Emesis in pregnancy - a qualitative study on trial recruitment failure from the EMPOWER internal pilot.

BACKGROUND: As part of the internal pilot of the EMPOWER trial investigating the second-line antiemetic therapies in severe emesis in pregnancy ( https://www.isrctn.com/ISRCTN16924692 ), a qualitative study of women's views was carried out, to improve our understanding of why women did, or did not, consent to participation in the trial. Interviews were also conducted with site research staff, to broaden our analysis and explore other factors affecting recruitment. METHODS: The sample comprised women who accepted or declined trial participation (n=21) and site research staff (n=22). A structured topic guide was used, in four email interviews and 17 telephone interviews with women, and semi-structured telephone interviews were carried out with staff. Of the women interviewed, seven had declined trial participation, and of the staff interviewed, 16 were research midwives/research nurses and six were principal investigators. All transcripts were checked for accuracy, anonymised and entered into NVIVO12 for indexing and retrieval. Data was analysed using a reflexive thematic analytic approach. In total, 72 codes were generated from the thematic analysis, and 36 from each sample group. RESULTS: Three key themes based on all the interviews were (a) the diversity of recruitment pathways and boundaries of care, (b) the impact of trial complexity on recruitment and staff morale and (c) the ethics of caring for a patient with emesis. Ethical issues discussed included the use of double dummy and time to treat, particularly those suffering severely from the effects of nausea and vomiting. To illustrate these themes, staff perspectives are given more prominence. CONCLUSIONS: The main reason the trial was stopped related to the high proportion of women ineligible for recruitment due to prior treatment with study drug(s) because of unanticipated changes in clinical practice. The qualitative results also demonstrate the impact of the trial on women and staff and highlight how the diversity of referral pathways, boundaries of care and the complexity of the trial and protocol resulted in additional barriers to successful trial recruitment. Qualitative work in pilot and feasibility studies of a clinical trial is recommended, to evaluate whether recruitment strategies remain viable in unanticipated contexts. TRIAL REGISTRATION: Trial registration number ISRCTN16924692 . Date: 08/01/2018.

Ondansetron and metoclopramide as second-line antiemetics in women with nausea and vomiting in pregnancy: the EMPOWER pilot factorial RCT.

BACKGROUND: Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. OBJECTIVES: To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. DESIGN: This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. PARTICIPANTS: Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation. INTERVENTIONS: Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. MAIN OUTCOME MEASURES: The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. RESULTS: Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. LIMITATIONS: The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. CONCLUSIONS: The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31. 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. 25, No. 63. See the NIHR Journals Library website for further project information.

Nausea and vomiting in pregnancy cause physical and emotional distress, and up to 30% of affected women require medical treatment. Guidelines on the use of anti-sickness drugs exist, but evidence is limited about which drugs work the best. The EMPOWER (EMesis in Pregnancy ­ Ondansetron With mEtoClopRamide) trial aimed to compare the clinical effectiveness and cost-effectiveness of two anti-sickness drugs [metoclopramide (metoclopramide hydrochloride, Actavis UK Ltd, Barnstable, UK; IV Ratiopharm GmbH, Ulm, Germany) and ondansetron (ondansetron hydrochloride dehydrate, Wockhardt UK Ltd, Wrexham, UK; IV Hameln Pharma plus GmbH, Hameln)] for the treatment of nausea and vomiting in pregnancy. Women who were < 17 weeks pregnant with severe nausea and vomiting who attended hospital because their first anti-sickness drug had failed to improve their symptoms were asked to take part in the trial. Participants received fluids and, with consent, were randomly allocated to one of four groups: (1) metoclopramide and dummy ondansetron, (2) ondansetron and dummy metoclopramide, (3) metoclopramide and ondansetron or (4) double dummy. Trial drugs were administered into a vein and then by tablet for 10 days. On advice from sufferers, the trial focused on treatment failure, but other outcomes, including drug side effects, costs and pregnancy outcome, were collected. The trial was unable to recruit enough women and, therefore, did not progress. Nearly 600 women at 11 hospitals were screened, of whom 122 (21%) were eligible and 33 were recruited. The main reason for ineligibility (68%) was prior use of trial drug (mostly ondansetron). Overall, 15 out of 30 evaluable women experienced treatment failure. Interviews with 21 women who were approached about the trial and 22 research staff identified complex hurdles to and enablers of recruitment. The main hurdles were the requirements of the study protocol in relation to guidelines on anti-sickness drugs and the diversity of pathways to care. The role of research staff was a key enabler. The trial was too small to draw useful conclusions and it highlights the challenges of conducting complex studies on sick pregnant women. Subsequent concerns about the safety of ondansetron highlight the need for further studies to help inform women and the NHS about the best care for nausea and vomiting in pregnancy.

Service user and staff acceptance of fetal ultrasound telemedicine.

OBJECTIVE: We present qualitative findings from interviews with frontline clinicians and service users of a fetal telemedicine service. METHODS: Semi-structured interviews with clinical stakeholders and service users were conducted, undertaken as part of a service evaluation. Data collection was undertaken by different teams, using interview schedules aligned to independent evaluation aims. Data were subjected to thematic analysis. RESULTS: Sonographers reported four main challenges: delivering a shared consultation; the requirement to resist scanning intuitively; communications during the scan; and restricted room space. Notwithstanding, all clinicians reported that participating women were accepting of the technology. Service users reported few concerns. The main benefits of fetal telemedicine were identified as upskilled staff, increased access to specialist support and improved management of complex pregnancies. Convenience was identified as the main benefit by service users, including savings in time and money from not having to travel, take time off work, and arrange childcare. CONCLUSIONS: Service users and clinical stakeholders were accepting of the service. Service users reported satisfaction with communications during the consultation and awareness that telemedicine had facilitated local access to clinical expertise. Whilst clinical stakeholders reported challenges, the iterative nature of the evaluation meant that concerns were discussed, responded to, and overcome as the pilot developed. Clinical stakeholders' perception of benefits for service users encouraged their acceptance. Moreover, the evaluation established that fetal ultrasound telemedicine is a viable method to access expertise safely and remotely. It provided demonstrable evidence of a potential solution to some of the healthcare challenges facing rural hospitals.

MRI in the diagnosis of fetal developmental brain abnormalities: the MERIDIAN diagnostic accuracy study.

BACKGROUND: Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately. OBJECTIVES: To assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality. DESIGN: A pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy. SETTING: Sixteen UK fetal medicine centres. PARTICIPANTS: Pregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks' gestation) with a suspected brain abnormality detected on ultrasonography. INTERVENTIONS: Participants underwent iuMRI and the findings were reported to their referring fetal medicine clinician. MAIN OUTCOME MEASURES: Pregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2-3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken. RESULTS: The primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18-23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed. CONCLUSIONS: iuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27626961. 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. 23, No. 49. See the NIHR Journals Library website for further project information.

Ultrasonography is routine in pregnancy to check that the baby's brain is developing as expected. However, no medical test is perfect and ultrasonography may miss some brain abnormalities, may get some brain abnormalities wrong or may diagnose an abnormality that is not really present. Magnetic resonance imaging (MRI) may help clarify difficult cases during pregnancy. We wanted to find out if MRI was better than ultrasonography alone in making an accurate diagnosis. We recruited pregnant women whose ultrasound scan, performed by an expert, suggested that their baby had a brain abnormality, and referred them for a MRI scan. The results of the two tests were compared with each other and to the final outcome of the pregnancy. Our results showed that using MRI in addition to ultrasonography improved the accuracy of the diagnosis in about one in four pregnancies. It changed the prediction of how the baby would develop in at least one in five cases. In many cases, the pregnancy was managed differently because of the MRI result. The MRI was acceptable to women, with 95% saying that they would have MRI again in a similar situation. Neither MRI nor ultrasonography accurately identified children who went on to have delayed development at the age of 2­3 years, but MRI was better than ultrasonography at ruling out developmental problems at this age. The MRI cost more than ultrasonography alone; therefore, whether or not it is worthwhile depends on the value placed on the decisions that changed as a result of its use.

Should I stay or should I go? A qualitative study exploring participation in a urology clinical trial.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to identify modifiable factors to improve recruitment in a urology clinical trial of women with recurrent urinary tract infection (rUTI). An embedded qualitative study was conducted with patients and recruiting clinicians in the first 8 months of the trial. We present a matrix of factors influencing how patients make decisions about trial participation. METHODS: This was a qualitative study using telephone interviews. When they were first approached about the trial, women were asked to complete an expression of interest form if they wished to be contacted for an interview. Data were analysed thematically. NVivo 10 software (Qualitative data analysis software. 10th ed: QSR International Pty Ltd; 2012) was used as a management tool. RESULTS: Thirty patients and 11 clinicians were interviewed. Influences on patient participation included the impact of rUTI on quality of life (QoL), understanding of antibiotic resistance, and previous experiences with antibiotics either positive or negative. Very few women who declined the trial agreed to be interviewed. However, some of those who participated had reservations about it. These included the perceived risk of trying a new treatment, trial length, and the burden of participating. One person interviewed left the trial because of repeated infections and difficulties getting general practitioner appointments. CONCLUSIONS: A combination of factors worked to influence women to decide to participate, to remain in, or to leave the trial. A better understanding of how these factors interact and work can assist in the recruitment and retention of individual trial participants.

"He looks gorgeous" - iuMR images and the transforming of foetal and parental identities.

The MERIDIAN study examined whether in-utero MRI (iuMRI) improves the accuracy of diagnosis of foetal brain abnormalities, when used as an adjunct to ultrasound anomaly scanning. A diagnostic iuMRI differs from routine ultrasound screening because of its infrequent use and scanning procedure. Nested within this trial, this sociological study explored the acceptability of iuMRI as a technology and its contribution to parental decision-making. Our sociological interpretation of the role of iuMR images in prenatal diagnosis draws on narrative interviews with women (and some partners) who underwent MRI imaging at three different centres. Overall, participants found iuMRI helpful in decision-making because it either confirmed or disconfirmed previous results, or provided additional information. Expectant couples experienced the iuMR imaging process as informative, but also as having emotive and practical value. Our paper extends the existing sociological literature on antenatal testing and visualising the foetus, by using iuMR diagnostic imaging to further explore the concept of the unborn entity. Our data suggest that alongside the iuMR images, the 'parental gaze' and accompanying commentary are used by parents to construct and transform foetal and parental identities despite ongoing uncertainties about, and shifting social contexts to their pregnancy.

MRI for Fetal Developmental Brain Abnormalities: Perspectives From the Pregnant Patient.

Ultrasound is routinely used as a prenatal screening and diagnostic tool but has limitations. Some anomalies in the developing fetal brain can be difficult to detect, and in utero magnetic resonance imaging (iuMRI) is increasingly used as an adjunct to ultrasound. However, understandings of patient perspectives of iuMRI technology are still developing. Our qualitative study of 41 mothers who experienced iuMRI was embedded in a diagnostic accuracy trial and aimed to inform policy recommendations that might stem from the clinical findings. Our analysis suggests that iuMRI is seen as useful, offering valuable additional information and helping women make decisions about care options at a difficult time. However, patients' experiences demonstrated the uncertainty and anxiety associated with the prenatal diagnosis (PND) process relating to brain anomalies including the challenges of their embodied contributions. Our findings suggest more could be done to reduce the impact on pregnant women during an already difficult, anxious period.

Health state descriptions to elicit stroke values: do they reflect patient experience of stroke?

BACKGROUND: To explore whether stroke health state descriptions used in preference elicitation studies reflect patients' experiences by comparing published descriptions with qualitative studies exploring patients' lived experience. METHODS: Two literature reviews were conducted: on stroke health state descriptions used in direct preference elicitation studies and the qualitative literature on patients' stroke experience. Content and comparative thematic analysis was used to identify characteristics of stroke experience in both types of study which were further mapped onto health related quality of life (HRQOL) domains relevant to stroke. Two authors reviewed the coded text, categories and domains. RESULTS: We included 35 studies: seven direct preference elicitation studies and 28 qualitative studies on patients' experience. Fifteen coded categories were identified in the published health state descriptions and 29 in the qualitative studies. When mapped onto domains related to HRQOL, qualitative studies included a wider range of categories in every domain that were relevant to the patients' experience than health state descriptions. CONCLUSIONS: Variation exists in the content of health state descriptions for all levels of stroke severity, most critically with a major disjuncture between the content of descriptions and how stroke is experienced by patients. There is no systematic method for constructing the content/scope of health state descriptions for stroke, and the patient perspective is not incorporated, producing descriptions with major deficits in reflecting the lived experience of stroke, and raising serious questions about the values derived from such descriptions and conclusions based on these values.

Situationally-sensitive knowledge translation and relational decision making in hyperacute stroke: a qualitative study.

Stroke is a leading cause of disability. Early treatment of acute ischaemic stroke with rtPA reduces the risk of longer term dependency but carries an increased risk of causing immediate bleeding complications. To understand the challenges of knowledge translation and decision making about treatment with rtPA in hyperacute stroke and hence to inform development of appropriate decision support we interviewed patients, their family and health professionals. The emergency setting and the symptomatic effects of hyper-acute stroke shaped the form, content and manner of knowledge translation to support decision making. Decision making about rtPA in hyperacute stroke presented three conundrums for patients, family and clinicians. 1) How to allow time for reflection in a severely time-limited setting. 2) How to facilitate knowledge translation regarding important treatment risks and benefits when patient and family capacity is blunted by the effects and shock of stroke. 3) How to ensure patient and family views are taken into account when the situation produces reliance on the expertise of clinicians. Strategies adopted to meet these conundrums were fourfold: face to face communication; shaping decisions; incremental provision of information; and communication tailored to the individual patient. Relational forms of interaction were understood to engender trust and allay anxiety. Shaping decisions with patients was understood as an expression of confidence by clinicians that helped alleviate anxiety and offered hope and reassurance to patients and their family experiencing the shock of the stroke event. Neutral presentations of information and treatment options promoted uncertainty and contributed to anxiety. 'Drip feeding' information created moments for reflection: clinicians literally made time. Tailoring information to the particular patient and family situation allowed clinicians to account for social and emotional contexts. The principal responses to the challenges of decision making about rtPA in hyperacute stroke were relational decision support and situationally-sensitive knowledge translation.

'Let the computer choose?': the experience of participants in a randomised preference trial of medical versus surgical termination of pregnancy.

The termination of pregnancy trial (Newcastle upon Tyne, UK), is the only randomised trial on termination of pregnancy methods incorporating a qualitative element that aimed to understand the experiences of women participating in the trial. Based on the results of this qualitative work, this article aims to provide insights into two strands of understanding; firstly, women's experience of participating in research about abortion and secondly, their experience of participating in a randomised preference trial. Semi-structured interviews were conducted of up to 90 minutes with 30 participants recruited at a single hospital site. A total of 20 women from the preference arm and 10 from the random arm were interviewed. The analysis and discussion of our findings use reflexive modernisation as a framework for understanding and interpreting some of the actions of social agents, that is, the participants and trial recruiters in the course of a clinical trial as an expert system. We found that the factors that shape women's experiences and decisions include trust in the expert system and reflexivity and agency on the part of both participants and trial recruiters.

Experiences of abortion: a narrative review of qualitative studies.

BACKGROUND: Although abortion or termination of pregnancy (TOP) has become an increasingly normalized component of women's health care over the past forty years, insufficient attention has been paid to women's experiences of surgical or medical methods of TOP. OBJECTIVE: To undertake a narrative review of qualitative studies of women's experiences of TOP and their perspectives on surgical or medical methods. METHODS: Keyword searches of Medline, CINAHL, ISI, and IBSS databases. Manual searches of other relevant journals and reference lists of primary articles. RESULTS: Qualitative studies (n = 18) on women's experiences of abortion were identified. Analysis of the results of studies reviewed revealed three main themes: experiential factors that promote or inhibit the choice to seek TOP; experiences of TOP; and experiential aspects of the environment in which TOP takes place. CONCLUSION: Women's choices about TOP are mainly pragmatic ones that are related to negotiating finite personal and family and emotional resources. Women who are well informed and supported in their choices experience good psychosocial outcomes from TOP. Home TOP using mifepristone appears attractive to women who are concerned about professionals' negative attitudes and lack of privacy in formal healthcare settings but also leads to concerns about management and safety.