Delivery of long-term-injectable agents for TB by lay carers: pragmatic randomised trial.

BACKGROUND: People with recurrent or drug-resistant TB require long courses of intramuscular injections. We evaluate a novel system in which patient-nominated lay carers were trained to deliver intramuscular injections to patients in their own homes. METHODS: A pragmatic, individually randomised non-inferiority trial was conducted at two hospitals in Malawi. Adults starting TB retreatment were recruited. Patients randomised to the intervention received home-based care from patient-nominated lay people trained to deliver intramuscular streptomycin. Patients receiving standard care were admitted to hospital for 2 months of streptomycin. The primary outcome was successful treatment (alive and on treatment) at the end of the intervention. RESULTS: Of 456 patients screened, 204 participants were randomised. The trial was terminated early due to futility. At the end of the intervention, 97/101 (96.0%) in the hospital arm were still alive and on treatment compared with 96/103 (93.2%) in the home-based arm (risk difference -0.03 (95% CI -0.09 to 0.03); p value 0.538). There were no differences in the proportion completing 8 months of anti-TB treatment; or the proportion experiencing 2-month sputum culture conversion. The mean cost of hospital-based management was US$1546.3 per person, compared to US$729.2 for home-based management. Home-based care reduced risk of catastrophic household costs by 84%. CONCLUSIONS: Although this trial failed to meet target recruitment, the available data demonstrate that training patient-nominated lay people has potential to provide a feasible solution to the operational challenges associated with delivering long-term-injectable drugs to people with recurrent or drug-resistant TB in resource-limited settings, and substantially reduce costs. Further data under operational conditions are required. TRIAL REGISTRATION NUMBER: ISRCTN05815615.

Towards the sustainable elimination of gambiense human African trypanosomiasis in Côte d'Ivoire using an integrated approach.

BACKGROUND: Human African trypanosomiasis is a parasitic disease caused by trypanosomes among which Trypanosoma brucei gambiense is responsible for a chronic form (gHAT) in West and Central Africa. Its elimination as a public health problem (EPHP) was targeted for 2020. Côte d'Ivoire was one of the first countries to be validated by WHO in 2020 and this was particularly challenging as the country still reported around a hundred cases a year in the early 2000s. This article describes the strategies implemented including a mathematical model to evaluate the reporting results and infer progress towards sustainable elimination. METHODS: The control methods used combined both exhaustive and targeted medical screening strategies including the follow-up of seropositive subjects- considered as potential asymptomatic carriers to diagnose and treat cases- as well as vector control to reduce the risk of transmission in the most at-risk areas. A mechanistic model was used to estimate the number of underlying infections and the probability of elimination of transmission (EoT) was met between 2000-2021 in two endemic and two hypo-endemic health districts. RESULTS: Between 2015 and 2019, nine gHAT cases were detected in the two endemic health districts of Bouaflé and Sinfra in which the number of cases/10,000 inhabitants was far below 1, a necessary condition for validating EPHP. Modelling estimated a slow but steady decline in transmission across the health districts, bolstered in the two endemic health districts by the introduction of vector control. The decrease in underlying transmission in all health districts corresponds to a high probability that EoT has already occurred in Côte d'Ivoire. CONCLUSION: This success was achieved through a multi-stakeholder and multidisciplinary one health approach where research has played a major role in adapting tools and strategies to this large epidemiological transition to a very low prevalence. This integrated approach will need to continue to reach the verification of EoT in Côte d'Ivoire targeted by 2025.

Quality of sexual and reproductive health services for adolescents and young people in public health facilities in Southwest Nigeria: a mystery client study.

BACKGROUND: To support the policy drive for the promotion of sexual and reproductive health (SRH) of adolescents and young people (AYP), it is necessary to understand the characteristics of the existing SRH services available to them. OBJECTIVE: To assess the provision and experiences of care in SRH services for AYP in a Nigerian setting. METHODS: Twelve male and female mystery clients (MCs) conducted 144 visits at 27 selected primary and secondary health facilities in two Local Government Areas (LGA) in Ogun State, Nigeria. A 27-item adolescent quality of care (AHQOC) index with a Cronbach's Alpha of 0.7 was used to obtain a quality-of-care score for each clinic visit. Linear panel-data random-effects regression models using the generalised least square estimator were used to assess quality associated factors. Sentiment analysis was done on the qualitative narrative summaries provided by MCs after each visit. RESULTS: There was an absence of the use of educational materials during the 60.4% of the visits. The MCs' medical history (90.3%), social record (63.9%), sexual/reproductive history (53.5%), and contraceptive experience (66.0%) were not obtained in most of the visits. Female MC visits had a lower AHQOC index rating on average compared to males (ß=-0.3, CI -1.6 - 1.0 p = 0.687), rural health facilities had a lower AHQOC index rating on average compared to urban (ß=-2.7, CI -5.1 - -0.2, p = 0.031), and a higher ranking of the health worker on the scale of 1-10 corresponded to a higher AHQOC index of the MC visit (ß = 1.9, CI 1.6-2.1, p < 0.001). There were more positive than negative sentiments about the clinic encounters. CONCLUSION: This study found gaps in the competencies of the health workers, non-usage of educational materials in clinic encounters with young people, as well as the differential perception of quality of care by male and female AYP.

Transforming access to care for serious mental disorders in slums (the TRANSFORM Project): rationale, design and protocol.

This paper introduces the TRANSFORM project, which aims to improve access to mental health services for people with serious and enduring mental disorders (SMDs - psychotic disorders and severe mood disorders, often with co-occurring substance misuse) living in urban slums in Dhaka (Bangladesh) and Ibadan (Nigeria). People living in slum communities have high rates of SMDs, limited access to mental health services and conditions of chronic hardship. Help is commonly sought from faith-based and traditional healers, but people with SMDs require medical treatment, support and follow-up. This multicentre, international mental health mixed-methods research project will (a) conduct community-based ethnographic assessment using participatory methods to explore community understandings of SMDs and help-seeking; (b) explore the role of traditional and faith-based healing for SMDs, from the perspectives of people with SMDs, caregivers, community members, healers, community health workers (CHWs) and health professionals; (c) co-design, with CHWs and healers, training packages for screening, early detection and referral to mental health services; and (d) implement and evaluate the training packages for clinical and cost-effectiveness in improving access to treatment for those with SMDs. TRANSFORM will develop and test a sustainable intervention that can be integrated into existing clinical care and inform priorities for healthcare providers and policy makers.

Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis.

BACKGROUND: Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. METHODS: A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. RESULTS: Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62 (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98). CONCLUSIONS: Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim.

Cost-effectiveness of community health systems strengthening: quality improvement interventions at community level to realise maternal and child health gains in Kenya.

INTRODUCTION: Improvements in maternal and infant health outcomes are policy priorities in Kenya. Achieving these outcomes depends on early identification of pregnancy and quality of primary healthcare. Quality improvement interventions have been shown to contribute to increases in identification, referral and follow-up of pregnant women by community health workers. In this study, we evaluate the cost-effectiveness of using quality improvement at community level to reduce maternal and infant mortality in Kenya. METHODS: We estimated the cost-effectiveness of quality improvement compared with standard of care treatment for antenatal and delivering mothers using a decision tree model and taking a health system perspective. We used both process (antenatal initiation in first trimester and skilled delivery) and health outcomes (maternal and infant deaths averted, as well as disability-adjusted life years (DALYs)) as our effectiveness measures and actual implementation costs, discounting costs only. We conducted deterministic and probabilistic sensitivity analyses. RESULTS: We found that the community quality improvement intervention was more cost-effective compared with standard community healthcare, with incremental cost per DALY averted of $249 under the deterministic analysis and 76% likelihood of cost-effectiveness under the probabilistic sensitivity analysis using a standard threshold. The deterministic estimate of incremental cost per additional skilled delivery was US$10, per additional early antenatal care presentation US$155, per maternal death averted US$5654 and per infant death averted US$37 536 (2017 dollars). CONCLUSIONS: This analysis shows that the community quality improvement intervention was cost-effective compared with the standard community healthcare in Kenya due to improvements in antenatal care uptake and skilled delivery. It is likely that quality improvement interventions are a good investment and may also yield benefits in other health areas.

Community stakeholders' perspectives on youth mental health in India: Problems, challenges and recommendations.

BACKGROUND: India has a large youth population whose mental health needs must be addressed. This includes promotion of positive mental health, with early detection and effective intervention for mental health disorders. Understanding the perspectives of community stakeholders working with youth is pivotal to this effort. Current study aimed to bring together a group of community stakeholders (eg, parents, teachers, policy makers) to understand their perspectives on youth mental health problems, challenges in provision of care, and to provide recommendations to address these concerns at national level. MATERIALS AND METHODS: The study was conducted across two sites in India: Chennai and New Delhi. Three group meetings were conducted involving 52 participants, including governmental, non-governmental and community representatives working with youth. The proceedings were manually recorded, transcribed, and analyzed using thematic analysis method. RESULTS: Many youth mental health problems were similar across the two sites. The commonest drivers of mental health problems were reported to be academic pressure, substance use and problematic internet/social media use. Stigma and lack of awareness were identified as the most important challenges acting as barriers to seeking mental health help by youth. Prioritizing youth mental health as a national programmes along with strong political will were the major recommendations suggested by the stakeholders. CONCLUSION: Initial findings suggest that prioritizing youth mental health programmes in India would be advantageous. Inclusive and collaborative approach, involving community stakeholders working with youth in providing services that promote mental health and early access to care will help in developing healthy young citizens.

Warwick-India-Canada (WIC) global mental health group: rationale, design and protocol.

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.

SEEP-CI: A Structured Economic Evaluation Process for Complex Health System Interventions.

The economic evaluation of health system interventions is challenging, and methods guidance on how to respond to these challenges is lacking. The REACHOUT consortium developed and evaluated complex interventions for community health program quality improvement in six countries in Africa and Asia. Reflecting on the challenges we faced in conducting an economic evaluation alongside REACHOUT, we developed a Structured Economic Evaluation Process for Complex Health System Interventions (SEEP-CI). The SEEP-CI aims to establish the threshold effect size that would justify investment in a complex intervention, and provide an assessment to a decision-maker of how likely it is that the intervention can achieve this impact. We illustrate how the SEEP-CI could have been applied to REACHOUT to identify outcomes where the intervention might have impact and causal mechanisms, through which that impact might occur, guide data collection by focusing on proximal outcomes most likely to illustrate the effectiveness of the intervention, identify the size of health gain required to justify investment in the intervention, and indicate the assumptions required to accept that such health gains are credible. Further research is required to determine the feasibility and acceptability of the SEEP-CI, and the contexts in which it could be used.

How do decision-makers use evidence in community health policy and financing decisions? A qualitative study and conceptual framework in four African countries.

Various investments could help countries deliver on the universal health coverage (UHC) goals set by the global community; community health is a pillar of many national strategies towards UHC. Yet despite resource mobilization towards this end, little is known about the potential costs and value of these investments, as well as how evidence on the same would be used in related decisions. This qualitative study was conducted to understand the use of evidence in policy and financing decisions for large-scale community health programmes in low- and middle-income countries. Through key informant interviews with 43 respondents in countries with community health embedded in national UHC strategies (Ethiopia, Kenya, Malawi, Mozambique) and at global institutions, we investigated evidence use in community health financing and policy decision-making, as well as evidentiary needs related to community health data for decision-making. We found that evidence use is limited at all levels, in part due to a perceived lack of high-quality, relevant evidence. This perception stems from two main areas: first, desire for local evidence that reflects the context, and second, much existing economic evidence does not deal with what decision-makers value when it comes to community health systems-i.e. coverage and (to a lesser extent) quality. Beyond the evidence gap, there is limited capacity to assess and use the evidence. Elected officials also face political challenges to disinvestment as well as structural obstacles to evidence use, including the outsized influence of donor priorities. Evaluation data must to speak to decision-maker interests and constraints more directly, alongside financiers of community health providing explicit guidance and support on the role of evidence use in decision-making, empowering national decision-makers. Improved data quality, increased relevance of evidence and capacity for evidence use can drive improved efficiency of financing and evidence-based policymaking.

Negative-pressure wound therapy compared with standard dressings following surgical treatment of major trauma to the lower limb: the WHiST RCT.

BACKGROUND: Major trauma is the leading cause of death in people aged < 45 years. Patients with major trauma usually have lower-limb fractures. Surgery to fix the fractures is complicated and the risk of infection may be as high as 27%. The type of dressing applied after surgery could potentially reduce the risk of infection. OBJECTIVES: To assess the deep surgical site infection rate, disability, quality of life, patient assessment of the surgical scar and resource use in patients with surgical incisions associated with fractures following major trauma to the lower limbs treated with incisional negative-pressure wound therapy versus standard dressings. DESIGN: A pragmatic, multicentre, randomised controlled trial. SETTING: Twenty-four specialist trauma hospitals representing the UK Major Trauma Network. PARTICIPANTS: A total of 1548 adult patients were randomised from September 2016 to April 2018. Exclusion criteria included presentation > 72 hours after injury and inability to complete questionnaires. INTERVENTIONS: Incisional negative-pressure wound therapy (n = 785), in which a non-adherent absorbent dressing covered with a semipermeable membrane is connected to a pump to create a partial vacuum over the wound, versus standard dressings not involving negative pressure (n = 763). Trial participants and the treating surgeon could not be blinded to treatment allocation. MAIN OUTCOME MEASURES: Deep surgical site infection at 30 days was the primary outcome measure. Secondary outcomes were deep infection at 90 days, the results of the Disability Rating Index, health-related quality of life, the results of the Patient and Observer Scar Assessment Scale and resource use collected at 3 and 6 months post surgery. RESULTS: A total of 98% of participants provided primary outcome data. There was no evidence of a difference in the rate of deep surgical site infection at 30 days. The infection rate was 6.7% (50/749) in the standard dressing group and 5.8% (45/770) in the incisional negative-pressure wound therapy group (intention-to-treat odds ratio 0.87; 95% confidence interval 0.57 to 1.33; p = 0.52). There was no difference in the deep surgical site infection rate at 90 days: 13.2% in the standard dressing group and 11.4% in the incisional negative-pressure wound therapy group (odds ratio 0.84, 95% confidence interval 0.59 to 1.19; p = 0.32). There was no difference between the two groups in disability, quality of life or scar appearance at 3 or 6 months. Incisional negative-pressure wound therapy did not reduce the cost of treatment and was associated with a low probability of cost-effectiveness. LIMITATIONS: Owing to the emergency nature of the surgery, we anticipated that some patients who were randomised would subsequently be unable or unwilling to participate. However, the majority of the patients (85%) agreed to participate. Therefore, participants were representative of the population with lower-limb fractures associated with major trauma. CONCLUSIONS: The findings of this study do not support the use of negative-pressure wound therapy in patients having surgery for major trauma to the lower limbs. FUTURE WORK: Our work suggests that the use of incisional negative-pressure wound therapy dressings in other at-risk surgical wounds requires further investigation. Future research may also investigate different approaches to reduce postoperative infections, for example the use of topical antibiotic preparations in surgical wounds and the role of orthopaedic implants with antimicrobial coatings when fixing the associated fracture. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12702354 and UK Clinical Research Network Portfolio ID20416. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 38. See the NIHR Journals Library for further project information.

WHAT DID THE TRIAL FIND?: We found no evidence of a difference in the rate of surgical site infection between those patients randomised to negative-pressure wound therapy and those patients randomised to standard wound dressings. There was no difference in the rate of other wound healing complications or in the patients' self-report of disability, health-related quality of life or scar healing. Negative-pressure wound therapy is very unlikely to be cost-effective for the NHS. In conclusion, and contrary to previous reports, the findings of this study do not support the use of negative-pressure wound therapy in patients having surgery for major trauma to their legs.

Major trauma is the leading cause of death worldwide in people aged < 45 years and a significant cause of short- and long-term health problems. In 85% of major trauma patients, the injury involves broken bones. Surgery to fix broken bones in the lower limbs is complicated and has risks, one of the main ones being wound infection. In these patients, rates of wound infection have been reported to be as high as 27%. One factor that may affect the risk of infection is the type of dressing applied after surgery. In this trial, we compared standard wound dressings with a new treatment called incisional negative-pressure wound therapy. Negative-pressure wound therapy is a special type of dressing whereby gentle suction is applied to the surface of the wound. A total of 1548 patients from 24 specialist trauma hospitals in the UK agreed to take part and were assigned at random to receive either a standard wound dressing or negative-pressure wound therapy after their surgery. We reviewed the recovery of the patients for 6 months. We recorded how many had an infection in the surgical wound and asked the patients to rate the extent of their disability, their quality of life and the scar healing. We also collected information about the cost of treatment.

Impact of the societal response to COVID-19 on access to healthcare for non-COVID-19 health issues in slum communities of Bangladesh, Kenya, Nigeria and Pakistan: results of pre-COVID and COVID-19 lockdown stakeholder engagements.

INTRODUCTION: With COVID-19, there is urgency for policymakers to understand and respond to the health needs of slum communities. Lockdowns for pandemic control have health, social and economic consequences. We consider access to healthcare before and during COVID-19 with those working and living in slum communities. METHODS: In seven slums in Bangladesh, Kenya, Nigeria and Pakistan, we explored stakeholder perspectives and experiences of healthcare access for non-COVID-19 conditions in two periods: pre-COVID-19 and during COVID-19 lockdowns. RESULTS: Between March 2018 and May 2020, we engaged with 860 community leaders, residents, health workers and local authority representatives. Perceived common illnesses in all sites included respiratory, gastric, waterborne and mosquitoborne illnesses and hypertension. Pre-COVID, stakeholders described various preventive, diagnostic and treatment services, including well-used antenatal and immunisation programmes and some screening for hypertension, tuberculosis, HIV and vectorborne disease. In all sites, pharmacists and patent medicine vendors were key providers of treatment and advice for minor illnesses. Mental health services and those addressing gender-based violence were perceived to be limited or unavailable. With COVID-19, a reduction in access to healthcare services was reported in all sites, including preventive services. Cost of healthcare increased while household income reduced. Residents had difficulty reaching healthcare facilities. Fear of being diagnosed with COVID-19 discouraged healthcare seeking. Alleviators included provision of healthcare by phone, pharmacists/drug vendors extending credit and residents receiving philanthropic or government support; these were inconsistent and inadequate. CONCLUSION: Slum residents' ability to seek healthcare for non-COVID-19 conditions has been reduced during lockdowns. To encourage healthcare seeking, clear communication is needed about what is available and whether infection control is in place. Policymakers need to ensure that costs do not escalate and unfairly disadvantage slum communities. Remote consulting to reduce face-to-face contact and provision of mental health and gender-based violence services should be considered.

Is quality affordable for community health systems? Costs of integrating quality improvement into close-to-community health programmes in five low-income and middle-income countries.

INTRODUCTION: Countries aspiring to universal health coverage view close-to-community (CTC) providers as a low-cost means of increasing coverage. However, due to lack of coordination and unreliable funding, the quality of large-scale CTC healthcare provision is highly variable and routine data about service quality are not trustworthy. Quality improvement (QI) approaches are a means of addressing these issues, yet neither the costs nor the budget impact of integrating QI approaches into CTC programme costs have been assessed. METHODS: This paper examines the costs and budget impact of integrating QI into existing CTC health programmes in five countries (Ethiopia, Indonesia, Kenya, Malawi, Mozambique) between 2015 and 2017. The intervention involved: (1) QI team formation; (2) Phased training interspersed with supportive supervision; which resulted in (3) QI teams independently collecting and analysing data to conduct QI interventions. Project costs were collected using an ingredients approach from a health systems perspective. Based on project costs, costs of local adoption of the intervention were modelled under three implementation scenarios. RESULTS: Annualised economic unit costs ranged from $62 in Mozambique to $254 in Ethiopia per CTC provider supervised, driven by the context, type of community health model and the intensity of the intervention. The budget impact of Ministry-led QI for community health is estimated at 0.53% or less of the general government expenditure on health in all countries (and below 0.03% in three of the five countries). CONCLUSION: CTC provision is a key component of healthcare delivery in many settings, so QI has huge potential impact. The impact is difficult to establish conclusively, but as a first step we have provided evidence to assess affordability of QI for community health. Further research is needed to assess whether QI can achieve the level of benefits that would justify the required investment.

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation.

BACKGROUND: At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-ß) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. OBJECTIVES: To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-ß and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other. REVIEW METHODS: Searches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health's risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis. RESULTS: In total, 6420 publications were identified, of which 63 relating to 35 randomised controlled trials (RCTs) were included. In total, 86% had a high risk of bias. There was very little difference between drugs in reducing moderate or severe relapse rates in RRMS. All were beneficial compared with BSC, giving a pooled rate ratio of 0.65 [95% confidence interval (CI) 0.56 to 0.76] for ARR and a hazard ratio of 0.70 (95% CI, 0.55 to 0.87) for time to disability progression confirmed at 3 months. NMA suggested that 20 mg of GA given subcutaneously had the highest probability of being the best at reducing ARR. Three separate cost-effectiveness searches identified > 2500 publications, with 26 included studies informing the narrative synthesis and model inputs. In the base case using a modified RSS the mean incremental cost was £31,900 for pooled DMTs compared with BSC and the mean incremental quality-adjusted life-years (QALYs) were 0.943, giving an ICER of £33,800 per QALY gained for people with RRMS. In probabilistic sensitivity analysis the ICER was £34,000 per QALY gained. In sensitivity analysis, using the assessment group inputs gave an ICER of £12,800 per QALY gained for pooled DMTs compared with BSC. Pegylated IFN-ß-1 (125 µg) was the most cost-effective option of the individual DMTs compared with BSC (ICER £7000 per QALY gained); GA (20 mg) was the most cost-effective treatment for CIS (ICER £16,500 per QALY gained). LIMITATIONS: Although we built a de novo model for CIS that incorporated evidence from our systematic review of clinical effectiveness, our findings relied on a population diagnosed with CIS before implementation of the revised 2010 McDonald criteria. CONCLUSIONS: DMTs were clinically effective for RRMS and CIS but cost-effective only for CIS. Both RCT evidence and RSS data are at high risk of bias. Research priorities include comparative studies with longer follow-up and systematic review and meta-synthesis of qualitative studies. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016043278. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Economic evaluation of the practical approach to lung health and informal provider interventions for improving the detection of tuberculosis and chronic airways disease at primary care level in Malawi: study protocol for cost-effectiveness analysis.

BACKGROUND: Chronic airway diseases pose a big challenge to health systems in most developing countries, particularly in Sub-Saharan Africa. A diagnosis for people with chronic or persistent cough is usually delayed because of individual and health system barriers. However, delayed diagnosis and treatment facilitates further transmission, severity of disease with complications and mortality. The objective of this study is to assess the cost-effectiveness of the practical approach to lung health strategy, a patient-centred approach for diagnosis and treatment of common respiratory illnesses in primary healthcare settings, as a means of strengthening health systems to improve the quality of management of respiratory diseases. METHODS/DESIGN: Economic evaluation nested in a cluster randomised controlled trial with three arms will be performed. Measures of effectiveness and costs for all arms of the study will be obtained from the cluster randomised controlled clinical trial. The main outcome measures are a combined rate of major respiratory diseases milestones and process indicators extracted from the practical approach to lung health strategy. For analysis, descriptive as well as regression techniques will be used. A cost-effectiveness analysis will be performed according to intention-to-treat principle and from a societal perspective. Cost-effectiveness ratios will be calculated using bootstrapping techniques. DISCUSSION: We hope to demonstrate the cost-effectiveness of the practical approach to lung health and informal healthcare providers, see an improvement in patients' quality of life, achieve a reduction in the duration and occurrence of episodes and the chronicity of respiratory diseases, and are able to report a decrease in the social cost. If the practical approach to lung health and informal healthcare provider's interventions are cost-effective, they could be scaled up to all primary healthcare centres. TRIAL REGISTRATION: PACTR: PACTR201411000910192.