Identifying actions to foster cross-disciplinary global health research: a mixed-methods qualitative case study of the IMPALA programme on lung health and tuberculosis in Africa

Objectives To identify actions for fostering cross-disciplinary research (CDR) skills and collaborations in global health, and to produce recommendations for improving the design, implementation and management of cross-disciplinary global health research programmes. Design Using a North–South global health research programme as a case study—and following an adapted framework—we conducted qualitative research using document reviews, semi-structured interviews (purposive sampling) and participatory observation. We used baseline survey findings to identify potential interviewees and tailor interview guides. Setting Our case study was a 4.5-year (2017–2021) programme, namely, the International Multidisciplinary Programme to Address Lung Health and Tuberculosis in Africa (IMPALA). Led by a UK research institute, IMPALA spanned 22 partner organisations from 13 countries (10 in sub-Saharan Africa), and involved five research discipline groups: clinical science, social science, health systems, health economics and policy/research capacity. Participants Thirty-one IMPALA members were interviewed (July 2018–November 2019), with interviewees evenly split by gender (16 female and 15 male) and by Global North/South institution (15 non-African and 16 African). Twenty-five (81%) were researchers, comprising 18 senior researchers (professors, readers, associate professors and senior lecturers) and seven early career researchers (assistant professors, lecturers, research fellows, postdocs, research assistants and PhD students). Twenty-four programme events were observed (September 2018–April 2020) and 49 documents were reviewed (December 2017–April 2020). All 66 IMPALA staff were sent the baseline survey, receiving 51 responses (43/56 researchers and 8/10 non-researchers). Results Fourteen themes emerged, which suggested that CDR—while valued by many—is not universally understood, and the time it requires is often underestimated. We found that fostering CDR and managing tensions needs planning and continuous discussions and interactions. A shared vision with explicitly agreed goals and roles and active management of cross-disciplinary activities is essential. Conclusions Active planning, implementation and management of cross-disciplinary activities are essential for the success of cross-disciplinary global health research and should be separate from the primary research activities

Letter to the editor: “Eliciting national and subnational sets of disability weights in mainland China: findings from the Chinese disability weight measurement study”

Lette

Study protocol for a single-centre observational study of household wellbeing and poverty status following a diagnosis of advanced cancer in Blantyre, Malawi - ‘Safeguarding the Family’ study

Background: Many households in low-and-middle income countries face the additional burden of crippling out-of-pocket expenditure when faced with a diagnosis of life-limiting illness. Available evidence suggests that receipt of palliative care supports cost-savings for cancer-affected households. This study will explore the relationship between receipt of palliative care, total household out-of-pocket expenditure on health and wellbeing following a first-time diagnosis of advanced cancer at Queen Elizabeth Central Hospital in Blantyre, Malawi. Protocol: Patients and their primary family caregivers will be recruited at the time of cancer diagnosis. Data on healthcare utilisation, related costs, coping strategies and wellbeing will be gathered using new and existing questionnaires (the Patient-and-Carer Cancer Cost Survey, EQ-5D-3L and the Integrated Palliative Care Outcome Score). Surveys will be repeated at one, three and six months after diagnosis. In the event of the patient’s death, a brief five-item questionnaire on funeral costs will be administered to caregivers not less than two weeks following the date of death. Descriptive and Poisson regression analyses will assess the relationship between exposure to palliative care and total household expenditure from baseline to six months. A sample size of 138 households has been calculated in order to detect a medium effect (as determined by Cohen’s f2=0.15) of receipt of palliative care in a regression model for change in total household out-of-pocket expenditure as a proportion of annual household income. Ethics and dissemination: The study has received ethical approval. Results will be reported using STROBE guidelines and disseminated through scientific meetings, open access publications and a national stakeholder meeting. Conclusions: This study will provide data on expenditure for healthcare by households affected by cancer in Malawi. We also explore whether receipt of palliative care is associated with a reduction in out-of-pocket expenditure at household level

Economic evaluation of short treatment for multidrugresistant tuberculosis, Ethiopia and South Africa : the STREAM trial

OBJECTIVE STREAM was a phase-III non-inferiority randomised controlled trial (RCT) to evaluate a shortened regimen for multi-drug resistant tuberculosis (MDR-TB), and included the first-ever within-trial economic evaluation of such regimens, reported here. METHODS We compared the costs of ‘Long’ (20-22 months) and ‘Short’ (9-11 months) regimens in Ethiopia and South Africa. Cost data were collected from trial participants, and health system costs estimated using ‘bottom-up’ and ‘top-down’ costing approaches. A cost-effectiveness analysis was conducted with the trial primary outcome as the measure of effectiveness, including a probabilistic sensitivity analysis (PSA) to illustrate decision uncertainty. FINDINGS The Short-regimen reduced healthcare costs per case by 21% in South Africa (US$8,341 Long vs US$6,619 Short) and 25% in Ethiopia (US$6,097 Long vs US$4,552 Short). The largest component of this saving was medication in South Africa (67%) and social support in Ethiopia (35%). In Ethiopia, participants on the Short-regimen reported reductions in dietary supplementation expenditure (US$225 per case (95$13 (95%CI 11-14), South Africa US$64 (95$19,000 (Ethiopia) or <US$14,500 (South Africa). CONCLUSION The Short-regimen provided substantial health system cost savings and reduced financial burden on participants. Shorter regimens are likely to be cost-effective in most settings, and an effective strategy to support the WHO goal of eliminating catastrophic costs in T

Palliative care within universal health coverage: the Malawi Patient-and-Carer Cancer Cost Survey

Objective Evidence of the role of palliative care to reduce financial hardship and to support wellbeing in low- and middle-income countries (LMIC) is growing, though standardised tools to capture relevant economic data are limited. We describe the development of the Patient-and-Carer Cancer Cost Survey (PaCCCt survey) which can be used to gather data on health care use and out-of-pocket expenditure (OOPE) in households affected by cancer in LMIC. Methods To identify relevant content qualitative data were gathered using Photovoice to detail concepts of wellbeing and cost areas of importance in households receiving palliative care in Blantyre, Malawi. Existing approaches and tools used to capture OOPE were mapped through a review of the literature. The WHO TB patient cost survey was chosen for adaptation. Face and content validity of a zero-draft of the PaCCCt survey were developed through review by health care professionals and a national stakeholder group. The final survey was translated into local language (Chichewa) and piloted. Results The PaCCCt survey is a tablet-based, third-party administered survey recording health care service utilisation and related direct and indirect costs. Coping strategies (loans and dissaving etc.), funeral costs and wellbeing at household level are included. Completion time is less than 30 minutes. Conclusion The PaCCCt survey can be used as part of economic evaluations in populations in need of palliative care in LMIC. Such evidence can support calls for the inclusion of palliative care within Universal Health Coverage which requires end-user protection from financial hardship

Cost of digital technologies and family-observed DOT for the 9-month injectable-containing MDR-TB regimen

Background: In 2017 WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT) for directly-observed treatment (DOT) of drug-susceptible TB, with no policy recommendations for multidrug-resistant TB (MDR-TB), which imposes considerably higher patient-costs. Given the COVID-related demand on health systems, the benefits of transitioning towards more patient-centred approaches are increasingly relevant. Design/Methods: A decision-tree model was developed to explore the cost-effectiveness of several DOT replacement approaches including VOT, 99DOTS and family-observed DOT. Assuming a 9-month, injectable-containing regimen (as evaluated within the STREAM trial), we constructed base-case models to reflect the standard-of-care in Ethiopia, India, and Uganda. The model used STREAM data supplemented with published studies, with sensitivity analyses conducted on key parameters. Results: Modelling suggested that standard-of-care is the most expensive strategy in India and Uganda, with considerable direct- and indirect-costs incurred by patients. In Ethiopia, implementing VOT and 99DOTS increased health-system costs by US$402 and US$17 respectively, but patient-costs remained lower than for standard-of-care. These higher health-system costs were largely caused by up-front technology expenditure, with 80% of Ethiopians not owning a smartphone. Sensitivity analyses showed costs were sensitive to both loss-to-follow-up and relapse rates. However, only the VOT strategy in Uganda exceeded standard-of-care DOT costs, by US$70 per patient, when the relapse rate was equalled to the upper-bound of the confidence interval. Modelling suggested each of VOT, 99DOTS, and family-observed DOT would halve patients’ out-of-pocket costs. Taking a patient perspective, each strategy appeared highly cost-effective across all countries, even if implemented solely in continuation phase. Conclusions: While data on the costs and efficacy of switching MDR-TB treatment management to new technologies are lacking, our modelling suggests alternative DOT support strategies can significantly reduce patient-costs. Health-system costs however are more country-specific, depending heavily on both internet availability and smartphone penetration within the population

Patient-cost survey for tuberculosis in the context of patient-pathway modelling.

ETTING: Eight tuberculosis treatment sites in Cavite Province, the Philippines, including two sites specialising in management of multidrug-resistant tuberculosis (MDR-TB).OBJECTIVE: To evaluate costs incurred by TB patients and to determine the proportion of households that faced catastrophic costs, then to consider cost survey responses alongside results of detailed patient-pathway modelling.DESIGN: Clustered cross-sectional survey using a field testing version of the WHO TB patient-costing tool and protocol; face-to-face interviews with 194 patients conducted in May-August 2016. Costs included direct-medical, direct non-medical and indirect costs using the human capital approach. Patients were deemed to incur catastrophic expenditure if TB-related costs exceeded 20% of annual household income. Patient pathways were modelled following multiple health staff interviews.RESULTS: Estimated mean cost incurred by patients with drug-susceptible TB was US$321 vs.$2356 for MDR-TB patients. Catastrophic costs were suffered by 28% of drug-susceptible and 80% of MDR-TB patients, with lost income being the largest contributor. Patient-pathway modelling suggested most patients had under-reported health visits.CONCLUSION: Survey results indicate that patient costs are large for all patients in Cavite, particularly for MDR-TB patients. Patient-pathway modelling suggests these costs are an underestimate due to poor recollection of health visits, suggesting that the WHO instrument and protocol could be improved to better capture the diagnostic journey

Multimorbidity healthcare expenditure in Belgium: a 4-year analysis (COMORB study)

Background: The complex management of health needs in multimorbid patients, alongside limited cost data, presents challenges in developing cost-effective patient-care pathways. We estimated the costs of managing 171 dyads and 969 triads in Belgium, taking into account the influence of morbidity interactions on costs. Methods: We followed a retrospective longitudinal study design, using the linked Belgian Health Interview Survey 2018 and the administrative claim database 2017–2020 hosted by the Intermutualistic Agency. We included people aged 15 and older, who had complete profiles (N = 9753). Applying a system costing perspective, the average annual direct cost per person per dyad/triad was presented in 2022 Euro and comprised mainly direct medical costs. We developed mixed models to analyse the impact of single chronic conditions, dyads and triads on healthcare costs, considering two-/three-way interactions within dyads/triads, key cost determinants and clustering at the household level. Results: People with multimorbidity constituted nearly half of the study population and their total healthcare cost constituted around three quarters of the healthcare cost of the study population. The most common dyad, arthropathies + dorsopathies, with a 14% prevalence rate, accounted for 11% of the total national health expenditure. The most frequent triad, arthropathies + dorsopathies + hypertension, with a 5% prevalence rate, contributed 5%. The average annual direct costs per person with dyad and triad were €3515 (95% CI 3093–3937) and €4592 (95% CI 3920–5264), respectively. Dyads and triads associated with cancer, diabetes, chronic fatigue, and genitourinary problems incurred the highest costs. In most cases, the cost associated with multimorbidity was lower or not substantially different from the combined cost of the same conditions observed in separate patients. Conclusion: Prevalent morbidity combinations, rather than high-cost ones, made a greater contribution to total national health expenditure. Our study contributes to the sparse evidence on this topic globally and in Europe, with the aim of improving cost-effective care for patients with diverse needs

Palliative care and catastrophic costs in Malawi after a diagnosis of advanced cancer: a prospective cohort study

Background Inclusive universal health coverage requires access to quality health care without financial barriers. Receipt of palliative care after advanced cancer diagnosis might reduce household poverty, but evidence from low-income and middle-income settings is sparse. Methods In this prospective study, the primary objective was to investigate total household costs of cancer-related health care after a diagnosis of advanced cancer, with and without the receipt of palliative care. Households comprising patients and their unpaid family caregiver were recruited into a cohort study at Queen Elizabeth Central Hospital in Malawi, between Jan 16 and July 31, 2019. Costs of cancer-related health-care use (including palliative care) and health-related quality-of-life were recorded over 6 months. Regression analysis explored associations between receipt of palliative care and total household costs on health care as a proportion of household income. Catastrophic costs, defined as 20% or more of total household income, sale of assets and loans taken out (dissaving), and their association with palliative care were computed. Findings We recruited 150 households. At 6 months, data from 89 (59%) of 150 households were available, comprising 89 patients (median age 50 years, 79% female) and 64 caregivers (median age 40 years, 73% female). Patients in 55 (37%) of the 150 households died and six (4%) were lost to follow-up. 19 (21%) of 89 households received palliative care. Catastrophic costs were experienced by nine (47%) of 19 households who received palliative care versus 48 (69%) of 70 households who did not (relative risk 0·69, 95% CI 0·42 to 1·14, p=0·109). Palliative care was associated with substantially reduced dissaving (median US$11, IQR 0 to 30 vs$34, 14 to 75; p=0·005). The mean difference in total household costs on cancer-related health care with receipt of palliative care was −36% (95% CI −94 to 594; p=0·707). Interpretation Vulnerable households in low-income countries are subject to catastrophic health-related costs following a diagnosis of advanced cancer. Palliative care might result in reduced dissaving in these households. Further consideration of the economic benefits of palliative care is justified. Funding Wellcome Trust; National Institute for Health Research; and EMMS International

Economic evaluation of shortened, bedaquiline-containing treatment regimens for rifampicin-resistant tuberculosis (STREAM stage 2): a within-trial analysis of a randomised controlled trial

BACKGROUND: The STREAM stage 2 trial assessed two bedaquiline-containing regimens for rifampicin-resistant tuberculosis: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug for the first 2 months. We did a within-trial economic evaluation of these regimens. METHODS: STREAM stage 2 was an international, phase 3, non-inferiority randomised trial in which participants with rifampicin-resistant tuberculosis were randomly assigned (1:2:2:2) to the 2011 WHO regimen (terminated early), a 9-month injectable-containing regimen (control regimen), a 9-month all-oral regimen with bedaquiline (oral regimen), or a 6-month regimen with bedaquiline and an injectable for the first 2 months (6-month regimen). We prospectively collected direct and indirect costs and health-related quality of life data from trial participants until week 76 of follow-up. Cost-effectiveness of the oral and 6-month regimens versus control was estimated in four countries (oral regimen) and two countries (6-month regimen), using health-related quality of life for cost-utility analysis and trial efficacy for cost-effectiveness analysis. This trial is registered with ISRCTN, ISRCTN18148631. FINDINGS: 300 participants were included in the economic analyses (Ethiopia, 61; India, 142; Moldova, 51; Uganda, 46). In the cost-utility analysis, the oral regimen was not cost-effective in Ethiopia, India, Moldova, and Uganda from either a provider or societal perspective. In Moldova, the oral regimen was dominant from a societal perspective. In the cost-effectiveness analysis, the oral regimen was likely to be cost-effective from a provider perspective at willingness-to-pay thresholds per additional favourable outcome of more than US$4500 in Ethiopia,$1900 in India, $3950 in Moldova, and$7900 in Uganda, and from a societal perspective at thresholds of more than $15 900 in Ethiopia,$3150 in India, and $4350 in Uganda, while in Moldova the oral regimen was dominant. In Ethiopia and India, the 6-month regimen would cost tuberculosis programmes and participants less than the control regimen and was highly likely to be cost-effective in both cost-utility analysis and cost-effectiveness analysis. Reducing the bedaquiline price from$1·81 to $1·00 per tablet made the oral regimen cost-effective in the provider-perspective cost-utility analysis in India and Moldova and dominate over the control regimen in the provider-perspective cost-effectiveness analysis in India. INTERPRETATION: At current costs, the oral bedaquiline-containing regimen for rifampicin-resistant tuberculosis is unlikely to be cost-effective in many low-income and middle-income countries. The 6-month regimen represents a cost-effective alternative if injectable use for 2 months is acceptable. FUNDING: USAID and Janssen Research & Development