Comparative effectiveness and persistence of TNFi and non-TNFi in juvenile idiopathic arthritis: a large paediatric rheumatology centre in the USA.

OBJECTIVE: To evaluate the persistence and effectiveness of TNF inhibitors (TNFi) vs non-TNFi among newly diagnosed JIA patients after initiation of biologic DMARD (bDMARD). METHODS: Using longitudinal patient-level data extracted from electronic medical records in a large Midwestern paediatric hospital from 2009 to 2018, we identified JIA patients initiating TNFi and non-TNFi treatment. Treatment effectiveness was assessed based on disease activity. Inverse probability of treatment weighting of propensity score was used to estimate the treatment effectiveness and Kaplan-Meier analyses were conducted to assess persistence. RESULTS: Of 667 JIA patients, most (92.0%) were prescribed one of the class of TNFi as their initial biologic treatment. Etanercept was the most frequently prescribed (67.1%) treatment, followed by adalimumab (27.5%). Only around 5% of patients were prescribed off-label bDMARDs as their first-course treatment; however, >20% were prescribed off-label biologics as their second-course therapy. Some 7.2% of patients received four or more bDMARDs. The median persistence of the first-course bDMARD is 320 days, with TNFi being significantly longer than the non-TNFi (395 vs 320 days, P = 0.010). The clinical Juvenile Disease Activity Score (cJADAS) reduction of TNFi users (6.6, 95% CI 5.7, 7.5) was significant greater compared with non-TNFi users (3.0, 95% CI 1.5, 4.6, P < 0.0001) at 6-month follow-up visit. CONCLUSION: Persistence was significantly longer among patients initiating TNFi as their first biologic therapy than those receiving non-TNFi. Patients receiving TNF therapy had significant greater reduction of cJADAS at the 6-month follow-up visit compared with patients in the non-TNF cohort.

Drug Expenditure, Price, and Utilization in the U.S. Medicaid: A Trend Analysis for SSRI and SNRI Antidepressants from 1991 to 2018.

BACKGROUND: SSRIs and SNRIs are antidepressants that have largely substituted old antidepressants like Monoamine Oxidase Inhibitors (MAOIs) and Tricyclic Antidepressants (TCAs). They have been widely used since 1987 when the FDA approved the first SSRI Fluoxetine and the first SNRI Venlafaxine in 1993. Since then, several new SSRIs and SNRIs have been approved and entered the market. Utilization, pricing, and spending trends of SSRIs and SNRIs have not been analyzed yet in Medicaid. AIM: To assess the trends of drug expenditure, utilization, and price of SSRI and SNRI antidepressants in the US Medicaid program, and to highlight the market share of SSRIs and SNRIs and the effect of generic drug entry on Medicaid drug expenditure. METHODS: A retrospective descriptive data analysis was conducted for this study. National pharmacy summary data for study brand and generic drugs were retrieved from the Medicaid State Outpatient Drug Utilization Data. These data were collected by the US Centers for Medicare and Medicaid Services (CMS). The study period was between 1991 and 2018. Study drugs include 12 different SSRI and SNRI brands and their generics available in the market, such as citalopram, escitalopram, paroxetine, fluoxetine, sertraline, venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran. Data were analyzed annually and categorized by total prescriptions (utilization), total reimbursement (spending), and cost per prescription as the proxy of the price for each drug. RESULTS: From 1991 to 2018, total prescriptions of SSRI and SNRI drugs rose by 3001%. Total Medicaid spending on SSRIs and SNRIs increased from USD 64.5 million to USD 2 billion in 2004, then decreased steadily until it reached USD 755 million in 2018. The SSRIs average utilization market share was 87% compared to 13% of the SNRIs utilization market share. About 72% of total Medicaid spending on the two groups goes to SSRIs, while the remaining 28% goes to SNRIs. Brand SSRIs and SNRIs prices increased over time. On the contrary, generic drugs prices steadily decreased over time. DISCUSSION: An increase in utilization and spending for both SSRI and SNRI drugs was observed. After each generic drug entered the market, utilization shifted from the brand name to the respective generic due to their lower price. These generic substitutions demonstrate a meaningful cost-containment policy for Medicaid programs. IMPLICATIONS FOR HEALTH POLICIES: Our findings show the overall view of Medicaid expenditure on one of the most commonly prescribed drug classes in the US. They also provide an important insight toward the antidepressant market and the importance of monitoring different drugs and their alternatives.

Twenty years of triptans in the United States Medicaid programs: Utilization and reimbursement trends from 1993 to 2013.

OBJECTIVE: After sumatriptan was approved by the Food and Drug Administration in 1992, triptans became first-line anti-migraine therapies. Rapidly rising triptan expenditures, however, led payers, including Medicaid, to implement cost-containment policies. We describe triptan utilization and reimbursement trends in Medicaid. METHODS: Using national summary files for outpatient drug utilization, utilization and expenditure data from 1993 to 2013 were extracted and summed for all triptan national drug codes reimbursed by Medicaid. Data were collected separately for tablets, injections and sprays. RESULTS: The number of triptan prescriptions increased from 87,348 in 1993 to 0.9 million in 2004; fell to 0.4 million in 2009; rose to 1 million in 2011; and rose 1.2 million in 2013. In 2013, Medicaid spent $96.8 million on triptans: 74.4%, 18.4% and 7.2% for tablets, injections and sprays, respectively. Average reimbursement per prescription was $54 for tablets, $351 for injections and $235 for sprays in 2013. From 1993 to 2013, sumatriptan was the most widely prescribed among the triptans. CONCLUSIONS: The substantial increase in triptan prescriptions from 2009 to 2011, without being convincingly explained by either rising migraine prevalence or rising Medicaid enrollment, is suggestive of reduced access to these medications prior to 2009. Cost-containment policies may have inadvertently prevented Medicaid migraineurs from obtaining appropriate pharmacotherapy. PRIOR PRESENTATIONS: An earlier version of this paper was presented as a poster at the Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research, Philadelphia, PA, May 2015, where it received a finalist award.

Off-label use of oral fluoroquinolone antibiotics in outpatient settings in the United States, 2006 to 2012.

PURPOSE: The aim of this study was to evaluate the practice pattern of off-label use of fluoroquinolones (FQs) in ambulatory settings and to identify the related risk factors. METHODS: The National Ambulatory Medical Care Surveys from 2006 through 2012 was used to identify subjects who received FQ off-label prescriptions. We defined off-label use as the use of FQs for indications other than those in the FDA-approved drug label. Descriptive statistics were calculated by using a series of weighted chi-squared statistics. Multivariate logistic regression was conducted to identify factors associated with off-label FQ drug use. RESULTS: There were 93 million ambulatory visits in which an FQ was prescribed, and 53.16% of these visits involved the prescribing of FQs in an off-label manner. The percentage of off-label prescriptions was the highest among individuals ≥80 years old (61.6%) and male patients (60.9%). The FQ drug prescribed most for an off-label indication in our study was ciprofloxacin (29.5% of the total visits). The multivariate analysis showed that age of ≥80 years and male patient was significantly associated with off-label use of FQs (adjusted odds ratio (OR) 3.66, 1.72-7.80 and OR 3.26, 2.32-4.56, respectively). Medicaid or private insurance versus Medicare were associated with significantly higher off-label prescribing of FQs (OR 2.53, 1.28-5.01 and 1.77, 1.03-3.03, respectively). CONCLUSION: The percentage of visits involving off-label FQs in US ambulatory settings is substantial. Efforts are needed consolidate and evaluate what high-quality scientific evidence is available and what is needed to support the safety and effectiveness of such off-label uses. Copyright © 2016 John Wiley & Sons, Ltd.

Comparative persistence on ß-blockers versus calcium channel blockers for ventricular rate control in nonelderly patients with atrial fibrillation.

BACKGROUND: For patients with atrial fibrillation (AF), early treatment is essential to prevent serious complications such as stroke. Several randomized clinical trials have shown that rate-control may be as effective as rhythm-control medications, whereas the latter have serious side effects. Little evidence exists, however, about which class of rate-control medication-ß-blockers (BBs) or calcium channel blockers (CCBs)-may be superior. OBJECTIVE: The objective was to compare the long-term persistence on BBs versus CCBs in nonelderly adult patients with AF. METHODS: A longitudinal retrospective cohort study for patients 40 to 60 years old with newly diagnosed AF (identified by ICD-9 code 427.31) was performed using data from Ohio Medicaid physician, institutional, and pharmacy claims from January 2006 through June 2011. A Cox proportional hazard regression, with time to change out of rate-control therapy as the dependent variable, was estimated to compare persistence on (proxy for effectiveness of) rate-control medication across drug classes. A propensity-score analysis was used to control for selection bias. Additional covariates included age, development of heart failure, and medication adherence. RESULTS: Out of 1239 patients included in the cohort, 1016 received a BB; 223 received a CCB. Over time, patients on CCBs were significantly more likely to switch out of rate-control therapy (hazard ratio = 1.89; 95% CI = 1.14-3.09) than patients on BBs. CONCLUSIONS: Evidence suggests that nonelderly AF patients, when prescribed rate-control therapy, persist longer on BBs than CCBs. Because this is the first long-term study comparing the 2 drug classes in the nonelderly population, further research is suggested.

Racial/Ethnic and Socioeconomic Disparities and Self-Reported Work Productivity in Urinary Incontinence Females Using the National Institute of Diabetes and Digestive and Kidney Diseases Data.

OBJECTIVE: To explore the relationship between racial/ethnic and socioeconomic disparities and self-reported work productivity in urinary incontinence females. METHOD: This was a retrospective observational and secondary analysis of the National Institute of Diabetes and Digestive and Kidney Diseases database trials. We included females with stress urinary incontinence and ≥ 21 years old. The primary outcome was self-reported work productivity evaluated using a proportional-odds regression model. A backward elimination method was utilized to create a final reduced model. The socioeconomic predictors were age, race/ethnicity, education, marital status, personal income, and language. RESULTS: We included 1252 participants with a median age of 52 years old. Whites accounted for 76.2% of total participants, while Hispanics constituted 11.4% only. Work productivity of Hispanic or non-Hispanic other group was greatly affected compared to whites (OR: 1.771, p value: 0.0008 and OR:1.592, p value= 0.0231 respectively). Work productivity of patients with higher education was less affected compared to less educated patients. Married females were less likely to report being greatly affected in work productivity than non-married females (OR 0.663, p-value 0.0005). Age, income, and language were not predictive of the outcome variable in the final model. CONCLUSION: Our finding showed that racial/ethnic and socioeconomic disparities play an important role in individuals' work productivity. Future research is needed to the influence of social determinants of health not captured by racial and socioeconomic factors.

Factors Associated with Statin Discontinuation Following Metabolic and Bariatric Surgery: A Retrospective Analysis of 2012-2021 Electronic Medical Records Network Data.

BACKGROUND: Bariatric surgery has been shown to improve hyperlipidemia, decreasing the need for statin medications. Although maintaining statin therapy post-surgery for those with a history of atherosclerotic cardiovascular disease (ASCVD) is advised, it is uncertain if discontinuation risks differ between those with and without ASCVD history. AIM: The study aims to analyze the rate and reasons for statin cessation post-bariatric surgery in the US using real-world data. METHODS: Using the TriNetX electronic medical records network from 2012 to 2021, the study involved patients aged 18 or older on statins at the time of bariatric surgery. They were categorized into primary and secondary prevention groups based on prior ASCVD. Statin discontinuation was defined as a 90-day gap post the last statin dosage. The Cox model assessed factors influencing statin cessation. RESULTS: Seven hundred and thirty-three statin users undergoing bariatric surgery were identified, with 564 (77%) in primary prevention. Six months post-surgery, 48% of primary prevention patients and 34.5% of secondary ones stopped statins. Primary prevention patients had a 30% higher likelihood of cessation compared to secondary prevention (hazard ratio, 1.30; 95% CI, 1.06-1.60) as shown by multivariable analysis. CONCLUSIONS: Post-bariatric surgery, primary prevention patients are more likely to discontinue statins than secondary prevention patients.

The Utilization, Expenditure, and Price of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in the US Medicaid Programs: Trends Over a 31 Year Period.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used for several indications including hypertension. Our aim is to evaluate the utilization, expenditure, and drug price of ACEIs and ARBs in the US Medicaid population. METHODS: A retrospective descriptive trend analysis was conducted using Medicaid State Drug Utilization outpatient pharmacy summary files managed by the Centers for Medicare and Medicaid Services from 1991 to 2021. Study drugs included ACEIs (e.g., captopril) and ARBs (e.g., losartan). Annual reimbursement and utilization were calculated for both classes. The average reimbursement per prescription was calculated as a proxy for drug prices. Market share competition between ACEIs and ARBs was analyzed over time. RESULTS: ACEI and ARB utilization rose by 25% from 1991 to 2021. Brand ACEIs utilization peaked in 2002 with 28 million prescriptions while brand ARBs utilization continued to increase until 2005 with over 23 million prescriptions. However, generic products took the lead and exceeded brand ACEI and ARB utilization in 2006 and 2012 respectively. Medicaid spent over $ 33.7 billion on ACEIs and ARBs over 31-year. Brand ACEIs and ARBs average prices increased sharply to $8,104 and $6,908 respectively in 2021. The total prescription market share for ACEIs was 68% compared to 32% of ARBs over the entire study. CONCLUSION: ACEIs and ARBs utilization increased over the last 31 years. Brand utilization switched over to generic resulting in less reimbursement. The average prices of brand ACEIs and ARBs continue to increase even after generics were introduced to the market.

A novel online survey approach designed to measure consumer sunscreen application thickness-implications for estimating environmental emissions.

BACKGROUND: The effects of ultraviolet (UV) filters in the aquatic environment have been well studied, but environmental exposures remain unclear and understudied. Consumer usage directly influences the amount of sunscreen products, and subsequently UV filters, potentially released into the environment. OBJECTIVE: To conduct a literature review of previous research into sunscreen application thickness, develop a questionnaire protocol designed to semi-quantify sunscreen usage by US consumers, and conduct a large-scale survey to determine a sunscreen application thickness (to face and body) that is more refined than conservative defaults. The United States Food & Drug Administration (US FDA) recommends a sunscreen application rate of 2 mg/cm2. This value is typically used as a worst-case assumption in environmental exposure assessments of UV filters. METHODS: Designed a novel approach to estimate lotion sunscreen application thickness using an online questionnaire protocol employing visual references and self-reported height and weight of the respondents. A literature review was also conducted to collect historical sunscreen usage. RESULTS: Over 9000 people were surveyed in the US, and after the dataset was refined, their sunscreen application thickness was estimated based on calculated body surface area and reported sunscreen amounts. The mean and median values for survey respondents are 3.00 and 1.78 mg/cm2, respectively, for facial application thickness and 1.52 and 1.35 mg/cm2, respectively, for body application thickness. Earlier research from 1985-2020 reported 36 of the 38 values are below the US FDA's recommended application thickness of 2 mg/cm2 (range 0.2-5 mg/cm2). IMPACT STATEMENT: This web-based survey is the first of its kind, designed specifically to quantify sunscreen application in a large and diverse set of consumers. This method provides a greater reach to larger populations thus enabling more granular data analysis and understanding. Exposure assessments of sunscreen ingredients typically use conservative parameters. These data can refine those assessments and allow for more informed and science-based risk management decisions.

Utilization, reimbursement, and price trends for Hepatitis C virus medications in the US Medicaid programs: 2001-2021.

Background: Hepatitis C Virus (HCV) remains a challenging health problem worldwide, with increasing incidence despite being curable with Direct Acting Antiviral (DAA) agents. Objective: This study aimed to describe the utilization, reimbursement, and price trends of HCV treatments and evaluate the influence of treatment guidelines and policies. Methods: A retrospective, descriptive drug utilization study conducted using the outpatient pharmacy data extracted from the Centers for Medicaid and Medicare Services State Drug Utilization Data between 2001 and 2021. All HCV treatments approved in the US were included, conventional therapy (CT), and DAA agents. The annual secular trends were calculated for each medication's total number of prescriptions, reimbursements, and prices. The average reimbursement per prescription was calculated and utilized as a proxy of prices. The HCV treatment guideline and policies and legislation were evaluated overtime to measure the impact on the trends. Results: Despite CT having a higher total utilization, DAA agents commanded significantly greater reimbursements, with 4.1 billion USD for CT and 19.45 billion USD for DAA agents. CT utilization increased rapidly and dominated the market until 2011, peaking at 379,696 prescriptions in 2003 but declining afterward. DAA agents' utilization increased rapidly in their first year: i.e., sofosbuvir reached 50,377 prescriptions with 1.3 billion USD in 2014, while ledipasvir/sofosbuvir reached 79,387 prescriptions with 2 billion USD in 2015. The average price per prescription was high for the DAA agents, like 24,992 USD for sofosbuvir and 22,787 USD for ledipasvir/sofosbuvir, compared to CT medications ribavirin, around 500 USD, and pegINF, around 3000 USD. The new DAA agents replaced CT, and initiating market competition among DAA agents. Conclusion: The introduction of multiple DAA agents slightly changed their prescription prices but remained high during the study period. The recent increase in HCV incidence cases indicates accessibility issues for costly and effective DAA agents, with treatment guidelines and policies playing a critical role in shaping these trends.

Evidence-based prediction of statin use with lipid-panel data from the National Health and Nutrition Examination Survey.

OBJECTIVES: This study compared actual use of individual statin drugs to expected use based on their efficacy and safety profiles. METHODS: Five panels covering the years 1999 to 2008 from the National Health and Nutrition Examination Survey provided interview, demographic, and laboratory data for 8769 (365,503,838 weighted) people aged 20 years or older who were not taking a statin medication. An individual's risk for coronary heart disease and low-density lipoprotein (LDL) cholesterol goal were determined, following the Adult Treatment Panel III Cholesterol Guidelines. The percentage LDL cholesterol lowering required to reach his/her LDL cholesterol level goal was calculated. Depending on the amount of LDL cholesterol lowering needed and on if the individual had a liver condition (i.e., enhanced risk of rhabdomyolysis) statins were hypothetically prescribed. Predicted use was compared to actual use by U.S. Medicaid beneficiaries in the third quarter of 2009, obtained from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare and Medicaid Services. RESULTS: Results showed that 72.34% of the population was in the lowest coronary heart disease risk group and that 86.30% required no statin therapy. Among the people who did require LDL cholesterol lowering, a significant majority (37.3 million or 10.22% of the population) needed 30% lowering or less. Only 314,784 (0.09%) required LDL cholesterol lowering of greater than 60%. Utilization shares based on safety and efficacy were estimated at 19.26% (rosuvastatin), 18.67% (atorvastatin), 16.48% (simvastatin), 16.30% (lovastatin), 14.93% (pravastatin), and 14.36% (fluvastatin). CONCLUSIONS: Actual statin use differed substantially from predicted use. It may be appropriate to develop and maintain policies that encourage use of less costly products that have essentially equivalent safety profiles and efficacy.

Utilization, spending, and price trends for benzodiazepines in the US Medicaid program: 1991-2009.

BACKGROUND: Although it is well-known that drug costs in the US have risen precipitously over the last 25 years, what is much less appreciated is how this rise in cost has occurred across so many seemingly distinct drug markets. OBJECTIVE: To describe trends in the utilization, spending, and average per-prescription cost of benzodiazepines individually, in subgroups, and overall, in the Medicaid program. Medicaid has been the primary public payer for benzodiazepines over the past 2 decades. METHODS: A retrospective, descriptive analysis was performed for the years 1991-2009 using the publicly available national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Services. Quarterly prescription counts and reimbursement amounts were calculated for all benzodiazepines reimbursed by Medicaid. Average per-prescription spending as a proxy for drug price was found by dividing reimbursement by the number of prescriptions. RESULTS: Prescriptions for benzodiazepines among Medicaid beneficiaries increased from 8.0 million in 1991 to 17.1 million in 2009. Expenditures rose from $131.6 million to $171.1 million over the same time period. The average per-prescription price was a little over $10 in 2009. Whereas utilization of intermediate- and long-acting agents increased over time, prescriptions for short-acting drugs fell from 1.1 million to 0.3 million (1991-2009). The percentage rise in Medicaid spending on benzodiazepines since 1991 (30.0%) was less than the general rate of inflation (57.5%), as measured by the percentage change in the consumer price index over the same time period. CONCLUSIONS: Relative to the rise in the number of Medicaid beneficiaries (more than doubled over the study period), there is no evidence of an extraordinary rise in the utilization of benzodiazepines. Moreover, both nominal and real average prices of benzodiazepines have fallen, primarily because of generic entry over the last 2 decades.

Safety and cost-effectiveness of ponatinib versus other tyrosine kinase inhibitors as second-line therapy in patients with chronic myeloid leukemia in the United States.

To evaluate the cost-effectiveness of ponatinib compared with second-line TKIs in the treatment of adult patients with CML who failed, or were intolerant to, first-line TKIs. A Markov state transition model was conducted. Model transition, adverse-effect probabilities, utility data and medical costs were obtained from clinical trials and literature. Measurements included medications, follow-ups, adverse events, allogeneic stem cell transplantation and quality-adjusted life years (QALYs). Univariable and Bayesian multivariable probabilistic sensitivity analyses were conducted using Monte Carlo simulations. Dasatinib resulted in an ICER of $79,086/QALY compared to nilotinib. Ponatinib yielded an ICER of $176,278/QALY and $141,563/QALY compared to dasatinib and nilotinib, respectively. Dasatinib was the optimal treatment at a $100,000/QALY threshold. The probability (36%-40%) for ponatinib or dasatinib optimal treatment was associated with thresholds of $160,000-$180,000/QALY. Dasatinib and ponatinib can be considered cost-effective options and provide clinical benefits compared to other second-line TKIs for CML in the US.

Risk of serious asthma exacerbations associated with long-acting beta agonists among patients with asthma: a retrospective cohort study.

BACKGROUND: After the Serevent Nationwide Surveillance clinical trial, controversy has surrounded the safety of long-acting beta agonists (LABAs). OBJECTIVE: Examine the association between LABAs and severe asthma exacerbations (SAEs). METHODS: From a multistate Medicaid database, for the years 2002-2007, a total of 940,449 patients (age <40) with asthma were selected and divided into a cohort with newly-diagnosed asthma and one with pre-existing asthma. SAEs included asthma-related emergency department (ED) visits, hospitalizations, and intubations. Patients' asthma severity was determined based on medication regimen as suggested by the 2002 National Asthma Guidelines. Specific use of inhaled corticosteroids (ICSs), LABAs, ICS/LABA combination drugs, short-acting beta agonists (SABAs), and other drugs was tracked. Cox proportional hazard regressions were estimated to assess the risk of SAEs associated with patient severity, drug use, and covariates. RESULTS: Compared to patients taking a SABA only, estimated SAE hazard ratios for newly diagnosed and pre-existing-asthma patients were as follows: 0.63 (95% CI 0.58-0.69) and 0.74 (0.70-0.79) for patients on a LABA without ICS, and 0.79 (0.77-0.81) and 0.90 (0.87-0.92) for those on a LABA/ICS single inhaler. Although hazard ratios were estimated to be similar for ED visits, LABA use was found to be positively associated with hospitalizations and intubations. Other key risk factors (P < .0001) included being African American, an alcohol/substance use disorder, pregnancy, and obesity. CONCLUSION: Relative to SABA-only therapy, LABA use is associated with a lower risk of ED visit. Certain patients with asthma, such as pregnant women and African Americans, are particularly vulnerable to SAE risk of all types.

Current Development and Practice of Pharmacoeconomic Evaluation Guidelines for Universal Health Coverage in China.

BACKGROUND: China has achieved near-universal health coverage (UHC) for 95 percent of its population (>1.3 billion lives) as a result of healthcare reforms that began in 2009. However, one of many remaining issues in the Chinese healthcare system is the need to better optimize the allocation and use of healthcare resources in order to meet growing healthcare demands. OBJECTIVES: The goals are to highlight the components of the China Guidelines for Pharmacoeconomic Evaluations (CGPE) 2020 Edition and discuss its future development for UHC in China. METHODS: We review the development process of the CGPE 2020 edition, discuss the contemporary practice of the CGPE for UHC in China, describe new opportunities and challenges to the CGPE, and provide suggestions on the future development of the CGPE based on the current state of the healthcare system in China. RESULTS: Pharmacoeconomics provides tools to evaluate the health returns and economic costs of pharmaceutical products in a scientific way for the optimal allocation of healthcare resources. Considering the great potential of pharmacoeconomics in China, demonstrated by its rapid development and recognition as a research field in the past decade, the standardization of pharmacoeconomic evaluations has become particularly important to improve the accuracy of evaluation results used for drug selection, price negotiations and adjustments. CONCLUSION: Suggestions are made for the integration of CGPE into current framework of UHC in China, including standardizing the pharmacoeconomic evaluation process and updating CGPE on topics such as ethics and real-world research. The CGPE 2020 edition offers a standard to improve the quality of pharmacoeconomic evaluation research and enhance the value and efficiency of UHC in China.

Off-label medication use in rare pediatric diseases in the United States.

Many pediatric patients with rare diseases use drugs off-label due to limited data in pediatric patients. Off-label treatment remains an important public health issue for neonates, infants, children, and adolescents, especially for pediatric patients with rare diseases. For patients with rare diseases, the majority of medications have no or limited information in labelling for pediatric use. Children present unique considerations in clinical trials due to ethical and clinical concerns, which have limited and even discouraged testing of drugs in the pediatric population. Numerous legislative measures have been enacted to address barriers in pediatric drug testing. This research reviewed off-label medication use in rare pediatric diseases, evaluated recent medication uses in pediatric clinical practice, discussed key regulations for rare pediatric diseases, and summarized recent drug approvals for rare pediatric diseases. This study demonstrates the ongoing medical need for newly approved medications to treat pediatric rare diseases and revealed the positive impact of regulations from the Orphan Drug Act of 1983 to the Research to Accelerate Cures and Equity (RACE) for Children Act on drug development and off-label medication practice in rare pediatric disease management. This article provides informative historical background and current considerations of off-label use of medications in neonates, infants, children, and adolescents with rare diseases.

Prescribing Patterns and Impact of Factors Associated with Time to Initial Biologic Therapy among Children with Non-systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: The aim of this study was to examine patterns of initial prescriptions, investigate time to initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs), and evaluate the impact of clinical and other baseline factors associated with the time to first bDMARD in treating children with newly diagnosed non-systemic juvenile idiopathic arthritis (JIA). METHODS: Using longitudinal patient-level data extracted from electronic medical records (EMR) in a large Midwestern pediatric hospital from 2009 to 2018, the initial prescriptions and prescribing patterns of bDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids within 3 months of JIA diagnosis were examined. Kaplan-Meier analyses were performed to assess time to initiation of bDMARDs. Cox proportional hazard models were used to identify factors associated with time to first bDMARD. RESULTS: Of 821 children, the proportion of patients with initial csDMARDs increased from 45.3% in 2009 to 60.3% in 2018. Around 57.5% of polyarthritis rheumatoid factor-positive (Poly RF+) patients and 43.2% of polyarthritis rheumatoid factor-negative (Poly RF-) patients received a bDMARD therapy within 3 months of diagnosis, 14.4% as monotherapy and 28.3% in combination with a csDMARD. Among patients who received combination therapy, combination of methotrexate with adalimumab increased from 16.7% in 2009 to 40% in 2018. The proportion of patients treated with adalimumab gradually increased and passed etanercept in 2016. The predictors of earlier initiation of biologic therapy were JIA category enthesitis-related arthritis (ERA) [hazard ratio (HR) vs persistent oligoarthritis 4.82; p < 0.0001], psoriatic arthritis (PsA) (HR 2.46; p = 0.0002), or Poly RF- (HR 2.43; p = 0.0002); the number of joints with limited range of motion (HR 1.02; p = 0.0222), and erythrocyte sedimentation rate (ESR, HR 1.01; p = 0.0033). CONCLUSIONS: There was a substantial increase in the proportion of patients receiving the combination of methotrexate and adalimumab among patients receiving combination therapy. Adalimumab overtook etanercept as the most frequently prescribed bDMARD. Multiple factors affect the time to biologic initiation, including the number of joints with limited range of motion, ESR, and JIA category.

School-based health centers: cost-benefit analysis and impact on health care disparities.

OBJECTIVES: We evaluated the impact of school-based health centers-which provide essential health care for students by aiming to eliminate many access barriers-on health care access disparities and conducted a cost-benefit analysis. METHODS: We employed a longitudinal quasi-experimental repeated-measures design. Primary data sources included the Ohio Medicaid claims, enrollment file with race/ethnicity, and survey reports from parents. We used hierarchical linear modeling to control unbalanced data because of student attrition. We assessed quarterly total Medicaid reimbursement costs for 5056 students in the SBHC and non-SBHC groups from 1997 to 2003. We calculated net social benefit to compare the cost of the SBHC programs with the value that SBHCs might save or create. RESULTS: With SBHCs, the gap of lower health care cost for African Americans was closed. The net social benefits of the SBHC program in 4 school districts were estimated as $1,352,087 over 3 years. We estimated that the SBHCs could have saved Medicaid about $35 per student per year. CONCLUSIONS: SBHCs are cost beneficial to both the Medicaid system and society, and may close health care disparity gaps.

A review of quantitative risk-benefit methodologies for assessing drug safety and efficacy-report of the ISPOR risk-benefit management working group.

OBJECTIVE: Although regulatory authorities evaluate the risks and benefits of any new drug therapy during the new drug-approval process, quantitative risk-benefit assessment (RBA) is not typically performed, nor is it presented in a consistent and integrated framework when it is used. Our purpose is to identify and describe published quantitative RBA methods for pharmaceuticals. METHODS: Using MEDLINE and other Internet-based search engines, a systematic literature review was performed to identify quantitative methodologies for RBA. These distinct RBA approaches were summarized to highlight the implications of their differences for the pharmaceutical industry and regulatory agencies. RESULTS: Theoretical models, parameters, and key features were reviewed and compared for the 12 quantitative RBA methods identified in the literature, including the Quantitative Framework for Risk and Benefit Assessment, benefit-less-risk analysis, the quality-adjusted time without symptoms and toxicity, number needed to treat (NNT), and number needed to harm and their relative-value-adjusted versions, minimum clinical efficacy, incremental net health benefit, the risk-benefit plane (RBP), the probabilistic simulation method, multicriteria decision analysis (MCDA), the risk-benefit contour (RBC), and the stated preference method (SPM). Whereas some approaches (e.g., NNT) rely on subjective weighting schemes or nonstatistical assessments, other methods (e.g., RBP, MCDA, RBC, and SPM) assess joint distributions of benefit and risk. CONCLUSIONS: Several quantitative RBA methods are available that could be used to help lessen concern over subjective drug assessments and to help guide authorities toward more objective and transparent decision-making. When evaluating a new drug therapy, we recommend the use of multiple RBA approaches across different therapeutic indications and treatment populations in order to bound the risk-benefit profile.