Unveiling the Biosimilar Paradox of Oncologists' Perceptions and Hesitations in South Korea: A Web-Based Survey Study.

INTRODUCTION: Biosimilars offer a cost-effective alternative to original biopharmaceuticals with comparable efficacy and safety. The perception and familiarity of prescribers toward biosimilars play a critical role in their market penetration. Yet, few studies have explored the perception of oncologists toward biosimilars, much less in Asia. OBJECTIVES: The objective of this study is to understand barriers of adopting biosimilars among oncologists and explore strategies to promote their use in clinical practice settings. METHODS: A web-based survey was conducted among Korean oncologists from September to October 2022, assessing their perception of biosimilars and prescribing practices. RESULTS: Among the 118 surveyed oncologists, 75.4% (89 out of 118) had previously prescribed biosimilars. When asked about their preference, 48.3% (57 out of 118) of the respondents preferred originators to biosimilars, whereas 16.1% (19 out of 118) favored biosimilars over the originators. The primary reason for preferring the originators was trust in safety and efficacy (94.7%, 54 out of 57). Still, a paradox was noted as 87.0% (47 out of 54) and 85.2% (46 out of 54) of these also acknowledged the comparable efficacy and safety of biosimilars. A relatively small number of the respondents (16.1%, 19 out of 118) did not consider prescribing biosimilars to biologic-naïve patients at all, and up to 56.8% (67 out of 118) expressed reluctance to switch prescriptions from originators to biosimilars. However, 90.7% (107 out of 118) of respondents considered changing their prescription to biosimilars if patients faced financial stress. Concerns regarding the efficacy when switching to biosimilars were expressed by 42.7% (38 out of 89) of oncologists with biosimilar prescribing experience, increasing to 69.0% (20 out of 29) among those without such experience. CONCLUSION: Korean oncologists perceived biosimilars to be as safe and effective as originators. However, there is a notable mismatch between this perception and their prescribing practices, particularly among those who have not prescribed biosimilars before. The financial burden of patients served as a significant driver for prescribing biosimilars, yet marginal price differences between originators and biosimilars may be associated with the low adoption rate of biosimilars in Korea. Active price competition may enhance market penetration of biosimilars.

Is the Availability of Biosimilar Adalimumab Associated with Budget Savings? A Difference-in-Difference Analysis of 14 Countries.

OBJECTIVE: The aim was to assess the influence of the presence of biosimilar adalimumab on adalimumab budget savings in 14 high- and upper-middle-income countries. METHODS: This study analyzed Multinational Integrated Data Analysis System (MIDAS)-IQVIA data from the fourth quarter (Q4) of 2018 to the Q4 of 2019, comparing adalimumab expenditure (in United States dollars) and consumption (in standard units [SU]) across 14 countries (Australia, Austria, Brazil, Canada, France, Germany, Italy, Japan, Korea, Singapore, South Africa, Spain, Sweden, and Taiwan). The countries were divided into two groups based on the availability of adalimumab biosimilars during the study period. A difference-in-difference design was employed to analyze the groups, focusing on changes from Q4 2018 to Q4 2019. Additionally, changes in adalimumab expenditure were decomposed into price, quantity, and drug mix during the study period. RESULTS: Among countries with adalimumab biosimilars, there was a significant decrease in expenditure (- $371.0 per gross domestic product per capita; p = 0.03) over four quarters, while the consumption significantly increased (1.0 SU per 1000 population; p = 0.02). This was consistent with visual observations and differed from countries without adalimumab biosimilar. Sensitivity analysis with a narrowed list of countries (12 high-income countries) showed a consistent trend. Adalimumab expenditure decreased by 14% during the study period in countries where adalimumab biosimilars were available, mainly due to the price changes (Pt = 0.85; - 15%) and the drug-mix effect (εt  = 0.88; - 12%). Yet, adalimumab expenditure (Et = 1.04; +4%) changed in a quantity-dependent manner (Qt = 1.06; +6%) in countries where adalimumab biosimilars were absent. CONCLUSION: The availability of biosimilars was associated with a decrease in adalimumab expenditure without compromising the consumption of adalimumab.

Price and Prejudice? The Value of Chimeric Antigen Receptor (CAR) T-Cell Therapy.

Although chimeric antigen receptor (CAR) T-cell therapy has shown a high response rate in lymphoma patients, its cost-effectiveness is controversial due to the high price and uncertainty of the clinical evidence. In addition to the high acquisition cost of CAR T-cell therapy, procedure and facility cost increase the financial burden considering the frequency of adverse events such as cytokine release syndrome. In clinical research, relatively short follow-up periods were used compared to traditional cancer agents. In addition, head-to-head comparative effectiveness data are unavailable, which is an important factor when evaluating the cost-effectiveness of a new treatment. Additional evidence that will compensate for the uncertainty of existing clinical data is needed for full evaluation of long-term efficacy, safety, and comparative effectiveness.

The Impact of Payment Scheme Changes on Medication Adherence and Persistence of Patients Diagnosed with Depression in Korea.

As of 1 July 2018, the Korean National Health Insurance Service (NHIS) changed the fee schedule for individual psychotherapy (IP). We sought to analyze the impact of the IP payment scheme changes on the medication adherence and persistence of patients diagnosed with depression in Korea. We utilized the NHIS claims database from 2017 to 2019. Patients who were newly diagnosed with depression and utilized IP and were prescribed antidepressants during the study period were included. Adherence was measured using the medication possession ratio (MPR), and persistence was measured using the length of therapy (LOT) during the follow-up period. Adherence and persistence during the pre-policy period (before the change of the payment scheme, from January 2018 until June 2018) and the post-policy period (after the change, from July 2018 until December 2019) were compared. During the study period, a total of 176,740 patients with depression were identified. The average MPR significantly increased from 0.20 to 0.33 in the pre- and post-policy periods, respectively (p < 0.001). The average LOT of the patients improved considerably from 36 to 56 days in the pre- and post-policy periods, respectively (p < 0.001). Poisson regression analysis showed that patients with depression who were female, 19-34 years of age (vs. 50-64 years or over 64 years), and in the post-policy period were significantly associated with greater adherence and persistence rates. Payment scheme changes were associated with an increased adherence and persistence of medication use among patients diagnosed with depression.

Cost-Effectiveness of Extending the National Influenza Vaccination Program in South Korea: Does Vaccination of Older Adults Provide Health Benefits to the Entire Population?

The South Korean government has successfully improved influenza vaccination coverage for individuals aged 65 years or older as part of its National Immunization Program (NIP). Those aged 50-64 years without funded vaccination care have significantly lower vaccination rates and face a substantial risk of influenza-related complications. We use a dynamic epidemiological and economic model to investigate the cost-effectiveness of expanding the universal vaccine fund to include those aged 50-64. The epidemiological model is estimated using the susceptibility-infection-recovery model and influenza and influenza-like illness incidence rates, which were calculated by the National Health Insurance Service-National Sample Cohort from the 2008/09 to 2012/13 influenza seasons but excluding the 2009/10 season for pandemic influenza A (H1N1). The decision tree economic model is assessed from societal and healthcare sector perspectives. The proposed policy would eliminate 340,000 annual influenza cases and prevent 119 unnecessary deaths. From a societal perspective, the proposed policy would reduce costs by USD 68 million. From a healthcare perspective, the cost is USD 4318 per quality-adjusted life years. Within the study range, sensitivity analyses found consistent cost-effectiveness results. The influenza vaccine for adults aged 50-64 appears to be cost-saving or cost-effective and, thus, should be considered for the NIP.

For Whom the Price Escalates: High Price and Uncertain Value of Cancer Drugs.

The price of cancer drugs has skyrocketed, yet it is not clear whether their value is commensurate with their price. More cancer drugs are approved under expedited review, which considers less rigorous clinical evidence, yet only 20% of them show an overall survival gain in the confirmatory trial. Moreover, clinical data are often generated based on small, single-arm studies with surrogate outcomes, challenging economic evaluation. With their high price and uncertain (marginal) clinical value, cancer drugs are frequently rejected by health technology assessment (HTA) bodies. Therefore, agencies, including the UK's National Institute for Health and Care Excellence (NICE), have adopted cancer drug funds (CDF) or risk-sharing schemes to provide extra access for expensive cancer drugs which fail to meet NICE's cost effectiveness threshold. With rising pricing and fewer new cancer medications with novel mechanisms of action, it is unclear if newly marketed cancer therapies address unmet clinical needs or whether we are paying too much. Transparency, equity, innovativeness, and sustainability are all harmed by a "special" approach for cancer medications. If early access is allowed, confirmatory trials within a certain time frame and economic evaluation should be conducted, and label changes or disinvestment should be carried out based on those evaluations.

Cost-Effectiveness of Influenza Vaccination Strategies in Adults: Older Adults Aged ≥65 Years, Adults Aged 50-64 Years, and At-Risk Adults Aged 19-64 Years.

The high disease burden of influenza in elderly and chronically ill adults may be due to the suboptimal effectiveness and mismatch of the conventional trivalent influenza vaccine (TIV). This study evaluated the cost-effectiveness of quadrivalent (QIV), adjuvanted trivalent (ATIV), and high-dose quadrivalent (HD-QIV) vaccines versus TIV used under the current Korean National Immunization Program (NIP) in older adults aged ≥65 years. We also evaluated the cost-effectiveness of programs for at-risk adults aged 19-64 and adults aged 50-64. A one-year static population model was used to compare the costs and outcomes of alternative vaccination programs in each targeted group. Influenza-related parameters were derived from the National Health Insurance System claims database; other inputs were extracted from the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed from a societal perspective. In the base case analysis (older adults aged ≥65 years), HD-QIV was superior, with the lowest cost and highest utility. Compared with TIV, ATIV was cost-effective (ICER $34,314/quality-adjusted life-year [QALY]), and QIV was not cost-effective (ICER $46,486/QALY). The cost-effectiveness of HD-QIV was robust for all parameters except for vaccine cost. The introduction of the influenza NIP was cost-effective or even cost-saving for the remaining targeted gr3oups, regardless of TIV or QIV.

Projecting Lifetime Health Outcomes and Costs Associated with the Ambient Fine Particulate Matter Exposure among Adult Women in Korea.

We sought to estimate the lifetime healthcare costs and outcomes associated with the exposure to the escalated concentration of fine particulate matter (particle size < 2.5 µm, PM2.5) among adult Korean women. We adapted a previously developed Markov model, and a hypothetical cohort composed of Korean women was exposed to either a standard (15 µg/m3) or increased (25 µg/m3) concentration of PM2.5. The time horizon of the analysis was 60 years, and the cycle length was 1 year. The outcomes were presented as direct healthcare costs and quality-adjusted life years (QALYs), and costs were discounted annually at 5%. Deterministic and probabilistic sensitivity analyses were performed. The model estimated that when the exposure concentration was increased by 10 µg/m3, the lifetime healthcare cost increased by USD 9309, which is an 11.3% increase compared to the standard concentration group. Women exposed to a higher concentration of PM2.5 were predicted to live 30.64 QALYs, compared to 32.08 QALYs for women who were exposed to the standard concentration of PM2.5. The tendency of a higher cost and shorter QALYs at increased exposure was consistent across a broad range of sensitivity analyses. The negative impact of PM2.5 was higher on cost than on QALYs and accelerated as the exposure time increased, emphasizing the importance of early intervention.

Validity of EQ-5D utility index and minimal clinically important difference estimation among patients with chronic obstructive pulmonary disease.

BACKGROUND: The discriminatory ability of multi-attribute utility (MAU) measures compared to condition-specific measures (CSM) in assessing health-related quality of life (HRQoL) among patients with chronic obstructive pulmonary disease (COPD) is an unsettled issue. This study investigated the quality of life of patients with COPD with three different HRQoL instruments and examined whether they could differentiate between adjacent severity groups in a statistically and clinically meaningful manner. In the process, the minimal clinically important differences (MCID) of the EQ-5D utility index were estimated. METHODS: Cross-sectional survey data were collected from patients with mild to very severe COPD in South Korea. In addition to demographic and clinical information, the following HRQoL questionnaires were used: The three-level five-dimensional Euro-Quality of Life tool (EQ-5D-3L), the EQ-Visual Analog Scale (EQ-VAS), and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). Patients' health-related quality of life was analyzed with reference to severity groups based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. To investigate the discriminatory ability of the HRQoL instruments between COPD severity groups, tests examining variance, covariance, and standardized mean difference were performed. After estimating the MCID of the EQ-5D utility index using the anchor-based method, we investigated whether the differences in the EQ-5D utility scores between groups exceeded the clinically meaningful minimum level. RESULTS: A total of 298 patients completed this study. All the quality of life scores showed statistically significant differences between the GOLD severity groups. The pooled MCID estimate for the EQ-5D utility index was 0.028 (range: 0.017-0.033). Even after adjusting for other factors affecting quality of life, the EQ-5D utility index differentiated the GOLD groups well. CONCLUSIONS: We conclude that the EQ-5D utility index is a valid instrument for measuring the quality of life of patients with COPD, and the pooled MCID estimate for the EQ-5D utility index was 0.028.

Mapping analysis to estimate EQ-5D utility values using the COPD assessment test in Korea.

BACKGROUND: There is no research on mapping algorithms between EQ-5D and COPD assessment test (CAT) in Korea. The purpose of this study was to develop mapping algorithms that predict EQ-5D-3 L utility from the CAT in patients with COPD. METHODS: Survey data of 300 COPD patients were collected from three tertiary teaching hospitals in Korea. To predict EQ-5D-3 L utility from the CAT, various models were assessed. Models were developed using randomly split training samples. Subsequently, the models were validated based on root mean square error (RMSE) and mean absolute error (MAE) in validation samples. The models were also validated using the bootstrap method, which involves iterative splitting, training, and validating of the sample data at least 10,000 times. Average RMSEs and MAEs were used as criteria for model selection. RESULTS: The recommended mapping algorithms were based on ordinary least squares (OLS) regression models, which revealed five CAT items (chest tightness, breathlessness, activity, leaving home, and energy) as statistically significant on the EQ-5D-3 L. The mapping models estimated the overall mean of EQ-5D-3 L utilities effectively, but EQ-5D-3 L utilities for severe (low utility) patients (< 0.6) were overestimated as the observed EQ-5D-3 L utilities were often distributed over 0.6. CONCLUSION: Mapping algorithms can be used to predict EQ-5D-3 L utilities from the CAT. However, mapping algorithms should be used cautiously when applied to groups with greater disease severity.

Cost-effectiveness of influenza vaccine strategies for the elderly in South Korea.

OBJECTIVES: Despite a high vaccine uptake rate of over 80% in South Korea, the disease burden of influenza is still high among the elderly, which may be due to low effectiveness of vaccines. Therefore, the cost-effectiveness of use among the elderly was analyzed in order to compare the current trivalent influenza vaccine (TIV) with a quadrivalent influenza vaccine (QIV) or MF59-adjuvanted trivalent influenza vaccine (ATIV). METHODS: A static lifetime Markov model was used. It was assumed that the model would be repeated until individuals reached the age of 100. Cost-effectiveness was analyzed across three age groups (65-74 years, 75-84 years, and ≥85 years), and the at-risk group was studied. RESULTS: Compared to the TIV, the QIV was expected to reduce the number of influenza infections by 342,873, complications by 17,011, hospitalizations by 8,568, and deaths by 2,031. The QIV was highly cost-effective when compared to the TIV, with a base case incremental cost-effectiveness ratio (ICER) estimated at USD 17,699/QALY (1USD = 1,151KRW), and the ICER decreased with age and was USD 3,431/QALY in the group aged 85 and above. Sensitivity analysis revealed that the ICER was sensitive to the QIV price, the proportion of influenza B, and vaccine mismatching. On the other hand, the ATIV was expected to reduce the number of influenza cases and complications by 1,812,395 and 89,747, respectively, annually, yielding cost-saving among all ages. ATIV price and vaccine efficacy were the most influential parameters for the ICER of ATIV. CONCLUSIONS: The QIV and ATIV strategies were considered more cost-effective in comparison to the TIV for vaccination strategies implemented for the elderly. However, owing to a lack of data on the effectiveness of ATIV among the elderly, a large-scale effectiveness study is required.

Nanostructured mucoadhesive microparticles for enhanced preocular retention.

We describe nanostructured microparticles (NMs) containing a mucoadhesive polymer for enhanced preocular retention and consider them as potential carriers of drugs to the eye. These NMs are each composed of entangled nanofibers to give an enlarged specific surface area, and thus can better adhere to the preocular mucus surface. This physical design allows the microparticles still to be composed mainly of a wall material, poly(lactic-co-glycolic acid), as required for controlled drug delivery, while the effects of an additive, mucoadhesive material, polyethylene glycol, can be synergistically improved via the nanostructured morphology. Thus, when formulated in a dry tablet dosage form, the NMs in this work show more than a 10-fold increase in preocular retention in vivo compared to conventional spherical microparticles. Therefore, we conclude that these mucoadhesive NMs can reside on the preocular surface for a prolonged period, and thus appear to be a promising system for topical drug delivery to the eye.