A real-world study to assess the association of cardiovascular adverse events (CVAEs) with ibrutinib as first-line (1L) treatment for patients with chronic lymphocytic leukaemia (CLL) in the United States.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, is often used as first-line (1L) treatment of chronic lymphocytic leukaemia (CLL); however, it is associated with an increased risk for cardiovascular adverse events (CVAEs). This real-world study adds to existing literature by simultaneously investigating the correlation between pre-existing CV risk factors and the relative cardiotoxicity of ibrutinib vs other therapies in CLL/small lymphocytic lymphoma (SLL). Using a real-world database, the risk of subsequent CVAEs (any CVAE, atrial fibrillation [AF], or hypertension) were compared among patients who received 1L ibrutinib monotherapy or another type of non-ibrutinib therapy, grouped as intensive (IT) or non-intensive therapy (NIT). Each patient's baseline CV risk was estimated using the Framingham risk score. Inverse probability treatment weighting was incorporated into a logistic regression model to reduce baseline imbalance. Results showed ibrutinib was significantly associated with higher risk of CVAEs regardless of baseline CV risk. Compared with IT, odds ratios of any CVAE, hypertension, or AF were 2.61, 3.66, and 3.02, respectively vs 1.88, 2.13, and 2.46, respectively, with NIT. Sensitivity analyses confirmed the findings were robust. These results suggest clinical caution should be taken when selecting ibrutinib for patients with CLL/SLL, especially in those with high baseline CV risk.

A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib.

Among patients with chronic lymphocytic leukemia (CLL) with deletion 17p (del[17p]), evidence from clinical trials for the effectiveness of single-agent ibrutinib as first-line therapy is limited. This retrospective analysis compared real-world clinical outcomes among patients with CLL, with and without del(17p), treated with first-line ibrutinib monotherapy. Overall survival, time to next treatment, time to treatment discontinuation, and reasons for ibrutinib discontinuation were evaluated. Using data from a real-world database, patients included were aged ≥18 years, had been diagnosed with CLL between January 1, 2011 and December 31, 2019, had undergone cytogenetic testing, and had received first-line ibrutinib monotherapy. A total of 1,069 patients were included in the analysis (62.7% male; median age 69 years); 23.8% (n=254) had del(17p). The median overall survival was significantly shorter in patients with del(17p) than in patients without (57.7 months vs. not reached; P=0.0006). Similar results were observed for median time to next treatment (49.4 months vs. not reached, P=0.0330). The median time to treatment discontinuation was non-significantly shorter in the group of patients with del(17p) (32.5 months vs. 42.9 months, P=0.3370). Results of an adjusted Cox proportional hazards model showed that the group with del(17p) was at significantly higher risk of death than was the group without del(17p) (hazard ratio=1.70, P=0.0031). Event rates for switching to new treatment and discontinuation were higher but not statistically significantly so. The most common reason for discontinuing ibrutinib treatment in both groups was toxicity, but discontinuation due to progression was significantly more frequent among patients with del(17p) (20% vs. 6%; P<0.0001). This study identifies an unmet need for more effective first-line therapeutic options in patients with CLL/small lymphocytic lymphoma and del(17p), despite the advent of ibrutinib.

Use of PD-1 and PD-L1 inhibitors after first-line therapy in esophageal cancer patients in the US.

INTRODUCTION: Esophageal cancer (EC) makes up 3.2% of all cancers but ranks sixth among cancer-related deaths worldwide. This real-world analysis determined the use of PD-1/PD-L1 (PD[L]1) inhibitors in EC patients after receiving first-line therapy. METHODS: Newly diagnosed EC patients initiating first-line treatment were identified in the IBM MarketScan administrative claims databases during the study period (1 May 2015 to 31 October 2020) using ICD-9/ICD-10 codes. Patients were assigned to either the chemotherapy only, radiation only, chemotherapy plus radiation (chemoradiation), or esophageal transhiatal/transthoracic surgery cohorts. RESULTS: 7276 EC patients started first-line therapy (chemotherapy only = 2502, radiation only = 3355, chemoradiation = 1180, surgery = 239). The average age at diagnosis was 62 years and 23% were female. The median time from start of first-line therapy to utilization of a PD(L)1 inhibitor was 259 days. Pembrolizumab (72%) was the most frequently used PD(L)1 inhibitor across the three cohorts, followed by nivolumab (25%). Furthermore, the number of patients receiving a PD(L)1 inhibitor increased each year with the majority (73%) of use occurring between 2018 and 2020. DISCUSSION: Findings from this real-world study suggest that PD(L)1 inhibitors are increasingly used after first-line therapies in EC, especially among patients initially receiving chemotherapy only. New immunological therapies such as PD(L)1 inhibitors hold great promise for patients with solid tumors. A clearer understanding of their real-world utilization is critical.

The Cost and Quality of Life of Malaysian Type 2 Diabetes Mellitus Patients with Chronic Kidney Disease and Anemia.

BACKGROUND: Anemia is common among patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) and an independent risk factor for renal disease progression. Health economic evidence is important in Malaysia and yet cost and quality-of-life (QOL) data are scarce. OBJECTIVES: To investigate prevalence, factors associated with anemia, and cost and QOL among T2DM patients with CKD. Here, we present the estimated 1-year cost and QOL related to anemia in this group. METHODS: A cross-sectional, observational study was performed at 20 government clinics. Treatment cost was calculated on the basis of resource utilization ascertained through data extracted from medical records and patient recall. QOL was elicited using the short form 36 health survey version 2 questionnaire. Propensity score matching was performed and costs and QOL were analyzed by anemia status and CKD stage. RESULTS: Data for 816 patients were obtained. The propensity score matching enabled a comparison of 257 patients with and without anemia. Annual treatment costs were significantly higher for patients with anemia (Ringgit Malaysia [RM] 4219 [US $983] vs. RM2705 [US $630]; P = 0.01). QOL scores were lower for patients with anemia but not statistically significant (physical component summary score: 44.8 vs. 46.2; P = 0.052; mental component summary score: 51.3 vs. 51.7; P = 0.562). Costs were higher and QOL lower among CKD stage 5 patients. CONCLUSIONS: This study was the first to examine anemia in this group of patients. Costs were significantly higher among anemic patients compared with nonanemic patients; patients with higher CKD stage 5 fared less well than did those in lower stages. This information suggests the need to increase detection, prevention, and early treatment of anemia when managing T2DM patients, particularly those with CKD.

Assessing the burden of pneumonia using administrative data from Malaysia, Indonesia, and the Philippines.

OBJECTIVES: To describe the incidence, mortality, cost, and length of stay (LOS) of hospitalized community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) in three Southeast Asian countries: Malaysia, Indonesia, and the Philippines. METHODS: Using Casemix system data from contributing hospitals, patients with International Classification of Diseases 10(th) revision (ICD-10) codes identifying pneumonia were categorized into CAP or HAP using a logical algorithm. The incidence among hospitalized patients, case fatality rates (CFR), mean LOS, and cost of admission were calculated. The population incidence was calculated based on Malaysian data. RESULTS: For every 100000 discharges, CAP and HAP incidences were 14245 and 5615 cases, respectively, in the Philippines, 4205 and 2187, respectively, in Malaysia, and 988 and 538, respectively, in Indonesia. The impact was greatest in the young and the elderly. The CFR varied from 1.4% to 4.2% for CAP and from 9.1% and 25.5% for HAP. The mean LOS was 6.1-8.6 days for CAP and 6.9-10.2 days for HAP. The cost of hospitalization was between USD 254 and USD 1208 for CAP and between USD 275 and USD 1482 for HAP. CONCLUSIONS: The burden of CAP and HAP is high. Results varied between the three countries, likely due to differences in socio-economic conditions, health system differences, and ICD-coding practices.

Cost-effectiveness study of pediatric atopic dermatitis in Asia: atopiclair vs. regular emollient (AD-ATOP).

BACKGROUND: Atopic dermatitis (AD) is a highly prevalent, chronic relapsing condition in childhood with significant financial burden and impact on the quality of life of patients and caregivers. Proactive maintenance treatment with moisturizing agents is the mainstay AD therapy. OBJECTIVES: The aim of this study was to assess the cost-effectiveness of a non-steroidal barrier cream (Atopiclair), compared to regular emollient in pediatric patients with mild-to-moderate AD. METHODS: A Markov decision model was developed to evaluate the cost-effectiveness of Atopiclair versus regular emollient in 12 Asia-Pacific countries, grouped by income categories based on gross domestic product (GDP) per capita. Data was obtained from structured literature review, expert opinion, fee schedules, and findings from a 2012 survey of 12 Asia-Pacific countries. Analysis was performed a societal perspective. RESULTS: In the base case analysis, Atopiclair was cost-effective against regular emollient, with USD786, USD499, and USD289 in cost savings per year for high, middle, and low-income countries, respectively. Sensitivity analyses showed that Atopiclair remained cost-effective versus regular emollient. CONCLUSIONS: Modelling analysis showed that Atopiclair is a cost-effective treatment compared to regular emollient for mild-to-moderate pediatric AD in the countries included in the study.

Quality of life among Patients with Acute Coronary Syndrome in Malaysia.

OBJECTIVES: This study's objectives were to estimate the quality of life (QOL) of Malaysian patients with acute coronary syndrome (ACS) during admission and at 12 months, to explore the factors associated with the QOL, and to compare utility scores derived from tariffs from local and foreign populations. METHODS: Data collected from patients with ACS between 2008 and 2009 for a study on cardiac rehabilitation at the Sarawak General Hospital were used for this study. QOL data were obtained using a validated version of the EuroQol five-dimensional questionnaire at baseline and at 12 months. Health utility scores were calculated using visual analogue scale scores and utility tariffs from Malaysia and the United Kingdom. RESULTS: Data from 104 subjects from the earlier study was used. The mean age was 56.1 years, with 88.5% being men. The mean hospitalization duration was 6.3 days. The mean utility score was 0.75 at baseline and 0.82 at 12 months. There was a statistically significant improvement in utility from baseline to 12 months based on the Malaysian tariff (P = 0.014) but not with the UK tariff (P = 0.086). The QOL of patients was associated with sex and diagnosis of ST-segment elevation myocardial infarction. CONCLUSIONS: Our results showed that there was a significant improvement in the QOL from baseline to 12 months. Only sex and diagnosis affected the QOL score at baseline because of limited variables available for testing. It also reconfirms the importance of applying the appropriate, country-specific utility tariffs in QOL studies. Despite limitations, the study is useful toward describing QOL among a group of Malaysian patients with ACS.

A review of accessibility of administrative healthcare databases in the Asia-Pacific region.

OBJECTIVE: We describe and compare the availability and accessibility of administrative healthcare databases (AHDB) in several Asia-Pacific countries: Australia, Japan, South Korea, Taiwan, Singapore, China, Thailand, and Malaysia. METHODS: The study included hospital records, reimbursement databases, prescription databases, and data linkages. Databases were first identified through PubMed, Google Scholar, and the ISPOR database register. Database custodians were contacted. Six criteria were used to assess the databases and provided the basis for a tool to categorise databases into seven levels ranging from least accessible (Level 1) to most accessible (Level 7). We also categorised overall data accessibility for each country as high, medium, or low based on accessibility of databases as well as the number of academic articles published using the databases. RESULTS: Fifty-four administrative databases were identified. Only a limited number of databases allowed access to raw data and were at Level 7 [Medical Data Vision EBM Provider, Japan Medical Data Centre (JMDC) Claims database and Nihon-Chouzai Pharmacy Claims database in Japan, and Medicare, Pharmaceutical Benefits Scheme (PBS), Centre for Health Record Linkage (CHeReL), HealthLinQ, Victorian Data Linkages (VDL), SA-NT DataLink in Australia]. At Levels 3-6 were several databases from Japan [Hamamatsu Medical University Database, Medi-Trend, Nihon University School of Medicine Clinical Data Warehouse (NUSM)], Australia [Western Australia Data Linkage (WADL)], Taiwan [National Health Insurance Research Database (NHIRD)], South Korea [Health Insurance Review and Assessment Service (HIRA)], and Malaysia [United Nations University (UNU)-Casemix]. Countries were categorised as having a high level of data accessibility (Australia, Taiwan, and Japan), medium level of accessibility (South Korea), or a low level of accessibility (Thailand, China, Malaysia, and Singapore). In some countries, data may be available but accessibility was restricted based on requirements by data custodians. CONCLUSIONS: Compared with previous research, this study describes the landscape of databases in the selected countries with more granularity using an assessment tool developed for this purpose. A high number of databases were identified but most had restricted access, preventing their potential use to support research. We hope that this study helps to improve the understanding of the AHDB landscape, increase data sharing and database research in Asia-Pacific countries.

The Cost and Utility of Renal Transplantation in Malaysia.

UNLABELLED: Kidney transplantation is the optimal therapy for the majority of patients with end-stage renal disease. However, the cost and health outcomes of transplantation have not been assessed in a middle-income nation with a low volume of transplantation, such as Malaysia. AIM AND METHODS: This study used microcosting methods to determine the cost and health outcomes of living and deceased donor kidney transplantation in adult and pediatric recipients. The perspective used was from the Ministry of Health Malaysia. Cost-effectiveness measures were cost per life year (LY) and cost per quality-adjusted LYs. The time horizon was the lifetime of the transplant recipient from transplant to death. RESULTS: Records of 206 KT recipients (118 adults and 88 children) were obtained for microcosting. In adults, discounted cost per LY was US $8609(Malaysian Ringgit [RM]29 482) and US $13 209(RM45 234) for living-donor kidney transplant (LKT) and deceased donor kidney transplant (DKT), respectively, whereas in children, it was US $10 485(RM35 905) and US $14 985(RM51 317), respectively. Cost per quality-adjusted LY in adults was US $8826 (RM30 224) for LKT and US $13 592(RM46 546) for DKT. Total lifetime discounted costs of adult transplants were US $119 702 (RM409 921) for LKT, US $147 152 (RM503 922) for DKT. Total costs for pediatric transplants were US $154 841(RM530 252) and US $159 313(RM545 566) for the 2 categories respectively. CONCLUSIONS: Both LKT and DKT are economically favorable for Malaysian adult and pediatric patients with ESRD and result in improvement in quality of life.

Prevalence of faecal incontinence and its related factors among patients in a Malaysian academic setting.

BACKGROUND: Prevalence data is essential for planning of healthcare services. The prevalence of faecal incontinence (FI) varies worldwide, and in Malaysia is not known. We sought to estimate its prevalence among patients with various conditions in a Malaysian academic setting. METHOD: A questionnaire-based survey was conducted among a convenience sample of adult patients and relatives who visited the Obstetrics and Gynaecology and General Surgery Clinics of University of Malaya Medical Centre (UMMC) from June 2009 to February 2010. Data collected included patient demographics and pre-existing medical conditions known to be FI risk factors. Severity of FI was assessed using the Wexner Continence Scale (WCS). RESULTS: Among the 1000 subjects recruited into the study, 760 (76%) were female and the median age was 38 years with an inter-quartile range of 24 years. The prevalence of FI among the study subjects was found to be 8.3%. Among them, 63 subjects (75.9%) were determined to have mild FI as measured by the WCS. The proportions of patients with moderate and severe FI were 18.3% and 6.0%, respectively. FI was found to be significantly associated with older age, presence of diabetes mellitus and increased duration of defaecation. There was no statistically significant association between FI and sex, defaecation frequency, or history of surgery. CONCLUSION: FI in our setting is prevalent enough to warrant targeted healthcare interventions, including the need to improve general public awareness of the condition in order to counter social stigma and embarrassment that may be faced by patients.

Economic Impact of Pneumococcal Protein-D Conjugate Vaccine (PHiD-CV) on the Malaysian National Immunization Programme.

OBJECTIVE: To assess the cost-effectiveness of introducing pneumococcal polysaccharide and nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in the National Immunization Programme of Malaysia. This study compared introducing PHiD-CV (10 valent vaccine) with current no vaccination, as well as against the alternative 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: A lifetime Markov cohort model was adapted using national estimates of disease burden, outcomes of pneumococcal disease, and treatment costs of disease manifestations including pneumonia, acute otitis media, septicemia, and meningitis for a hypothetical birth cohort of 550,000 infants. Clinical information was obtained by review of medical records from four public hospitals in Malaysia from the year 2008 to 2009. Inpatient cost from the four study hospitals was obtained from a diagnostic-related group-based costing system. Outpatient cost was estimated using clinical pathways developed by an expert panel. The perspective assessed was that of the Ministry of Health, Malaysia. RESULTS: The estimated disease incidence was 1.2, 3.7, 70, and 6.9 per 100,000 population for meningitis, bacteremia, pneumonia, and acute otitis media, respectively. The Markov model predicted medical costs of Malaysian ringgit (RM) 4.86 billion (US $1.51 billion) in the absence of vaccination. Vaccination with PHiD-CV would be highly cost-effective against no vaccination at RM30,290 (US $7,407) per quality-adjusted life-year gained. On comparing PHiD-CV with PCV13, it was found that PHiD-CV dominates PCV13, with 179 quality-adjusted life-years gained while saving RM35 million (US $10.87 million). CONCLUSIONS: It is cost-effective to incorporate pneumococcal vaccination in the National Immunization Programme of Malaysia. Our model suggests that PHiD-CV would be more cost saving than PCV13 from the perspective of the Ministry of Health of Malaysia.

Estimating an EQ-5D value set for Malaysia using time trade-off and visual analogue scale methods.

OBJECTIVES: To estimate a EQ-5D value set for Malaysia by using time trade-off (TTO) and visual analogue scale (VAS) valuation methods. METHODS: TTO and VAS valuations were obtained from face-to-face surveys of a convenience sample of patients, caregivers, and health professionals conducted at nine government hospitals in 2004 and 2005. Forty-five EQ-5D questionnaire health states were valued, divided into five sets of 15 health states. Analysis was conducted by using linear additive regression models applying N3 and D1 specifications. Model selection was based on criteria of coefficient properties, statistical significance, and goodness of fit. RESULTS: One hundred fifty-two respondents were interviewed, yielding 2174 TTO and 2265 VAS valuations. Respondents found TTO valuations to be more difficult than VAS valuations, and there were more inconsistencies in TTO valuations. All the independent variables in the models were statistically significant and consistent with expected signs and magnitude, except for the D1 specification modeled on TTO valuations. The N3 model provided the best fit for the VAS valuation data, with a mean absolute error of 0.032. CONCLUSION: This study provides a Malaysian EQ-5D questionnaire value set that can be used for cost-utility studies despite survey limitations.

Cost efficiency and cost effectiveness of cataract surgery at the Malaysian Ministry of Health ophthalmic services.

PURPOSE: To determine the cost efficiency and to compare the cost effectiveness of conventional extracapsular cataract surgery (ECCE) and phacoemulsification at three hospitals of the Malaysian Ministry of Health (MOH). METHODS: Patient demography, pre-operative visual acuity, intra-operative complications, post-operative complications and post-operative visual acuity were recorded for two hundred and forty seven of the 400 patients who underwent cataract surgery during a 2-week period. The cost of surgery, which included capital, staff and overhead, and patient care consumable costs were assessed prospectively in 8 randomly sampled patients over a 3-month period. Cost efficiency refers to cost per cataract surgery. Cost effectiveness refers to cost per successful cataract surgery. This is estimated by the ratio of cost efficiency to the proportion of successful cataract surgery. Successful surgery was defined as best-corrected visual acuity (BCVA) of better than 6/12 at 3 months post-operatively. RESULTS: Proportion of patients who had post-operative visual acuity of 6/12 or better was higher in phacoemulsification group (94%) than in the ECCE group (81%). Conventional extracapsular cataract surgery with intraocular lens implant costs RM3442 (USD 905.79) and phacoemulsification with intraocular lens implant costs RM4288 (USD 1128.42). DISCUSSION: There was no significant difference in cost effectiveness between ECCE and phacoemulsification. The cost of cataract surgery in the MOH hospital was found to be high due to the high overhead costs.