Cost-effectiveness of pegfilgrastim versus filgrastim for prevention of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review.

BACKGROUND: Febrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is more effective than filgrastim as prophylaxis for FN. However, its usage has been limited because of its higher cost. Pegfilgrastim's value for money remains unclear. OBJECTIVE: To systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library databases, and Google Scholar. The most widely used economic evaluations (cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis) were included in the review. Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards checklist, and the quality of reviewed articles was assessed using the Joanna Briggs Institute (JBI) checklist. Cost-effectiveness data were rigorously summarized and synthesized narratively. Costs were adjusted to US$ 2020. RESULTS: We identified eight economic evaluation studies (two cost-utility analyses, three cost-effectiveness analyses, and three studies reporting both cost-effectiveness and cost-utility analyses). Half of these studies were from Europe (n = 4), the other half were from Iran, USA, Canada, and Singapore. Six studies met > 80% of the JBI quality assessment criteria. Cost-effectiveness estimates in the majority (n = 6) of these studies were for Non-Hodgkin Lymphoma patients receiving myelosuppressive chemotherapy with high-risk of FN (> 20%). The studies considered a wide range of baseline FN risk (17-97.4%) and mortality rates (5.8-8.9%). Reported incremental cost-effectiveness ratios ranged from US$ 2199 to US$ 8,871,600 per quality-adjusted life-year (QALY) gained, dominant to US$ 44,358 per FN averted, and US$ 4261- US$ 7251 per life-years gained. The most influential parameters were medication and hospitalization costs, the relative risk of FN, and assumptions of mortality benefit. CONCLUSIONS: Most studies showed that pegfilgrastim is cost-effective compared to filgrastim as primary and secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma at a cost-effectiveness threshold of US$ 50,000 per QALY gained. The findings could assist clinicians and healthcare decision-makers to make informed decisions regarding resource allocation for the management of chemotherapy-induced FN in settings similar to those studied.

Cost-utility analysis of caspofungin and fluconazole for primary treatment of invasive candidiasis and candidemia in Ethiopia.

BACKGROUND: Invasive candidiasis and/or candidemia (IC/C) is a common fungal infection leading to significant health and economic losses worldwide. Caspofungin was shown to be more effective than fluconazole in treating inpatients with IC/C. However, cost-effectiveness of caspofungin for treating IC/C in Ethiopia remains unknown. We aimed to assess the cost-utility of caspofungin compared to fluconazole-initiated therapies as primary treatment of IC/C in Ethiopia. METHODS: A Markov cohort model was developed to compare the cost-utility of caspofungin versus fluconazole antifungal agents as first-line treatment for adult inpatients with IC/C from the Ethiopian health system perspective. Treatment outcome was categorized as either a clinical success or failure, with clinical failure being switched to a different antifungal medication. Liposomal amphotericin B (L-AmB) was used as a rescue agent for patients who had failed caspofungin treatment, while caspofungin or L-AmB were used for patients who had failed fluconazole treatment. Primary outcomes were expected quality-adjusted life years (QALYs), costs (US$2021), and the incremental cost-utility ratio (ICUR). These QALYs and costs were discounted at 3% annually. Cost data was obtained from Addis Ababa hospitals while locally unavailable data were derived from the literature. Cost-effectiveness was assessed against the recommended threshold of 50% of Ethiopia's gross domestic product/capita (i.e.,US$476). Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the findings. RESULTS: In the base-case analysis, treatment of IC/C with caspofungin as first-line treatment resulted in better health outcomes (12.86 QALYs) but higher costs (US$7,714) compared to fluconazole-initiated treatment followed by caspofungin (12.30 QALYs; US$3,217) or L-AmB (10.92 QALYs; US$2,781) as second-line treatment. Caspofungin as primary treatment for IC/C was not cost-effective when compared to fluconazole-initiated therapies. Fluconazole-initiated treatment followed by caspofungin was cost-effective for the treatment of IC/C compared to fluconazole with L-AmB as second-line treatment, at US$316/QALY gained. Our findings were sensitive to medication costs, drug effectiveness, infection recurrence, and infection-related mortality rates. At a cost-effectiveness threshold of US$476/QALY, treating IC/C patient with fluconazole-initiated treatment followed by caspofungin was more likely to be cost-effective in 67.2% of simulations. CONCLUSION: Our study showed that the use of caspofungin as primary treatment for IC/C in Ethiopia was not cost-effective when compared with fluconazole-initiated treatment alternatives. The findings supported the use of fluconazole-initiated therapy with caspofungin as a second-line treatment for patients with IC/C in Ethiopia.

Charting current evidence on the health and non-health benefits and equity impacts of pandemic/epidemic individual-level economic relief programmes: a scoping review protocol.

INTRODUCTION: The emergence of a regional or global scale infectious disease outbreak often requires the implementation of economic relief programmes in affected jurisdictions to sustain societal welfare and, presumably, population health. While economic relief programmes are considered essential during a regional or global health crisis, there is no clear consensus in the literature about their health and non-health benefits and their impact on promoting equity. Thus, our objective is to map the current state of the literature with respect to the types of individual-level economic relief programmes implemented during infectious disease outbreaks and the impact of these programmes on the effectiveness of public health measures, individual and population health, non-health benefits and equity. METHODS AND ANALYSIS: Our scoping review is guided by the updated Arksey and O'Malley scoping review framework. Eligible studies will be identified in eight electronic databases and grey literature using text words and subject headings of the different pandemic and epidemic infectious diseases that have occurred, and economic relief programmes. Title and abstract screening and full-text screening will be conducted independently by two trained study reviewers. Data will be extracted using a pretested data extraction form. The charting of the key findings will follow a thematic narrative approach. Our review findings will provide in-depth knowledge on whether and how benefits associated with pandemic/epidemic individual-level economic relief programmes differ across social determinants of health factors.This information is critical for decision-makers as they seek to understand the role of pandemic/epidemic economic mitigation strategies to mitigate the health impact and reduce inequity gap. ETHICS AND DISSEMINATION: Since the scoping review methodology aims to synthesise evidence from literature, this review does not require ethical approval. Findings of our review will be disseminated to health stakeholders at policy meetings and conferences; published in a peer-review scientific journal; and disseminated on various social media platforms.

Cost-utility analysis of antimicrobial stewardship programme at a tertiary teaching hospital in Ethiopia.

OBJECTIVE: Antimicrobial stewardship (AMS) significantly reduces inappropriate antibiotic use and improves patient outcomes. In low-resource settings, AMS implementation may require concurrent strengthening of clinical microbiology capacity therefore additional investments. We assessed the cost-effectiveness of implementing AMS at Tikur Anbessa Specialised Hospital (TASH), a tertiary care hospital in Ethiopia. DESIGN: We developed a Markov cohort model to assess the cost-utility of pharmacist-led AMS with concurrent strengthening of laboratory capacity compared with usual care from a 'restricted societal' perspective. We used a lifetime time horizon and discounted health outcomes and cost at 3% annually. Data were extracted from a prospective study of bloodstream infections among patients hospitalised at TASH, supplemented by published literature. We assessed parameter uncertainty using deterministic and probabilistic sensitivity analyses. SETTING: Tertiary care hospital in Ethiopia, with 800 beds and serves over half a million patients per year. POPULATION: Cohort of adults and children inpatient population aged 19.8 years at baseline. INTERVENTION: Laboratory-supported pharmacist-led AMS compared with usual care. Usual care is defined as empirical initiation of antibiotic therapy in the absence of strong laboratory and AMS. OUTCOME MEASURES: Expected life-years, quality-adjusted life-years (QALYs), costs (US$2018) and incremental cost-effectiveness ratio. RESULTS: Laboratory-supported AMS strategy dominated usual care, that is, AMS was associated with an expected incremental gain of 38.8 QALYs at lower expected cost (incremental cost savings:US$82 370) per 1000 patients compared with usual care. Findings were sensitive to medication cost, infection-associated mortality and AMS-associated mortality reduction. Probabilistic sensitivity analysis demonstrated that AMS programme was likely to be cost-effective at 100% of the simulation compared with usual care at 1%-51% of gross domestic product/capita. CONCLUSION: Our study indicates that laboratory-supported pharmacist-led AMS can result in improved health outcomes and substantial healthcare cost savings, demonstrating its economic advantage in a tertiary care hospital despite greater upfront investments in a low-resource setting.

Cost-Utility Analysis of Dolutegravir- Versus Efavirenz-Based Regimens as a First-Line Treatment in Adult HIV/AIDS Patients in Ethiopia.

BACKGROUND: In several countries, the dolutegravir (DTG)-based regimen is generally preferred as first-line antiretroviral therapy (ART) over the efavirenz (EFV)-based regimen, but the evidence in low-income countries is limited. OBJECTIVE: Our study aimed to evaluate the cost effectiveness of DTG- versus EFV-based first-line human immunodeficiency virus (HIV) treatment in Ethiopia. METHODS: We developed a microsimulation model for the progression of HIV/acquired immune deficiency syndrome (AIDS) to examine the cost effectiveness of DTG-based first-line ART compared with an EFV-based regimen from a healthcare payer perspective. We used a lifetime horizon with a 1-month cycle length and a 3% annual discount rate. The primary outcomes were a lifetime cost in US dollars ($), quality-adjusted life-months (QALMs) that converted to QALYs using the formula QALY = QALM/12, and incremental cost-effectiveness ratio (ICER). Deterministic sensitivity analysis was conducted to account for parameter uncertainty. RESULTS: Compared with the EFV-based regimen, the DTG-based regimen was associated with an expected lifetime cost of $12,709 (vs. $12,701) and expected QALYs of 15.3 (vs. 14.7 QALYs) per patient, resulting in an ICER value of $13.33 per QALY. From an alternative analysis with a 5-year time horizon, DTG-based ART was found to be dominant, with expected gains of 0.17 QALYs at a lower cost of $1 per patient. The deterministic sensitivity analysis depicted that the maximum increase in ICER value was $72 per QALY, and all ICER values were below the estimated threshold value. CONCLUSIONS: The DTG-based first-line regimen appears to be cost effective compared with the EFV-based regimen for the treatment of HIV/AIDS patients in an Ethiopian setting.

Health-related quality of life of patients with HIV/AIDS at a tertiary care teaching hospital in Ethiopia.

BACKGROUND: Patients' health-related quality of life (HRQoL) and health state utility values are critical inputs in the clinical and economic evaluation of treatments for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). However, information on health state utility values is lacking in the context of Ethiopia. Here, we aimed to assess HRQoL and determine health state utility values and factors that influence the values among HIV/AIDS patients in Ethiopia. METHODS: A cross-sectional study was conducted among 511 HIV/AIDS patients at Tikur Anbessa Specialized Hospital in Ethiopia. Patients aged 18 years or older were eligible for the interview and those who were mentally unstable and with hearing impairment were excluded from the study. We performed face-to-face interviews using EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) in combination with EuroQol-Visual Analog Scales (EQ-VAS). Level-specific disutility coefficients obtained from the general population were used for computing utility values. Patients' health profiles were described using percentages and different statistical analysis were conducted to determine factors associated with the EQ-5D index and EQ-VAS scores. RESULTS: A total of 511 patients participated in the study. A higher proportion of patients reported slight or more severe problems on the anxiety/depression (55.2%) and pain/discomfort (51.3%) dimensions. The overall median utility value of HIV/AIDS patients was 0.94 (IQR = 0.87, 1) from the EQ-5D index and 80% (IQR = 70%, 90%) from the EQ-VAS scores. Demographic characteristics including age, occupational status, and household monthly income significantly affected patient's utility values. Moreover, statistically significant (p < 0.001) differences were seen between the EQ-5D index values of patients with different CD4 count intervals. Furthermore, number of medicines that the patients were taking at the time of the study and comorbidities were significantly associated with the EQ-5D utility index and EQ-VAS score, p < 0.001. CONCLUSIONS: The anxiety/depression and pain/ discomfort dimensions were identified to have critical influence in reducing the HRQoL of adult HIV/AIDS patients in the context of Ethiopia. The study is also the first to use the EQ-5D-5L tool to identify health state utility values for Ethiopian adult HIV/AIDS patients. Future economic evaluations of HIV/AIDS interventions are encouraged to employ the identified utility values.

Assessment of Knowledge and Attitude of Tuberculosis Patients in Direct Observation Therapy Program towards Multidrug-Resistant Tuberculosis in Addis Ababa, Ethiopia: A Cross-Sectional Study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is becoming a major challenge of tuberculosis (TB) control program globally but more serious in developing countries like Ethiopia. In 2013, a survey result showed that in Ethiopia, tuberculosis patients from new cases and retreatment cases had resistance to at least isoniazid and rifampicin with a significant increase over time. Inadequate knowledge and wrong perception about MDR-TB by patients were detrimental to TB control programs. The study aimed at assessing the knowledge and attitude of TB patients of direct observation therapy program towards multidrug-resistant tuberculosis in health centres of Addis Ababa, Ethiopia. METHODS: A cross-sectional study was conducted in 10 health centres of Addis Ababa which were selected by simple random sampling technique. A total of 422 TB patients were included in the study, and participants from each health centres were taken proportional to the number of clients in each health centres. Data was entered and analyzed using SPSS version 20. Association between outcome and independent variables was explored using logistic regression. RESULTS: The level of knowledge of TB patients about MDR-TB was poor and only 55.0% of TB patients attained good overall knowledge. A significant association was found between good knowledge and attending tertiary level of education (AOR = 4.3, 95%CI = 1.9, 9.8), gender (AOR = 1.62, 95%CI = 1.1, 2.4), income of respondents' family (OR = 0.4, 95%CI = 0.2, 0.9), and sleeping practice (AOR = 8.0, 95%CI = 4.0, 15.7). Nearly three-fourths (73.5%) of TB patients had a favourable attitude towards MDR-TB. Occupational status (AOR = 4.4, 95%CI = 2.5, 7.6) and sleeping practices (AOR = 2.4, 95%CI = 1.2, 5.0) were significantly associated with the attitude of the TB patients. CONCLUSIONS: Knowledge of TB patients toward MDR-TB was poor. Although a large proportion of patients had a favourable attitude, it still needs to be improved. Hence, efforts should be made to implementing health education to improve awareness of TB patients about MDR-TB.

Catastrophic healthcare expenditure and coping strategies among patients attending cancer treatment services in Addis Ababa, Ethiopia.

BACKGROUND: With the rapid increase in magnitude and mortality of cancer, which is costly disease to manage, several patients particularly in developing countries are facing a huge financial burden. The study aimed to examine the incidence of catastrophic health expenditure (CHE), identify associated factors and coping strategies among patients attending cancer treatment services in Addis Ababa, Ethiopia. METHODS: A hospital-based cross-sectional survey of patients with cancer was conducted in public and private hospitals between January and March 2018. Data was collected using a structured questionnaire. All direct medical and nonmedical expenditures were measured and reported as expenditure (US$) per patient (1US$ equivalent to 23.41 Ethiopian Birr). The CHE was estimated using a threshold of 10% of annual household income. RESULTS: A total of 352 (response rate of 87.1%) participants were interviewed. Majority (73.3%) of the respondents were females; most (94%) from public hospitals and their mean (±SD) age was 48 ± 13.2 years. Vast majority (74.4%) of patients experienced CHE with mean overall expenditure of $2366 per patient (median: $1708). Medical expenditure shared the highest overall expenditure (83.6%) with mean medical and nonmedical costs of $1978 (median: $1394) and $388 (median: $222), respectively. Patients who took greater than six cycles of chemotherapy (AOR: 3.64; 95% CI: 1.11-11.92), and age (AOR: 1.03; 95% CI: 1.01-1.06) were significantly associated with CHE. Household saving (85.5%) followed by financial support received (43.0%) was the main coping strategy. CONCLUSION: A substantial number of patients with cancer were exposed to CHE with a considerable medical expenditure. Hence, in addition to the popularization of the already introduced health insurance scheme, other better prepayment or insurance mechanisms should also be considered to ensure financial risk protection and realize universal health coverage for patients with cancer.

Valuing Health State: An EQ-5D-5L Value Set for Ethiopians.

OBJECTIVES: There is a growing interest in health technology assessment and economic evaluations in developing countries such as Ethiopia. The objective of this study was to derive an EQ-5D-5L value set from the Ethiopian general population to facilitate cost utility analysis. METHODS: A nationally representative sample (N = 1050) was recruited using a stratified multistage quota sampling technique. Face-to-face, computer-assisted interviews using the EuroQol Portable Valuation Technology (EQ-PVT) protocol of composite time trade-off (c-TTO) and discrete choice experiments (DCEs) were undertaken to elicit preference scores. The feasibility of the EQ-PVT protocol was pilot tested in a sample of the population (n = 110). A hybrid regression model combining c-TTO and DCE data was used to estimate the final value set. RESULTS: In the pilot study, the acceptability of the tasks was good, and there were no special concerns with undertaking the c-TTO and DCE tasks. The coefficients generated from a hybrid model were logically consistent. The predicted values for the EQ-5D-5L ranged from -0.718 to 1. Level 5 anxiety/depression had the largest impact on utility decrement (-0.458), whereas level 5 self-care had the least impact (-0.222). The maximum predicted value beyond full health was 0.974 for the 11112 health state. CONCLUSIONS: This is the first EQ-5D-5L valuation study in Africa using international valuation methods (c-TTO and DCE) and also the first using the EQ-PVT protocol to derive a value set. We expect that the availability of this value set will facilitate health technology assessment and health-related quality-of-life research and inform policy decision making in Ethiopia.

Reliability and validity of the Amharic version of European Organization for Research and Treatment of cervical Cancer module for the assessment of health related quality of life in women with cervical cancer in Addis Ababa, Ethiopia.

BACKGROUND: Cervical cancer is among the leading gynecological cancers affecting women worldwide. Maintenance and improvement of cervical cancer patients'health related quality of life (HRQoL) is an important issue. The cervical cancer specific quality of life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-CX24) is the most commonly used tool, however, it is not validated in Ethiopia. Hence, the present study aimed to assess the psychometric properties of the tool among Ethiopian cervical cancer patients. METHODS: Hospital based cross-sectional study was done in Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia from January to February, 2018. The module was translated through forward-backward translation approach and pilot tested according to the EORTC Guidelines. One hundered and seventy one patients with confirmed cervical cancer were enrolled for the study. Amharic versions of EORTC QLQ-C30 and EORTC QLQ-CX24 were used to collect data along with socio-demographic and clinical characteristics. Descriptive statistics were used to assess socio-demographic and clinical characteristics of patients. The Psychometric properties of the EORTC QLQ-CX24 were evaluated in terms of acceptability, internal consistency, construct, concurrent and known group validity using SPSS version 22. RESULTS: One hundred seventy one cervical cancer patients were enrolled in the study, with a mean age of 52.15 ± 10.4 years. The EORTC QLQ-CX24 was found to be acceptable with high compliance and low missing responses. The Cronbach's alpha ranged from 0.70-0.84, indicating the reliability of the scales. Convergent and discriminant validity in multitrait scaling analysis was adequate. The EORTC QLQ-C30 subscales and EORTC QLQ-CX24 subscales had a weak to strong correlation, indicating concurrent validity. The scales and single-item measures were able to discriminate between subgroups of patients differing with regard to performance status, cancer stage and treatment status, indicating clinical validity. CONCLUSION: Amharic version of the EORTC QLQ-CX24 questionnaire is a valid and reliable tool and could be used for clinical and epidemiological cancer researches to study the HRQoL of patients with cervical cancer in Ethiopia.

Opportunities and barriers to implementing antibiotic stewardship in low and middle-income countries: Lessons from a mixed-methods study in a tertiary care hospital in Ethiopia.

BACKGROUND: Global action plans to tackle antimicrobial resistance (AMR) include implementation of antimicrobial stewardship (AMS), but few studies have directly addressed the challenges faced by low and middle-income countries (LMICs). Our aim was to explore healthcare providers' knowledge and perceptions on AMR, and barriers/facilitators to successful implementation of a pharmacist-led AMS intervention in a referral hospital in Ethiopia. METHODS: Tikur Anbessa Specialized Hospital (TASH) is an 800-bed tertiary center in Addis Ababa, and the site of an ongoing 4-year study on AMR. Between May and July 2017, using a mixed approach of quantitative and qualitative methods, we performed a cross-sectional survey of pharmacists and physicians using a pre-tested questionnaire and semi-structured interviews of purposively selected respondents until thematic saturation. We analyzed differences in proportions of agreement between physicians and pharmacists using χ2 and fisher exact tests. Qualitative data was analyzed thematically. FINDINGS: A total of 406 survey respondents (358 physicians, 48 pharmacists), and 35 key informants (21 physicians and 14 pharmacists) were enrolled. The majority of survey respondents (>90%) strongly agreed with statements regarding the global scope of AMR, the need for stewardship, surveillance and education, but their perceptions on factors contributing to AMR and their knowledge of institutional resistance profiles for common bacteria were less uniform. Close to 60% stated that a significant proportion of S. aureus infections were caused by methicillin-resistant strains (an incorrect statement), while only 48% thought a large proportion of gram-negative infections were caused by cephalosporin-resistant strains (a true statement). Differences were noted between physicians and pharmacists: more pharmacists agreed with statements on links between use of broad-spectrum antibiotics and AMR (p<0.022), but physicians were more aware that lack of diagnostic tests led to antibiotic overuse (p<0.01). More than cost, fear of treatment failure and of retribution from senior physicians were major drivers of antibiotic prescription behavior particularly among junior physicians. All respondents identified high turnover of pharmacists, poor communication between the laboratory, pharmacists and clinicians as potential challenges; but the existing hierarchical culture and academic setting were touted as opportunities to implement AMS in Ethiopia. CONCLUSIONS: This knowledge and perceptions survey identified specific educational priorities and implementation strategies for AMS in our setting. This is likely also true in other LMICs, where expertise and infrastructure may be lacking.