Medications influencing the risk of fall-related injuries in older adults: case-control and case-crossover design studies.

BACKGROUND: Medications influencing the risk of fall-related injuries (FRIs) in older adults have been inconsistent in previous guidelines. This study employed case-control design to assess the association between FRIs and medications, and an additional case-crossover design was conducted to examine the consistency of the associations and the transient effects of the medications on FRIs. METHODS: This study was conducted using a national claims database (2002-2015) in Korea. Older adults (≥ 65 years) who had their first FRI between 2007 and 2015 were matched with non-cases in 1:2 ratio. Drug exposure was examined for 60 days prior to the date of the first FRI (index date) in the case-control design. The hazard period (1-60 days) and two control periods (121-180 and 181-240 days prior to the index date) were investigated in the case-crossover design. The risk of FRIs with 32 medications was examined using conditional logistic regression after adjusting for other medications that were significant in the univariate analysis. In the case-crossover study, the same conditional model was applied. RESULTS: In the case-control design, the five medications associated with the highest risk of FRIs were muscle relaxants (adjusted odd ratio(AOR) = 1.35, 95% confidence interval (CI) = 1.31-1.39), anti-Parkinson agents (AOR = 1.30, 95%CI = 1.19-1.40), opioids (AOR = 1.23, 95%CI = 1.19-1.27), antiepileptics (AOR = 1.19, 95%CI = 1.12-1.26), and antipsychotics (AOR = 1.16, 95%CI = 1.06-1.27). In the case-crossover design, the five medications associated with the highest risk of FRIs were angiotensin II antagonists (AOR = 1.87, 95%CI = 1.77-1.97), antipsychotics (AOR = 1.63, 95%CI = 1.42-1.83), anti-Parkinson agents (AOR = 1.58, 95%CI = 1.32-1.85), muscle relaxants (AOR = 1.42, 95%CI = 1.35-1.48), and opioids (AOR = 1.35, 95%CI = 1.30-1.39). CONCLUSIONS: Anti-Parkinson agents, opioids, antiepileptics, antipsychotics, antidepressants, hypnotics and sedatives, anxiolytics, muscle relaxants, and NSAIDs/antirheumatic agents increased the risk of FRIs in both designs among older adults. Medications with a significant risk only in the case-crossover analysis, such as antithrombotic agents, calcium channel blockers, angiotensin II antagonists, lipid modifying agents, and benign prostatic hypertrophy agents, may have transient effects on FRIs at the time of initiation. Corticosteroids, which were only associated with risk of FRIs in the case-control analysis, had more of cumulative than transient effects on FRIs.

Use of budget savings from patent expiration of cancer drugs to improve affordability and accessibility.

BACKGROUND: The introduction of generics after the loss of patent exclusivity plays a major role in budget savings by significantly decreasing drug prices. The aims of this study were to estimate the budget savings from off-patent cancer drugs in 2020-2024 and to inform decision makers on how these savings could be used to improve the affordability of innovative cancer treatments in South Korea. METHODS: A model was developed to calculate budget savings from off-patent cancer drug use in Korea over 5 years (2020-2024). Cancer drugs with one or more valid patents that expire between 2020 and 2024 in Korea were selected. Key input parameters in the model included market share of generics, market growth, and prices of originators and generics. To reflect market dynamics after patent expiration, the trends of the off-patent market were estimated using historical sales volume data of IQVIA from 2012 to 2018. The study assumed that the prices of off-patent drugs decreased according to the price regulations set by the Korean government and that the off-patent market sales volume did not grow. Sensitivity analyses were performed to investigate the uncertainty in model input parameters. RESULTS: A total of 24 cancer drugs which met selection criteria were identified. In the base case analysis, patent expiration of cancer drugs between 2020 and 2024 could lead to a spending reduction of ₩234,429 million ($203 million), which was 20% of the cancer drug expenditure in the 5-year period. The savings ranged from ₩157,633 million ($136 million) to ₩434,523 million ($376 million) depending on the scenarios in sensitivity analyses. CONCLUSIONS: The findings indicate that patent loss of cancer drugs could lead to a 20% reduction in spending on cancer drugs over the next 5 years in South Korea. The savings could be used to improve the affordability of innovative, advanced cancer drugs for 94,000 cancer patients by reallocating the budget savings from patent expiration.

The risk of vancomycin toxicity in patients with liver impairment.

BACKGROUND: The influence of liver disease on the pharmacokinetic profile, the risk of acute kidney injury, and excessive drug exposure in patients treated with vancomycin was examined. METHODS: A retrospective cohort study was performed with patients discharged from a medical center between January 2011 and June 2018 who received vancomycin therapy. Patients were stratified according to liver dysfunction (no to mild liver dysfunction (NMLD) and moderate to severe liver dysfunction (MSLD) based on the Child-Pugh score. The risk of acute kidney injury was compared between patients who were stratified by the attainment of a target serum trough concentration (10 mg/dL to 20 mg/dL) and the vancomycin ratio formed between the area under the curve and minimum inhibitory concentration. The impact of liver dysfunction and a daily dose of vancomycin on the risk of acute kidney injury and vancomycin AUC:MIC > 600 were tested using logistic regression with and without adjusting for the study variables. RESULTS: A total of 408 patients empirically treated with vancomycin were included in this study (237 with NMLD and 171 with MSLD). Mean vancomycin trough concentrations (17.5 ± 8.4 mg/dL versus 15.3 ± 5.2 mg/dL, p = 0.0049) and AUC:MIC ratios (549.4 ± 217.2 versus 497.5 ± 117.3, 0.0065) were significantly higher in the MSLD group when compared to the NMLD group, respectively. Vancomycin clearance was also lower in the MSLD group and corresponded to a longer half-life. The proportion of patients who developed acute kidney injury was greater in patients with MSLD when compared to NMLD (7.6% versus 3.8%, respectively; p = 0.0932); however, the difference was statistically insignificant. Furthermore, supratherapeutic serum trough concentrations and AUC:MIC ratios were more common in the MSLD group versus the NMLD group (27.5% versus 13.9%, p = 0.0007 and 28.7% versus 17.3%, respectively; p = 0.0063). CONCLUSIONS: MSLD correlates with an increased risk of supratherapeutic vancomycin exposure. Although patients with MSLD had a higher risk of acute kidney injury, the difference was not significant.

Osteoporotic Fractures of the Spine, Hip, and Other Locations after Adjuvant Endocrine Therapy with Aromatase Inhibitors in Breast Cancer Patients: a Meta-analysis.

BACKGROUND: Aromatase inhibitors (AIs) play an important role in the endocrine therapy of postmenopausal breast cancer patients, with a recent tendency to extend the duration of their use. However, AIs may increase the risk of osteoporotic bone fractures. This meta-analysis evaluated the risk of osteoporotic fractures of the hip, spine, and other locations in breast cancer patients using AIs. METHODS: We performed a systematic search to identify randomized controlled clinical trials that investigated osteoporotic fractures in breast cancer patients on AI therapy. The main outcomes were the incidence and risk of osteoporotic fractures in general and of hip, vertebral, and non-vertebral fractures in AI users and controls. RESULTS: The systematic review found a total of 30 randomized controlled trials including 117,974 participants. The meta-analysis showed a higher incidence of osteoporotic fracture in AI users: The crude risk ratio for all osteoporotic fractures was 1.35 (95% confidence interval [CI], 1.29-1.42; P < 0.001), for hip fractures 1.18 (95% CI, 1.02-1.35; P < 0.001), for vertebral fractures 1.84 (95% CI, 1.36-2.49; P < 0.001), and for non-vertebral fractures 1.18 (95% CI, 1.02-1.35; P < 0.001), respectively, compared to the controls. CONCLUSION: Our meta-analysis suggested an increased risk of osteoporotic fractures for AI therapy in patients with breast cancer that was most expressed for vertebral fractures. Breast cancer patients on AIs need to be monitored for osteoporosis and osteoporotic fractures, and active prevention measures should be implemented.

The association of socioeconomic and clinical characteristics with health-related quality of life in patients with psoriasis: a cross-sectional study.

BACKGROUND: This study aimed to determine the socioeconomic and clinical characteristics affecting health-related quality of life (HRQoL) in patients with psoriasis. METHODS: A cross-sectional study was conducted between March and June 2015 using data obtained via an Internet-based survey completed by a psoriasis patient group in Korea. The survey included items regarding demographic, socioeconomic, and clinical characteristics and HRQoL. Patients' HRQoL impairment was classified as severe if their Dermatology Life Quality Index Scores were ≥ 11. Factors influencing HRQoL impairment were identified using multivariate logistic regression analysis. RESULTS: Of the 299 respondents, 161 (53.8%) exhibited severe HRQoL impairment. The Dermatology Life Quality Index scores were significantly associated with gender, annual income, neck psoriasis, psoriasis-related resignation from work, and use of oral and herbal medications. The severity of HRQoL impairment in women was twice that observed in men (odds ratio [OR] = 2.00, 95% confidence interval (CI): 1.05-3.80). Patients with psoriasis on the neck exhibited significantly greater HRQoL impairment than those with psoriasis on other areas of their bodies (OR = 2.30, 95% CI: 1.20-4.43). With respect to the socioeconomic status, patients who earned > 40 million KRW (approximately 34,000 USD; high-income group) showed less HRQoL impairment compared with those who had lower incomes (OR = 0.47, 95% CI: 0.28-0.80). Patients with severe HRQoL impairment used oral (OR = 2.04, 95% CI: 1.20-3.44) and herbal (OR = 1.86, 95% CI: 1.04-3.34) medications more often relative to patients with less severe HRQoL impairment. CONCLUSIONS: HRQoL in patients with psoriasis was significantly associated with their demographic and socioeconomic characteristics and employment status. The presence of psoriasis on exposed areas of the body was significantly associated with patients' HRQoL and employment status. Further research is required to evaluate the impact of psoriasis on patients' productivity.

Mediation effects of medication information processing and adherence on association between health literacy and quality of life.

BACKGROUND: To examine whether medication related information processing defined as reading of over-the-counter drug labels, understanding prescription instructions, and information seeking-and medication adherence account for the association between health literacy and quality of life, and whether these associations may be moderated by age and gender. METHODS: A sample of 305 adults in South Korea was recruited through a proportional quota sampling to take part in a cross-sectional survey on health literacy, medication-related information processing, medication adherence, and quality of life. Descriptive statistics and structural equation modeling (SEM) were performed. RESULTS: Two mediation pathways linking health literacy with quality of life were found. First, health literacy was positively associated with reading drug labels, which was subsequently linked to medication adherence and quality of life. Second, health literacy was positively associated with accurate understanding of prescription instructions, which was associated with quality of life. Age moderation was found, as the mediation by reading drug labels was significant only among young adults whereas the mediation by understanding of medication instruction was only among older adults. CONCLUSION: Reading drug labels and understanding prescription instructions explained the pathways by which health literacy affects medication adherence and quality of life. The results suggest that training skills for processing medication information can be effective to enhance the health of those with limited health literacy.

Daily Mean Temperature and Urolithiasis Presentation in Six Cities in Korea: Time-Series Analysis.

Seasonal variation in urinary stone presentation is well described in the literature. However, previous studies have some limitations. To explore overall cumulative exposure-response and the heterogeneity in the relationships between daily meteorological factors and urolithiasis incidence in 6 major Korean cities, we analyzed data on 687,833 urolithiasis patients from 2009 to 2013 for 6 large cities in Korea: Seoul, Incheon, Daejeon, Gwangju, Daegu, and Busan. Using a time-series design and distributing lag nonlinear methods, we estimated the relative risk (RR) of mean daily urolithiasis incidence (MDUI) associated with mean daily meteorological factors, including the cumulative RR for a 20-day period. The estimated location-specific associations were then pooled using multivariate meta-regression models. A positive association was confirmed between MDUI and mean daily temperature (MDT), and a negative association was shown between MDUI and mean daily relative humidity (MDRH) in all cities. The lag effect was within 5 days. The multivariate Cochran Q test for heterogeneity at MDT was 12.35 (P = 0.136), and the related I² statistic accounted for 35.2% of the variability. Additionally, the Cochran Q test for heterogeneity and I² statistic at MDHR were 26.73 (P value = 0.148) and 24.7% of variability in the total group. Association was confirmed between daily temperature, relative humidity and urolithiasis incidence, and the differences in urolithiasis incidence might have been partially attributable to the different frequencies and the ranges in temperature and humidity between cities in Korea.

The evolving value assessment of cancer therapies: Results from a modified Delphi study.

The move toward early detection and treatment of cancer presents challenges for value assessment using traditional endpoints. Current cancer management rarely considers the full economic and societal benefits of therapies. Our study used a modified Delphi process to develop principles for defining and assessing value of cancer therapies that aligns with the current trajectory of oncology research and reflects broader notions of value. 24 experts participated in consensus-building activities across 5 months (16 took part in structured interactions, including a survey, plenary sessions, interviews, and off-line discussions, while 8 participated in interviews). Discussion focused on: 1) which oncology-relevant endpoints should be used for assessing treatments for early-stage cancer and access decisions for early-stage treatments, and 2) the importance of additional value components and how these can be integrated in value assessments. The expert group reached consensus on 4 principles in relation to the first area (consider oncology-relevant endpoints other than overall survival; build evidence for endpoints that provide earlier indication of efficacy; develop evidence for the next generation of predictive measures; use managed entry agreements supported by ongoing evidence collection to address decision-maker evidence needs) and 3 principles in relation to the second (routinely use patient reported outcomes in value assessments; assess broad economic impact of new medicines; consider other value aspects of relevance to patients and society).

Comparison of three societally derived health-state classification values among older African Americans with depressive symptoms.

PURPOSE: To compare societal values across three health-state classification systems in older African Americans with depression and to describe the association of these instruments to depression severity. METHODS: We summarized baseline values for EQ-5D (US weights) and HUI2/3 (Canadian weights) and their subscales for 118 older African American participants enrolled in a randomized depression treatment trial and calculated correlations between the different instruments. We evaluated ceiling and floor effects for each instrument by comparing the proportion at the highest and lowest possible score for each tool. Also, utility scores were assessed by level of depression severity (mild, moderate, moderate severe, severe) scores as measured by the Patient Health Questionnaire (PHQ-9). RESULTS: Mean utility values were 0.58 (SD = 0.21) for EQ-5D, 0.52 (SD = 0.21) for HUI2, and 0.36 (SD = 0.31) for HUI3. For the EQ-5D, 72 % of participants reported having some problems on the anxiety/depression domain. On the emotion domain for the HUI2, 23 % reported the highest level of impairment compared to only 3 % on the HUI3. No participant scored at the floor for the EQ-5D, HUI2, or HUI3 index; one participant scored at the ceiling value on the HUI3 index. Correlations ranged from 0.63 to 0.82 (all of which were significant at an alpha level of 0.05). In general, utility scores trended inversely with depression level. CONCLUSION: Small differences in the three preference-weighted health-state classification systems were evident for this sample of older African Americans with depressive symptoms, with HUI scores lower than EQ-5D. For this sample, utility scores were lower (i.e., poorer) than the general United States population with depression on each utility measure.

Cost Effectiveness of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Patients with Knee Osteoarthritis.

OBJECTIVES: The aim of this study was to assess the cost effectiveness of allogeneic umbilical cord blood-derived mesenchymal stem cells with sodium hyaluronate (hUCB-MSC) compared with microfracture in patients with knee cartilage defects caused by osteoarthritis (OA) in South Korea. METHODS: A partitioned survival model approach was taken consisting of five mutually exclusive health states: excellent, good, fair, poor, and death over a 20-year time horizon. Utility values were obtained from a randomized clinical trial. Cost data were extracted from a database provided by the Health Insurance Review & Assessment Service, and the utilization of healthcare services was estimated from an expert panel of orthopedic surgeons using a structured questionnaire. The incremental cost-effectiveness ratio (ICER) in terms of quality-adjusted life-years (QALY) was calculated. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case, the incremental costs of US$14,410 for hUCB-MSC therapy along with its associated QALY gain of 0.857 resulted in an ICER of US$16,812 (₩18,790,773) per QALY (95% confidence interval [CI] US$13,408-US$20,828) when compared with microfracture treatment from a healthcare payer perspective. From a societal perspective, the ICER was US$268 (₩299,255) per QALY (95% CI -US$2915 to US$3784). When using a willingness-to-pay threshold of US$22,367/QALY, the probability of hUCB being cost effectiveness compared with microfracture was 99% from the healthcare payer perspective and 100% from the societal perspective. CONCLUSIONS: The study demonstrated that hUCB-MSC therapy was cost effective compared with microfracture when treating patients with knee OA. These findings should inform health policy decision makers about considerations for cost-effective therapy for treating knee OA to ultimately enhance population health.

Nurses' practice environments, error interception practices, and inpatient medication errors.

PURPOSE: Medication errors remain a threat to patient safety. Therefore, the purpose of this study was to determine the relationships among characteristics of the nursing practice environment, nurse staffing levels, nurses' error interception practices, and rates of nonintercepted medication errors in acute care hospitals. DESIGN: This study, using a nonexperimental design, was conducted in a sample of 82 medical-surgical units recruited from 14 U.S. acute care hospitals. Registered nurses (RNs) on the 82 units were surveyed, producing a sample of 686 staff nurses. METHODS: Data collected for the 8-month study period included the number of medication errors per 1,000 patient days and the number of RN hours per patient day. Nurse survey data included the Practice Environment Scale of the Nursing Work Index as a measure of environmental characteristics; a metric of nurses' interception practices was developed for the study. All survey measures were aggregated to the unit level prior to analysis with hierarchical linear modeling. FINDINGS: A supportive practice environment was positively associated with error interception practices among nurses in the sample of medical-surgical units. Importantly, nurses' interception practices were inversely associated with medication error rates. CONCLUSIONS: A supportive practice environment enhances nurses' error interception practices. These interception practices play a role in reducing medication errors. CLINICAL RELEVANCE: When supported by their practice environments, nurses employ practices that can assist in interrupting medication errors before they reach the patients.

Health Literacy Level and Comprehension of Prescription and Nonprescription Drug Information.

The aim of this study was to investigate the level of misunderstanding of medication information in Korean adults after stratifying by level of health literacy and to identify the factors influencing the misunderstanding of medication information and reading amounts of information on OTC drug labels. A cross-sectional survey was performed with 375 adult participants using the survey instrument. Multiple linear regression analyses were performed to identify factors which influence misunderstanding of medication information. Participants misunderstood 20% of words on OTC drug labels, 9% of prescription drug instructions, and 9% of pictograms. Participants on average read 59% of the overall contents of the OTC drug labels. As prescription drugs' dosing regimens became more complicated, the level of misunderstanding instructions increased. The level of misunderstanding words on OTC drug labels significantly decreased as participants had adequate health literacy (ß = −18.11, p < 0.001) and higher education levels (ß = −6.83, p < 0.001), after adjusting for the study variables. The level of misunderstanding instructions for prescription drugs increased as participants became older (ß = 8.81, p < 0.001) and had lower education levels (ß = −5.05, p < 0.001), after adjusting for the study variables. The level of misunderstanding pictograms was similar to that of misunderstanding instructions for prescription drug labels. The amount of reading information on OTC drug labels significantly increased as respondents had adequate health literacy (ß = 9.27, p < 0.001), were older (ß = 12.49, p < 0.001), or had chronic diseases (ß = 7.49, p = 0.007). Individuals' health literacy level, reading behaviors, and complexity of medication instructions are associated with misunderstanding of medication information. Appropriate word choices in drug labels and an improved format of medication instructions could increase understanding of medication information and prevent adverse drug reactions.

Risk of Fall-Related Injuries Associated with Antidepressant Use in Elderly Patients: A Nationwide Matched Cohort Study.

Previous studies have reported a higher risk of falls among tricyclic antidepressant (TCA) users compared to selective serotonin reuptake inhibitor (SSRI) users, yet SSRIs are known as a safer antidepressant class for use in older adults. This study examined the effects of antidepressant use on the risk of fall-related injuries after classifying antidepressant drugs, polypharmacy, and central nervous system (CNS) drugs by therapeutic classes and identifying factors influencing risk of fall-related injuries. A retrospective matched cohort study based on propensity scores was conducted among older adults, aged 70-89 years, who initiated antidepressant use between 1 January 2012 and 31 December 2014 using the national health insurance system senior cohort in Korea. The proportional hazard Cox regression model was used to examine the association between fall-related injuries and antidepressants. The subgroup analyses were performed to assess the risk of fall-related injuries by the number of concurrently administered medications, therapeutic classes of antidepressants, and CNS class medications. This study found that duloxetine, escitalopram, paroxetine, amitriptyline, imipramine, and trazodone significantly increased the risk of fall-related injuries in older adults. When antidepressants were prescribed to older adults, prescribers carefully considered factors including the dose, number of concurrently administered medications, and therapeutic classes of CNS.

Validation of Operational Definition to Identify Patients with Osteoporotic Hip Fractures in Administrative Claims Data.

As incidences of osteoporotic hip fractures (OHFs) have increased, identifying OHFs has become important to establishing the medical guidelines for their management. This study was conducted to develop an operational definition to identify patients with OHFs using two diagnosis codes and eight procedure codes from health insurance claims data and to assess the operational definition's validity through a chart review. The study extracted data on OHFs from 522 patients who underwent hip surgeries based on diagnosis codes. Orthopedic surgeons then reviewed these patients' medical records and radiographs to identify those with true OHFs. The validities of nine different algorithms of operational definitions, developed using a combination of three levels of diagnosis codes and eight procedure codes, were assessed using various statistics. The developed operational definition showed an accuracy above 0.97 and an area under the receiver operating characteristic curve above 0.97, indicating excellent discriminative power. This study demonstrated that the operational definition that combines diagnosis and procedure codes shows a high validity in detecting OHFs and can be used as a valid tool to detect OHFs from big health claims data.

The Effect of Extracorporeal Shock Wave Therapy on Pain Intensity and Neck Disability for Patients With Myofascial Pain Syndrome in the Neck and Shoulder: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of the study was to investigate the efficacy of extracorporeal shock wave therapy on myofascial pain syndrome in the neck and shoulder compared with that of other treatments. DATA SOURCES: PubMed, Embase, and Web of Science were systematically searched until May 30, 2019, to select randomized controlled trials. REVIEW METHODS: The randomized controlled trials comparing extracorporeal shock wave therapy with sham extracorporeal shock wave therapy or other treatments for patients with myofascial pain syndrome in the neck and shoulder patients were included. Two reviewers independently identified eligible studies. The Cochrane Handbook was used to evaluate the methodological quality of the included randomized controlled trials. Main outcomes associated with pain intensity, pressure pain threshold, and neck disability were selected. The study was registered with PROSPERO (Registration Number CRD 42019137459). RESULTS: A total of 11 randomized controlled trials were finally included. The results indicated that extracorporeal shock wave therapy had a large effect size on improving pain intensity (standardized mean difference [SMD] = 0.67, 95% confidence interval = 0.11 to 1.23, P = 0.02) and pressure pain threshold (SMD = 1.19, 95% confidence interval = 0.27 to l2.12, P = 0.01) at postintervention. However, there was no significant effect on neck disability at postintervention (SMD = 0.03, 95% confidence interval = -0.76 to 0.83, P = 0.93). After the subgroup analyses on the type of extracorporeal shock wave therapy, focused extracorporeal shock wave therapy had a significant effect on improving pain intensity (SMD = 0.75, 95% confidence interval = 0.13 to 1.36, P = 0.02) and pressure pain threshold (SMD = 1.70, 95% confidence interval = 0.21 to 3.18, P = 0.03) at postintervention in comparison with that of other treatments. CONCLUSIONS: Extracorporeal shock wave therapy is superior to other treatments in terms of alleviating the pain intensity and pressure pain threshold of patients with myofascial pain syndrome in the neck and shoulder at postintervention. In particular, focused extracorporeal shock wave therapy shows significant improvement in pain relief. However, radical extracorporeal shock wave therapy for myofascial pain syndrome treatment still remains unclear.

Effect of Treatment with the PD-1/PD-L1 Inhibitors on Key Health Outcomes of Cancer Patients.

BACKGROUND: Recent studies have shown that treatment with the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor class could significantly improve survival outcomes in several oncology indications. However, there is some clinical uncertainty. OBJECTIVE: This study aimed to obtain high-level estimates of the impact of treatment with PD-1/PD-L1 inhibitor class to oncology treatment on key health outcomes in real-world situations and to inform public health policy decisions about cancer care after reducing uncertainties around new immuno-oncology therapy options in South Korea. METHODS: A model was developed to estimate the impact of PD-1/PD-L1 inhibitors on outcomes in situations wherein both anti-PD-1/PD-L1s and standard of care (SOC) were available versus SOC only. A partitioned survival model was utilized to estimate the impact of introducing anti-PD-1/PD-L1s on outcomes, including life-years gained, quality-adjusted life-years gained, progression-free survival-years obtained, and grade 3 or higher adverse events avoided for six indications over 5 years. An exponential distribution was fitted to the survival function of the SOC based on visual inspection. Outcomes associated with anti-PD-1/PD-L1s were estimated using a piecewise modeling approach with Kaplan-Meier analysis followed by best-fitting survival analysis. The incident number of patients and market share of anti-PD-1/PD-L1s during 2020-2024 were projected using published literature and Korean market survey data. Sensitivity analyses were performed to test the uncertainty of input parameters. RESULTS: During the next 5-year period (2020-2024), introducing the anti-PD-1/PD-L1 class led to a gain of 22,001 life-years (+ 31%), 19,073 quality-adjusted life-years (+ 38%), and 22,893 progression-free survival-years (+ 82%); it also avoided 3610 adverse events (- 11%) compared with SOC alone. Most adverse events associated with anti-PD-1/PD-L1s were attributed to combination therapy with cytotoxic chemotherapy (91%). In a scenario wherein the time to reimbursement of the anti-PD-1/PD-L1s was accelerated by 1 year, the life-years gained increased by 14% compared with the base-case scenario. CONCLUSIONS: Anti-PD-1/PD-L1 therapy is expected to provide marked survival benefits for patients with cancer. This study demonstrated the potentially beneficial health impacts of utilizing the anti-PD-1/PD-L1 class at the population level. The findings could inform health policy decision makers about cancer care and ultimately enhance population health through rapid access to innovative cancer drugs.

International Price Comparisons of Anticancer Drugs: A Scheme for Improving Patient Accessibility.

BACKGROUND: The demand for implementing a new listing scheme to expedite patient access to novel oncology drugs has increased in South Korea. This study was conducted to compare the prices of anticancer drugs between eight countries and to explore the feasibility of a 'pre-listing and post-evaluation' scheme to expedite patient access to oncology drugs. METHODS: This study included 34 anticancer drugs, which were reimbursed between 1 January 2007 and 31 December 2017. The unit price and sales volume of the study drugs were collected from eight countries and IQVIA data, respectively. The prices were adjusted to estimate the ex-factory prices using the discount/rebate rate suggested by the Health Insurance Review Agency (HIRA). The four price indices of Laspeyres, Paasche, Fisher, and the unweighted index were calculated using the price in each country, the average price, and lowest price among the study countries. Each currency was converted using the currency exchange rate and purchasing power parity (PPP). The budget impact of implementing the proposed pre-listing and post-evaluation scheme on payers was calculated. RESULTS: Based on the currency exchange rate, anticancer drug prices were higher in other countries (index range: 1.05-2.78) compared to Korea. The prices in Korea were similar to countries with the lowest prices. When the PPP was applied, prices were higher in the US, Germany, Italy, and Japan than in Korea (range: 1.10-2.13); however, the prices were lower in the UK, France, and Switzerland than in Korea (range: 0.72-0.99). The financial burden of implementing the pre-listing and post-evaluation scheme was calculated at 0.83% of the total anticancer drug sales value in Korea from 2013-2017. CONCLUSIONS: The prices of anticancer drugs in Korea were similar to the lowest prices among the seven other study countries. A pre-listing and post-evaluation scheme should be considered to improve patient access to novel anticancer drugs by reducing the reimbursement review time and uncertainties.

Economic evaluation of childhood 7-valent pneumococcal conjugate vaccination in Korea.

BACKGROUND: Streptococcus pneumoniae (sp) is a leading cause of invasive and noninvasive bacterial disease in children. 7-valent pneumococcal conjugate vaccine (PCV-7) has been shown to significantly reduce the incidence of pneumococcal diseases, such as meningitis, bacteremia, pneumonia, and otitis media. Although PCV-7 was introduced in Korea in 2003, it is not yet included in the universal immunization program. OBJECTIVE: To evaluate the health outcomes, costs, and cost-effectiveness of universal vaccination with PCV-7 in Korean infants and to estimate the break-even price for PCV-7 from a societal perspective. METHODS: A decision analytic model was used to evaluate the cost-effectiveness of immunization with PCV-7 in a birth cohort of Korean infants born in 2006. A universal vaccination strategy was compared with no vaccination in terms of costs and life years gained (LYG) over a 5-year time horizon. The birth cohort size, incidence of disease, resource utilization, and associated costs were obtained from the Korea National Statistical Office, the Korean Centers for Disease Control and Prevention, the Korean National Health and Nutrition Examination Survey, and the Korean Ministry of Health and Welfare. Inputs on the probabilities of clinical treatment pathways (e.g., tympanostomy) were derived from international literature if data specific to Korea did not exist. To estimate the benefits of universal immunization, the serotype-specific efficacy of PCV-7 was derived from studies conducted by Northern California Kaiser Permanente and by the Finnish Otitis Media Vaccine Study and applied to the serotypes isolated in Korean children with sp infections. The effects of vaccination on quality of life, herd immunity, benefits after the first 5 years of life, and patient copayments were not considered. A 4-dose schedule was used in the base-case analysis. A 3-dose schedule was also evaluated. The assumed price per dose was Korean won (KW) 70,000 (approximately US$54; 2009 exchange rate US$1 = KW1,300). Univariate and probabilistic sensitivity analyses were performed. RESULTS: Implementing a 4-dose universal PCV-7 vaccination strategy in a birth cohort of 451,514 infants in Korea would prevent 96,728 cases of pneumococcal-related infections (591 meningitis, 1,379 bacteremia, 43,950 pneumonia, and 50,808 otitis media cases) and 218 deaths (199 discounted deaths averted, 575 discounted LYG over 5 years). The medical and nonmedical cost burden of pneumococcal diseases offset with vaccination was KW44,033 million (US$33.87 million). The incremental discounted cost of universal vaccination was estimated to be KW86,384 million (US$66.45 million). The incremental cost per LYG was KW150.2 million (US$115,549) for the 4-dose schedule and KW103.91 million (US$79,955) for the 3-dose schedule. The break-even costs were KW22,100 and KW28,100 per dose for the 4- and 3-dose schedules, respectively. CONCLUSIONS: Universal PCV-7 vaccination of infants in Korea could substantially reduce pneumococcal disease morbidity, mortality, and related costs by preventing pneumococcal infections. However, at current market prices for the vaccine, a universal vaccination strategy is not cost-effective. The literature suggests that factors not considered in this analysis, including vaccine price reduction and indirect effects on public health (e.g., herd immunity), have the potential to make the public health impact and cost-effectiveness of universal PCV-7 vaccination in Korea more favorable.

The risk of cardiac events in patients who received concomitant levofloxacin and amiodarone.

OBJECTIVES: Levofloxacin and amiodarone are both known to prolong the QT interval. This study was conducted to estimate the risk of cardiac events in patients receiving concomitant levofloxacin and amiodarone. METHODS: The study included patients who were admitted to a large academic community medical center from 1/2012 to 12/2015 and received both levofloxacin and amiodarone at some point during their hospitalization. Patients received concomitant or non-concomitant levofloxacin and amiodarone during hospitalization. The primary outcome was the occurrence of cardiac events during therapy. The secondary outcome was the proportion of patients with an electrocardiogram performed before and after initiation of therapy. Odds ratios for cardiac events were calculated using a multivariable logistic regression model with and without adjusting for the study variables. The concomitant group was further evaluated for predictors of the primary outcome using multivariable logistic regression. RESULTS: This study included 240 patients, 164 (68.3%) of whom received concomitant levofloxacin and amiodarone. Concomitant medication therapy was associated with a greater than six-fold increased risk of cardiac events after adjusting for the study variables (Odds Ratio=6.20; 95% Confidence Interval=1.34-28.62). CONCLUSIONS: Patients receiving concomitant amiodarone and levofloxacin experienced a five-fold increase in cardiac events compared to patients given either medication alone.

Improving Patient Access to New Drugs in South Korea: Evaluation of the National Drug Formulary System.

This study reviews and evaluates the national drug formulary system used to improve patient access to new drugs by making reimbursement decisions for new drugs as part of the South Korean national health insurance system. The national health insurance utilizes three methods for improving patient access to costly drugs: risk-sharing agreements, designation of essential drugs, and a waiver of cost-effectiveness analysis. Patients want reimbursement for new drugs to be processed quickly to improve their access to these drugs, whereas payers are careful about listing them given the associated financial burden and the uncertainty in cost-effectiveness. However, pharmaceutical companies are advocating for drug prices above certain thresholds to maintain global pricing strategies, cover the costs of drug development, and fund future investments into research and development. The South Korean government is expected to develop policies that will improve patient access to drugs with unmet needs for broadening health insurance coverage. Simultaneously, the designing of post-listing management methods is warranted for effectively managing the financial resources of the national health insurance system.