Title: Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment
Funder: Department of Health (England)

Abstract: Design: The study will involve 5 components. (i) Development of care pathways used to structure subsequent evidence synthesis (ii) systematic review of randomised controlled trials and non-randomised controlled studies for clinical effectiveness and population-based case series for adverse events fetal outcomes and outcomes following assisted feeding (e.g. those receiving total parenternal nutrition); (iii) narrative synthesis meta-analysis of clinical effectiveness outcomes (iv) economic modelling of the effectiveness adverse events and cost-effectiveness comparing non-pharmacological and pharmacological treatments for hyperemesis gravidarum and (v) future reseach needs informed by value of information analysis.Setting: Community primary care hospital outpatients and hospital inpatients.Target population: Women experiencing severe nausea vomiting and/or retching in pregnancy where recruitment to a trial took place up to 20 weeks gestation for relative effectiveness.Health technologies to be considered: All pharmacological and non-pharmacological interventions relevant to the NHS in the community and in hospital (inpatient or outpatient treatment). These interventions will include: Dietary/lifestyle interventions; vitamins such as vitamin B6 and vitamin B12; ginger; acupressure/acupuncture; hypnosis; antiemetic drugs such as antihistamines; dopamine antagonists 5-hydroxytryptamine (HT)-receptor antagonists; corticosteroids; and intravenous fluids; nasogastric enteral feeding and total parenteral nutrition.Outcome measures: The primary outcome is the reduction of nausea and vomiting measured by the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score the Rhodes Index of Nausea Vomiting and Retching the McGill Nausea Questionnaire the Nausea and Vomiting of Pregnancy Instrument and Visual Analogue scales. Secondary outcomes include health-related quality of life healthcare utilisation including admission to hospital fetal outcomes patient satisfaction costs and cost-effectiveness of interventions. For the economic model the primary outcome is incremental cost per QALY from the perspective of the NHS and PSS and QALYs to the woman. Search strategy: Based upon a comprehensive search of MEDLINE CINAHL EMBASE PsycInfo Allied and Complementary Medicine Database (AMED) British Nursing Index Cochrane CENTRAL NHS Economic Evaluation Database (NHS EED) Health Economics Evaluation Database (HEED) Scopus and Web of Science along with sources of grey literature. Further focused searches will be conducted to identify cost and utility data required for the economic evaluation.Measurement of costs and outcomes: (a) Systematic review and meta-analysis: Identified titles and abstracts will be examined and full text papers of studies that potentially meet the inclusion criteria will be sought. These will be assessed for inclusion by two independent researchers. Any disagreements at this stage will be resolved by discussion either by the two researchers or in consultation with another team member. Data on effectiveness fetal outcomes and adverse events will be tabulated and described in a narrative review. A meta-analysis is planned carried out using fixed- or random-effect models as appropriate. The team will investigate the validity of performing mixed treatment (indirect) comparisons using appropriate methods to compare interventions that have not been compared directly with each other. Heterogeneity will be explored through consideration of study populations methods and interventions by visualisation of results and in statistical terms by the chi-squared test for homogeneity and the I2 statistic. Evidence of publication bias will be examined by funnel plots. (b) Economic evaluation: Data from the systematic review and meta-analysis will be combined in a micro-simulation cost-effectiveness economic model. The structure of the model will be based upon care pathways that represent a range of plausible pathways describing the key events in women’s care outcomes and areas of resource use. An existing data set will be used to help derive relevant utilities. Where necessary (to estimate treatment cost) study specific costs will be derived. Point estimates of costs QALYs and incremental cost per QALY will be estimated. Cost-effectiveness acceptability curves will be used to represent the imprecision surrounding estimates of cost-effectiveness. The economic model will be used to conduct a value of information analysis to inform future research.Research timetable: Research project conducted over 15 months. Month 1 First Expert panel convened; months 1-3 Develop protocol care pathways Develop and run literature searches develop tools for data abstraction and quality assessment; months 3-12 Systematic reviews; month 13 Second Expert panel convened; months 9-13 Statistical analysis; months 3-15 Economic modelling; months 13-15 Report writing.Expertise in team: The research project team contains all the disciplines required to successfully conduct this research. Including expertise in evidence synthesis (Vale robson Newbury-Birch Bryant Robalino) systematic review (Newbury-Birch Robson Bryant McParlin Vale) information science (Robalino); meta-analysis (Muirhead Bryant) health economics (Vale) and clinical practitioner expertise (Robson McParlin Nelson-Piercy Norman Yates). It is supported by expert advisors in patient and public involvement and clinical care. Flow diagram: see upload.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH