The acceptability of emergency cervical cerclage within a randomised controlled trial for cervical dilatation with exposed membranes at 16 – 27 + 6 weeks gestation: Findings from a qualitative process evaluation of the C-STICH2 pilot trial

Objective: C-STICH2 is a randomised controlled trial of emergency cervical cerclage (ECC) vs routine care in women who present in pregnancy with premature cervical dilatation and exposed unruptured fetal membranes. Within the proposed trial an internal pilot was performed with an embedded qualitative process evaluation (QPE) to explore the feasibility of recruitment. The QPE aimed to collect and analyse data exploring the experiences of health care professionals (HCPs) involved in recruitment, and women approached about the trial. Methods: Semi-structured interviews (telephone or face-to-face) were held with eligible participants who had consented to participate in the QPE. Interviews were audio-recorded, transcribed, and analysed to identify main themes. Interview transcripts were analysed using qualitative thematic analysis (QTA). Results: 11 women and 23 HCPs were interviewed. Three super-ordinate themes of Fluidity of Equipoise, A Complex Obstetric History , and the Influence of Gestation were identified. Within these, the five main themes which influenced trial participation were: 1) Complex decision-making processes; 2) Predicting outcomes; 3) The importance of terminology and initial RCT approach; 4) Women ’ s understanding of the need for research in this area; 5) Changes in practice which are trial influenced. Conclusions: For both HCPs and women and their families, there was a conflation of the potential risks and outcomes of ECC with those of elective cerclage and the complexity around ECC placement was not always well understood by those with less experience and understanding of the intervention. Decision making was shown to be complex and multi-factorial for both HCPs and women. For complex trials in rare conditions with treatment uncertainty, clinical equipoise is likely to be fluid and influenced by multiple factors.


Introduction
Elective cerclage is an established treatment in the prevention of second trimester miscarriage and preterm birth. Most elective cerclage are placed based on previous history or ultrasound indicated based on a shortened, closed cervix. ECC involves placing a cerclage when there is cervical dilatation with exposed unruptured fetal membranes. Under these circumstances the evidence is unclear regarding the risks and benefits of ECC placement. NICE Guidelines for Preterm Birth [1] advise considering ECC but acknowledges this uncertainty and recommend further RCTs or a well-designed observational study. Usual care with or without ECC may include hospital admission, antibiotics, bed rest and treatments such as progesterone or tocolytics as indicated by individual circumstances. C-STICH2 is a national RCT funded by the NIHR comparing the use of ECC with expectant management in preventing pregnancy loss in women presenting with cervical dilatation and exposed unruptured fetal membranes between 16 + 0 and 27 + 6 weeks of pregnancy. Historically RCTs are challenging to recruit to [2]. RCTs in maternity care are perceived to be more challenging due to the potential complexity of the population and whether the trial is focused on pregnancy management options or improving the health of baby or mother [3,11].
The C-STICH2 pilot embedded QPE was designed to explore the feasibility and acceptability of ECC within the context of randomisation, and experiences of women and HCPs in accepting and offering trial entry. The QPE aimed to collect and analyse data exploring the experiences of HCPs, and potential or recruited participants to identify themes and indicate how trial processes (design and recruitment) could be optimised. Identified barriers and facilitators to RCT recruitment for both women and HCPs were used to provide learning which could be implemented to improve recruitment [4].

Study aims
The qualitative process evaluation aimed to: • qualitatively explore the feasibility, acceptability and appropriateness of the trial and intervention for women and healthcare professionals (HCPs).

Qualitative process evaluation
The QPE used semi-structured qualitative interviews to collect data. Semi-structured interviews follow a guide and can be used to explore participants' thoughts, beliefs, and feelings around a pre-specified topic [5].

Participant eligibility and recruitment Women
Women were eligible to participate in the QPE having been approached about C-STICH2, regardless of their agreement to participate in the trial. A discussion about consent to contact took place alongside or following the trial approach at site. All interviews took place using spoken English, therefore for inclusion women needed to be able to converse in English.

Healthcare professionals
HCPs were eligible for the QPE if they had been involved in caring for women with this condition and either involved in discussions about eligibility of potential participants who were being considered for C-STICH2 participation, or in the trial approach. Direct contact with HCPs was made by the QRT following either screening or recruitment of women into the trial and/or the QPE.

Data collection
Semi-structured interview guides were developed for women and HCPs and developed flexibly and iteratively as interviews progressed ( Supplementary Information 1 and 2). Interviews took place either faceto-face or via telephone. Signed written consent was received for all interviews prior to participation. Confidentiality and right to withdraw was discussed further before audio-recording of each interview began and consent was verbally reconfirmed. Interview recordings were transcribed by a GDPR compliant transcription company. Transcripts were anonymised and checked against the recordings.

Data analysis Qualitative thematic analysis
Interview transcripts were uploaded to NVivo-12 Plus and analysed using QTA. QTA is an inductive approach which searches for patterns within the data, whilst allowing for unexpected findings to also be considered. The interview guides were utilised to explore the data and identify themes. Each transcript was read and coded line by line. Clusters of similar codes were grouped to form describable themes. These were grouped into themes across the data set. As the interviews progressed, transcripts were re-read and re-analyzed to identify other occurrences of these initial codes and themes. Further interviews were analyzed using the codes and themes generated in the initial coding and analysis, as well as exploration and identification of any further codes and themes.

PPI involvement
Study design, recruitment pathways, inclusion and exclusion criteria were all discussed with PPI representatives prior to starting the QPE.

Participant recruitment
Eleven women were interviewed: those who had declined randomisation (n = 8); and those who accepted randomisation (ECC = 2 and expectant management = 1). Twenty-three HCPs were interviewed: research midwives (n = 10), and senior clinicians (n = 13). Tables 1 and 2 describe demographic information for women and HCPs.

Qualitative thematic analysis
Following QTA of all transcripts, three super-ordinate themes of Fluidity of Equipoise, A Complex Obstetric History, and the Influence of Gestation were identified as influencing factors on lower-level (main) themes. Five main themes were identified as factors and beliefs which affected trial offering and acceptance: 1) Decision-making is complex for HCPs and women 2) Making predictions 3) The influence of terminology and pre-priming around ECC 4) Women's understanding of the need for research in this area 5) Changes in practice which are trial influenced Tables which illustrate these main themes are attached in supplementary information, A4: Complex Decision Making, and A5 Main Themes 2-5 (Tables 3 and 4, respectively).
Interactions between super-ordinate and main themes are modelled in Figs. 1 and 2.

Fluidity of equipoise
Individual clinician's equipoise was shown to be fluid, meaning it was dynamic rather than static and related exclusively to the intervention within the context of multiple influencing factors for each individual decision. Influencing factors for decisions surrounding the offer  Table 3 Decision making is complex and influenced by multiple factors.

Sub-themes Illustrative quotes
It is not an easy decision to make "The real benefit of the trial, this is the real perk is you are faced with this awful decision, you will never know if it was the right one you made but you've still got the potential to feel guilty if you picked one over the other, whereas this takes it out of your hands, it makes the decision for you, and it might improve care generally so that other people don't have to make that awful decision." (C20 -Research Midwife) "But it still feels difficult to make a decision once potentially [you know] you could lose your baby. (W17 -declined randomisationpreference for ECC)" "But it was such a difficult choice to make that one, especially when your head is already all over the place, because you're just like oh my god they have already… they told us at [hospital] that was absolutely no hope, and we would deliver her that night and it would just be a late term miscarriage, we wouldn't even get a birth certificate, you wouldn't get a death certificate, because she was under the 24 weeks." (W23 -declined randomisationpreference for expectant management) "It's difficult because you have to counsel the women in equipoise, you have to say there are these options available of do nothing or give you progesterone which is probably just witchcraft, versus put a stitch in, my belief is put a stitch in but we don't really know […] do you want a stitch, or do you want to be part of this trial that will randomise you to nothing/ witchcraft, I don't say that, but to nothing/witchcraft versus an active step, but that then goes back to the we're just going to toss a coin and see whether we fulfil your wish to save your baby, I think that's quite hard to recruit them into the trial, because that's the choice they are faced with." (C29 -Senior Clinician) Just knowing what [you have] to do it feels like there is no decision to be made.
"Yeah pretty much we said give us five minutes but actually probably within about a minute of them leaving the room we'd already decided, so it wasn't too bad […] So yeah, we really had to… it was our only option really." (W13 -declined randomisationpreference for ECC) "In my head I knew that I wanted the stitch, at the end of the day because I was umm-ing and ah-ing and I was like well no I do want it, yeah. I had already made that decision before they even explained anything, I think you know yeah I want to try or… unless they had told us I'm going to give you the stitch and you're going to die, that's probably the only way I wouldn't have had the stitch sort of thing." (W06 -declined randomisationpreference for ECC) "I think we reached the decision ourselves as well, it was a no brainer to us, and it seemed common sense to take that small risk of the membranes rupturing, they could rupture anyhow, and it just seemed like the most logical decision to make at that time that perhaps as specialists…? I don't know." (W07 -declined randomisationpreference for ECC).

Cultural and religious influences impact on decision making
"She was very religious, and so was her partner, and they were not native to this country and she was saying, "I want my family nearby me, I want my friends nearby me," and a lot of her friends and family were people from the church. So she sought out their opinion in this as well, and she I guess interpreted that situation as leaving it down to God, being randomised that is" (C01-Research midwife) "I was just like if it picks me then I guess that's great and if it doesn't I have the saying of saying 'Alhamdulillah' which is it's worked out for the best, God knows everything. So I kind of just went along with it" (W19 -accepted randomisationrandomised to ECC [failed]) "I think religion is one of the things that informs our health, informing some of our… we were like okay we don't know really the situation, and we have got this very strong faith that if a life has to come in this world it will come at the time when it has to come, and at the place where it has to come, and the time for life and death is already determined by God, and no matter what you do you cannot probably influence it much. So we were like okay if this is something that is already not in our hands, and anyway we go for the procedure or not we cannot stop labour from happening, and if we go for the procedure we are going to probably introduce certain types of risks if we get procedure, and if you don't go for it then there's not much evidence that it will help, any implication really." (W24 -declined randomisationpreference for expectant management) Previous experiences of offering ECC (for HCPs) "Most consultants have experience that this is something that we have seen work in certain circumstances, even the most negative people will have had experience of it's worked in that particular person, and then women are more than happy to accept something that they think might work." (C03 -Senior Clinician) "The few cases I had seen had all had emergency cerclage and some had, well I think the majority had not been successful. But my understanding is that if we did nothing there is a very high chance they would go on to labour and deliver, but I just wasn't clear whether that chance came down significantly by actually doing the suture." (C17 -Senior Clinician) Which clinician (is available) matters "I think it's really important to collect up the factors that might influence it, particularly who does the stitch, how many stitches they have done before, what experience they have got" (C05 -Senior Clinician) There is a wide diversity of information sources, and information seeking behaviourand these have different levels of influence on individual decision making "Another element which is the foreign population where they can consult with doctors outside the UK, and then the opinions become even wider. So I tend to investigate these things with patients to be honest because patients are well "So what they did was they kept me there overnight, and of course I was frantically on the internet searching for anything that I could find to help me, because at that point I was only 20 plus two, and I read that bedrest on an inverted tilt helps, so I was like, "Right put my bed in an inverted tilt," and they were like what? And I was like, "Just put my bed in inverted tilt."" (W23 -declined randomisationpreference for expectant management) "After she gave me the leaflet I was reading through it, and obviously this was the night before, and I'm quite a big researcher myself so straight onto everything I could find on the internet, onto every [charity] website that I could find, every leaflet there was." (W15 -Randomised to ECC) Is doing something always better than doing nothing? The perception of an active versus a passive treatment option.
"I think that is quite a difficult concept for people to sign up to when one option is something and one option is nothing, because sometimes if there are two treatments and you say I don't know which is better they will say well actually okay if you don't know which is better, then flip the coin essentially and I'll see which one I get, but if you're saying one is something and one is nothing I think that is harder for families to give themselves that lack of choice in." (C04 -Senior Clinician) "I think the challenge is in terms of if you offer someone an intervention that might work, so you mentioned suture, then even though it is maybe the high risk of rupturing the membranes, blah, blah, blah, I think people will latch on to that, and will want to try something rather than do nothing at all." (C09 -Senior Clinician) This definition encompasses the finding that the evidence from the QPE and fluidity of equipoise relates to individuals potentially moving in and out of equipoise on a case-by-case basis due to their interpretation of each specific case, and their clinical experience of such cases, and the use of ECC in similar or different scenarios, rather than being in equipoise or having a lack of equipoise in all circumstances for this intervention. This also linked to Decision-making is Complex and the Influence of Terminology (3.4.1 and 3.4.3). Some women were also influenced by their perceptions of the HCPs preferences.

"I could be wrong, but I always thought that yes they [surgeons] wanted us to go ahead with the stitch." (W07 -Declined randomisation -Opted for emergency cervical cerclage)
A complex obstetric history A complex obstetric history was identified as influencing HCPs and women (see 3.4.1 Decision Making is Complex). Differences in the perception of 'risk' for the current pregnancy were based on previous history of pregnancy loss or struggles with infertility.
"I think the women who being prima gravida, in their first pregnancy they are more of the, this is what life and popular culture tells you to expect, and actually it's massively shocking to say this is all going horribly wrong guys and we have… there may or may not be something we can do for you, and it may be a situation where we say we can't do anything at all, and you may end up with a horribly disabled child at the end of it. It is a massive shock, and I think that can make them less able to accept it than maybe a mum who has lost her baby before, because she's actually aware that bad things happen." (C29 -Senior Clinician) This meant that for families with a complex obstetric history, treatment options were identified as preference, but actually were more about what was considered to be necessity. In this context, randomisation was perceived as risking losing access to this 'preferred' treatment.
"It [expectant management] wasn't really an option for us, because of my age and it took us a while to get pregnant, and we'd already had a miscarriage, we just felt really, it's just we have to do everything we could to at least try" (W13 -declined randomisationopted for emergency cervical cerclage)

Influence of gestation
The influence of gestation described the way in which usual management of cervical dilatation within the target population (16-27 + 6 weeks) was also predicated on gestation at presentation. Gestational influence was identified to vary across 3 gestational windows: previability (<22 weeks), peri-viability and beyond 24 weeks. At earlier gestations the inherent perception of risk of immediate pregnancy loss "Probably about two thirds of the women want… "we want a stitch, we just want a stitch, I've read about it, I've been on Facebook", I've got one at the moment she's been on the Facebook group she says, "I know it's bad for me but everyone on Facebook says you've got to get your doctor to put a stitch in, they all say you've got… if your cervix gets short you've got to get your consultant to put a stitch in and you've got to stay in bed the whole pregnancy."" (C02 -Senior Clinician) Please do anythingsaving my baby "I feel that in the moment the other physical risks to the women I feel that for me if I was in that position I think it would be more than okay to take that risk knowing that the benefit you may get from that.    "A few years ago doing a rescue stitch at about 20 weeks, 21 weeks maybe and she only got a couple of weeks, she was clearly infected afterwards when I had put it in and she sromed at about 23 weeks, but she has taken her baby home and supposedly it's intact, but that for me was a big failure for me, but actually she was absolutely ecstatic and more than happy and she's got her baby, whereas I was thinking, oh my God at 23

Main theme and description
Sub-theme Illustrative quotes they might present via the prematurity clinic, they might present via the assessment unit, they might present via delivery suite, via ultrasound, and to get a consistency of approach is quite tricky" (C02 -Senior Clinician).
"I think with this bulging membranes population, I think, if they come in the middle of the night, someone quite junior or even a midwife they know that there is a possibility because they hear that we've rescued these situations, but actually maybe they don't quite realise how difficult that is, and actually it's 50/50 whether we can get a stitch in" (C08 -Senior Clinician).
"I think probably before the trial if somebody had presented I think probably we wouldn't necessarily… I might not have seen it but I think the initial counselling probably would have been this is happening, we could give you a stitch do you want to try it?" (C28 -Research Midwife) "A consultant assessed me and she said indeed I was 23 mm dilated, well that's what they saw at the time, and that they could see the membranes coming down into my vagina. So they admitted me that day and they discussed briefly the issues and said that they would be doing a stitch the following day." (W17declined randomisation, preference for ECC) "He said that there could be a stitch and what would I prefer. At that time I didn't know what would be the best option, so we didn't have to make a decision, we weren't pressured to make a decision." (W07 -declined randomisation for ECC) Who wouldn't want to be rescued? Emergencies are time pressuredbut there is no certainty of outcome.
"Rescue does give the connotation that we are the big hero that's going to come in and save the baby for them doesn't it? It does put that whole dramatic perspective on it, whatever dramatic perspective you get from things like wording around a crash section as well. It has got a bit embedded in the terminology hasn't it?
(continued on next page) E. Molloy et al.

Risk of randomisation
"For me it was like okay so all of these inputs and whatever I could get at that point we just thought that probably if it has to happen it has to happen whether we go for this or not, and we have got all these extra things and we don't have any scientific evidence, nothing to rely upon, we don't have any specific statistics and not anything about… even the risks we don't know what's the exact percentage of people who actually go into labour or who actually have these cervical damage or whatever. So we were like okay we don't have anything to rely upon then probably best that we just leave it to nature, and it will just take care of it. So that's how we then decided that okay not going to go for it" (W24 -declined randomisationpreference for EM) "I am very pro research and I understand the importance of knowing… I understand that the more that you do these studies the more information that you have and therefore the more information you can give to mothers, because I would have liked that information for me, I would have liked to "I was just like if it picks me then I guess that's great and if it doesn't I have the saying of saying 'Alhamdulillah' which is it's worked out for the best, God knows everything. So I kind of just went along with it." (W17agreed to randomisation) was deemed to outweigh any risks of ECC placement.
"If you examined someone and you could see the membranes and they were less than 24 weeks you would call it an inevitable miscarriage. So, you would expect that if you see that scenario that they are likely to miscarry if you don't do anything" (C04 -Senior Clinician) The closer a pregnancy was to viability the more risk was perceived around ECC (dependant on clinical equipoise) i.e., ROM.  "…the rescue cerclage itself could trigger labour, and the procedure is a high-risk procedure in terms of breaking the membranes." (C15 -Senior Clinician) Many HCPs indicated they would not offer ECC after 24-weeks because of uncertainty about outcomes and lack of experience to inform the evidence-base, and because of improvements in neonatal care.
"We're not used to dealing with or we're absolutely not used to placing sutures at that gestation [over 24 weeks] so I think it would just be that we would be venturing into unknown territory with it, (C17 -Senior Clinician) "I know NICE talk about you could put sutures up to 28 weeks, but we don't tend to do that just because I think neonatal care is so much more advanced, and I think as I say my concern is there's usually infection around in these extremely premature babies, and to leave a prem baby that's infected is far worse than getting a slightly more premature baby out that's not as infected in my opinion and therefore we generally just leave them to it as such." (C08 -Senior Clinician) Women's decision-making about trial entry was also based on their own perceptions of gestation, viability, and risk.
"We said we can't justify doing it [trial entry] at 24 weeks because the survival rate the statistics at that time we were given were very low, but if my body can get to 25 weeks, because they jump so much higher, then we wanted to go ahead with the trial and try and get some more weeks after that" (W09 -accepted randomisationrandomised to expectant management)

Decision-making is complex for HCPs and women
Both HCP and women experienced complex decision-making processes around trial offering and entry which were influenced by multiple factors. See Table 3 (Complex Decision-Making).
Many HCPs and some women viewed expectant management as offering no treatment. This perception of an active versus passive treatment influenced HCPs comfort with offering the trial, and assumptions about what women might want. Women's decision-making was also predicated on prioritising their baby's safety above their own.
"I've got to save myself I know, but I just said just leave her in as long as my life is not immediately at risk" (W06 -Declined randomisation -Opted for emergency cervical cerclage) Information seeking was important for many women following diagnosis this sometimes resulted in conflating ECC outcomes with elective cerclage outcomes which influenced treatment preferences. For some HCPs, availability of clinicians to perform ECC influenced trial offering.

Making predictions
HCPs with previous experiences of ECC and/or of this condition tried to predict the likelihood of successful ECC placement and continuation of this pregnancy. Predictions were influenced by current presentation and perceptions of what worked last time.
"You try to pick out of what you have done which are the ones that are going to work and which aren't." (C02 Senior Clinician) Predicting outcomes also implied judgement of definitions of success. HCPs and women's perceptions of success did not always coincide ( Table 4).

The influence of terminology and pre-priming around Emergency Cervical Cerclage
Women and HCPs both described that 'rescue' carried different connotations of success, which may influence likelihood of offering or accepting randomisation. Terminology at sites between HCPs influenced ECC perception. This subsequently influenced site equipoise and led to pre-priming. Pre-priming was defined as the discussion of ECC as a management option prior to discussion around trial-entry and the lack of consensus of the evidence-base.
"We went for our 20-week scan, found that basically we needed a stitch" (W12 -Declined randomisation -Opted for emergency cervical cerclage)

Women's understanding of the need for research in this area
Women voiced frustration about the lack of clear information around ECC outcomes and wanted more research to support their own decisionmaking.
"I would have liked to know which of the two options was better, and you can only do that with having done studies, but I didn't feel like I could take the chance of having to stay in hospital [for EM]." (W17 -declined randomisationopted for emergency cervical cerclage)

Changes in practice which are trial influenced
Usual practice around ECC varied between sites and was often based on HCP experience. Implementing C-STICH2 allowed some sites to expand their practice within the trial.
"So I feel more comfortable in putting it in women that ordinarily I would have thought no I probably shouldn't be doing that, it gives us the push to say this is something that's okay to do." (CO3 -Senior Clinician).

Main findings
The main influences on HCPs trial offering trial entry were complex obstetric history interlinked with influence of gestation and fluidity of equipoise.
Clinical expertise and usual practice around ECC varied. Decisionmaking for women and HCP was complex and multi-factorial and HCP equipoise was fluid influenced by gestation and obstetric history. Women's decision-making was influenced by their own obstetric history, perceptions of risks of ECC and expectant management, lack of distinction between elective cerclage and ECC, and pre-priming.

Interpretation
Research has indicated that one overriding focus for women who agree to clinical trial entry in otherwise normal pregnancies is keeping baby free from harm [6]. Management preferences varied with gestational age, and gestational age at presentation influenced trial-offering and acceptability of randomisation/ECC. There is a potential ethical dilemma around using ECC on the cusp of viability [14], potentially translating pre-viable pregnancies to borderline survival, with consequential long-term outcomes related to extreme prematurity [13,15].
There are limited data on obstetric emergency research [9] although barriers and facilitators to trial entry in maternity care have been described [8,[10][11][12].
Trials are at increased risk of low recruitment where clinical equipoise is in doubt or where a rare condition means experience across the clinical body is lower [14]. Miller and Joffe argue that RCTs and equipoise are necessary to continue to evaluate interventions without an adequate evidence base, to support implementation as standard care [15]. This assumes an infrequently used intervention where participants receive usual care outside of the trial. Within C-STICH2, ECC may be usual site practice thus randomisation to expectant managment, may not be considered usual care as implemented outside of the trial.
Perceived risks of randomisation to non-active treatment arms influence HCPs decision making about offering trial entry [19]. Some HCPs considered expectant management as comparable to offering 'nothing' which implied negative consequences.
Research around randomisation descriptions indicates that where HCPs find gambling metaphors helpful, participants dislike the idea of random chance and do not find metaphors such as 'tossing a coin' or 'drawing straws' useful [2,8,16]. Women may not want to leave their babies survival 'to chance', and some participants do not want to lose decision making control [2] women also declined randomisation because they wanted personalised decisions made about their care [7].
Terminology used at sites had implications about the perception of ECC. Using 'rescue' implied higher chances of success. Careful and considered use of language is important in research around obstetric emergencies [17]. The lack of consistent terminology may exacerbate elective cerclage and ECC conflation given the more widespread knowledge around elective cerclage placement and outcomes [18]. Many online resources discuss elective cerclage and placement contraindications [19][20][21]. None provide information about iatrogenic risks of ECC [22].
Risk limitation is described as a reason for declining entry into trials in pregnancy [24,25]. We showed that women with an intervention preference were unwilling to accept randomisation as they perceived this risked losing access to their preferred option, and therefore increased the threat to their pregnancy continuation [7,10]. While women understood the necessity for the trial, their altruism was predicated on perceived risks to their baby [6,23,26,27].
Reasons for declining randomisation included practical considerations [8], for example, randomisation to extended bed-rest as a hospital in-patient, with a young family at home. Not all women who declined trial entry preferred ECC. Some participants reported decision-making being influenced by faith-based beliefs. Either that randomisation was contrary to a larger (natural) plan as to how/if the pregnancy should continue [8] or conversely that by accepting randomisation, the outcome would be the will of God/Allah.
Women who entered C-STICH2 talked about trusting the recruiting team at site. Open communication and having questions answered has been indicated to increase trial participation [12,23]. When recruiting HCPs were not those performing the procedure this increased families confidence that the trial information was not biased.

Strengths
A range of HCPs (n = 23) participated in the QPE across multiple sites. This captured the range of experience and a more accurate snapshot of current UK ECC practice. Over half the women interviewed declined trial entry (n = 8). This gave a depth of understanding of the myriad of influences on women's decision-making in complex situations.

Limitations
Only a small number of interviews with women were undertaken. The women interviewed who had accepted randomisation were recruited through one site where ECC is not offered as usual practice and is currently only offered within C-STICH2. These women may have accepted randomisation hoping to receive ECC as their preferred intervention.

Practical recommendations
1. Some sites may find having a robust on-call rota of experienced HCPs useful (whilst ensuring that this does not induce pre-priming).
2. Support and education around gestational cut-off guidelines may increase the likelihood of sites approaching participants who present outside of locally accepted limits for ECC (e.g., 24-wks plus). 3. Performing earlier qualitative studies exploring clinical equipoise may highlight areas which influence intervention understanding prior to trial initiation.

Research recommendations
1. Recruitment to RCTs may be improved by increasing awareness of the evidence-base around the question therefore reducing the risks of pre-priming. 2. Continuous support and education at sites may increase the likelihood of potential participants being approached appropriately. 3. Continuing complex RCTs helps support evidence-based discussions and informed decision-making for potential participants. 4. Embedding QPEs in a pilot trial can influence recruitment approaches in real time.

Conclusions
Decision-making about offering and accepting trial entry was shown to be complex and multi-factorial for HCPs and women, respectively. Where complex trials focus on rare conditions with treatment uncertainty, equipoise is likely to be fluid and influenced by multiple factors. Within C-STICH2 the factors with the widest influence on equipoise were gestational age at presentation, and complex obstetric histories. Women's' personal circumstances, pre-existing views including prepriming for ECC, understanding of the options, and trust in the trial team all influence decisions to accept or decline randomisation. Any or all of these may be relevant at the same time. Not all HCPs involved in trials will discuss participation where they perceive this would have negative consequences for a potential participant. Embedding qualitative research into the pilot stage of complex RCTs allows the exposition and exploration of factors which may influence trial offering and entry, and thus optimises the chances of successful trial delivery.

Declaration of Competing Interest
Ms Eleanor Molloy is a Qualitative Research Fellow in the Institute of Applied Health Research at the University of Birmingham. Eleanor is an experienced qualitative researcher whose main interests are around challenging, and sensitive research questions in pregnancy and birth healthcare, and access to care for marginalised populations. Eleanor is also completing her Health Sciences PhD at Warwick Medical School, University of Warwick. Eleanor's PhD is a mixedmethods study exploring the experiences of marginalized groups when seeking support for PTSD symptoms related to birth trauma. Dr Nicole Pilarski is an obstetrics and gynaecology trainee and is currently undertaking a postgraduate research degree at the University of Birmingham. Nicole has an interest in clinical obstetrics research including prevention of preterm birth and the use of emergency cervical cerclage. Dr Victoria Hodgetts-Morton is an NIHR clinical lecturer and trainee in Obstetrics and Gynaecology with a specialist interest in preterm birth prevention. She is the research fellow on two NIHR HTA funded preterm birth prevention trials C-STICH and C-STICH2. Dr Hodgetts-Morton is co-founder of the preterm birth prevention service at Birmingham Women's Hospital and works at a regional and national level to improve care in the prediction and management of preterm birth.
Dr Laura Jones is an Associate Professor of Qualitative and Mixed-Methods Applied Health Research in the Institute of Applied Health Research at the University of Birmingham. Laura is an experienced applied health researcher, and she focusses on undertaking qualitative and mixed-methods research to answer challenging questions around women's and maternal health and within maternity care. She is the chief investigator of the largest UK qualitative study of female genital mutilation. Laura also leads several qualitative process evaluations in trials of women's and maternal health. This research focuses on successful design and delivery of challenging and complex trials.