Potential impact of blood cholesterol guidelines on statin treatment in the U.S. population using interrupted time series analysis.

BACKGROUND: The 2013 ACC/AHA Guideline was a paradigm shift in lipid management and identified the four statin-benefit groups. Many have studied the guideline's potential impact, but few have investigated its potential long-term impact on MACE. Furthermore, most studies also ignored the confounding effect from the earlier release of generic atorvastatin in Dec 2011. METHODS: To evaluate the potential (long-term) impact of the 2013 ACC/AHA Guideline release in Nov 2013 in the U.S., we investigated the association of the 2013 ACC/AHA Guideline with the trend changes in 5-Year MACE survival and three other statin-related outcomes (statin use, optimal statin use, and statin adherence) while controlling for generic atorvastatin availability using interrupted time series analysis, called the Chow's test. Specifically, we conducted a retrospective study using U.S. nationwide de-identified claims and electronic health records from Optum Labs Database Warehouse (OLDW) to follow the trends of 5-Year MACE survival and statin-related outcomes among four statin-benefit groups that were identified in the 2013 ACC/AHA Guideline. Then, Chow's test was used to discern trend changes between generic atorvastatin availability and guideline potential impact. RESULTS: 197,021 patients were included (ASCVD: 19,060; High-LDL: 33,907; Diabetes: 138,159; High-ASCVD-Risk: 5,895). After the guideline release, the long-term trend (slope) of 5-Year MACE Survival for the Diabetes group improved significantly (P = 0.002). Optimal statin use for the ASCVD group also showed immediate improvement (intercept) and long-term positive changes (slope) after the release (P < 0.001). Statin uses did not have significant trend changes and statin adherence remained unchanged in all statin-benefit groups. Although no other statistically significant trend changes were found, overall positive trend change or no changes were observed after the 2013 ACC/AHA Guideline release. CONCLUSIONS: The 2013 ACA/AHA Guideline release is associated with trend improvements in the long-term MACE Survival for Diabetes group and optimal statin use for ASCVD group. These significant associations might indicate a potential positive long-term impact of the 2013 ACA/AHA Guideline on better health outcomes for primary prevention groups and an immediate potential impact on statin prescribing behaviors in higher-at-risk groups. However, further investigation is required to confirm the causal effect of the 2013 ACA/AHA Guideline.

Explaining why increases in generic use outpace decreases in brand name medicine use in multisource markets and the role of regulation.

BACKGROUND: Healthcare systems worldwide face escalating pharmaceutical expenditures despite interventions targeting pricing and generic substitution. Existing studies often overlook unwarranted volume increases in multisource markets due to differential physician perceptions of brand name and generics. OBJECTIVE: This study aims to explain the outpacing of generic medicine use over brand name use in multisource markets and assess the regulatory role, specifically examining the impact of reference pricing on volume and intensity increases. METHODS: Analyzing German multisource prescription medicine markets from 2011 to 2014, we evaluate regulatory mechanisms and explore whether brand name and generic medicines constitute separate market segments. Using an Oaxaca-Blinder decomposition approach, we divide the differential in brand name versus generic medicine use rates into market structure and unobserved segment effects. RESULTS: Generic use rates surpass same-market brand name substitution by 3.87 prescriptions per physician and medicine, on average. Reference pricing mitigated volume increase, treatment intensity and expenditure. Disparities in quantity and expenditure dynamics between brand name and generic segments are partially explained by market structure and segment effects. CONCLUSION: Generic medicine use effectively reduces expenditures but contributes to increased net prescription rates. Reference pricing may control medicine use, but divergent physician perceptions of brand name and generics, revealed by identified segment effects, call for nuanced policy interventions.

Bioequivalence trials for the approval of generic drugs in Saudi Arabia: a descriptive analysis of design aspects.

BACKGROUND: This retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017. METHODS: This was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence. RESULTS: A total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). Most of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 × 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n = 21 [41.2%]). CONCLUSION: This comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.

Prescription-based cost analysis of medicines for cardiovascular risk factors at Indian Council of Medical Research-Rational Use of Medicine Centre Hospitals of India.

OBJECTIVES: India has taken several initiatives to provide health care to its population while keeping the related expenditure minimum. Since cardiovascular diseases are the most prevalent chronic conditions, in the present study, we aimed to analyze the difference in prices of medicines prescribed for three cardiovascular risk factors, based on (a) listed and not listed in the National List of Essential Medicines (NLEM) and (b) generic and branded drugs. MATERIALS AND METHODS: Outpatient prescriptions for diabetes mellitus, hypertension, and dyslipidemia were retrospectively analyzed from 12 tertiary centers. The prices of medicines prescribed were compared based on presence or absence in NLEM India-2015 and prescribing by generic versus brand name. The price was standardized and presented as average price per medicine per year for a given medicine. The results are presented in Indian rupee (INR) and as median (range). RESULTS: Of the 4,736 prescriptions collected, 843 contained oral antidiabetic, antihypertensive, and/or hypolipidemic medicines. The price per medicine per year for NLEM oral antidiabetics was INR 2849 (2593-3104) and for non-NLEM was INR 5343 (2964-14364). It was INR 806 (243-2132) for generic and INR 3809 (1968-14364) for branded antidiabetics. Antihypertensives and hypolipidemics followed the trend. The price of branded non-NLEM medicines was 5-22 times higher compared to generic NLEM which, for a population of 1.37 billion, would translate to a potential saving of 346.8 billion INR for statins. The variability was significant for sulfonylureas, angiotensin receptor blockers, beta-blockers, diuretics, and statins (P < 0.0001). CONCLUSION: The study highlights an urgent need for intervention to actualize the maximum benefit of government policies and minimize the out-of-pocket expenditure on medicines.

Therapeutic efficacy of generic artemether-lumefantrine in the treatment of uncomplicated malaria in Ghana: assessing anti-malarial efficacy amidst pharmacogenetic variations.

BACKGROUND: Despite efforts made to reduce morbidity and mortality associated with malaria, especially in sub-Saharan Africa, malaria continues to be a public health concern that requires innovative efforts to reach the WHO-set zero malaria agenda. Among the innovations is the use of artemisinin-based combination therapy (ACT) that is effective against Plasmodium falciparum. Generic artemether-lumefantrine (AL) is used to treat uncomplicated malaria after appropriate diagnosis. AL is metabolized by the cytochrome P450 family of enzymes, such as CYP2B6, CYP3A4 and CYP3A5, which can be under pharmacogenetic influence. Pharmacogenetics affecting AL metabolism, significantly influence the overall anti-malarial activity leading to variable therapeutic efficacy. This study focused on generic AL drugs used in malarial treatment as prescribed at health facilities and evaluated pharmacogenomic influences on their efficacy. METHODS: Patients who have been diagnosed with malaria and confirmed through RDT and microscopy were recruited in this study. Blood samples were taken on days 1, 2, 3 and 7 for parasite count and blood levels of lumefantrine, artemisinin, desbutyl-lumefantrine (DBL), and dihydroartemisinin (DHA), the active metabolites of lumefantrine and artemether, respectively, were analysed using established methods. Pharmacogene variation analysis was undertaken using iPLEX microarray and PCR-RFLP. RESULTS: A total of 52 patients completed the study. Median parasite density from day 1 to 7 ranged from 0-2666/µL of blood, with days 3 and 7 recording 0 parasite density. Highest median plasma concentration for lumefantrine and desbutyl lumefantrine, which are the long-acting components of artemisinin-based combinations, was 4123.75 ng/mL and 35.87 ng/mL, respectively. Day 7 plasma lumefantrine concentration across all generic ACT brands was ≥ 200 ng/mL which potentially accounted for the parasitaemia profile observed. Monomorphism was observed for CYP3A4 variants, while there were observed variations in CYP2B6 and CYP3A5 alleles. Among the CYP3A5 genotypes, significant differences in genotypes and plasma concentration for DBL were seen on day 3 between 1/*1 versus *1/*6 (p = 0.002), *1/*3 versus *1/*6 (p = 0.006) and *1/*7 versus *1/*6 (p = 0.008). Day 7 plasma DBL concentrations showed a significant difference between *1/*6 and *1/*3 (p = 0.026) expressors. CONCLUSIONS: The study findings show that CYP2B6 and CYP3A5 pharmacogenetic variations may lead to higher plasma exposure of AL metabolites.

Availability of essential, generic medicines before and during COVID-19 at selected public pharmaceutical supply agencies in Ethiopia: a comparative cross-sectional study.

OBJECTIVES: Lockdowns and border closures impacted medicine availability during the COVID-19 pandemic. This study aimed to assess the availability of essential, generic medicines for chronic diseases at public pharmaceutical supply agencies in Ethiopia. DESIGN: Comparative cross-sectional study. SETTING: The availability of essential, generic medicines for chronic diseases was assessed at two public pharmaceutical supply agency hubs. PARTICIPANTS: The current study included public supply agency hub managers, warehouse managers and forecasting officers at the study setting. OUTCOMES: The assessment encompassed the availability of chronic medicines on the day of data collection, as well as records spanning 8 months before the outbreak and 1 year during the pandemic. A total of 22 medicines were selected based on their inclusion in the national essential drug list for public health facilities, including 17 medicines for cardiovascular disease and 5 for diabetes mellitus. RESULTS: The results of the study indicate that the mean availability of the selected basket medicines was 43.3% (95% CI: 37.1 to 49.5) during COVID-19, which was significantly lower than the availability of 67.4% (95% CI: 62.2 to 72.6) before the outbreak (p<0.001). Prior to COVID-19, the overall average line-item fill rate for the selected products was 78%, but it dropped to 49% during the pandemic. Furthermore, the mean number of days out of stock per month was 11.7 (95% CI: 9.9 to 13.5) before the outbreak of COVID-19, which significantly increased to 15.7 (95% CI: 13.2 to 18.2) during the pandemic, indicating a statistically significant difference (p<0.001). Although the prices for some drugs remained relatively stable, there were significant price hikes for some products. For example, the unit price of insulin increased by more than 130%. CONCLUSION: The COVID-19 pandemic worsened the availability of essential chronic medicines, including higher rates of stockouts and unit price hikes for some products in the study setting. The study's findings imply that the COVID-19 pandemic has aggravated already-existing medicine availability issues. Efforts should be made to develop contingency plans and establish mechanisms to monitor medicine availability and pricing during such crises.

Navigating the Management of Chronic Phase CML in the Era of Generic BCR::ABL1 Tyrosine Kinase Inhibitors.

Over the past several years, advances in research, treatment, and market dynamics have impacted treatment strategies in chronic myeloid leukemia in chronic phase (CML-CP). They include the broader availability of cost-effective generic imatinib, and soon other generic second-generation tyrosine kinase inhibitors (TKIs). Access to affordable generics means that all patients with CML-CP should have access to safe and highly effective lifelong therapies. When overall survival is the treatment endpoint, imatinib provides a good treatment value. Second-generation TKIs may be the best frontline strategy when treatment-free remission is the goal. Recent studies have shown maintained efficacy and reduced toxicity when TKIs are used at reduced dosing. Reduced-dose schedules of second-generation TKIs (which are less toxic and induce faster deep molecular responses) may render generic second-generation TKIs a more attractive treatment option. Adjusting the dose of TKI in the presence of mild-to-moderate, or even severe but reversible, adverse events may be preferable to switching to a different TKI. The selection of second-line and beyond therapies depends on the evolving patterns observed with frontline treatment. Dose-adjusted ponatinib schedules have demonstrated improved efficacy and safety in patients resistant to second-generation TKIs or those with T315I-mutated disease. For asciminib, longer-term follow-up is needed to better evaluate its safety and efficacy compared with ponatinib. Allogeneic stem cell transplantation represents a valid alternative to newer-generation TKIs, with a better treatment value when TKIs are priced at >$40,000/year.

Patents on Risk Evaluation and Mitigation Strategies for Prescription Drugs and Generic Competition.

This cross-sectional study identifies the prevalence of patents on risk evaluation and mitigation strategies and their association with delaying generic competition.

Out-of-pocket prescription drug costs for adults with cardiovascular risk factors under Amazon's direct-to-consumer pharmacy service.

BACKGROUND: US adults often overpay for generic prescription medications, which can lead to medication nonadherence that negatively impacts cardiovascular outcomes. As a result, new direct-to-consumer online medication services are growing in popularity nationwide. Amazon recently launched a $5/month direct-to-consumer medication subscription service (Amazon RxPass), but it is unclear how many US adults could save on out-of-pocket drug costs by using this new service. OBJECTIVES: To estimate out-of-pocket savings on generic prescription medications achievable through Amazon's new direct-to-consumer subscription medication service for adults with cardiovascular risk factors and/or conditions. METHODS: Cross-sectional study of adults 18-64 years in the 2019 Medical Expenditure Panel Survey. RESULTS: Of the 25,280,517 (SE ± 934,809) adults aged 18-64 years with cardiovascular risk factors or conditions who were prescribed at least 1 medication available in the Amazon RxPass formulary, only 6.4% (1,624,587 [SE ± 68,571]) would achieve savings. Among those achieving savings, the estimated average out-of-pocket savings would be $140 (SE ± $15.8) per person per year, amounting to a total savings of $228,093,570 (SE ± $26,117,241). In multivariable regression models, lack of insurance coverage (adjusted odds ratio [OR] 3.5, 95%CI 1.9-6.5) and being prescribed a greater number of RxPass-eligible medications (2-3 medications versus 1 medication: OR 5.6, 95%CI 3.0-10.3; 4+ medications: OR 21.8, 95%CI 10.7-44.3) were each associated with a higher likelihood of achieving out-of-pocket savings from RxPass. CONCLUSIONS: Changes to the pricing structure of Amazon's direct-to-consumer medication service are needed to expand out-of-pocket savings on generic medications to a larger segment of the working-age adults with cardiovascular risk factors and/or diseases.

A comparative study on vildagliptin brand and its generic equivalents using dissolution test as quality control measure tool.

Market drugs including brand or generic with poor quality, don't meet the acceptable standard guidelines. Vildagliptin is an important antidiabetic drugs used in monotherapy or in combinations protocols for treatment of diabetes mellites. The main goal of the current study is to assess the pharmaceutical equivalence of two marketed generics of vildagliptin 50 mg tablets compared to the branded product (Galvus 50 mg). The in vitro dissolution test was used as a quality control tool to obtain the dissolution profile of vildagliptin compared to the reference drug. The results revealed that all tested samples showed dissolution behavior like standard drug. Whole samples dissolution reached after 15 min in accordance with the standard. According to the similarity factors records, tested vildagliptin samples showed a comparable dissolution to the reference drug. The current work presents an in vitro protocol for quality evaluation of recently released generic drugs.

Immunosuppression with Generics in Liver and Kidney Transplantation: A Real-World Evidence Study.

Purpose: This study evaluates the use, benefit-risk profile, and economic impact of generic immunosuppressants (tacrolimus-TAC, cyclosporine-CsA, and mycophenolate-MYC) in kidney and liver transplant recipients compared to brand-name drugs. Patients and Methods: A retrospective multicentre observational study, involving four Italian regions, was conducted based on the national transplant Information system and regional healthcare claims data. The analysis focused on incident patients who received kidney and liver transplants between 2013 and 2019 and evaluated the use of generic of CsA, TAC, and MYC during the 30-day period following discharge. For each type of transplant and immunosuppressive agent, the benefit-risk profile of generic vs branded drugs in a two-year window was estimated by multivariate Cox models (HR; 95% CI). Furthermore, the potential cost savings per person associated with one year of treatment using generics were calculated. Results: The utilization of generic drugs showed a significant increase; over the study years, the proportion of users among kidney recipients ranged from 14.2% to 40.5% for TAC, from 36.9% to 56.7% for MYC, and from 18.2% to 94.7% for CsA. A great variability in generic uptake for region was found. A comparable risk-benefit profile between generic and branded formulations was shown for all immunosuppressors considered. Choosing generic immunosuppressants during maintenance could result in yearly savings of around 2000 euros per person for each therapy ingredient. Conclusion: The study shows an increasing proportion of patients using generic immunosuppressive drugs over time suggesting a growing acceptance of generics within the transplant community and reveals comparable risk-benefit profiles between the generic and branded formulations of TAC, CsA, and MYC. A significant variability in the use of generics immunosuppressive agents was found both at the regional level and among transplant centers and future research should delve into regional prescribing variations.

Perception of pharmacological equivalence of generics or biosimilars in healthcare professionals in Vienna.

PURPOSE: Due to constantly rising therapy costs, biosimilars and generic drugs have gained tremendous importance through recent decades. Nevertheless, the acceptance among healthcare workers regarding biosimilars and generic drugs in previously published international studies is considerably lower than the scientific data on equivalent safety and efficacy would suggest. The aim of this questionnaire-based survey was to determine the perception and knowledge regarding generic drugs and biosimilars by medical professionals from different healthcare facilities in Vienna, Austria. METHODS: The online questionnaire was sent to public and religious hospitals in Vienna, including the university hospital "Vienna General Hospital." In addition, doctors' offices were reached by sending out the questionnaire in the weekly news of the Vienna Medical Association. RESULTS: A total of 282 physicians and 311 graduated nurses took part in the study. 63% and 62% of the participants were convinced that generic respective biosimilar drugs were clinically equivalent to the original reference drug. On average, 1.6 out of 4 knowledge questions were answered correctly about generics, while only 0.87 out of 4 questions were answered accurately about biosimilars. CONCLUSION: The results of this study support the outcome from previous surveys demonstrating that a large proportion of healthcare professionals is still skeptical about generics and biosimilars. According to the results of this study, better education of the medical staff might ensure greater acceptance of these types of drugs.

Study of Factors to Increase the Usage Rate of Generic Drugs in Platelet Aggregation Inhibitors.

To reduce pharmacy-related medical expenses, it is necessary to reduce drug costs. One way to achieve this is by increasing the usage rate of generic drugs. The purpose of this study was to identify platelet aggregation inhibitors (PAIs) that contribute to high drug costs and are sold as brand-name drugs in order to increase the usage rate of generic drugs, and to analyze the factors that affect the usage rate of generic drug. We conducted a cross-sectional study based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data Japan (NODJ) of the Ministry of Health, Labor and Welfare and datasets containing related medical information from official statistical surveys such as the Basic Survey on Wage Structure. Monthly personal income in each prefecture were negatively correlated with outpatient out-of-hospital and outpatient in-hospital prescriptions of the PAIs clopidogrel (75 mg), cilostazol (50 mg), cilostazol (100 mg), and ticlopidine (100 mg), but not between monthly personal income and outpatient out-of-hospital prescription of ticlopidine (100 mg). For outpatient out-of-hospital prescriptions and outpatient in-hospital prescriptions, negative correlation was generally observed between the usage rate of generic drug and monthly personal income, except for ticlopidine (100 mg), which has the lowest price among the brand-name drugs. The usage rate of generic PAIs is negatively correlated with monthly personal income. Promoting the use of generic drugs among high-income earners might be necessary to further increase the usage rate of generic drug.

Effectiveness of generic sofosbuvir in the treatment of chronic hepatitis C virus infection in Saudi patients.

OBJECTIVES: To assess the effectiveness of generic sofosbuvir (SOF) and branded daclatasvir (DCV) for the treatment of chronic hepatitis C virus (HCV)infected patients. METHODS: This retrospective study, performed in a single center in Saudi Arabia between August 2017 and July 2022, we enrolled 140 consecutive patients with HCV who received generic SOF and branded DCV. The primary outcome was sustained virologic response at week 12 (SVR12). RESULTS: The majority of the patients were female (62.1%), infected with genotype 4 (57.9%), and treatment-naïve in 120 (85.7%) patients with baseline cirrhosis in 55 (39.3%). The mean patient age was 61±13.6 years. In the intention-to-treat analysis, 131 (93.6%) patients achieved SVR12. Moreover, 85.7%, 100%, 100%, 88.9%, and 96.3% of genotypes 1a, 1b, 2, 3, and 4, respectively, achieved SVR12. In the per-protocol analysis, 131 (96.3%) patients achieved an SVR of 12. Additionally, 92.3%, 100%, 100%, 88.9%, and 98.7% of the patients with genotypes 1a, 1b, 2, 3, and 4, respectively, achieved SVR12. No HCV virologic breakthroughs occurred. In the subgroup analysis, SVR12 rates were comparable regardless of baseline characteristics, such as treatment history, cirrhosis, and hepatocellular carcinoma. Patients achieving SVR12 showed a significant improvement in post-treatment serum liver enzyme and total bilirubin levels. CONCLUSION: The findings of our study confirm the effectiveness of generic sofosbuvir as a treatment option for HCV infection.

Evolution of antiseizure medication use and cost in the United States of America 2006-2021.

OBJECTIVE: To describe the evolution in use and cost of antiseizure medications (ASM) in the United States of America (USA). METHODS: Retrospective descriptive study using the IBM MarketScan Commercial Database (data of privately-insured patients) for the years 2006 to 2021. We identified patients with epilepsy who were on ASM. We adjusted cost for inflation with the Gross Domestic Product Implicit Price Deflator. RESULTS: We evaluated 347,158 patients (46.9 % males; median (p25-p75) age: 33 (17-49) years; 28 % with pediatric-onset epilepsy and 72 % with adult-onset epilepsy) with a total of 1,385,382 person-years and 588,285,065 ASM prescription days. The most commonly prescribed (as percentage of prescription days) ASMs in 2006 were valproate (18 %) and lamotrigine (17 %) in pediatric-onset epilepsy and phenytoin (21 %) and carbamazepine (17 %) in adult-onset epilepsy, but starting in the 2010s, levetiracetam and lamotrigine became the most commonly prescribed ASMs in both pediatric-onset (in 2021, levetiracetam 25 %, lamotrigine 16 %) and adult-onset (in 2021, levetiracetam 27 %, lamotrigine 20 %) epilepsy. The proportion of generic ASM use increased 3.6-fold: from 23 % of prescription days in 2006 to 83 % of prescription days in 2021. The median (p25-p75) average wholesale price (AWP) per person-year increased by 102 % from $2,684 ($990-$5,509) in 2006 to $5,417 ($2,858-$12,310) in 2021. The increases were greater in absolute terms for brand-name ASMs by 419 %: $3,109 ($1,564-$5,068 in 2006 and $16,149 ($12,950-$23,377) in 2021 than for generic ASMs by 462 %: $699 ($457-$1,678) in 2006 and $3,931 ($2,618-$6,081) in 2021. The costs directly borne by the patient (copay, coinsurance, deductibles, and pharmacy processing fees) increased by 69 % for brand-name ASMs from $393 ($246-$570) in 2006 to $665 ($335-$1,308) in 2021, but decreased by 37 % for generic ASMs from $147 ($98-$213) in 2006 to $92 ($51-$141) in 2021. CONCLUSIONS: The median cost of ASMs per person-year approximately doubled from 2006 to 2021. The increase in use of generic ASMs probably helped buffer the growing costs of ASMs. However, generic ASMs already represent 83 % of prescription days in 2021, with limited room to further contain costs by just increasing the proportion of generics.