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Objective To determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes.Design A multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation.Setting Three inner-city UK National Health Service hospitals in London.Participants Pregnant women with gestational diabetes treated with medication.Interventions 2 g of metformin (intervention) or placebo (control) from delivery until 1 year postnatally.Primary outcome measures Rates of recruitment, randomisation, follow-up, attrition and adherence to the intervention.Secondary outcome measures Preliminary estimates of glycaemic effects, qualitative exploration, acceptability of the intervention and costs.Results Out of 302 eligible women, 57.9% (175/302) were recruited. We randomised 82.3% (144/175) of those recruited, with 71 women in the metformin group and 73 women in the placebo group. Of the participants remaining in the study and providing any adherence information, 54.1% (59/109) took at least 75% of the target intervention dose; the overall mean adherence was 64% (SD 33.6). Study procedures were found to be acceptable to women and healthcare professionals. An increased perceived risk of developing type 2 diabetes, or a positive experience of taking metformin during pregnancy, encouraged participation and adherence to the intervention. Barriers to adherence included disruption to the medication schedule caused by the washout periods ahead of each study visit or having insufficient daily reminders.Conclusions It is feasible to run a full-scale definitive trial on the effectiveness of metformin to prevent type 2 diabetes in women with gestational diabetes, during the early postnatal period. Adherence and engagement with the study could be improved with more regular reminders and potentially the addition of ongoing educational or peer support to reinforce messages around type 2 diabetes prevention.Trial registration number ISRCTN20930880.

Objective The ACROBAT pilot trial of early cryoprecipitate for severe postpartum haemorrhage used deferred consent procedures. Pretrial discussions with a patient and public involvement group found mixed views towards deferred consent. This study aimed to build an understanding of how the deferred consent procedures worked in practice, to inform plans for a full-scale trial.Setting Qualitative interview study within a cluster-randomised pilot trial, involving four London maternity services.Participants Individual interviews were conducted postnatally with 10 women who had received blood transfusion for severe postpartum haemorrhage and had consented to the trial. We also interviewed four ‘recruiters’—two research midwives and two clinical trials practitioners who conducted trial recruitment.Results Consent procedures in the ACROBAT pilot trial were generally acceptable and the intervention was viewed as low risk, but most women did not remember much about the consent conversation. As per trial protocol, recruiters sought to consent women before hospital discharge, but this time pressure had to be balanced against the need to ensure women were not approached when distressed or very unwell. Extra efforts had to be made to communicate trial information to women due to the exhaustion of their recovery and competing demands for their attention. Participant information was further complicated by explanations about the cluster design and change in transfusion process, even though the consent sought was for access to medical data.Conclusion Our findings indicate that deferred consent procedures raise similar concerns as taking consent when emergency obstetric research is occurring—that is, the risk that participants may conflate research with clinical care, and that their ability to process trial information may be impacted by the stressful nature of recovery and newborn care. A future trial may support more meaningful informed consent by extending the window of consent discussion and ensuring trial information is minimal and easy to understand.Trial registration number ISRCTN12146519.

Abstract Background Subfertility is a common problem for which in vitro fertilisation (IVF) treatment is commonly recommended. Success rates following IVF are suboptimal and have remained static over the last few years. This imposes a considerable financial burden on overstretched healthcare resources. Time-lapse imaging (TLI) of developing embryos in IVF treatment is hypothesised to improve the success rates of treatment. This may be either by providing undisturbed culture conditions or by improving the predictive accuracy for optimal embryo selection from a cohort of available embryos. However, the current best evidence for its effectiveness is inconclusive. Methods The time-lapse imaging trial is a pragmatic, multi-centre, three-arm parallel-group randomised controlled trial using re-randomisation. The primary objective of the trial is to determine if the use of TLI or undisturbed culture in IVF treatment results in a higher live birth rate when compared to current standard methods of embryo incubation and assessment. Secondary outcomes include measures of clinical efficacy and safety. The trial will randomise 1575 participants to detect an increase in live birth from 26.5 to 35.25%. Discussion In the absence of high-quality evidence, there is no current national guidance, recommendation or policy for the use of TLI. The use of TLI is not consistently incorporated into standard IVF care. A large, pragmatic, multi-centre, trial will provide much needed definitive evidence regarding the effectiveness of TLI. If proven to be effective, its incorporation into standard care would translate into significant clinical and economic benefits. If not, it would allow allocation of resources to more effective interventions. Trial registration ISRCTN registry ISRCTN17792989 . Prospectively registered on 18 April 2018

Abstract Background Data collection consumes a large proportion of clinical trial resources. Each data item requires time and effort for collection, processing and quality control procedures. In general, more data equals a heavier burden for trial staff and participants. It is also likely to increase costs. Knowing the types of data being collected, and in what proportion, will be helpful to ensure that limited trial resources and participant goodwill are used wisely. Aim The aim of this study is to categorise the types of data collected across a broad range of trials and assess what proportion of collected data each category represents. Methods We developed a standard operating procedure to categorise data into primary outcome, secondary outcome and 15 other categories. We categorised all variables collected on trial data collection forms from 18, mainly publicly funded, randomised superiority trials, including trials of an investigational medicinal product and complex interventions. Categorisation was done independently in pairs: one person having in-depth knowledge of the trial, the other independent of the trial. Disagreement was resolved through reference to the trial protocol and discussion, with the project team being consulted if necessary. Key results Primary outcome data accounted for 5.0% (median)/11.2% (mean) of all data items collected. Secondary outcomes accounted for 39.9% (median)/42.5% (mean) of all data items. Non-outcome data such as participant identifiers and demographic data represented 32.4% (median)/36.5% (mean) of all data items collected. Conclusion A small proportion of the data collected in our sample of 18 trials was related to the primary outcome. Secondary outcomes accounted for eight times the volume of data as the primary outcome. A substantial amount of data collection is not related to trial outcomes. Trialists should work to make sure that the data they collect are only those essential to support the health and treatment decisions of those whom the trial is designed to inform.

Objectives To determine the feasibility and acceptability of conducting a randomised trial on the effects of myo-inositol in preventing gestational diabetes in high-risk pregnant women.Design A multicentre, double-blind, placebo-controlled, pilot randomised trial with nested qualitative evaluation.Setting Five inner city UK National Health Service hospitalsParticipants Multiethnic pregnant women at 12+0 and 15+6 weeks’ gestation with risk factors for gestational diabetes.Interventions 2 g of myo-inositol or placebo, both included 200 µg folic acid, twice daily until delivery.Primary outcome measures Rates of recruitment, randomisation, adherence and follow-up.Secondary outcome measures Glycaemic indices (including homoeostatic model assessment-insulin resistance HOMA-IR), gestational diabetes (diagnosed using oral glucose tolerance test at 28 weeks and by delivery), maternal, perinatal outcomes, acceptability of intervention and costs.Results Of the 1326 women screened, 58% (773/1326) were potentially eligible, and 27% (205/773) were recruited. We randomised 97% (198/205) of all recruited women (99 each in intervention and placebo arms) and ascertained outcomes in 90% of women (178/198) by delivery. The mean adherence was 52% (SD 44) at 28 weeks’ and 34% (SD 41) at 36 weeks’ gestation. HOMA-IR and serum insulin levels were lower in the myo-inositol vs placebo arm (mean difference −0.6, 95% CI −1.2 to 0.0 and −2.69, 95% CI −5.26 to −0.18, respectively). The study procedures were acceptable to women and healthcare professionals. Women who perceived themselves at high risk of gestational diabetes were more likely to participate and adhere to the intervention. The powder form of myo-inositol and placebo, along with nausea in pregnancy were key barriers to adherence.Conclusions A future trial on myo-inositol versus placebo to prevent gestational diabetes is feasible. The intervention will need to be delivered in a non-powder form to improve adherence. There is a signal for efficacy in reducing insulin resistance in pregnancy with myo-inositol.Trial registration number ISRCTN48872100.

Introduction Women with gestational diabetes are at increased risk of developing type 2 diabetes later in life. In at-risk general populations, Mediterranean-style diet helps prevent type 2 diabetes. But its effect on postnatal women with a history of gestational diabetes is not known. Prior to a full-scale trial on Mediterranean-style diet in the postnatal period to prevent type 2 diabetes, a feasibility study is required to assess the acceptability of the diet and evaluate the trial processes.Methods and analysis MEditerranean diet for pReventIon of type 2 diabeTes is a single-arm feasibility study (65 women) with qualitative evaluation of women who have recently given birth and had gestational diabetes. The intervention is a Mediterranean-style diet supplemented with nuts and olive oil, with dietary advice and an action plan. A dedicated Health Coach will interact with participants through an interactive lifestyle App. Women will follow the intervention from 6 to 13 weeks post partum until 1 year post partum. The primary outcomes are rates of recruitment, follow-up, adherence and attrition. The secondary outcomes are maternal dysglycaemia, cost and quality of life outcomes, and acceptability of the intervention to participants, and to healthcare professionals delivering the intervention. Feasibility outcomes will be reported using descriptive statistics.Ethics and dissemination Ethical approval was obtained through the South Central—Berkshire Research Ethics Committee (19/SC/0064). Study findings will be disseminated via publication in peer-reviewed journals, as well as via newsletters made available to participants and members of Katie’s Team (a women’s health patient and public advisory group).Trial registration number ISRCTN40582975.

Abstract Background One of the top three research priorities for the UK clinical trial community is to address the gap in evidence-based approaches to improving participant retention in randomised trials. Despite this, there is little evidence supporting methods to improve retention. This paper reports the PRioRiTy II project, a Priority Setting Partnership (PSP) that identified and prioritised unanswered questions and uncertainties around trial retention in collaboration with key stakeholders. Methods This PSP was conducted in collaboration with the James Lind Alliance, a non-profit making initiative, to support key stakeholders (researchers, patients, and the public) in jointly identifying and agreeing on priority research questions. There were three stages. (1) First an initial online survey was conducted consisting of six open-ended questions about retention in randomised trials. Responses were coded into thematic groups to create a longlist of questions. The longlist of questions was checked against existing evidence to ensure that they had not been answered by existing research. (2) An interim stage involved a further online survey where stakeholders were asked to select questions of key importance from the longlist. (3) A face-to-face consensus meeting was held, where key stakeholder representatives agreed on an ordered list of 21 unanswered research questions for methods of improving retention in randomised trials. Results A total of 456 respondents yielded 2431 answers to six open-ended questions, from which 372 questions specifically about retention were identified. Further analysis included thematically grouping all data items within answers and merging questions in consultation with the Steering Group. This produced 27 questions for further rating during the interim survey. The top 21 questions from the interim online survey were brought to a face-to-face consensus meeting in which key stakeholder representatives prioritised the order. The ‘Top 10’ of these are reported in this paper. The number one ranked question was ’What motivates a participant’s decision to complete a clinical trial?’ The entire list will be available at www.priorityresearch.ie. Conclusion The Top 10 list can inform the direction of future research on trial methods and be used by funders to guide projects aiming to address and improve retention in randomised trials.

Introduction Up to half of all women diagnosed with gestational diabetes mellitus develop type 2 diabetes within 5 years after delivery. Metformin is effective in preventing type 2 diabetes in high-risk non-pregnant individuals, but its effect when commenced in the postnatal period is not known. We plan to assess the feasibility of evaluating metformin versus placebo in minimising the risk of dysglycaemia including type 2 diabetes after delivery in postnatal women with a history of gestational diabetes through a randomised trial.Methods and analysis Optimising health outcomes with Metformin to prevent diAbetes After pregnancy (OMAhA) is a multicentre placebo-controlled double-blind randomised feasibility trial, where we will randomly allocate 160 postnatal women with gestational diabetes treated with medication to either metformin (intervention) or placebo (control) tablets to be taken until 1 year after delivery. The primary outcomes are rates of recruitment, randomisation, adherence and attrition. The secondary outcomes are maternal dysglycaemia, cost and quality of life outcomes in both arms, and acceptability of the study and intervention, which will be evaluated through a nested qualitative study. Feasibility outcomes will be summarised using descriptive statistics, point estimates and 95% CIs.Ethics and dissemination The OMAhA study received ethics approval from the London-Brent Research Ethics Committee (18/LO/0505). Trial findings will be published in a peer-reviewed journal, disseminated at conferences, through our Patient and Public Involvement advisory group (Katie’s Team) and through social media platforms.Trial registration number ISRCTN20930880

Background: Caesarean section is associated with blood loss and maternal morbidity. Excessive blood loss requires transfusion of donor (allogeneic) blood, which is a finite resource. Cell salvage returns blood lost during surgery to the mother. It may avoid the need for donor blood transfusion, but reliable evidence of its effects is lacking. Objectives: To determine if routine use of cell salvage during caesarean section in mothers at risk of haemorrhage reduces the rates of blood transfusion and postpartum maternal morbidity, and is cost-effective, in comparison with standard practice without routine salvage use. Design: Individually randomised controlled, multicentre trial with cost-effectiveness analysis. Treatment was not blinded. Setting: A total of 26 UK obstetric units. Participants: Out of 3054 women recruited between June 2013 and April 2016, we randomly assigned 3028 women at risk of haemorrhage to cell salvage or routine care. Randomisation was stratified using random permuted blocks of variable sizes. Of these, 1672 had emergency and 1356 had elective caesareans. We excluded women for whom cell salvage or donor blood transfusion was contraindicated. Interventions: Cell salvage (intervention) versus routine care without salvage (control). In the intervention group, salvage was set up in 95.6% of the women and, of these, 50.8% had salvaged blood returned. In the control group, 3.9% had salvage deployed. Main outcome measures: Primary – donor blood transfusion. Secondary – units of donor blood transfused, time to mobilisation, length of hospitalisation, mean fall in haemoglobin, fetomaternal haemorrhage (FMH) measured by Kleihauer–Betke test, and maternal fatigue. Analyses were adjusted for stratification factors and other factors that were believed to be prognostic a priori. Cost-effectiveness outcomes – costs of resources and service provision taking the UK NHS perspective. Results: We analysed 1498 and 1492 participants in the intervention and control groups, respectively. Overall, the transfusion rate was 2.5% in the intervention group and 3.5% in the control group [adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42 to 1.01; p = 0.056]. In a planned subgroup analysis, the transfusion rate was 3.0% in the intervention group and 4.6% in the control group among emergency caesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 1.8% in the intervention group and 2.2% in the control group among elective caesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46, suggesting that the difference in effect between subgroups was not statistically significant). Secondary outcomes did not differ between groups, except for FMH, which was higher under salvage in rhesus D (RhD)-negative women with RhD-positive babies (25.6% vs. 10.5%, adjusted OR 5.63, 95% CI 1.43 to 22.14; p = 0.013). No case of amniotic fluid embolism was observed. The additional cost of routine cell salvage during caesarean was estimated, on average, at £8110 per donor blood transfusion avoided. Conclusions: The modest evidence for an effect of routine use of cell salvage during caesarean section on rates of donor blood transfusion was associated with increased FMH, which emphasises the need for adherence to guidance on anti-D prophylaxis. We are unable to comment on long-term antibody sensitisation effects. Based on the findings of this trial, cell salvage is unlikely to be considered cost-effective. Future work: Research into risk of alloimmunisation among women exposed to cell salvage is needed. Trial registration: Current Controlled Trials ISRCTN66118656. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 2. See the NIHR Journals Library website for further project information.

BackgroundExcessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement.Methods and findingsWe conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects.ConclusionsThe overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant.Trial registrationThis trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656.

Background: Psychosocial work environments influence employee well-being. There is a need for an evaluation of organisational-level interventions to modify psychosocial working conditions and hence employee well-being. Objective: To test the acceptability of the trial and the intervention, the feasibility of recruitment and adherence to and likely effectiveness of the intervention within separate clusters of an organisation. Design: Mixed methods: pilot cluster randomised controlled trial and qualitative study (in-depth interviews, focus group and observation). Participants: Employees and managers of a NHS trust. Inclusion criteria were the availability of sickness absence data and work internet access. Employees on long-term sick leave and short-term contracts and those with a notified pregnancy were excluded. Intervention: E-learning program for managers based on management standards over 10 weeks, guided by a facilitator and accompanied by face-to-face meetings. Three clusters were randomly allocated to receive the guided e-learning intervention; a fourth cluster acted as a control. Main outcome measures: Recruitment and participation of employees and managers; acceptability of the intervention and trial; employee subjective well-being using the Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS); and feasibility of collecting sickness absence data. Results: In total, 424 employees out of 649 approached were recruited and 41 managers out of 49 were recruited from the three intervention clusters. Of those consenting, 350 [83%, 95% confidence interval (CI) 79% to 86%] employees completed the baseline assessment and 291 (69%, 95% CI 64% to 73%) completed the follow-up questionnaires. Sickness absence data were available from human resources for 393 (93%, 95% CI 90% to 95%) consenting employees. In total, 21 managers adhered to the intervention, completing at least three of the six modules. WEMWBS scores fell slightly in all groups, from 50.4 to 49.0 in the control group and from 51.0 to 49.9 in the intervention group. The overall intervention effect was 0.5 (95% CI –3.2 to 4.2). The fall in WEMWBS score was significantly less among employees whose managers adhered to the intervention than among those employees whose managers did not (–0.7 vs. 1.6, with an adjusted difference of 1.6, 95% CI 0.1 to 3.2). The intervention and trial were acceptable to managers, although our study raises questions about the widely used concept of ‘acceptability’. Managers reported insufficient time to engage with the intervention and lack of senior management ‘buy-in’. It was thought that the intervention needed better integration into organisational processes and practice. Conclusions: The mixed-methods approach proved valuable in illuminating reasons for the trial findings, for unpacking processes of implementation and for understanding the influence of study context. We conclude from the results of our pilot study that further mixed-methods research evaluating the intervention and study design is needed. We found that it is feasible to carry out an economic evaluation of the intervention. We plan a further mixed-methods study to re-evaluate the intervention boosted with additional elements to encourage manager engagement and behaviour change in private and public sector organisations with greater organisational commitment. Study registration: Current Controlled Trials ISRCTN58661009. Funding: This project was funded by the NIHR Public Health Research programme and will be published in full in Public Health Research; Vol. 3, No. 9. See the NIHR Journals Library website for further project information.

Background: Subfertility is a common problem for which in vitro fertilisation (IVF) treatment is commonly recommended. Success rates following IVF are suboptimal and have remained static over the last few years. This imposes a considerable financial burden on overstretched healthcare resources. Time-lapse imaging (TLI) of developing embryos in IVF treatment is hypothesised to improve the success rates of treatment. This may be either by providing undisturbed culture conditions or by improving the predictive accuracy for optimal embryo selection from a cohort of available embryos. However, the current best evidence for its effectiveness is inconclusive.Methods: The time-lapse imaging trial is a pragmatic, multi-centre, three-arm parallel-group randomised controlled trial using re-randomisation. The primary objective of the trial is to determine if the use of TLI or undisturbed culture in IVF treatment results in a higher live birth rate when compared to current standard methods of embryo incubation and assessment. Secondary outcomes include measures of clinical efficacy and safety. The trial will randomise 1575 participants to detect an increase in live birth from 26.5 to 35.25%.Discussion: In the absence of high-quality evidence, there is no current national guidance, recommendation or policy for the use of TLI. The use of TLI is not consistently incorporated into standard IVF care. A large, pragmatic, multi-centre, trial will provide much needed definitive evidence regarding the effectiveness of TLI. If proven to be effective, its incorporation into standard care would translate into significant clinical and economic benefits. If not, it would allow allocation of resources to more effective interventions.Trial Registration: ISRCTN registry ISRCTN17792989 . Prospectively registered on 18 April 2018. [ABSTRACT FROM AUTHOR]

Background: Data collection consumes a large proportion of clinical trial resources. Each data item requires time and effort for collection, processing and quality control procedures. In general, more data equals a heavier burden for trial staff and participants. It is also likely to increase costs. Knowing the types of data being collected, and in what proportion, will be helpful to ensure that limited trial resources and participant goodwill are used wisely.Aim: The aim of this study is to categorise the types of data collected across a broad range of trials and assess what proportion of collected data each category represents.Methods: We developed a standard operating procedure to categorise data into primary outcome, secondary outcome and 15 other categories. We categorised all variables collected on trial data collection forms from 18, mainly publicly funded, randomised superiority trials, including trials of an investigational medicinal product and complex interventions. Categorisation was done independently in pairs: one person having in-depth knowledge of the trial, the other independent of the trial. Disagreement was resolved through reference to the trial protocol and discussion, with the project team being consulted if necessary.Key Results: Primary outcome data accounted for 5.0% (median)/11.2% (mean) of all data items collected. Secondary outcomes accounted for 39.9% (median)/42.5% (mean) of all data items. Non-outcome data such as participant identifiers and demographic data represented 32.4% (median)/36.5% (mean) of all data items collected.Conclusion: A small proportion of the data collected in our sample of 18 trials was related to the primary outcome. Secondary outcomes accounted for eight times the volume of data as the primary outcome. A substantial amount of data collection is not related to trial outcomes. Trialists should work to make sure that the data they collect are only those essential to support the health and treatment decisions of those whom the trial is designed to inform. [ABSTRACT FROM AUTHOR]

Introduction The incidence of severe postpartum haemorrhage (PPH) that requires blood transfusion is on the increase. Fibrinogen levels have been shown to drop early and significantly during PPH, which is associated with worse outcomes. Early fibrinogen replacement could potentially improve outcomes. No studies have investigated the clinical impact of early cryoprecipitate transfusion in PPH. Prior to performing a full-scale trial, a pilot study is needed to determine feasibility of the intervention and recruitment. Methods ACROBAT is a cluster-randomised pilot study with a qualitative evaluation. Four large London maternity units are randomised to either the intervention or control group. The intervention group will adapt their major obstetric haemorrhage procedures to administer cryoprecipitate early for primary PPH. The control group will retain their standard of care. We include women at >24 weeks gestation who are actively bleeding within 24 hours of delivery and for whom transfusion of red blood cells (RBCs) has been started. We exclude women who decline blood transfusions in advance or have inherited Factor XIII or fibrinogen deficiency. Due to the emergency nature of the intervention, informed consent for administering the intervention is waived. The primary objective is to assess the feasibility of administering cryoprecipitate within 90 min of RBC request, as compared with standard treatment where cryoprecipitate is given later or not at all. Secondary objectives include the feasibility of recruitment and data collection, reasons for and barriers to consent, preliminary maternal clinical outcomes, identification of the optimal infrastructure pathways for study delivery, and acceptability of the intervention and outcomes. Ethics and dissemination The trial has approvals from the London—Brighton & Sussex Research Ethics Committee (ref. 18/LO/2062), the Confidentiality Advisory Group (ref. 18/CAG/0199) and Health Research Authority (IRAS number 237959). Data analysis and publication of manuscripts will start in Q3 2020. [ABSTRACT FROM AUTHOR]

Introduction Up to half of all women diagnosed with gestational diabetes mellitus develop type 2 diabetes within 5 years after delivery. Metformin is effective in preventing type 2 diabetes in high-risk non-pregnant individuals, but its effect when commenced in the postnatal period is not known. We plan to assess the feasibility of evaluating metformin versus placebo in minimising the risk of dysglycaemia including type 2 diabetes after delivery in postnatal women with a history of gestational diabetes through a randomised trial. Methods and analysis Optimising health outcomes with Metformin to prevent diAbetes After pregnancy (OMAhA) is a multicentre placebo-controlled doubleblind randomised feasibility trial, where we will randomly allocate 160 postnatal women with gestational diabetes treated with medication to either metformin (intervention) or placebo (control) tablets to be taken until 1 year after delivery. The primary outcomes are rates of recruitment, randomisation, adherence and attrition. The secondary outcomes are maternal dysglycaemia, cost and quality of life outcomes in both arms, and acceptability of the study and intervention, which will be evaluated through a nested qualitative study. Feasibility outcomes will be summarised using descriptive statistics, point estimates and 95% CIs. Ethics and dissemination The OMAhA study received ethics approval from the London-Brent Research Ethics Committee (18/LO/0505). Trial findings will be published in a peer-reviewed journal, disseminated at conferences, through our Patient and Public Involvement advisory group (Katie’s Team) and through social media platforms. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the cost-effectiveness of routine use of cell salvage during caesarean section in mothers at risk of haemorrhage compared with current standard of care. Design Model-based cost-effectiveness evaluation alongside a multicentre randomised controlled trial. Three main analyses were carried out on the trial data: (1) based on the intention-to-treat principle; (2) based on the perprotocol principle; (3) only participants who underwent an emergency caesarean section. Setting 26 obstetric units in the UK. Participants 3028 women at risk of haemorrhage recruited between June 2013 and April 2016. Interventions Cell salvage (intervention) versus routine care without salvage (control). Primary outcome measures Cost-effectiveness based on incremental cost per donor blood transfusion avoided. Results In the intention-to-treat analysis, the mean difference in total costs between cell salvage and standard care was £83. The estimated incremental costeffectiveness ratio (ICER) was £8110 per donor blood transfusion avoided. For the per-protocol analysis, the mean difference in total costs was £92 and the ICER was £8252. In the emergency caesarean section analysis, the mean difference in total costs was £55 and the ICER was £13 713 per donor blood transfusion avoided. This ICER is driven by the increased probability that these patients would require a higher level of postoperative care and additional surgeries. The results of these analyses were shown to be robust for the majority of deterministic sensitivity analyses. Conclusions The results of the economic evaluation suggest that while routine cell salvage is a marginally more effective strategy than standard care in avoiding a donor blood transfusion, there is uncertainty in relation to whether it is a less or more costly strategy. The lack of long-term data on the health and quality of life of patients in both arms of the trial means that further research is needed to fully understand the cost implications of both strategies. [ABSTRACT FROM AUTHOR]

Background: Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement.Methods and Findings: We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects.Conclusions: The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant.Trial Registration: This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656. [ABSTRACT FROM AUTHOR]

Background: One of the top three research priorities for the UK clinical trial community is to address the gap in evidence-based approaches to improving participant retention in randomised trials. Despite this, there is little evidence supporting methods to improve retention. This paper reports the PRioRiTy II project, a Priority Setting Partnership (PSP) that identified and prioritised unanswered questions and uncertainties around trial retention in collaboration with key stakeholders.Methods: This PSP was conducted in collaboration with the James Lind Alliance, a non-profit making initiative, to support key stakeholders (researchers, patients, and the public) in jointly identifying and agreeing on priority research questions. There were three stages. (1) First an initial online survey was conducted consisting of six open-ended questions about retention in randomised trials. Responses were coded into thematic groups to create a longlist of questions. The longlist of questions was checked against existing evidence to ensure that they had not been answered by existing research. (2) An interim stage involved a further online survey where stakeholders were asked to select questions of key importance from the longlist. (3) A face-to-face consensus meeting was held, where key stakeholder representatives agreed on an ordered list of 21 unanswered research questions for methods of improving retention in randomised trials.Results: A total of 456 respondents yielded 2431 answers to six open-ended questions, from which 372 questions specifically about retention were identified. Further analysis included thematically grouping all data items within answers and merging questions in consultation with the Steering Group. This produced 27 questions for further rating during the interim survey. The top 21 questions from the interim online survey were brought to a face-to-face consensus meeting in which key stakeholder representatives prioritised the order. The 'Top 10' of these are reported in this paper. The number one ranked question was 'What motivates a participant's decision to complete a clinical trial?' The entire list will be available at www.priorityresearch.ie .Conclusion: The Top 10 list can inform the direction of future research on trial methods and be used by funders to guide projects aiming to address and improve retention in randomised trials. [ABSTRACT FROM AUTHOR]