HeAlth System StrEngThening in four sub-Saharan African countries (ASSET) to achieve high-quality, evidence-informed surgical, maternal and newborn, and primary care: protocol for pre-implementation phase studies.

To achieve universal health coverage, health system strengthening (HSS) is required to support the of delivery of high-quality care. The aim of the National Institute for Health Research Global Research Unit on HeAlth System StrEngThening in Sub-Saharan Africa (ASSET) is to address this need in a four-year programme, with three healthcare platforms involving eight work-packages. Key to effective health system strengthening (HSS) is the pre-implementation phase of research where efforts focus on applying participatory methods to embed the research programme within the existing health system. To conceptualise the approach, we provide an overview of the key methods applied across work-package to address this important phase of research conducted between 2017 and 2021.Work-packages are being undertaken in publicly funded health systems in rural and urban areas in Ethiopia, Sierra Leone, South Africa, and Zimbabwe. Stakeholders including patients and their caregivers, community representatives, clinicians, managers, administrators, and policymakers are the main research participants.In each work-package, initial activities engage stakeholders and build relationships to ensure co-production and ownership of HSSIs. A mixed-methods approach is then applied to understand and address determinants of high-quality care delivery. Methods such as situation analysis, cross-sectional surveys, interviews and focus group discussions are adopted to each work-package aim and context. At the end of the pre-implementation phase, findings are disseminated using focus group discussions and participatory Theory of Change workshops where stakeholders from each work package use findings to select HSSIs and develop a programme theory.ASSET places a strong emphasis of the pre-implementation phase in order to provide an in-depth and systematic diagnosis of the existing heath system functioning, needs for strengthening and stakeholder engagement. This common approach will inform the design and evaluation of the HSSIs to increase effectiveness across work packages and contexts, to better understand what works, for whom, and how.

Effectiveness of a task-sharing collaborative care model for identification and management of depressive symptoms in patients with hypertension attending public sector primary care clinics in South Africa: pragmatic parallel cluster randomised controlled trial.

BACKGROUND: We tested the real-world effectiveness of a collaborative task-sharing model on depressive symptom reduction in hypertensive Primary Health Care (PHC) patients in South Africa. METHOD: A pragmatic parallel cluster randomised trial in 20 clinics in the Dr Kenneth Kaunda district, North West province. PHC clinics were stratified by sub-district and randomised in a 1:1 ratio. Control clinics received care as usual (CAU), involving referral to PHC doctors and/or mental health specialists. Intervention clinics received CAU plus enhanced mental health training and a lay counselling referral service. Participant inclusion criteria were ≥ 18 years old, Patient Health Questionnaire-9 (PHQ-9) score ≥ 9 and receiving hypertension medication. Primary superiority outcome was ≥ 50% reduction in PHQ-9 score at 6 months. Statistical analyses comprised mixed effects regression models and a non-inferiority analysis. TRIAL REGISTRATION NUMBER: NCT02425124. RESULTS: Between April 2015 and October 2015, 1043 participants were enrolled (504 intervention and 539 control); 82% were women; half were ≥ 55 years. At 6 and 12 months follow-up, 91% and 89% of participants were interviewed respectively. One control group participant committed suicide. There was no significant difference in the primary outcome between intervention (N=256/456) and control (N=232/492) groups (55.9% versus 50.9%; adjusted risk difference = -0.04 ([95% CI = -0.19; 0.11], p = 0.6). The difference in PHQ-9 scores was within the defined equivalence limits at 6 and 12 months for the non-inferiority analysis. LIMITATIONS: The trial was limited by low exposure to depression treatment by trial participants and by observed co-intervention in control clinics CONCLUSIONS: Incorporating lay counselling services within collaborative care models does not produce superior nor inferior outcomes to models with specialist only counselling services. FUNDING: This work was supported by the UK Department for International Development [201446] as well as the National Institute of Mental Health, United States of America, grant number 1R01MH100470-01. Graham Thornicroft is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) South London at King's College London and King's College Hospital NHS Foundation Trust.

Comorbidities between tuberculosis and common mental disorders: a scoping review of epidemiological patterns and person-centred care interventions from low-to-middle income and BRICS countries.

BACKGROUND: There is increasing evidence that the substantial global burden of disease for tuberculosis unfolds in concert with dimensions of common mental disorders. Person-centred care holds much promise to ameliorate these comorbidities in low-to-middle income countries (LMICs) and emerging economies. Towards this end, this paper aims to review 1) the nature and extent of tuberculosis and common mental disorder comorbidity and 2) person-centred tuberculosis care in low-to-middle income countries and emerging economies. MAIN TEXT: A scoping review of 100 articles was conducted of English-language studies published from 2000 to 2019 in peer-reviewed and grey literature, using established guidelines, for each of the study objectives. Four broad tuberculosis/mental disorder comorbidities were described in the literature, namely alcohol use and tuberculosis, depression and tuberculosis, anxiety and tuberculosis, and general mental health and tuberculosis. Rates of comorbidity varied widely across countries for depression, anxiety, alcohol use and general mental health. Alcohol use and tuberculosis were significantly related, especially in the context of poverty. The initial tuberculosis diagnostic episode had substantial socio-psychological effects on service users. While men tended to report higher rates of alcohol use and treatment default, women in general had worse mental health outcomes. Older age and a history of mental illness were also associated with pronounced tuberculosis and mental disorder comorbidity. Person-centred tuberculosis care interventions were almost absent, with only one study from Nepal identified. CONCLUSIONS: There is an emerging body of evidence describing the nature and extent of tuberculosis and mental disorders comorbidity in low-to-middle income countries. Despite the potential of person-centred interventions, evidence is limited. This review highlights a pronounced need to address psychosocial comorbidities with tuberculosis in LMICs, where models of person-centred tuberculosis care in routine care platforms may yield promising outcomes.

PACK Child: the development of a practical guide to extend the scope of integrated primary care for children and young adolescents.

Pioneering strategies like WHO's Integrated Management of Childhood Illness (IMCI) have resulted in substantial progress in addressing infant and child mortality. However, large inequalities exist in access to and the quality of care provided in different regions of the world. In many low-income and middle-income countries, childhood mortality remains a major concern, and the needs of children present a large burden upon primary care services. The capacity of services and quality of care offered require greater support to address these needs and extend integrated curative and preventive care, specifically, for the well child, the child with a long-term health need and the child older than 5 years, not currently included in IMCI. In response to these needs, we have developed an innovative method, based on experience with a similar approach in adults, that expands the scope and reach of integrated management and training programmes for paediatric primary care. This paper describes the development and key features of the PACK Child clinical decision support tool for the care of children up to 13 years, and lessons learnt during its development.

Socioeconomic predictors and consequences of depression among primary care attenders with non-communicable diseases in the Western Cape, South Africa: cohort study within a randomised trial.

BACKGROUND: Socioeconomic predictors and consequences of depression and its treatment were investigated in 4393 adults with specified non-communicable diseases attending 38 public sector primary care clinics in the Eden and Overberg districts of the Western Cape, South Africa. METHODS: Participants were interviewed at baseline in 2011 and 14 months later, as part of a randomised controlled trial of a guideline-based intervention to improve diagnosis and management of chronic diseases. The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) was used to assess depression symptoms, with higher scores representing more depressed mood. RESULTS: Higher CESD-10 scores at baseline were independently associated with being less educated (p = 0.004) and having lower income (p = 0.003). CESD-10 scores at follow-up were higher in participants with less education (p = 0.010) or receiving welfare grants (p = 0.007) independent of their baseline scores. Participants with CESD-10 scores of ten or more at baseline (56 % of all participants) had 25 % higher odds of being unemployed at follow-up (p = 0.016), independently of baseline CESD-10 score and treatment status. Among participants with baseline CESD-10 scores of ten or more, antidepressant medication at baseline was independently more likely in participants who had more education (p = 0.002), higher income (p < 0.001), or were unemployed (p = 0.001). Antidepressant medication at follow up was independently more likely in participants with higher income (p = 0.023), and in clinics with better access to pharmacists (p = 0.053) and off-site drug delivery (p = 0.013). CONCLUSIONS: Socioeconomic disadvantage appears to be both a cause and consequence of depression, and may also be a barrier to treatment. There are opportunities for improving the prevention, diagnosis and treatment of depression in primary care in inequitable middle income countries like South Africa. TRIAL REGISTRATION: The trial is registered with Current Controlled Trials ( ISRCTN20283604 ).

Cost-effectiveness of nurse-led versus doctor-led antiretroviral treatment in South Africa: pragmatic cluster randomised trial.

OBJECTIVE: To estimate the cost-effectiveness of nurse-led versus doctor-led antiretroviral treatment (ART) for HIV-infected people. DESIGN: Cost-effectiveness analysis alongside a pragmatic cluster randomised controlled trial in 31 primary care clinics (16 intervention, 15 controls) in Free State Province, South Africa. Participants were HIV-infected patients, aged ≥16 years. Cohort 1 (CD4 count ≤350 cells/µl, not yet receiving ART at enrolment): consisted of 5 390 intervention patients and 3 862 controls; Cohort 2 (already received ART for ≥6 months at enrolment) of 3 029 intervention patients and 3 202 controls. Nurses were authorised and trained to initiate and represcribe ART. Management and ART provision were decentralised to primary care clinics. In control clinics, doctors initiated and re-prescribed ART, nurses monitored ART. Main outcome measure(s) were health service costs, death (cohort 1) and undetectable viral load (<400 copies/ml) (cohort 2) during the 12 months after enrolment. RESULTS: For Cohort 1, the intervention had an estimated incremental cost of US$102.52, an incremental effect of 0.42% fewer deaths and an incremental cost-effectiveness ratio (ICER) of US$24 500 per death averted. For Cohort 2, the intervention had an estimated incremental cost of US$59.48, an incremental effect of 0.47% more undetectable viral loads and an ICER of US$12 584 per undetectable viral load. CONCLUSIONS: Nurse-led ART was associated with higher mean health service costs than doctor-led care, with small effects on primary outcomes, and a high associated level of uncertainty. Given this, and the shortage of doctors, further implementation of nurse-led ART should be considered, although this may increase health service costs.

Task shifting of antiretroviral treatment from doctors to primary-care nurses in South Africa (STRETCH): a pragmatic, parallel, cluster-randomised trial.

BACKGROUND: Robust evidence of the effectiveness of task shifting of antiretroviral therapy (ART) from doctors to other health workers is scarce. We aimed to assess the effects on mortality, viral suppression, and other health outcomes and quality indicators of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) programme, which provides educational outreach training of nurses to initiate and represcribe ART, and to decentralise care. METHODS: We undertook a pragmatic, parallel, cluster-randomised trial in South Africa between Jan 28, 2008, and June 30, 2010. We randomly assigned 31 primary-care ART clinics to implement the STRETCH programme (intervention group) or to continue with standard care (control group). The ratio of randomisation depended on how many clinics were in each of nine strata. Two cohorts were enrolled: eligible patients in cohort 1 were adults (aged ≥16 years) with CD4 counts of 350 cells per µL or less who were not receiving ART; those in cohort 2 were adults who had already received ART for at least 6 months and were being treated at enrolment. The primary outcome in cohort 1 was time to death (superiority analysis). The primary outcome in cohort 2 was the proportion with undetectable viral loads (<400 copies per mL) 12 months after enrolment (equivalence analysis, prespecified difference <6%). Patients and clinicians could not be masked to group assignment. The interim analysis was blind, but data analysts were not masked after the database was locked for final analysis. Analyses were done by intention to treat. This trial is registered, number ISRCTN46836853. FINDINGS: 5390 patients in cohort 1 and 3029 in cohort 2 were in the intervention group, and 3862 in cohort 1 and 3202 in cohort 2 were in the control group. Median follow-up was 16·3 months (IQR 12·2-18·0) in cohort 1 and 18·0 months (18·0-18·0) in cohort 2. In cohort 1, 997 (20%) of 4943 patients analysed in the intervention group and 747 (19%) of 3862 in the control group with known vital status at the end of the trial had died. Time to death did not differ (hazard ratio [HR] 0·94, 95% CI 0·76-1·15). In a preplanned subgroup analysis of patients with baseline CD4 counts of 201-350 cells per µL, mortality was slightly lower in the intervention group than in the control group (0·73, 0·54-1.00; p=0·052), but it did not differ between groups in patients with baseline CD4 of 200 cells per µL or less (0·94, 0·76-1·15; p=0·577). In cohort 2, viral load suppression 12 months after enrolment was equivalent in intervention (2156 [71%] of 3029 patients) and control groups (2230 [70%] of 3202; risk difference 1·1%, 95% CI -2·4 to 4·6). INTERPRETATION: Expansion of primary-care nurses' roles to include ART initiation and represcription can be done safely, and improve health outcomes and quality of care, but might not reduce time to ART or mortality. FUNDING: UK Medical Research Council, Development Cooperation Ireland, and Canadian International Development Agency.

A morbidity survey of South African primary care.

BACKGROUND: Recent studies have described the burden of disease in South Africa. However these studies do not tell us which of these conditions commonly present to primary care providers, how these conditions may present and how providers make sense of them in terms of their diagnoses. Clinical nurse practitioners are the main primary care providers and need to be better prepared for this role. This study aimed to determine the range and prevalence of reasons for encounter and diagnoses found among ambulatory patients attending public sector primary care facilities in South Africa. METHODOLOGY/PRINCIPAL FINDINGS: The study was a multi-centre prospective cross-sectional survey of consultations in primary care in four provinces of South Africa: Western Cape, Limpopo, Northern Cape and North West. Consultations were coded prior to analysis by using the International Classification of Primary Care-Version 2 in terms of reasons for encounter (REF) and diagnoses. Altogether 18856 consultations were included in the survey and generated 31451 reasons for encounter (RFE) and 24561 diagnoses. Women accounted for 12526 (66.6%) and men 6288 (33.4%). Nurses saw 16238 (86.1%) and doctors 2612 (13.9%) of patients. The top 80 RFE and top 25 diagnoses are reported and ongoing care for hypertension was the commonest RFE and diagnosis. The 20 commonest RFE and diagnoses by age group are also reported. CONCLUSIONS/SIGNIFICANCE: Ambulatory primary care is dominated by non-communicable chronic diseases. HIV/AIDS and TB are common, but not to the extent predicted by the burden of disease. Pneumonia and gastroenteritis are commonly seen especially in children. Women's health issues such as family planning and pregnancy related visits are also common. Injuries are not as common as expected from the burden of disease. Primary care providers did not recognise mental health problems. The results should guide the future training and assessment of primary care providers.

Task shifting and integration of HIV care into primary care in South Africa: the development and content of the streamlining tasks and roles to expand treatment and care for HIV (STRETCH) intervention.

BACKGROUND: Task shifting and the integration of human immunodeficiency virus (HIV) care into primary care services have been identified as possible strategies for improving access to antiretroviral treatment (ART). This paper describes the development and content of an intervention involving these two strategies, as part of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) pragmatic randomised controlled trial. METHODS: DEVELOPING THE INTERVENTION: The intervention was developed following discussions with senior management, clinicians, and clinic staff. These discussions revealed that the establishment of separate antiretroviral treatment services for HIV had resulted in problems in accessing care due to the large number of patients at ART clinics. The intervention developed therefore combined the shifting from doctors to nurses of prescriptions of antiretrovirals (ARVs) for uncomplicated patients and the stepwise integration of HIV care into primary care services. RESULTS: COMPONENTS OF THE INTERVENTION: The intervention consisted of regulatory changes, training, and guidelines to support nurse ART prescription, local management teams, an implementation toolkit, and a flexible, phased introduction. Nurse supervisors were equipped to train intervention clinic nurses in ART prescription using outreach education and an integrated primary care guideline. Management teams were set up and a STRETCH coordinator was appointed to oversee the implementation process. DISCUSSION: Three important processes were used in developing and implementing this intervention: active participation of clinic staff and local and provincial management, educational outreach to train nurses in intervention sites, and an external facilitator to support all stages of the intervention rollout.The STRETCH trial is registered with Current Control Trials ISRCTN46836853.

Differences in access and patient outcomes across antiretroviral treatment clinics in the Free State province: a prospective cohort study.

OBJECTIVE: To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public sector treatment facilities in the Free State province, South Africa. DESIGN: Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across 36 facilities between May 2004 and December 2007, and assessed percentage initiating ART and percentage dead at 1 year after enrolment. Multivariable logistic regression was used to estimate associations of facility-level and patient-level characteristics with both mortality and treatment status. RESULTS: Of 44 866 patients enrolled, 15 219 initiated treatment within 1 year; 8 778 died within 1 year, 7 286 before accessing ART. Outcomes at 1 year varied greatly across facilities and more variability was explained by facility-level factors than by patient-level factors. The odds of starting treatment within 1 year improved over calendar time. Patients enrolled in facilities with treatment initiation available on site had higher odds of starting treatment and lower odds of death at 1 year compared with those enrolled in facilities that did not offer treatment initiation. Patients were less likely to start treatment if they were male, severely immunosuppressed (CD4 count ≤50 cells/µl), or underweight (<50 kg). Men were also more likely to die in the first year after enrolment. CONCLUSIONS: Although increasing numbers of patients started ART between 2004 and 2007, many patients died before accessing ART. Patient outcomes could be improved by decentralisation of treatment services, fast-tracking the most immunodeficient patients and improving access, especially for men.

Outcomes in patients waiting for antiretroviral treatment in the Free State Province, South Africa: prospective linkage study.

OBJECTIVE: In South Africa, many HIV-infected patients experience delays in accessing antiretroviral therapy (ART). We examined pretreatment mortality and access to treatment in patients waiting for ART. DESIGN: Cohort of HIV-infected patients assessed for ART eligibility at 36 facilities participating in the Comprehensive HIV and AIDS Management (CHAM) program in the Free State Province. METHODS: Proportion of patients initiating ART, pre-ART mortality and risk factors associated with these outcomes were estimated using competing risks survival analysis. RESULTS: Forty-four thousand, eight hundred and forty-four patients enrolled in CHAM between May 2004 and December 2007, of whom 22 083 (49.2%) were eligible for ART; pre-ART mortality was 53.2 per 100 person-years [95% confidence interval (CI) 51.8-54.7]. Median CD4 cell count at eligibility increased from 87 cells/µl in 2004 to 101 cells/µl in 2007. Two years after eligibility an estimated 67.7% (67.1-68.4%) of patients had started ART, and 26.2% (25.6-26.9%) died before starting ART. Among patients with CD4 cell counts below 25 cells/µl at eligibility, 48% died before ART and 51% initiated ART. Men were less likely to start treatment and more likely to die than women. Patients in rural clinics or clinics with low staffing levels had lower rates of starting treatment and higher mortality compared with patients in urban/peri-urban clinics, or better staffed clinics. CONCLUSIONS: Mortality is high in eligible patients waiting for ART in the Free State Province. The most immunocompromised patients had the lowest probability of starting ART and the highest risk of pre-ART death. Prioritization of these patients should reduce waiting times and pre-ART mortality.

Cost-effectiveness of educational outreach to primary care nurses to increase tuberculosis case detection and improve respiratory care: economic evaluation alongside a randomised trial.

OBJECTIVE: To evaluate the cost-effectiveness of an educational outreach intervention to improve primary respiratory care by South African nurses. METHODS: Cost-effectiveness analysis alongside a pragmatic cluster randomised controlled trial, with individual patient data. The intervention, the Practical Approach to Lung Health in South Africa (PALSA), comprised educational outreach based on syndromic clinical practice guidelines for tuberculosis, asthma, chronic obstructive pulmonary disease, pneumonia and other respiratory diseases. The study included 1999 patients aged 15 or over with cough or difficult breathing, attending 40 primary care clinics staffed by nurses in the Free State province. They were interviewed at first presentation, and 1856 (93%) were interviewed 3 months later. RESULTS: The intervention increased the tuberculosis case detection rate by 2.2% and increased the proportion of patients appropriately managed (that is, diagnosed with tuberculosis or prescribed an inhaled corticosteroid for asthma or referred with indicators of severe disease) by 10%. It costs the health service $68 more for each extra patient diagnosed with tuberculosis and $15 more for every extra patient appropriately managed. Analyses were most sensitive to assumptions about how long training was effective for and to inclusion of household and tuberculosis treatment costs. CONCLUSION: This educational outreach method was more effective and more costly than usual training in improving tuberculosis, asthma and urgent respiratory care. The extra cost of increasing tuberculosis case detection was comparable to current costs of passive case detection. The syndromic approach increased cost-effectiveness by also improving care of other conditions. This educational intervention was sustainable, reaching thousands of health workers and hundreds of clinics since the trial.

Systems for the management of respiratory disease in primary care--an international series: South Africa.

INTRODUCTION: Progress to democracy in South Africa in 1994 was followed by the adoption of a primary health care approach with free access for all. State health facilities serve 80% of the population, and a private sector comprising general practitioners, specialists and private hospitals, serves the remainder. NATIONAL POLICIES AND MODELS: There are national prescribing guidelines for common diseases, and these specify the medicines on the Essential Drugs List that are available at primary care facilities for respiratory diseases including asthma, COPD, pneumonia and tuberculosis. EPIDEMIOLOGY: Asthma prevalence is average among children (13%) but morbidity is high. COPD rates are high owing to concurrent risk factors of smoking (in both men and women), occupational exposures, biomass fuel use and previous lung infections including tuberculosis. Tuberculosis and HIV are rampant, and together with pneumococcal co-infection account for considerable mortality. ACCESS TO CARE: Primary care facilities are within reach of most communities, but major barriers to care include loss of income, waiting times in clinics, cost of transportation, and inconvenient hours. FACILITIES AVAILABLE: The country is divided into districts each served by a hospital, several community health centres and many fixed or mobile clinics. The latter provide predominantly nurse-led care by nurse practitioners with additional qualifications. Some clinics and most community health centres are served by doctors. Referrals are made to secondary and tertiary hospitals served by specialists. FUTURE: Innovations to address staff shortages include the creation of the specialty of family medicine for physicians and development of the clinical associate who is trained to perform a limited clinical role, as well as in-service on-site training of nurses through programmes of integrated care for infectious and chronic diseases. There is an urgent need to address low staff morale and medical migration resulting from a decade of poor leadership and AIDS denialism. CONCLUSIONS: The structures and policies for primary care in South Africa provide some grounds for optimism that services may begin to match the promise of quality care for all, but the burden of disease and resource constraints - particularly in terms of qualified personnel - mitigate against an early delivery of this promise.

Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting.

Methods for analyzing cost effectiveness data from cluster randomized trials.

BACKGROUND: Measurement of individuals' costs and outcomes in randomized trials allows uncertainty about cost effectiveness to be quantified. Uncertainty is expressed as probabilities that an intervention is cost effective, and confidence intervals of incremental cost effectiveness ratios. Randomizing clusters instead of individuals tends to increase uncertainty but such data are often analysed incorrectly in published studies. METHODS: We used data from a cluster randomized trial to demonstrate five appropriate analytic methods: 1) joint modeling of costs and effects with two-stage non-parametric bootstrap sampling of clusters then individuals, 2) joint modeling of costs and effects with Bayesian hierarchical models and 3) linear regression of net benefits at different willingness to pay levels using a) least squares regression with Huber-White robust adjustment of errors, b) a least squares hierarchical model and c) a Bayesian hierarchical model. RESULTS: All five methods produced similar results, with greater uncertainty than if cluster randomization was not accounted for. CONCLUSION: Cost effectiveness analyses alongside cluster randomized trials need to account for study design. Several theoretically coherent methods can be implemented with common statistical software.