Fluidity of Equipoise in a Multi-Centred Pilot RCT:Influences on Clinician Decision-Making in Offering Trial Entry

Objectives: The embedded Qualitative Process Evaluation (QPE) within the CSTICH- Pilot RCT explored facilitators and barriers to recruitment within the Pilot. This study reports a secondary analysis of the overarching theme of Fluidity of Equipoise and the influences on individual and community clinical equipoise around the use of Emergency Cervical Cerclage (ECC). Study design: RCT recruitment assumes clinical equipoise and is defined as genuine uncertainty about an intervention. The ability of trial recruiters to convey this equipoise is also key to participant recruitment and fully informed consent. This exploratory qualitative process evaluation used semi-structured interviews with healthcare professionals (HCPs) involved in trial recruitment. Interviews were audio-recorded, transcribed, and analysed using codebook thematic analysis. Results: 23 HCPs were interviewed. Clinical equipoise around the use of ECC was variable and influenced by a multitude of factors including: (1) obstetric history; (2) gestation; (3) standard site practice, and (4) HCPs previous experiences of ECC. We have interpreted this variability as ‘fluidity of equipoise’. Conclusions: Clinical equipoise around complex pregnancy related conditions was fluid and influenced by the complexities of obstetric histories and gestation at presentation. Equipoise of HCPs involved in trial recruitment should be considered carefully as it can impact the nuances of recruitment, particularly in more challenging trials such as CSTICH-2. Study-specific documents and training can be used to increase staff and patient awareness of uncertainty in the evidence base for interventions under investigation. Further research is needed around the potential consequences of equipoise fluidity

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

C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth—study protocol for a randomised controlled trial

Abstract Background Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach. Methods C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0–27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children’s Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat. Discussion To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies. Trial registration ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018

The role of emergency cervical cerclage in the prevention of pregnancy loss:A systematic review and meta-analysis

Introduction: The optimal management of women presenting with premature cervical dilatation and exposed fetal membranes (CDEM) remains uncertain and controversial. This systematic review forms part of a larger broad systematic review aiming to summarise all existing evidence relating to the management of this condition to inform and support women, their families and healthcare professionals in decision-making.Methods: Five databases were searched according to a prospectively published protocol (CRD42021286275). Inclusion criteria was met if the population included women with CDEM and reported clinical outcomes. Searches identified 3165 Abstracts, 389 full texts were reviewed and 172 studies were eligible for inclusion across 5 comparison groups. 22 papers were included for comparison of emergency cervical cerclage (ECC) and expectant management (EM). 102 observational ECC studies with no comparison group were separately analysed to improve understanding of complication rates of ECC.Results: Women receiving ECC are significantly less likely to experience pregnancy loss than those receiving EM (All pregnancies: RR 0.43 95% CI 0.31–0.59, 14 studies, high risk of bias) and remain pregnant for longer (mean difference 38.82 days 95% CI 24.68–52.95, 11 studies). However, with women receiving ECC remaining pregnant for a mean of 60.5 days (SD 21.2) survival is related to gestation at presentation. Analysis of studies with no comparison group is ongoing.Discussion: ECC appears to reduce the risk of pregnancy loss although the quality of evidence is poor and reporting of complications limited. A prospective randomised trial remains imperative for understanding the role of ECC in preventing pregnancy loss in this condition

What are the differences in pregnancy outcomes and complication rates after emergency cervical cerclage compared to ultrasound-indicated or history-indicated cervical cerclage? A systematic review and meta-analysis

Introduction: There is good evidence to support the use of ultrasound- (USS) or history- indicated cerclage to prevent preterm birth in certain at-risk populations [1]. However, the role of emergency cervical cerclage (ECC) in women with premature cervical dilatation and exposed membranes (CDEM) remains uncertain with a limited evidence-base. This systematic review forms part of a larger broad systematic review of ECC and the management of CDEM.Methods: 5 databases were searched according to a prospectively published protocol (CRD42021286275). Studies were eligible if the population included women with CDEM and reported clinical outcomes. Searches identified 3165 Abstracts, 389 full texts were reviewed and 172 studies eligible for inclusion across 5 comparison groups. Primary outcome was pregnancy loss (miscarriage, neonatal death, termination, stillbirth), secondary outcomes included pregnancy prolongation, preterm birth, and maternal and neonatal outcomes. 23 eligible studies compared ECC with planned cerclage.Results: Women receiving ECC were significantly more likely to experience pregnancy loss than women undergoing a planned cerclage (all pregnancies: RR 3.69 95% CI 2.62–5.20, 21 studies). Women receiving ECC were also more likely to deliver early (PTB <28/40 RR 4.84 95% CI 3.62–6.47, 4 studies), experience premature rupture of membranes (RR 2.57 95% CI 1.53–4.30, 6 studies) and develop chorioamnionitis (RR 3.02 95% CI 2.01–4.54, 9 studies).Discussion: ECC may have a role in the management of women with CDEM however it is important that patients are counselled appropriately regarding the limitations of the evidence and that pregnancy outcomes and complication rates are not conflated with those from planned cerclage

What are the differences in pregnancy outcomes and complication rates after emergency cervical cerclage compared to ultrasound-indicated or history-indicated cervical cerclage? A systematic review and meta-analysis

Introduction: There is good evidence to support the use of ultrasound- (USS) or history- indicated cerclage to prevent preterm birth in certain at-risk populations [1]. However, the role of emergency cervical cerclage (ECC) in women with premature cervical dilatation and exposed membranes (CDEM) remains uncertain with a limited evidence-base. This systematic review forms part of a larger broad systematic review of ECC and the management of CDEM.Methods: 5 databases were searched according to a prospectively published protocol (CRD42021286275). Studies were eligible if the population included women with CDEM and reported clinical outcomes. Searches identified 3165 Abstracts, 389 full texts were reviewed and 172 studies eligible for inclusion across 5 comparison groups. Primary outcome was pregnancy loss (miscarriage, neonatal death, termination, stillbirth), secondary outcomes included pregnancy prolongation, preterm birth, and maternal and neonatal outcomes. 23 eligible studies compared ECC with planned cerclage.Results: Women receiving ECC were significantly more likely to experience pregnancy loss than women undergoing a planned cerclage (all pregnancies: RR 3.69 95% CI 2.62–5.20, 21 studies). Women receiving ECC were also more likely to deliver early (PTB <28/40 RR 4.84 95% CI 3.62–6.47, 4 studies), experience premature rupture of membranes (RR 2.57 95% CI 1.53–4.30, 6 studies) and develop chorioamnionitis (RR 3.02 95% CI 2.01–4.54, 9 studies).Discussion: ECC may have a role in the management of women with CDEM however it is important that patients are counselled appropriately regarding the limitations of the evidence and that pregnancy outcomes and complication rates are not conflated with those from planned cerclage