Fh Shabaruddin

Cost–effectiveness analysis in pharmacogenomics

The existence of finite healthcare budgets drives the need to consider opportunity cost and demonstrate that pharmacogenomic interventions offer added value, in terms of the relative costs and benefits, compared with current practice. This is where the framework of cost-effectiveness analysis is useful. Existing systematic reviews of economic evaluations of genetic technologies have all highlighted the need to improve the quality of the economics evidence base. More recent cost-effectiveness analyses of pharmacogenomics are generally of higher quality. The future will see an increase in the number of published cost-effectiveness analyses. Critical appraisal of these analyses is necessary to ensure the evidence base is sufficiently robust to inform resource allocation decisions at local and national levels.

A Systematic Review of Utility Values for Chemotherapy-Related Adverse Events

BackgroundChemotherapy offers cancer patients the potential benefits of improved mortality and morbidity but may cause detrimental outcomes due to adverse drug events (ADEs), some of which requiring time-consuming, resource-intensive and costly clinical management. To appropriately assess chemotherapy agents in an economic evaluation, ADE-related parameters such as the incidence, (dis)utility and cost of ADEs should be reflected within the model parameters. To date, there has been no systematic summary of the existing literature that quantifies the utilities of ADEs due to healthcare interventions in general and chemotherapy treatments in particular.ObjectiveThis review aimed to summarize the current evidence base of reported utility values for chemotherapy-related ADEs.MethodsA 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.ResultsEighteen 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.LimitationsThis 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.ConclusionsThis 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.

Economic evaluations of personalized medicine: existing challenges and current developments.

Personalized medicine, with the aim of safely, effectively, and cost-effectively targeting treatment to a prespecified patient population, has always been a long-time goal within health care. It is often argued that personalizing treatment will inevitably improve clinical outcomes for patients and help achieve more effective use of health care resources. Demand is increasing for demonstrable evidence of clinical and cost-effectiveness to support the use of personalized medicine in health care. This paper begins with an overview of the existing challenges in conducting economic evaluations of genetics- and genomics-targeted technologies, as an example of personalized medicine. Our paper illustrates the complexity of the challenges faced by these technologies by highlighting the variations in the issues faced by diagnostic tests for somatic variations, generally referring to genetic variation in a tumor, and germline variations, generally referring to inherited genetic variation in enzymes involved in drug metabolic pathways. These tests are typically aimed at stratifying patient populations into subgroups on the basis of clinical effectiveness (response) or safety (avoidance of adverse events). The paper summarizes the data requirements for economic evaluations of genetics and genomics-based technologies while outlining that the main challenges relating to data requirements revolve around the availability and quality of existing data. We conclude by discussing current developments aimed to address the challenges of assessing the cost-effectiveness of genetics and genomics-based technologies, which revolve around two central issues that are interlinked: the need to adapt available evaluation methods and identifying who is responsible for generating evidence for these technologies.

Understanding chemotherapy treatment pathways of advanced colorectal cancer patients to inform an economic evaluation in the United Kingdom

Background:Accurate description of current practice within advanced colorectal cancer (CRC) specialties were needed to inform an economic evaluation of the UGT1A1 pharmacogenetic test for irinotecan in the United Kingdom.Methods:The study was based on a literature review and elicitation of expert opinion. The expert panel comprised 44 consultant oncologists in NHS Hospital Trusts across England.Results:Ten first-line, 10 second-line and 12 third-line chemotherapy regimens were reported, reflecting wide variations in treatment pathways. Predominant pathways emerged with: first-line treatment with oxaliplatin-based regimens, second-line treatment with irinotecan-based regimens and third-line treatment with mitomycin-based regimens. Experts estimated the frequency of febrile neutropaenia 8.4% (95% CI: 6.7–10.0), septic neutropaenia 4.7% (95% CI: 3.4–6.0) and severe diarrhoea 13.1% (95% CI: 10.8–15.5). Approaches for the clinical management of neutropaenia within the NHS were described.Conclusions:This study identified wide variations in the clinical management of advanced CRC patients. Descriptions of current treatment pathways are necessary for economic evaluations. Variations in clinical practice must be reflected in the model to ensure the findings from an economic evaluation of UGT1A1 testing are sufficient to inform policy regarding the cost-effective use of NHS resources.

Is universal HLA‐B*15:02 screening a cost‐effective option in an ethnically diverse population? A case study of Malaysia

A strong association has been documented between HLA‐B*15:02 and carbamazepine‐induced severe cutaneous adverse reactions (SCARs) in Asians. Human leucocyte antigen testing is potentially valuable in many countries to facilitate early recognition of patient susceptibility to SCARs.

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia.

Background The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods. 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.

Hepatocellular Carcinoma in Malaysia and Its Changing Trend

Hepatocellular carcinoma (HCC) is one of the leading causes of death globally. In Malaysia liver cancer is the eighth most common cause of cancer for both gender and fifth most common cause of cancer for males. Liver cancer is a cause of premature death in Malaysia: The trend from 1990 to 2010 was observed upward. Since 1990, the annual years of life lost (YLLs) from liver cancer have increased by 31.5%. Older persons are at higher risk and there is male predominance observed. Curative surgical resection, liver transplantation, and supportive symptomatic care, including percutaneous ethanol injection and radiofrequency ablation (RFA), and noncurative transarterial chemoembolization (TACE) are among available treatment facilities. Yet the survival rate is very poor as majority of patients present at very advanced stage. Hepatitis B virus (HBV) remained the leading cause of HCC in Malaysia. Several studies showed cryptogenic causes, which are mainly nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) among the predominant causes of HCC in Malaysia than hepatitis C virus (HCV), alcohol, or any other reason. This mainly correlates with the increasing incidence of diabetes and obesity in Malaysia. How to cite this article: Raihan R, Azzeri A, Shabaruddin FH, Mohamed R. Hepatocellular Carcinoma in Malaysia and Its Changing Trend. Euroasian J Hepato-Gastroenterol 2018;8(1):54-56.

PCN57 EXAMINING PATIENT-BASED COSTS FOR IRINOTECAN CHEMOTHERAPY: UK PRACTICE-BASED MICROCOSTING STUDY

and indirect (the “cost of illness” analysis), connected with patient treatment at different stage of disease treatment. Epidemiology of ÍÑÑ in Russia was investigated: prevalence, incidence, structure of disease depending on age, disease progression, and death rate indicators. The expert opinion of real practice of HCC treatment was collected. All these methods allowed to estimate the direct and indirect costs of HCC. RESULTS: HCC incidence rate was 2.4 patients per 100,000 population (85% in the structure of primary liver cancer). HCC incidence rate index was 8658 patients as of 2008. In the HCC, structure intermediate stage prevails—61%, the terminal and local stages—30% and 9% correspondingly. HCC treatment costs were 2370 bln RUB (c67.7 mln) (2008). Direct medical costs were 2208 bln RUB (c63.1 mln) including inpatient care (90%), outpatient care (6.6%), and diagnostics (3.4%). Indirect costs were 0.161 bln RUB (c4.6 mln) including GDP loses (26%) and payment related with temporary disability (74%) The current HCC treatment standards do not correspond to international approaches. Very few patients with primary liver cancer get target pharmacotherapy. The analysis of actual practice of managing patients with HCC shows prevalence of drugs with no indications for usage from the point of view of the existing standards and recommendations (form 33% according to regional reimbursement to 58% according to Federal reimbursement). CONCLUSIONS: Developing of new standards of HCC treatment including target therapy can reduce the cost of illness by reducing off-label use and optimizing the treatment strategy.

Risk of upper gastrointestinal adverse events in Malaysian rheumatic patients on long-term non-steroidal antiinflammatorydrugs

Background: Non-steroidal anti-inflammatory drug (NSAID)-induced upper gastrointestinal (GI) adverse events are well-described in the Western population but data is lacking in Asian patients. This study aims to describe the incidence and predictive factors for NSAID-induced upper GI complications in a cohort of multi-ethnic patients in Malaysia. Methods and Findings: A retrospective cohort study was conducted in adult patients with rheumatoid arthritis (RA) and/or osteoarthritis (OA) from 2010-2013 in four main rheumatology centres in Malaysia with computerized clinical and pharmaceutical records. Clinical, pharmaceutical and demographic data over a 24-months follow-up period were analysed in subjects who were prescribed long-term NSAID therapy (defined as a minimum duration of four weeks). 634 patients were included in the final analysis with the following characteristics: mean age 53.4 ± 12.5 years, 89.9% female, diagnosis: RA 59.5%, OA 10.2% and RA/OA combination 30.3%. 371 (58.5%) patients received non-selective NSAIDs and 263 (41.5%) patients received COX-2 inhibitors. There were a total of 84 GI adverse events during the period of study, giving an incidence rate of 66.2 per 1000 person-years and a risk of 13.2%. The majority of upper GI adverse events was dyspepsia (92.9%), and only 7.1% with peptic ulcer disease/ upper GI bleeding. Multivariate analysis showed that the only independent predictive factor of upper GI adverse event in this cohort was a history of upper GI disease (O.R. 2.073, 95% C.I. 1.029 – 4.176). COX-2 inhibitor showed a trend towards, but not independently predictive of, GI protection in this analysis (OR 0.643; 95% C.I. 0.397 – 1.043). Conclusion: Malaysian rheumatic patients on long-term NSAID therapy, managed at referral centres, have a 13.2% risk of upper GI adverse events, with dyspepsia being the commonest complication. Patients with a history of upper GI disease were twice as likely to develop further upper GI adverse events with the use of long-term NSAIDs.

Projections of the Healthcare Costs and Disease Burden due to Hepatitis C Infection under Different Treatment Policies in Malaysia, 2018–2040

IntroductionThe World Health Organisation (WHO) has set ambitious goals to reduce the global disease burden associated with, and eventually eliminate, viral hepatitis.ObjectiveTo 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.MethodsWe 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.ResultsScenario 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