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Purpose: The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports., Participants: Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at., Findings to Date: This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be 'markedly ill', 'severely ill' or 'among the most extremely ill' by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year., Future Plans: Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared., Trial Registration Number: NCT03013595., Competing Interests: Competing interests: SPS is part-funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care West Midlands (NIHR CLAHRC WM), now recommissioned as NIHR Applied Research Collaboration West Midlands. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. PS is the co-inventor of the HealthTrackerTM and is the Chief Executive Officer and shareholder in HealthTracker Ltd. FF is a Chief Technical Officer and AK is the Chief Finance Officer employed by HealthTracker Ltd respectively. FCV publishes the Dutch translations of ASEBA, from which he receives remuneration. AM was a speaker and advisor for Neurim, Shire, Infectopharm and Lilly (all not related to transition research)., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The primary aim of the National Institute of Health Research-funded global health research group, Warwick-India-Canada (WIC), is to reduce the burden of psychotic disorders in India. India has a large pool of undetected and untreated patients with psychosis and a treatment gap exceeding 75%. Evidence-based packages of care have been piloted, but delivery of treatments still remains a challenge. Even when patients access treatment, there is minimal to no continuity of care. The overarching ambition of WIC programme is to improve patient outcomes through (1) developing culturally tailored clinical interventions, (2) early identification and timely treatment of individuals with mental illness and (3) improving access to care by exploiting the potential of digital technologies., Methods and Analysis: This multicentre, multicomponent research programme, comprising five work packages and two cross-cutting themes, is being conducted at two sites in India: Schizophrenia Research Foundation, Chennai (South India) and All India Institute of Medical Sciences, New Delhi (North India). WIC will (1) develop and evaluate evidence-informed interventions for early and first-episode psychosis; (2) determine pathways of care for early psychosis; (3) investigate the efficacy and cost-effectiveness of community care models, including digital and mobile technologies; (4) develop strategies to reduce the burden of mental illnesses among youth; (5) assess the economic burden of psychosis on patients and their carers; and (6) determine the feasibility of an early intervention in psychosis programme in India., Ethics and Dissemination: This study was approved by the University of Warwick's Biomedical and Scientific Research Ethics Committee (reference: REGO-2018-2208), Coventry, UK and research ethics committees of all participating organisations. Research findings will be disseminated through peer-reviewed scientific publications, presentations at learnt societies and visual media., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: A December 2019 WHO rapid communication recommended the use of 9-month all-oral regimens for treating multidrug-resistant tuberculosis (MDR-TB). Besides the clinical benefits, they are thought to be less costly than the injectable-containing regimens, for both the patient and the health system. STREAM is the first randomised controlled trial with an economical evaluation to compare all-oral and injectable-containing 9-11-month MDR-TB treatment regimens., Methods and Analysis: Health system costs of delivering a 9-month injectable-containing regimen and a 9-month all-oral bedaquiline-containing regimen will be collected in Ethiopia, India, Moldova and Uganda, using 'bottom-up' and 'top-down' costing approaches. Patient costs will be collected using questionnaires that have been developed based on the STOP-TB questionnaire. The primary objective of the study is to estimate the cost utility of the two regimens, from a health system perspective. Secondary objectives include estimating the cost utility from a societal perspective as well as evaluating the cost-effectiveness of the regimens, using both health system and societal perspectives. The effect measure for the cost-utility analysis will be the quality-adjusted life years (QALY), while the effect measure for the cost-effectiveness analysis will be the efficacy outcome from the clinical trial., Ethics and Dissemination: The study has been evaluated and approved by the Ethics Advisory Group of the International Union Against Tuberculosis and Lung Disease and also approved by ethics committees in all participating countries. All participants have provided written informed consent. The results of the economic evaluation will be published in a peer-reviewed journal., Trial Registration Number: ISRCTN18148631., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: Young people moving from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS) are faced with significant challenges. To improve this state of affairs, there needs to be a recognition of the problem and initiatives and an urgent requirement for appropriate tools for measuring readiness and outcomes at the transfer boundary (16-18 years of age in Europe). The objective of this study was to develop and validate the Transition Readiness and Appropriateness Measure (TRAM) for assessing a young person's readiness for transition, and their outcomes at the transfer boundary., Design: MILESTONE prospective study., Setting: Eight European Union (EU) countries participating in the EU-funded MILESTONE study., Participants: The first phase (MILESTONE validation study) involved 100 adolescents (pre-transition), young adults (post-transition), parents/carers and both CAMHS and AMHS clinicians. The second phase (MILESTONE cohort study and nested cluster randomised trial) involved over 1000 young people., Results: The development of the TRAM began with a literature review on transitioning and a review of important items regarding transition by a panel of 34 mental health experts. A list of 64 items of potential importance were identified, which together comprised the TRAM. The psychometric properties of the different versions of the TRAM were evaluated and showed that the TRAM had good reliability for all versions and low-to-moderate correlations when compared with other established instruments and a well-defined factor structure. The main results of the cohort study with the nested cluster randomised trial are not reported., Conclusion: The TRAM is a reliable instrument for assessing transition readiness and appropriateness. It highlighted the barriers to a successful transition and informed clinicians, identifying areas which clinicians on both sides of the transfer boundary can work on to ease the transition for the young person., Trial Registration Number: ISRCTN83240263 (Registered 23 July 2015), NCT03013595 (Registered 6 January 2017); Pre-results., Competing Interests: Competing interests: PS is the co-inventor of the HealthTracker and is the Chief Executive Officer and shareholder in HealthTracker. FF is a Chief Technical Officer and KL is a Project Manager employed by HealthTracker. FV is the Dutch distributor of ASEBA from which he receives remuneration. SPS is part-funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care WM (NIHR CLAHRC WM)., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Low-income and middle-income settings like India have large treatment gaps in mental healthcare. People with severe mental disorders face impediments to their clinical and functional recovery, and have large unmet needs. The infrastructure and standards of care are poor in colonial period psychiatric hospitals, with no clear pathways to discharge and successfully integrate recovered individuals into the community. Our aim is to study the impact of psychiatric hospital reform on individual patient outcomes in a psychiatric hospital in India., Methods and Analysis: Structured Individualised inTervention And Recovery (SITAR) is a two-arm pragmatic randomised controlled trial, focusing on patients aged 18-60 years with a hospital stay of 12-120 months and a primary diagnosis of psychosis. It tests the effectiveness of structural and process reform with and without an individually tailored recovery plan on patient outcomes of disability (primary outcome WHO Disability Assessment Scale), symptom severity, social and occupational functioning and quality of life. A computer-generated permuted block randomisation schedule will allocate recruited subjects to the two study arms. We aim to recruit 100 people into each trial arm. Baseline and outcome measures will be undertaken by trained researchers independent to the case managers providing the individual intervention. A health economic analysis will determine the costing of implementing the individually tailored recovery plan., Ethics and Dissemination: The study will provide answers to important questions around the nature and process of reforms in institutional care that promote recovery while being cognizant of protecting human rights, and dignity. Ethical approval for SITAR was obtained from a registered ethics committee in India (Institutional Ethics Committee VikasAnvesh Foundation, VAF/2018-19/012 dated 6 December 2018) and the University of Warwick's Biomedical and Scientific Research Ethics Committee (REGO-2019-2332, dated 21 March 2019), and registered on the Central Trial Registry of India (CTRI/2019/01/017267). Trial results will be published in accordance to CONSORT guidelines., Competing Interests: Competing interests: This trial is part of the PhD programme undertaken by the TR. She is an employee of the Tata Trusts and the Tata Trusts External Individual educational grants programme funds the PhD won on basis of merit., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To test the feasibility of implementing a brief but intensive hybrid cognitive behavioural therapy (Hybrid CBT) for pain-related insomnia., Design: Mixed-methods, with qualitative process evaluation on a two-arm randomised controlled feasibility trial., Setting: Primary care., Participants: Twenty-five adult patients with chronic pain and insomnia., Intervention: Hybrid CBT or self-help control intervention., Primary and Secondary Outcome Measures: Primary outcomes measures were the Insomnia Severity Index and interference scale of the Brief Pain Inventory (BPI). Secondary outcomes measures were the present pain intensity rating from the BPI, Multidimensional Fatigue Inventory, Hospital Anxiety and Depression Scale and EQ-5D-5L., Results: Fourteen participants were randomised to receive Hybrid CBT, 11 to receive the self-help control treatment. Of the 14 in the Hybrid CBT group, 9 (64%) completed all four treatment sessions (4 discontinued due to poor health; 1 due to time constraints). Adherence to the self-help control treatment was not monitored. The total number of participants completing the 12-week and 24-week follow-ups were 12 (6 in each group; Hybrid CBT: 43%; self-help: 55%) and 10 (5 in each group; Hybrid CBT: 36%; self-help: 45%). Based on the data available, candidate outcome measures appeared to be sensitive to changes associated with interventions. Thematic analysis of pre-postintervention interview data revealed satisfaction with treatment content among those who completed the Hybrid CBT, whereas those in the self-help control treatment wanted more contact hours and therapist guidance. Other practical suggestions for improvement included shortening the duration of each treatment session, reducing the amount of assessment paperwork, and minimising the burden of sleep and pain monitoring., Conclusion: Important lessons were learnt with regard to the infrastructure required to achieve better patient adherence and retention. Based on the qualitative feedback provided by a subset of treatment completers, future trials should also consider lowering the intensity of treatment and streamlining the data collection procedure., Trial Registration Number: ISRCTN17294365., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form. HKS and SP are directors of Health Psychology Services, which in part provides psychological treatments for those with chronic pain. HKS is chief investigator and co-investigator on other NIHR funded projects. MU was Chair of the NICE accreditation advisory committee until March 2017 for which he received a fee. He is chief investigator or co-investigator on multiple previous and current research grants from the UK National Institute for Health Research, Arthritis Research UK and is a co-investigator on grants funded by the Australian NHMRC. He is an NIHR Senior Investigator. He has received travel expenses for speaking at conferences from the professional organisations hosting the conferences. He is a director and shareholder of Clinvivo that provides electronic data collection for health services research. He is part of an academic partnership with Serco related to return to work initiatives. He is a co-investigator on a study receiving support in kind from Stryker. He has accepted honoraria for teaching/lecturing from CARTA & Sterling Events. He is an editor of the NIHR journal series, and a member of the NIHR Journal Editors Group, for which he receives a fee. NKYT received grant funding as co-investigator from NIHR for other projects and current funding from the Medical Research Council as principal investigator. NKYT is also a member of the trial steering committee of an ongoing trial funded by the NIHR., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Supervised community treatment (SCT) for people with serious mental disorders has become accepted practice in many countries around the world. In England, SCT was adopted in 2008 in the form of community treatment orders (CTOs). CTOs have been used more than expected, with significant variations between people and places. There is conflicting evidence about the effectiveness of SCT; studies based on randomised controlled trials (RCTs) have suggested few positive impacts, while those employing observational designs have been more favourable. Robust population-based studies are needed, because of the ethical challenges of undertaking further RCTs and because variation across previous studies may reflect the effects of sociospatial context on SCT outcomes. We aim to examine spatial and temporal variation in the use, effectiveness and cost of CTOs in England through the analysis of routine administrative data., Methods and Analysis: Four years of data from the Mental Health Services Dataset (MHSDS) will be analysed using multilevel models. Models based on all patients eligible for CTOs will be used to explore variation in their use. A subset of CTO-eligible patients comprising a treatment group (CTO patients) and a matched control group (non-CTO patients) will be used to examine variation in the association between CTO use and study outcomes. Primary outcome will be total time in hospital. Secondary outcomes will include time to first readmission and mortality. Outputs from these models will be used to populate predictive models of healthcare resource use., Ethics and Dissemination: Ethical approval has been granted by the National Health Service Data Access and Advisory Group and Warwick University. To ensure patient confidentiality and to meet data governance requirements, analyses will be carried out in a secure microdata laboratory using de-identified data. Study findings will be disseminated through academic channels and shared with mental health policy-makers and other stakeholders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Inpatient mental healthcare continues to be an area of high risk and where patients report negative experiences. To ensure the patient voice is heard, National Health Service (NHS) Trusts are required to collect feedback from patients routinely. We do not know what kinds of feedback are most important or what management processes are needed to translate this into effective action plans. Further, we do not know if this makes any difference to the patients themselves. This study seeks to explore which of the many different approaches to collecting and using patient experience data are the most useful for supporting improvements in inpatient mental healthcare. The overarching aim of the study is to arrive at recommendations for best practice in the collection and use of patient experience data in NHS England adult inpatient mental health settings. We present the protocol for Realist Evaluation of the Use of Patient Experience Data to Improve the Quality of Inpatient Mental Health Care study (EURIPIDES)., Methods and Analysis: The study is composed of five work packages (WPs), including a systematic review of patient experiences (WP1); a telephone survey to assist the selection of case sites (WP2); six indepth case studies involving interviews with service users, carers and staff to enable a realist evaluation of the use of patient experience to improve quality in adult inpatient mental health services (WP3); an economic evaluation of patient experience feedback activity (WP5); and a consensus conference (WP4). We discuss the methodological rationale for the five WPs., Ethics and Dissemination: This study has received approval from West Midlands/South Birmingham NHS Research Ethics Committee. The outcome of the consensus conference meeting (WP4) will form the basis of the outputs to be disseminated to NHS providers. Dissemination will also take place through publications and presentations at relevant conferences., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Patients with closed high-energy injuries associated with major trauma have surprisingly high rates of surgical site infection in incisions created during fracture fixation. One factor that may reduce the risk of surgical site infection is the type of dressing applied over the closed surgical incision. In this multicentre randomised clinical trial, negative-pressure wound therapy will be compared with standard dressings with outcomes of deep infection, quality of life, pain and disability., Methods and Analysis: Adult patients presenting to hospital within 72 hours of sustaining major trauma, requiring a surgical incision to treat a fractured lower limb, are eligible for inclusion. Randomisation, stratified by trial centre, open/closed fracture at presentation and Injury Severity Score (ISS) ≤15 versus ISS ≥16 will be administered via a secure web-based service using minimisation. The random allocation will be to either standard wound management or negative-pressure wound therapy.Trial participants will usually have clinical follow-up at the local fracture clinic for a minimum of 6 months, as per standard National Health Service practice. Diagnosis of deep infection will be recorded at 30 days. Functional, pain and quality of life outcome data will be collected using the Disability Rating Index, Douleur Neuropathique Questionnaire and Euroqol - 5 Dimension - 5 level (EQ-5D-5L) questionnaires at 3 months and 6 months postinjury. Further data will be captured on resource use and any late postoperative complications.Longer term outcomes will be assessed annually for 5 years and reported separately., Ethics and Dissemination: National Research Ethics Committee approved this study on 16 February 2016 16/WM/0006.The National Institute for Health Research Health Technology Assessment monograph and a manuscript to a peer-reviewed journal will be submitted on completion of this trial. The results of this trial will inform clinical practice on the clinical and cost-effectiveness of the treatment of this injury., Trial Registration Number: ISRCTN12702354; Pre-results., Competing Interests: Competing interests: MLC is a member of the UK NIHR HTA General Board., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Disruption of care during transition from child and adolescent mental health services (CAMHS) to adult mental health services may adversely affect the health and well-being of service users. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Healthcare) study evaluates the longitudinal course and outcomes of adolescents approaching the transition boundary (TB) of their CAMHS and determines the effectiveness of the model of managed transition in improving outcomes, compared with usual care., Methods and Analysis: This is a cohort study with a nested cluster randomised controlled trial. Recruited CAMHS have been randomised to provide either (1) managed transition using the Transition Readiness and Appropriateness Measure score summary as a decision aid, or (2) usual care for young people reaching the TB. Participants are young people within 1 year of reaching the TB of their CAMHS in eight European countries; one parent/carer and a CAMHS clinician for each recruited young person; and adult mental health clinician or other community-based care provider, if young person transitions. The primary outcome is Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) measuring health and social functioning at 15 months postintervention. The secondary outcomes include mental health, quality of life, transition experience and healthcare usage assessed at 9, 15 and 24 months postintervention. With a mean cluster size of 21, a total of 840 participants randomised in a 1:2 intervention to control are required, providing 89% power to detect a difference in HoNOSCA score of 0.30 SD. The addition of 210 recruits for the cohort study ensures sufficient power for studying predictors, resulting in 1050 participants and an approximate 1:3 randomisation., Ethics and Dissemination: The study protocol was approved by the UK National Research Ethics Service (15/WM/0052) and equivalent ethics boards in participating countries. Results will be reported at conferences, in peer-reviewed publications and to all relevant stakeholder groups., Trial Registration Number: ISRCTN83240263; NCT03013595 (pre-results)., Competing Interests: Competing interests: PS is the director and shareholder of HealthTracker. FCV publishes the Dutch translations of ASEBA, from which he receives remuneration., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To compare assessments of health-related quality of life outcomes of care home residents reported by residents and care staff acting as proxies., Design: Linear regression and bivariate modelling of paired assessments from care home residents and care staff., Setting: 78 care homes in 2 regions in England., Participants: 556 care home residents aged 65 years or older and care staff., Main Outcome Measures: EQ-5D utility scores and responses to individual EQ-5D dimensions., Results: The depression status, cognitive function, physical function, activities of daily living, social engagement, pain and dementia diagnosis of care home residents all predicted discrepancies in EQ-5D reporting. For residents with no depressive symptoms, care staff underestimated residents' mean EQ-5D utility score by 0.134 (95% CI 0.097 to 0.171) and for those with severe depressive symptoms they overstated mean utility scores by 0.222 (95% CI 0.104 to 0.339). With increasing levels of pain in residents the care staff progressively estimated EQ-5D utilities above self-reported values; by 0.236 (95% CI 0.003 to 0.469) in those with the second highest pain scores. For those with no cognitive impairment, proxies overstated mean utility scores by 0.097 (95% CI 0.049 to 0.146), while for those with severe cognitive impairment they underestimated mean utility scores by 0.192 (95% CI 0.143 to 0.241)., Conclusions: Care home residents and staff appear to differ fundamentally in their assessment of the health-related quality of life, as measured by the EQ-5D, of residents with different levels of depression, pain and/or cognitive impairment. This could lead to interventions evaluated using proxy-based quality-adjusted life year estimates being wrongly rejected on cost-effectiveness grounds and may also make it difficult for carers to act as advocates with health and social care professionals for certain groups of residents. A more resident-focussed approach to assessment of health-related quality of life is needed., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Introduction: Multidrug-resistant tuberculosis (MDR-TB) poses a serious financial challenge to health systems and patients. The current treatment for patients with MDR-TB takes up to 24 months to complete. Evidence for a shorter regimen which differs from the standard WHO recommended MDR-TB regimen and typically lasts between 9 and 12 months has been reported from Bangladesh. This evaluation aims to assess the economic impact of a shortened regimen on patients and health systems. This evaluation is innovative as it combines patient and health system costs, as well as operational modelling in assessing the impact., Methods and Analysis: An economic evaluation nested in a clinical trial with 2 arms will be performed at 4 facilities. The primary outcome measure is incremental cost to the health system of the study regimen compared with the control regimen. Secondary outcome measures are mean incremental costs incurred by patients by treatment outcome; patient costs by category (direct medical costs, transport, food and accommodation costs, and cost of guardians/accompanying persons and lost time); health systems cost by category and drugs; and costs related to serious adverse events., Ethics and Dissemination: The study has been evaluated and approved by the Ethics Advisory Group of the International Union Against Tuberculosis and Lung Disease; South African Medical Research Ethics Committee; Wits Health Consortium Protocol Review Committee; University of the Witwatersrand Human Research Ethics Committee; University of Kwazulu-Natal Biomedical Research Ethics Committee; St Peter TB Specialized Hospital Ethical Review Committee; AHRI-ALERT Ethical Review Committee, and all participants will provide written informed consent. The results of the economic evaluation will be published in a peer-reviewed journal., Trial Registration Number: ISRCTN78372190., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy., Design: Systematic review and meta-analysis of published studies., Data Sources: PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015., Eligibility Criteria for Selecting Studies: English language journal articles describing case-control studies with ≥ 15 trisomy cases or cohort studies with ≥ 50 pregnant women who had been given NIPT and a reference standard., Results: 41, 37 and 30 studies of 2012 publications retrieved were included in the review for Down, Edwards and Patau syndromes. Quality appraisal identified high risk of bias in included studies, funnel plots showed evidence of publication bias. Pooled sensitivity was 99.3% (95% CI 98.9% to 99.6%) for Down, 97.4% (95.8% to 98.4%) for Edwards, and 97.4% (86.1% to 99.6%) for Patau syndrome. The pooled specificity was 99.9% (99.9% to 100%) for all three trisomies. In 100,000 pregnancies in the general obstetric population we would expect 417, 89 and 40 cases of Downs, Edwards and Patau syndromes to be detected by NIPT, with 94, 154 and 42 false positive results. Sensitivity was lower in twin than singleton pregnancies, reduced by 9% for Down, 28% for Edwards and 22% for Patau syndrome. Pooled sensitivity was also lower in the first trimester of pregnancy, in studies in the general obstetric population, and in cohort studies with consecutive enrolment., Conclusions: NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases., Trial Registration Number: CRD42014014947., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)