Cost-effectiveness modelling studies of all preventive measures against rabies: A systematic review.

Rabies is one of the most feared infectious diseases worldwide, predominantly occurring in Asia and Africa where rabies is endemic in domestic dog populations. Whereas previous studies have demonstrated mass dog vaccination and post-exposure prophylaxis (PEP) as the most effective control strategies, successful rabies elimination has yet to be realized as these recognized effective interventions continue to face challenges of limited accessibility. In the light of new evidence towards improving programmatic feasibility and clinical practice in rabies control especially among endemic countries, a systematic review was undertaken to identify cost-effectiveness modelling studies of rabies preventive measures and to provide a critical review of published evidence through comparative evaluation and model quality assessment, and a synthesis of key findings based thereon. Our search through MEDLINE and SCOPUS identified a total of 17 studies which mostly focused on estimating the impact of increasing PEP and pre-exposure prophylaxis (PrEP) access, human rabies elimination scenarios using mass dog vaccinations only or complemented with PEP strategy. While no significant methodological inconsistency across studies was identified and the extent of reporting is generally high, we note several points for quality and internal validity improvement. Assessment of modelling approach showed that decision tree models had similar pathways. The results of the studies suggest that interventions would be cost-effective at the cost-effectiveness threshold of 1 to 3 times per capita Gross Domestic Product (GDP) as recommended by the Commission on Macroeconomics and Health's GDP based thresholds, compared with no intervention in rabies endemic countries. When compared across studies which reported incremental cost-effectiveness ratio (ICER) as cost per QALY gained or DALY averted in international dollars adjusted by purchasing power parity conversion rate, PEP vaccination yields less cost per DALY averted or QALY gained due to one year-horizon assessment compared to canine vaccination at 4- or 10-year-time horizon

Cost-utility analysis of adjuvant trastuzumab therapy for HER2-positive early-stage breast cancer in the Philippines

Abstract Background Breast cancer is the leading malignancy among Filipino women, with about 23.50% of cases characterized by human epidermal growth factor receptor-2 (HER2) overexpression. Trastuzumab, in addition to standard chemotherapy, is currently recommended as primary treatment for HER2-positive early-stage breast cancer (EBC) in the adjuvant settings, and has been listed in the Philippine National Formulary (PNF) since 2008, but with no current evidence yet on its value for money, to date. Hence, despite several policy enablers, its accessibility remains to be limited in the Philippines. We performed an economic evaluation to assess the cost-effectiveness and budget impact of adjuvant trastuzumab therapy for HER2-positive EBC in the Philippines, using healthcare system and societal perspectives, in aid of guiding coverage decisions. Methods A Markov model-based cost-utility and budget impact analyses were conducted to estimate the total costs incurred and outcomes gained in using 1 year of adjuvant trastuzumab added to standard chemotherapy versus standard chemotherapy alone, over a lifetime horizon. We discounted both costs and outcomes at 3.5% per annum. Parameters were estimated using country survival data, systematic review and meta-analysis of the relative treatment effect, local and international cost data, and published utility data. Univariate and probabilistic sensitivity analyses were used to account for parameter uncertainty. Results Trastuzumab therapy was dominated with an incremental cost-effectiveness ratio (ICER) at PHP 453,505 per QALY gained from a healthcare system perspective or PHP 458,686 per QALY gained from a societal perspective, with 10% cost-effectiveness probability at the country cost-effectiveness threshold of PHP 120,000 per QALY gained. National implementation will cost an additional amount of PHP 13,909 million in year one alone, plus about PHP 2000 to 3000 million annually for the succeeding fiscal years. Conclusion At its current cost, 1 year of adjuvant trastuzumab therapy compared to standard chemotherapy alone for HER2-positive EBC does not represent value for money in the Philippines. Its current cost will have to significantly lower down by one-half to achieve cost-effectiveness. </jats:sec

Systematic Review with Meta-Analysis: Efficacy and Safety of Direct-Acting Antivirals for Chronic Hepatitis C Genotypes 5 and 6

Direct-acting antivirals (DAAs) are modern treatments for chronic hepatitis C infection, but majority of available evidence on its treatment effect covers genotypes 1 to 4. Therefore, the efficacy and safety of DAAs for genotypes 5 and 6 need to be analysed. Studies were identified from Medline, Scopus, and CENTRAL and a Chinese database CNKI, from inception until Dec 4, 2018. Clinical trials were included if they enrolled patients with genotypes 5 and/or 6 infection, any type of second-generation DAAs was studied, and sustained virological response was assessed at the 12th week after treatment (SVR12) as outcome measure. Meta-analysis using metaprop statistical program was applied for pooling proportions if data were sufficient (i.e., at least 2 studies). Thirteen studies were included in the analysis. Four studies assessed the efficacy of four DAA regimens in genotype 5 patients, which were mainly sofosbuvir (SOF) plus pegylated-interferon/ribavirin (PR) or other DAAs, with SVR12 ranging from 94.4% to 100%. Twelve studies assessed the efficacy of seven DAA regimens among genotype 6 patients, but only two DAA regimens (i.e., SOF + PR and SOF/ledipasvir) had sufficient data for pooling. The pooled SVR12 rates (95% CI) were 99.6% (92.2 to 100) for SOF + PR and 99.2% (96.5 to 100) for SOF/ledipasvir. No treatment-related serious adverse event was reported, while the nonserious adverse events were comparable to other genotypes. In conclusion, DAAs are effective and may be safe for the treatment of chronic hepatitis C genotypes 5 and 6. However, our evidence is based on noncomparative studies; hence, further larger-scale randomized controlled trials in these genotypes are still required.</jats:p

Adjuvant trastuzumab regimen for HER2-positive early-stage breast cancer: a systematic review and meta-analysis

Objective: Breast cancer remains to be the globally leading female cancer. About 15% to 20% of breast cancers have human epidermal growth factor receptor 2 (HER2)-positive tumors – a more aggressive breast cancer subtype with shortened survival. In the light of new and updated trial data on trastuzumab therapy for HER2-positive early-stage breast cancer (EBC), we conducted a systematic review and meta-analysis to update the pooling of its relative treatment effects. Methods: Systematic search was performed through Pubmed and Scopus to identify studies comparing survival outcomes and risks of heart toxicity effects of adjuvant trastuzumab with chemotherapy versus chemotherapy alone for HER2-positive EBC patients. Results: Based on the eight included studies in the review, combining trastuzumab with chemotherapy continues to show lowered death and relapse risks by one-third. The decision to initiate trastuzumab, however, needs to be prudently deliberated as two to three times more cardiotoxicity risk was shown to be associated with its use. Conclusion: Administering adjuvant trastuzumab in a weekly cycle concurrently with anthracycline-taxane chemotherapy regimen appears to be a preferable option to optimize its favorable effect in improving DFS and to prevent significantly higher risk for cardiotoxic effects.</p

Estimating the EQ-5D-5L value set for the Philippines

Abstract Background The Philippines has recommended the use of Quality-Adjusted Life Years (QALYs) in government health technology assessments (HTA). We aimed to develop a value set for the EQ-5D-5L based on health preferences of the healthy general adult population in the Philippines. Methods Healthy, literate adults were recruited from the Philippine general population with quota targets based on age, sex, administrative region, type of residence, education, income, and ethnolinguistic groups. Each participant’s preference was elicited by completing Composite Time Trade-Off (C-TTO) and Discrete Choice Experiment (DCE) tasks. Tasks were computer-assisted using the EuroQol Valuation Technology 2.0. To estimate the value set, we explored 20- and 8-parameter models that either use c-TTO-only data or both c-TTO and DCE (also called hybrid models). Final model choice was guided by principles of monotonicity, out-of-sample likelihood, model fit, and parsimony. Results We recruited 1000 respondents with demographic characteristics that approximate the general population such as 49.6% Female, 82% Roman Catholic, 40% in urban areas, and 55% finished high school. None of the 20-parameter models demonstrated monotonicity (logical worsening of coefficients with increasing severity). From the 8-parameter models, the homoscedastic TTO-only model exhibited the best fit. From this model, mobility and pain/ discomfort had the highest effect on utilities. Conclusion The selected model for representing the Philippine general population preferences for EQ-5D-5L health states was an 8-parameter homoscedastic TTO-only model. This value set is recommended for use in QALY calculations in support of HTA-informed coverage decisions in the Philippines. </jats:sec

What, where, and how to collect real-world data and generate real-world evidence to support drug reimbursement decision-making in Asia : a reflection into the past and a way forward

Background: Globally, there is increasing interest in the use of real-world data (RWD) and real-world evidence (RWE) to inform health technology assessment (HTA) and reimbursement decision-making. Using current practices and case studies shared by eleven health systems in Asia, a non-binding guidance that seeks to align practices for generating and using RWD/RWE for decision-making in Asia was developed by the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) Working Group, addressing a current gap and needs among HTA users and generators. Methods: The guidance document was developed over two face-to-face workshops, in addition to an online survey, a face-to-face interview and pragmatic search of literature. The specific focus was on what, where and how to collect RWD/RWE. Results: All 11 REALISE member jurisdictions participated in the online survey and the first in-person workshop, 10 participated in the second in-person workshop, and 8 participated in the in-depth face-to-face interviews. The guidance document was iteratively reviewed by all working group members and the International Advisory Panel. There was substantial variation in: (a) sources and types of RWD being used in HTA, and (b) the relative importance and prioritization of RWE being used for policy-making. A list of national-level databases and other sources of RWD available in each country was compiled. A list of useful guidance on data collection, quality assurance and study design were also compiled. Conclusion: The REALISE guidance document serves to align the collection of better quality RWD and generation of reliable RWE to ultimately inform HTA in Asia