OBJECTIVE: This review aimed to summarize the current evidence base of reported utility values for chemotherapy-related ADEs.
METHODS: A structured electronic search combining terms for utility, utility valuation methods and generic terms for cancer treatment was conducted in MEDLINE and EMBASE in June 2011. Inclusion criteria were: (1) elicitation of utility values for chemotherapy-related ADEs and (2) primary data. Two reviewers identified studies and extracted data independently. Any disagreements were resolved by a third reviewer.
RESULTS: Eighteen studies met the inclusion criteria from the 853 abstracts initially identified, collectively reporting 218 utility values for chemotherapy-related ADEs. All 18 studies used short descriptions (vignettes) to obtain the utility values, with nine studies presenting the vignettes used in the valuation exercises. Of the 218 utility values, 178 were elicited using standard gamble (SG) or time trade-off (TTO) approaches, while 40 were elicited using visual analogue scales (VAS). There were 169 utility values of specific chemotherapy-related ADEs (with the top ten being anaemia [34 values], nausea and/or vomiting [32 values], neuropathy [21 values], neutropenia [12 values], diarrhoea [12 values], stomatitis [10 values], fatigue [8 values], alopecia [7 values], hand-foot syndrome [5 values] and skin reaction [5 values]) and 49 of non-specific chemotherapy-related adverse events. In most cases, it was difficult to directly compare the utility values as various definitions and study-specific vignettes were used for the ADEs of interest.
LIMITATIONS: This review was designed to provide an overall description of existing literature reporting utility values for chemotherapy-related ADEs. The findings were not exhaustive and were limited to publications that could be identified using the search strategy employed and those reported in the English language.
CONCLUSIONS: This review identified wide ranges in the utility values reported for broad categories of specific chemotherapy-related ADEs. There were difficulties in comparing the values directly as various study-specific definitions were used for these ADEs and most studies did not make the vignettes used in the valuation exercises available. It is recommended that a basic minimum requirement be developed for the transparent reporting of study designs eliciting utility values, incorporating key criteria such as reporting how the vignettes were developed and presenting the vignettes used in the valuation tasks as well as valuing and reporting the utility values of the ADE-free base states. It is also recommended, in the future, for studies valuing the utilities of chemotherapy-related ADEs to define the ADEs according to the National Cancer Institute (NCI) definitions for chemotherapy-related ADEs as the use of the same definition across studies would ease the comparison and selection of utility values and make the overall inclusion of adverse events within economic models of chemotherapy agents much more straightforward.
METHODS: An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.
RESULTS: In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.
CONCLUSIONS: The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia.
Materials and Methods: This was a retrospective cohort study that included all patients with AF who were treated with NOACs (dabigatran or rivaroxaban) in HKL and HSDG. Data were obtained from medical records and pharmacy databases. Adherence was assessed using proportion of days covered (PDC) over a 1-year duration. High adherence was defined as PDC ≥80%. A gap of >60 days between two consecutive refills was used to define non-persistence.
Result: There were 281 patients who met the inclusion criteria, with 54.1% (n = 152) male. There were 75.1% (n = 211) patients on dabigatran and others on rivaroxaban. Only 66.9% (n = 188) of patients achieved high adherence with PDC ≥80% and 69.8% (n = 196) were persistence with >60-day gap over 12 months. Adherence and persistence were both influenced by treatment center, whereas polypharmacy only influenced adherence.
Conclusion: Overall adherence and persistence to NOACs were suboptimal and varied between treatment centers, potentially due to institution-specific administrative and clinical practice differences. Clinical care and outcomes can potentially be optimized by identifying factors affecting adherence and persistence and by implementing interventions to improving them.
OBJECTIVE: To assist with achieving these goals and to inform the development of a national strategic plan for Malaysia, we estimated the long-term burden incurred by the care and management of patients with chronic hepatitis C virus (HCV) infection. We compared cumulative healthcare costs and disease burden under different treatment cascade scenarios.
METHODS: We attached direct costs for the management/care of chronically HCV-infected patients to a previously developed clinical disease progression model. Under assumptions regarding disease stage-specific proportions of model-predicted HCV patients within care, annual numbers of patients initiated on antiviral treatment and distribution of treatments over stage, we projected the healthcare costs and disease burden [in disability-adjusted life-years (DALY)] in 2018-2040 under four treatment scenarios: (A) no treatment/baseline; (B) pre-2018 standard of care (pegylated interferon/ribavirin); (C) gradual scale-up in direct-acting antiviral (DAA) treatment uptake that does not meet the WHO 2030 treatment uptake target; (D) scale-up in DAA treatment uptake that meets the WHO 2030 target.
RESULTS: Scenario D, while achieving the WHO 2030 target and averting 253,500 DALYs compared with the pre-2018 standard of care B, incurred the highest direct patient costs over the period 2018-2030: US$890 million (95% uncertainty interval 653-1271). When including screening programme costs, the total cost was estimated at US$952 million, which was 12% higher than the estimated total cost of scenario C.
CONCLUSIONS: The scale-up to meet the WHO 2030 target may be achievable with appropriately high governmental commitment to the expansion of HCV screening to bring sufficient undiagnosed chronically infected patients into the treatment pathway.
METHODS: This study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications.
RESULTS: The stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years.
DISCUSSION: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.
METHODS: We developed a decision analytic model to estimate the lifetime costs and quality-adjusted life-years (QALYs) accrued through BRCA mutation testing or routine clinical surveillance (RCS) for a hypothetical cohort of 1000 early-stage breast cancer patients aged 40 years. In the model, patients would decide whether to accept testing and to undertake risk-reducing mastectomy, oophorectomy, tamoxifen, combinations or neither. We calculated the incremental cost-effectiveness ratio (ICER) from the health system perspective. A series of sensitivity analyses were performed.
RESULTS: In the base case, testing generated 11.2 QALYs over the lifetime and cost US$4815 per patient whereas RCS generated 11.1 QALYs and cost US$4574 per patient. The ICER of US$2725/QALY was below the cost-effective thresholds. The ICER was sensitive to the discounting of cost, cost of BRCA mutation testing and utility of being risk-free, but the ICERs remained below the thresholds. Probabilistic sensitivity analysis showed that at a threshold of US$9500/QALY, 99.9% of simulations favoured BRCA mutation testing over RCS.
CONCLUSIONS: Offering BRCA mutation testing to early-stage breast cancer patients identified using a locally-validated risk-assessment tool may be cost effective compared to RCS in Malaysia.
OBJECTIVES: To estimate the required coverage and costs of a national screening strategy to inform the launch of an HCV elimination program.
METHODS: We designed an HCV screening strategy based on a "stepwise" approach. This approach relied on targeting of people who inject drugs in the early years, with delayed onset of widespread general population screening. Annual coverage requirements and associated costs were estimated to ensure that the World Health Organization elimination treatment targets were met.
RESULTS: In total, 6 million individuals would have to be screened between 2018 and 2030. Targeting of people who inject drugs in the early years would limit annual screening coverage to less than 1 million individuals from 2018 to 2026. General population screening would have to be launched by 2026. Total costs were estimated at MYR 222 million ($58 million). Proportional to coverage targets, 60% of program costs would fall from 2026 to 2030.
CONCLUSIONS: This exercise was one of the first attempts to conduct a detailed analysis of the required screening coverage and costs of a national HCV elimination strategy. These findings suggest that the stepwise approach could delay the onset of general population screening by more than 5 years after the program's launch. This delay would allow additional time to mobilize investments required for a successful general population screening program and also minimize program costs. This strategy prototype could inform the design of effective screening strategies in other countries.
METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate 3 strategies for treating newly diagnosed epilepsy among adults: (i) CBZ initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to CBZ initiation; and (iii) alternative prescribing without HLA-B*15:02 screening. The model was populated with real-world inputs derived from the Malaysian population. From a societal perspective, base-case analysis and sensitivity analyses estimated the costs and outcomes over a lifetime. Incremental cost-effectiveness ratios were calculated.
RESULTS: In the base-cases analysis, universal HLA-B*15:02 screening yielded the lowest total costs and the highest total quality-adjusted life years (QALYs) gained. Compared with current practice, universal screening was less costly by USD100 and more effective by QALYs increase of 0.1306, while alternative prescribing resulted in 0.1383 QALYs loss at additional costs of USD332. The highest seizure remission rate (56%) was estimated for universal HLA-B*15:02 screening vs. current practice (54%) and alternative prescribing (48%).
CONCLUSION: Our study suggests that universal HLA-B*15:02 screening is a cost-effective intervention in Malaysia. With the demonstrated value of real-world evidence in economic evaluations, more relevant standardization efforts should be emphasized to better inform decision-making.
METHODS: An 8-step generic economic model development process was applied to the use case of human leukocyte antigen (HLA)-B*15:02genotyping for prediction of carbamazepine-induced cutaneous reactions, with a user-friendly decision-making tool relying on user-provided input values. This generic model was transparently documented and validated, including cross-validation comparing cost-effectiveness results with 3 country-specific models.
RESULTS: A generic pharmacogenomic use case cost-effectiveness model with decision-making tool was successfully developed and cross-validated using input values for 6 populations which produced consistent results for HLA-B*15:02 screening at country-specific cost-effectiveness threshold values. Differences between the generic and country-specific model results were largely due to differences in model structure and assumptions.
CONCLUSION: This proof on concept demonstrates the feasibility of generic models to provide useful PM economic evidence, supporting their use as a pragmatic and timely approach to address a growing need.
OBJECTIVES: To determine the cost-effectiveness of universal HLA-B*15:02 screening in preventing carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in an ethnically diverse Malaysian population.
METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed epilepsy among adults: (i) carbamazepine initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to carbamazepine initiation; and (iii) alternative treatment [sodium valproate (VPA)] prescribing without HLA-B*15:02 screening. Base-case analysis and sensitivity analyses were performed over a lifetime time horizon. Incremental cost-effectiveness ratios were calculated.
RESULTS: Both universal HLA-B*15:02 screening and VPA prescribing were dominated by current practice. Compared with current practice, universal HLA-B*15:02 screening resulted in a loss of 0·0255 quality-adjusted life years (QALYs) at an additional cost of 707 U.S. dollars (USD); VPA prescribing resulted in a loss of 0·2622 QALYs at an additional cost of USD 4127, owing to estimated differences in antiepileptic treatment efficacy.
CONCLUSIONS: Universal HLA-B*15:02 screening is unlikely to be a cost-effective intervention in Malaysia. However, with the emergence of an ethnically diverse population in many other countries, this may render HLA-B*15:02 screening a viable intervention when an increasing proportion of the population is at risk and an equally effective yet safer antiepileptic drug is available.