \u003cp\u003e \u003cem\u003eYes, my husband would always say coming up to the next one that was due, he noticed that I was getting a bit tired and just a bit, you know, stayed in bed a bit more and then said he'd noticed that after a few days after the transfusion, I would perk up again and have a bit more energy and work wise and doing the school run so he could see a pattern. (Trial participant 20, intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eIn the staff interviews, clinicians also described seeing health benefits in patients following transfusion.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI think definitely in the patients who have lots of admissions to hospital, I've definitely seen, you know, women have good outcomes following, you know, outpatients have said compared to previous pregnancies when they've had the intervention arm, there's a second pregnancy they've been you know, that much better and flown through the pregnancy and they've not had any of the crises, and did not need any emergency transfusions, so I think definitely it does help prevent a lot of those crises and things. (Consultant Haematologist, Staff interview 12)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eWhilst the interviews highlighted many positive experiences of SPEBT, participants also reported negatives included side effects, issues with cannulation, and the effort/cost of attending appointments.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec29\" class=\"Section2\"\u003e \u003ch2\u003eNegative experiences of transfusion\u003c/h2\u003e \u003cdiv id=\"Sec30\" class=\"Section3\"\u003e \u003ch2\u003eSide-effects\u003c/h2\u003e \u003cp\u003eAll side effects mentioned in the interviews by trial participants or staff were within the range of common, anticipated side effects from SPEBT including dizziness, pins and needles and headaches. One participant explained how she had a reaction and felt dizzy and very unwell which was treated with calcium. Staff also recounted examples of negative reactions from transfusions including citrate toxicity.\u003c/p\u003e \u003cp\u003e \u003cem\u003eThe only side effects we have had were one of the ladies got the toxicity from the citrate, but that is the normal side effect from the transfusion. (Research Nurse, Staff interview 4)\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec31\" class=\"Section2\"\u003e \u003ch2\u003eCannulation\u003c/h2\u003e \u003cp\u003eCannulation had been painful for some patients, either during the procedure or from painful bruising at the cannulation site afterwards. One trial participant explained the pain from the cannulation made them initially consider leaving the trial, though they had persevered and completed the trial.\u003c/p\u003e \u003cp\u003e \u003cem\u003eCannulas, \u0026hellip; it was a new experience for me because I never experienced that\u0026hellip;Because it was very painful, I could not bend my hand. And I was beginning to have terrible pain. Because the Nurse insisted like that was the only place she could place it. So it got too much. (Trial participant 9, intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eOne participant withdrew from the trial after multiple attempts to put in a line which she had found painful and distressing.\u003c/p\u003e \u003cp\u003eFor many women, attending transfusion sessions could involve complex plans to arrange care for other children, and/or take time off work, and travel to the outpatient department.\u003c/p\u003e \u003cp\u003e \u003cem\u003eIt was juggling having a two year old, obviously being pregnant, working and having to fit this in amongst appointments and I had midwife appointments anyway I found [it] hard and then obviously... it was on the Thursday so Thursday was my only day off during the week, which meant I had to then plan child care which I had to pay for because we don't live next to family and on top of paying for child care which was 60/70 pounds a day I then had to obviously pay for my transport to get into London, and my lunch in London. (Trial participant 2, intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec32\" class=\"Section2\"\u003e \u003ch2\u003eReasons for patients withdrawing from trial\u003c/h2\u003e \u003cp\u003eOf the trial participants interviewed, three had withdrawn from the trial before completing. All three had hoped to be allocated to usual care but had been randomised to SPEBT. Two women withdrew before starting SPEBT when they found out they had been allocated to the intervention arm. Another had no strong preference for which trial arm she was allocated, but withdrew from the trial due to experiencing cannulation difficulties; she had multiple unsuccessful cannulations attempts which she found painful and distressing.\u003c/p\u003e \u003cp\u003e \u003cem\u003eThis time, 20 needles did not work, I was so, it was, at that time I felt like I don't want to go for it, like\u0026hellip;I can't tolerate this anymore. I have got bruises and it was so horrible and I had to take some paracetamol for a week. (Trial participant 28, intervention arm, dropped out of trial)\u003c/em\u003e \u003c/p\u003e \u003cdiv id=\"Sec33\" class=\"Section3\"\u003e \u003ch2\u003eTheme 3. Improving recruitment and trial experiences for future trials\u003c/h2\u003e \u003cp\u003eTrial participants, decliners and staff interviewees were asked for suggestions on improving any future trial of SPEBT. Findings provided two subthemes: recommendations on improving recruitment, and recommendations on improving the experience and/or delivery of the trial itself.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec34\" class=\"Section3\"\u003e \u003ch2\u003eImproving trial recruitment\u003c/h2\u003e \u003cp\u003eTo improve recruitment, participants suggested raising general awareness of SPEBT and the clinical trial through increased activity on social media, NHS and charity websites and posters within participating Trusts. This could potentially enable women referred into SCD specialist centres to become aware of the trial, even before being approached by a recruiting clinician.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI've been thinking about this and it can be quite intimidating...women have told me this...when they're approached by a health care professional, so would a half-way house be just giving them some information on social media, targeted stuff, things like on posters, first they'll get an idea when they see it around...on Twitter, on Instagram, whatever else they're looking at...TikTok... just to build awareness rather than trying to recruit, that awareness first of all because so many times that I approached women and they had no idea at all a) that we did research, \"what, are you allowed to do that on pregnant women?\" and then also sickle cell disease as well, so I think building an awareness I think would be a good thing to do. (Research Midwife, Staff interview 7)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eStaff also recommended raising wider awareness among clinical colleagues through existing clinical networks, such as regional Haemoglobinopathy Coordinating Centres (HCC).\u003c/p\u003e \u003cp\u003eAll staff interviewees, as well as many trial participants, considered providing high quality, easily understandable information was crucial to support patient\u0026rsquo;s decision making when assessing the risks and benefits of SPEBT. They suggested including information about: the increased risk of SCD complications during pregnancy; explaining SPEBT including the procedure involved; blood safety and side effects; as well as the potential clinical benefits of SPEBT to pregnant women and their babies. Participants agreed the format of delivering this information was important, particularly highlighting the value of video peer testimonies from patients about their own experiences of transfusion during pregnancy.\u003c/p\u003e \u003cp\u003e \u003cem\u003eHopefully the more the message gets out there and we get involved with user groups. ...I have noticed that people with sickle cell tend to be quite active on social media so anything we can do in that way would be helpful. But yes, I think when we have someone with sickle cell talking [in a video] about it, it is more powerful than somebody like me, because I'm like, for want of a better a term, I'm like from an authoritarian side of things really. Telling them what is all about when I can never know but it is coming across from someone who does know what they are talking about. (Research Midwife, Staff interview 1).\u003c/em\u003e \u003c/p\u003e \u003cp\u003eMaking information openly and easily accessible (e.g. through social media or websites) could enable it to be accessed by partners and families, who can influence patients\u0026rsquo; decisions. Making the information accessible to a multi linguistic population through the use of lay language, pictures and videos could also maximise accessibility.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI think that (using videos] could be helpful because people learn in different ways, sometimes when there's a lot of information on paper, it can be overwhelming and sometimes just having it broken down visually can be helpful for people that need that, as well (Decliner Participant 11)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eSeveral staff suggested that online patient information sessions could incorporate a range of information likely to be of topical interest to patients, as well as information on the trial itself.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eImproving trial experiences\u003c/h3\u003e\n\u003cp\u003eKey recommendations from trial participants to improve any future trial included the need to provide clearer pre-transfusion advice to patients on how to reduce issues with venous access, particularly the need to drink plenty of fluids before the procedure.\u003c/p\u003e \u003cp\u003e \u003cem\u003eSo I think going forward if they just mention make sure when you come for the appointments give yourself enough time to have a good breakfast, drink lots of fluids because that will really help in terms of being able to get your blood vessels and things... because I was like, \u0026lsquo;Oh OK\u0026rsquo;. (Trial participant 2, intervention arm, completer)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eSeveral trial participants who had to juggle childcare commitments and/or long journeys to the hospital suggested that support with childcare and travel costs would be welcomed in a future trial. Staff interviewees also suggested that helping trial participants with travel expenses would help mitigate trial burden and allow more women to take part. Most participants were happy with the proposed choice of trial outcomes, but several participants suggested the use of additional patient reported outcome measures such as the impact of SCD on a patient\u0026rsquo;s occupation (e.g. employment or homecare tasks), their experience of transfusion reactions, and the woman\u0026rsquo;s own perception about how the pregnancy was going.\u003c/p\u003e \u003cp\u003eThe main recommendation which emerged from staff interviews for any future trial was to find ways to ensure adequate apheresis capacity, for example through additional funding or ringfencing resources. Whilst provision of SPEBT for trial patients had not been an issue at some sites, at others it had felt a major struggle.\u003c/p\u003e \u003cp\u003e \u003cem\u003eIf there was a big study you would have to look at the funding better, because we've really struggled in terms of staffing over here. We don't have sickle midwives, we don't have a decent size apheresis team, you know, every exchange we've done as part of TAPS2 we've had to scrabble about and beg for people to put lines in, and beg for apheresis to do it, so if we were to take part it would need to be much better funded. (Obstetric Consultant, Staff interview 11).\u003c/em\u003e \u003c/p\u003e\n\u003ch3\u003eFuture study design\u003c/h3\u003e\n\u003cp\u003eShortly after interviews started, the topic guides for participants and decliners were revised to add a question about whether the interviewee would have been willing to take part in a future observational study. This approach would aim to capture outcome data from pregnant women with SCD who did not want to be randomised but were willing to have their data included in research. Among those who were asked about this, there was strong support from trial participants and decliners for this idea. Eleven of the 12 decliners said that they would have participated in the trial if an observational arm was included.\u003c/p\u003e \u003cp\u003e \u003cem\u003eI would have happily taken part in the [observational study] and if you had things like questionnaires and focus groups, I would happily be a part in it, but anything that kind of is intrusive, then I wouldn't do it. (Decliner, interview 9)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eAll staff interviewees supported including an observational arm to the trial, with many pointing out this this could capture valuable outcome data from patients which would otherwise be missed. Additionally, this would ensure clinical outcomes could be recorded for the increasing number of women already receiving SPEBT who would be excluded from a future trial, but whose data could contribute to our understanding of how best this intervention can be used to improve the health of women with SCD in pregnancy.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis qualitative study explored the views of trial participants, decliners and staff on the feasibility and acceptability of a RCT to assess SPEBT versus usual care in pregnant women with SCD. Whilst SPEBT is increasingly used for women with SCD during pregnancy in clinical practice, recommendations about the use of SPEBT in this population have not yet been incorporated within clinical guidelines due to the paucity of evidence. This study provides the first qualitative report on participant experiences within a feasibility RCT of SPEBT during pregnancy.\u003c/p\u003e \u003cdiv id=\"Sec38\" class=\"Section2\"\u003e \u003ch2\u003eKey findings and interpretation in the context of existing research\u003c/h2\u003e \u003cp\u003eThe target population for the TAPS2 trial represents a unique group of individuals who must manage multiple identities: they are pregnant women; living with a potentially life-threatening chronic condition; and (as in the UK SCD largely affects those from Black African and Black Caribbean backgrounds), they are part of a minority ethnic group. A recognition of these intersecting identities is essential when interpreting the findings from our study.\u003c/p\u003e \u003cp\u003eData from all interview groups agreed that the main factor determining patients\u0026rsquo; willingness to participate in the trial was based on their treatment views and preferences, especially whether potential participants felt the likely benefits of receiving SPEBT outweighed the perceived risks. As pregnant women, potential participants in the TAPS2 trial had to consider the risk/benefit balance to their baby as well as for themselves. Other studies in pregnant women generally show that the primary determinant for agreeing to participate in research is the potential benefit to the health of their baby,[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] a finding echoed in our study. Benefit to the woman\u0026rsquo;s own health and also altruism were secondary motivations mentioned by the participants we interviewed, consistent with a survey investigating the willingness of pregnant women to participate in clinical trials.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] As a patient group who are well-informed about their own condition, we found that in general both decliners and trial participants understood the importance of research and were positive about opportunities to be involved. This was reflected in the willingness of many decliners to take part in our qualitative sub-study: it was the invasive nature of the intervention in TAPS2 which they were less sure about. Our finding that both decliners and trial participants made an informed and careful decision about participation, is also supported by a similar finding from a study of non-pregnant people with SCD invited to take part in high-risk clinical research.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003ePotential participants in the TAPS2 trial were concerned about risk of infection, \u0026lsquo;getting the wrong blood\u0026rsquo; or having side effects. A few believed that SPEBT could lead to sickle crises or adversely affect their pregnancy. Previous literature has reported participants decline participation if the intervention is unacceptable.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] Set against these risks, many patients hoped that SPEBT could lead to a healthier pregnancy and baby. This is consistent with other literature identifying positive attitudes and belief in treatment benefits as facilitators for recruitment.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Many women with mild or asymptomatic SCD questioned the relevance of SPEBT to their situation, especially if they had previous successful pregnancies without needing transfusions. Among women with more severe SCD, motivation to receive SPEBT appeared higher. The finding that patients with SCD evaluate the risk and potential benefits in light of their SCD experiences has been previously reported in people with SCD considering participating in clinical research who were not pregnant.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAll participant groups in our study noted that partner or family views were important to some women in their decision making. Negative experiences of transfusion among relatives or the wider community were also cited as influencing decisions about participation. In a study of reasons for participation in a clinical trial targeting women at a high risk of pre-eclampsia, pregnant women identified that whilst views of significant others was important, it did not influence their decision.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] Our finding that partner or family views were given greater weight in decision making may reflect both the higher-risk nature of the intervention in TAPS2 and also the fact there is considerable lived experience of SCD amongst families and communities due to the high concentration of individuals with SCD within certain groups.\u003c/p\u003e \u003cp\u003eExperiences of trial participation appeared generally positive and acceptable to most patients. Participants allocated to the intervention reported benefits included increased energy, fewer SCD crises, and fewer hospitalisations. No unexpected side effects were reported, and all side effects/reactions appeared to have been treated and/or resolved. With the exception of one patient who withdrew after problems with cannulation, participants in the intervention group generally perceived the intervention as acceptable. Several participants highlighted the cost and effort involved in attending for SPEBT (e.g. travel, childcare), with individual-level barriers such as these commonly cited as reasons for pregnant women not to participate in clinical research trials.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] Among participants allocated to the control group, all reported that taking part in the trial had been acceptable. Trial burden was perceived as minimal, with trial questionnaires and assessments having been completed at routine care appointments for their pregnancy.\u003c/p\u003e \u003cp\u003eFeedback from staff interviewees highlighted difficulties in recruitment caused by the Covid pandemic, with the need to ensure that patients entered the trial before the 18-week entry threshold made more challenging by Covid-related disruptions to healthcare systems and processes. Ensuring timely recruitment was especially difficult if the patient was unsure about participation and needed time to consider their options. A recent mixed-methods study concluded that the pandemic exacerbated negative experiences of healthcare experienced by people living with SCD in the UK.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] Although Covid-19 was not explicitly cited by women in our study as a key influencing factor in participation, it may have adversely impacted recruitment to the main TAPS2 trial (and this study) given the incongruence between advice to \u0026lsquo;shield\u0026rsquo; yet being invited to participate in a trial potentially requiring additional lengthy hospital visits.\u003c/p\u003e \u003cp\u003eThe capacity to provide a well-staffed apheresis service was a key concern among staff, with some staff reporting having to repeatedly chase the service themselves to ensure women allocated to the intervention were offered SPEBT in a timely manner. This finding was reflected by a recent qualitative study of health care professionals in two UK haematology units, which highlighted the complexity of managing transfusions within an already overwhelmed service.[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSCD has been described as one of the most \u0026lsquo;racialized\u0026rsquo; medical conditions,[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] and numerous studies have described the stigma and bias experienced by individuals living with SCD in the UK and other HIC.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] Many individuals with SCD experience a lack of timely and appropriate care (particularly in emergency contexts),[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] and their own often \u0026lsquo;expert\u0026rsquo; understanding of their own condition[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] contrasts with poor knowledge about SCD among many healthcare professionals. Whilst research in the US has identified distrust of the medical community as a barrier to participation in clinical trials,[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] the evidence base for the UK is less clear.[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] In our study only staff explicitly raised this as a potential barrier; however, patient participants may have been unwilling to disclose these sensitive concerns to us during interviews. Clinicians reflected the importance of establishing rapport and trust with their patients in order to support decision making around trial participation. Some trial participants also alluded to good relationships with their clinical team, evidenced by supportive discussions around whether to participate in the trial, and then later on efforts to minimise the impact of trial participation for example by combining hospital visits where possible.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec39\" class=\"Section2\"\u003e \u003ch2\u003eRecommendations for future studies\u003c/h2\u003e \u003cp\u003eBased on our findings, future RCTS of SPEBT in this study population should include recruitment strategies to address concerns from all \u0026lsquo;groups\u0026rsquo; of pregnant women with SCD: those with mild disease, those with severe disease, those with \u0026lsquo;good\u0026rsquo; relationships with their clinical team, and those who have previously had negative experiences within the healthcare system. This includes approaches to address how patients make decisions and factors that influence them including how they evaluate the risk/benefit of SPEBT. We propose three complementary strategies to support future studies of this intervention in this population.\u003c/p\u003e \u003cp\u003e- \u003cem\u003ePatient Education\u003c/em\u003e\u003c/p\u003e \u003cp\u003eFirstly, for all patients: patient education may reduce the barriers to recruiting especially for the many patients who were unwilling to take part; those with \u0026lsquo;mild\u0026rsquo; SCD, those with previously successful pregnancies, those unaware of the increased risks of complications during pregnancy, those with no prior transfusion history and those with concerns about the risks of the intervention, including their significant others. Recommendations on patient education are summarised in Box 2.\u003c/p\u003e \u003cp\u003e- \u003cem\u003eStudy design\u003c/em\u003e\u003c/p\u003e \u003cp\u003eSecondly, through adapting the study design or including strategies to accommodate those with a strong treatment preference. This could be achieved by including an observational arm in a future definitive RCT, or a patient preference RCT design. This option would enable the inclusion of patients who are not willing to be randomised, as well as those currently excluded from the trial e.g. those already receiving SPEBT. Women with SCD in pregnancy are a small patient population and assessing clinical outcomes for this whole patient cohort will inform the overall evidence base of usual care (including SPEBT) during pregnancy. Our data showed that the majority of decliners would have participated in an observational study if the option was provided, and those who randomised to SPEBT but withdrew from the trial because they had not wanted transfusions.\u003c/p\u003e \u003cp\u003e- \u003cem\u003eAdditional support for specific patients\u003c/em\u003e\u003c/p\u003e \u003cp\u003eIn addition, strategies should be particularly considered when recruiting the following patients:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eThose patients who mistrust the intervention and/or clinicians: those who are referred in to specialist centres; and those who have had negative transfusions or medical experiences in the past. Clinicians need to take the time with these patients to build rapport and develop a trusting relationship this will enable these patients to safely disclose and discuss their concerns.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eStrategies to reduce the risk of drop outs which could bias the trial outcomes. For example, for recruiters to discuss and understand the strength of patient treatment preferences in those willing to be randomised so they can communicate the potential implications to patients.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eStrategies to support participants to cover the costs associated with trial participation, in particular, for those in the intervention group \u0026ndash; which would ensure this research is inclusive.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003ctable class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eBox 2. Recommendations on patient education strategies to address barriers to recruitment and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003esupport patient decision-making\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eContent of patient education:\u003c/strong\u003e\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eInformation needs to be balanced and focussed on issues of most concern to patients, as well as addressing common myths or misunderstandings about transfusions.\u003c/li\u003e\n \u003cli\u003eParticipants recommended the use of videoed peer testimonies from patients who have received SPEBT during pregnancy to explain the treatment procedure, their experiences and benefits and side effects, which will also allay cultural mistrust.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eInformation needs to include the increased risk of SCD complications during pregnancy, as well as the potential benefits of transfusion, along with information about the safety and risks of blood transfusions from trusted sources. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eInclusion of videos and information from trusted clinicians, to address those patients with mild SCD who are concerned about the risks and see no benefit from receiving transfusion. \u0026nbsp;\u0026nbsp;Some staff recommended inviting women to come and visit the day unit and talk to other women having transfusions.\u003c/li\u003e\n \u003cli\u003eTo make patients aware of the trial, earlier in pregnancy or ideally even before they became pregnant through more posters in hospital clinics, online information including websites and social media, patient support organisations.\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDelivery of patient education\u003c/strong\u003e\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eOnline information and social media offer a means of getting information to patients not yet recruited, as well as to partners and families who may contribute to the patient\u0026rsquo;s decision.\u003c/li\u003e\n \u003cli\u003eInformation needs to be inclusive to recruit from a diverse population e.g. translated or use of pictures/videos to ensure potential participants with limited English or their partners or families are not excluded.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTo make patients aware of the trial, earlier in pregnancy or ideally even before they became pregnant through posters in hospital clinics and online information including websites and social media, patient support organisations.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e \u003cdiv id=\"Sec40\" class=\"Section3\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eOur study achieved the planned sample size and through purposive sampling, ensured a wide range of experiences and perspectives were sought. We achieved coherent findings, including a depth understanding of the barriers to participation in this study population, drawn from interviews with trial participant, staff and decliners, providing a breadth of perspective. A key limitation to this study was the brevity of some of the interviews, especially those with decliners. Nevertheless, though relatively brief, these interviews provided valuable first-hand insights on why some patients chose not to take part. Whilst many staff interviewees reflected on the issue of patient-clinician trust, this issue was not talked about by trial participants or decliners. It is possible that conducting interviews by phone, and by white interviewers, may have made it harder for women of colour to feel able to share their feelings on these sensitive issues.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eRecognising and addressing the unique concerns and treatment preferences of pregnant women living with Sickle Cell Disease (SCD) through empathetic, participant-centred recruitment and design strategies is essential for maximising recruitment in future trials. We identified that participants treatment preferences and evaluation of the risk-benefits of the intervention played a key role in their decisions to take part in this feasibility trial. These factors need to be considered to avoid unnecessary \u0026lsquo;drop outs\u0026rsquo; in the main trial or potentially biasing the future trial sample. Including an observational study arm as part of a future definitive RCT, along with other strategies, would maximise the evidence base and understanding of clinical outcomes in pregnant women with SCD.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRandomised control trial\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSickle cell disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSPEBT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSerial prophylactic exchange blood transfusion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTAPS2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThe \u003cb\u003eT\u003c/b\u003eransfusion \u003cb\u003eA\u003c/b\u003entenatally in \u003cb\u003eP\u003c/b\u003eregnant Women with \u003cb\u003eS\u003c/b\u003eickle Cell Disease study\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCompleters\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePatients who joined the TAPS2 study and completed participation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDecliners\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePatients who were invited into the trial but declined to participate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eETHICAL APPROVAL AND CONSENT TO PARTICIPATE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study received NHS ethics approval on 28 March 2019 from the London\u0026ndash;Surrey Borders Research Ethics Committee (REC reference 18/LO/2070). Written informed consent was obtained from all participants including consent to their anonymised verbatim quotes being included in publications, with verbal re-consent obtained at the start of the interviews.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT FOR PUBLICATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAVAILABILITY OF DATA AND MATERIALS.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0317-20024). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funder had no role in the design of the study, in the writing of the protocol, or the decision to submit for publication.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORS CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSB led the study, overseeing the design, ethical approval and conduct of the study. SB prepared all study materials, collected study data, led the analysis of decliner interviews, contributed to the analysis of other interviews, and co-led the interpretation of data. LO contributed to the study design, ethical approvals, study materials, study conduct, collected study data, and contributed to data analysis and interpretation. CMcD conducted the analysis of the trial and staff interviews, led the combined analysis, and co-led interpretation of data. VR led ethical approval as part of approvals for the feasibility trial, facilitated participant recruitment, and contributed to data interpretation. JJ contributed to study materials, data interpretation and the plain English summary. EO was chief investigator of the feasibility RCT and led the funding application, and contributed to ethical approval and data interpretation. SB drafted the initial manuscript and with significant input from CMcD and LO. All authors read, reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe want to acknowledge and thank all of the study participants who agreed, and gave up their time, to take part in this study. Many thanks to all those involved at our participating study sites, who recruited trial participants as well as the \u0026lsquo;trial decliners\u0026rsquo; into the study. \u0026nbsp;Finally, we wish to acknowledge our PPI group who reviewed the research proposal and study documents and offered advice from the patients\u0026rsquo; perspective.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWare RE, de Montalembert M, Tshilolo L, Abboud MR: \u003cstrong\u003eSickle cell disease\u003c/strong\u003e. \u003cem\u003eThe Lancet \u003c/em\u003e2017, \u003cstrong\u003e390\u003c/strong\u003e(10091):311-323.\u003c/li\u003e\n\u003cli\u003ePiel FB, Steinberg MH, Rees DC: \u003cstrong\u003eSickle cell disease\u003c/strong\u003e. \u003cem\u003eNew England Journal of Medicine \u003c/em\u003e2017, \u003cstrong\u003e376\u003c/strong\u003e(16):1561-1573.\u003c/li\u003e\n\u003cli\u003eOteng-Ntim E, Ayensah B, Knight M, Howard J: \u003cstrong\u003ePregnancy outcome in patients with sickle cell disease in the UK \u0026ndash; a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease\u003c/strong\u003e. \u003cem\u003eBritish Journal of Haematology \u003c/em\u003e2015, \u003cstrong\u003e169\u003c/strong\u003e(1):129-137.\u003c/li\u003e\n\u003cli\u003eOteng-Ntim E, Meeks D, Seed PT, Webster L, Howard J, Doyle P, Chappell LC: \u003cstrong\u003eAdverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis\u003c/strong\u003e. \u003cem\u003eBlood \u003c/em\u003e2015, \u003cstrong\u003e125\u003c/strong\u003e(21):3316-3325.\u003c/li\u003e\n\u003cli\u003eSmith-Whitley K: \u003cstrong\u003eComplications in pregnant women with sickle cell disease\u003c/strong\u003e. \u003cem\u003eHematology \u003c/em\u003e2019, \u003cstrong\u003e2019\u003c/strong\u003e(1):359-366.\u003c/li\u003e\n\u003cli\u003eEarly ML, Eke AC, Gemmill A, Lanzkron S, Pecker LH: \u003cstrong\u003eSevere maternal morbidity and mortality in sickle cell disease in the National Inpatient Sample, 2012-2018\u003c/strong\u003e. \u003cem\u003eJAMA Network Open \u003c/em\u003e2023, \u003cstrong\u003e6\u003c/strong\u003e(2):e2254552-e2254552.\u003c/li\u003e\n\u003cli\u003eJain D, Atmapoojya P, Colah R, Lodha P: \u003cstrong\u003eSickle cell disease and pregnancy\u003c/strong\u003e. \u003cem\u003eMediterranean journal of hematology and infectious diseases \u003c/em\u003e2019, \u003cstrong\u003e11\u003c/strong\u003e(1).\u003c/li\u003e\n\u003cli\u003eAdesina OO, Brunson A, Fisch SC, Yu B, Mahajan A, Willen SM, Keegan TH, Wun T: \u003cstrong\u003ePregnancy outcomes in women with sickle cell disease in California\u003c/strong\u003e. \u003cem\u003eAmerican journal of hematology \u003c/em\u003e2023, \u003cstrong\u003e98\u003c/strong\u003e(3):440-448.\u003c/li\u003e\n\u003cli\u003eSharif J, Byrd L, Stevenson K, Raddats J, Morsman E, Ryan K: \u003cstrong\u003eTransfusion for sickle cell disease in pregnancy: a single-centre survey\u003c/strong\u003e. \u003cem\u003eTransfusion Medicine \u003c/em\u003e2018, \u003cstrong\u003e28\u003c/strong\u003e(3):231-235.\u003c/li\u003e\n\u003cli\u003eOteng-Ntim E, Pavord S, Howard R, Robinson S, Oakley L, Mackillop L, Pancham S, Howard J, Committee tBSfHG: \u003cstrong\u003eManagement of sickle cell disease in pregnancy. 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In: \u003cem\u003eClinical guideline.\u003c/em\u003e London: NICE; 2012.\u003c/li\u003e\n\u003cli\u003eCorbie-Smith G, Thomas SB, Williams MV, Moody-Ayers S: \u003cstrong\u003eAttitudes and beliefs of african americans toward participation in medical research\u003c/strong\u003e. \u003cem\u003eJournal of General Internal Medicine \u003c/em\u003e1999, \u003cstrong\u003e14\u003c/strong\u003e(9):537-546.\u003c/li\u003e\n\u003cli\u003eSmart A, Harrison E: \u003cstrong\u003eThe under-representation of minority ethnic groups in UK medical research\u003c/strong\u003e. \u003cem\u003eEthnicity \u0026amp; Health \u003c/em\u003e2017, \u003cstrong\u003e22\u003c/strong\u003e(1):65-82.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sickle cell disease, pregnancy, serial prophylactic exchange blood transfusions, qualitative, feasibility trial, recruitment barriers, patient decision-making, treatment preferences","lastPublishedDoi":"10.21203/rs.3.rs-6577176/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6577176/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePregnancy in women living with sickle cell disease (SCD) is associated with increased risk of morbidity and mortality for mother and baby. Outside of pregnancy, serial prophylactic exchange blood transfusion (SPEBT) has proven efficacy as a treatment for acute SCD complications, however, there is inadequate evidence for the safety and benefit for SCD during pregnancy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAim: \u003c/strong\u003eTo explore health professionals and women’s view on the acceptability and feasibility of a randomised control trial of SPEBT versus usual care in pregnant women with SCD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eSemi-structured telephone interviews were conducted with TAPS2 trial participants, trial decliners and clinical staff working on the TAPS2 trial. Interviews were analysed using reflexive thematic analysis\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eWe interviewed 19 trial participants, 12 trial decliners and 15 clinical staff. Three overarching themes were identified; (1) factors affecting patient decisions on participation; (2) experiences of the TAPS2 trial; and (3) recommendation for a future RCT.\u003c/p\u003e\n\u003cp\u003e(1) Motivations for participation included hope that SPEBT would lead to a healthier pregnancy, and/or help other women with SCD. Factors deterring women from participating included concerns about SPEBT, e.g. perceived risk of infections, side effects, or transfusion reactions.\u003c/p\u003e\n\u003cp\u003e(2) Participants allocated to SPEBT recounted health benefits as well as ‘expected’ side effects. The time and cost involved in attending transfusion sessions had been difficult for some patients. For staff at some sites, pressures on local apheresis capacity made delivering the intervention challenging.\u003c/p\u003e\n\u003cp\u003e(3) Participants offered suggestions to improve recruitment and delivery for a definitive trial. Recommendations included: providing accessible, evidenced-based patient education to patients, partners and families to enable informed decision-making. There was strong support for including an observational arm in any future trial to enable patients unwilling, or unable, to be randomised to take part.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eAddressing pregnant SCD women’s treatment concerns and preferences is key to maximising recruitment/retention in future trials. Addressing information gaps or misinformation through accessible patient education is needed. Including an observational study arm as part of a future definitive RCT, along with other highlighted strategies, will ensure that the evidence base and understanding of clinical outcomes in pregnant women with SCD is maximised for future research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e : NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19)\u003c/p\u003e","manuscriptTitle":"The acceptability and feasibility of a randomised controlled trial of serial prophylactic exchange blood transfusion (SPEBT) versus usual care in pregnant women with SCD. A qualitative study with recommendations for recruitment strategies for a future definitive trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-04 08:20:55","doi":"10.21203/rs.3.rs-6577176/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-09T18:17:46+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-20T01:59:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-16T16:48:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-11T20:11:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-10T15:06:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-09T22:11:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"158655615902804836219407602524223644103","date":"2025-06-06T14:48:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"229371100301696100545596621489702785010","date":"2025-06-05T22:09:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-03T15:39:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"194637453824713156099419411597411472454","date":"2025-06-03T12:31:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"48151412493036755000986477231853601666","date":"2025-06-02T11:37:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"225127667902828902651243841363059357548","date":"2025-05-30T11:46:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"209174066663152887306165722498700121801","date":"2025-05-28T14:16:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-28T11:12:04+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-05T05:17:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-03T00:18:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-03T00:16:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2025-05-02T09:25:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c018a35c-0709-4494-9552-0d615667b31e","owner":[],"postedDate":"June 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T17:54:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-04 08:20:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6577176","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6577176","identity":"rs-6577176","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}