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.

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.

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.

Strategies to reduce out-of-pocket medication costs for Canadians with peripheral arterial disease.

BACKGROUND: Given that peripheral arterial disease (PAD) disproportionately affects people of lower socioeconomic status, out-of-pocket expenses for preventive medications are a major barrier to their use. We carried out a cost comparison of drug therapies for PAD to identify prescribing strategies that minimize out-of-pocket expenses for these medications. METHODS: Between March and June 2019, we contacted outpatient pharmacies in Hamilton, Ontario, Canada, to assess pricing of pharmacologic therapies at dosages included in the 2016 American College of Cardiology/American Heart Association guideline for management of lower extremity PAD. We also gathered pricing information for supplementary charges, including delivery, pill splitting and blister packaging. We calculated prescription prices with and without dispensing fees for 30-day brand-name and generic prescriptions, and 90-day generic prescriptions. RESULTS: Twenty-four pharmacies, including hospital-based, independent and chain, were included in our sample. In the most extreme scenario, total 90-day medication costs could differ by up to $1377.26. Costs were affected by choice of agent within a drug class, generic versus brand-name drug, quantity dispensed, dispensing fee and delivery cost, if any. CONCLUSION: By opting for prescriptions for 90 days or as long as possible, selecting the lowest-cost generic drugs available in each drug class, and identifying dispensing locations with lower fees, prescribers can minimize out-of-pocket patient medication expenses. This may help improve adherence to guideline-recommended therapies for the secondary prevention of vascular events in patients with PAD.

Reimbursement to Pharmacies for Generic Drugs by Medicare Part D Sponsors.

This study evaluates whether organizations that offer Medicare Part D plans (referred to as Part D sponsors) overpay pharmacies for generic drugs.

The Problem of Limited-Supply Agreements for Medicare Price Negotiation.

This Viewpoint discusses how limited-supply agreements (introduction of generic products in reduced volumes) might thwart efforts to negotiate lower prices on prescription drugs in the US.

Patents and Regulatory Exclusivities on GLP-1 Receptor Agonists.

Importance: Glucagon-like peptide 1 (GLP-1) receptor agonists were first approved for the treatment of type 2 diabetes in 2005. Demand for these drugs has increased rapidly in recent years, as indications have expanded, but they remain expensive. Objective: To analyze how manufacturers of brand-name GLP-1 receptor agonists have used the patent and regulatory systems to extend periods of market exclusivity. Evidence Review: The annual US Food and Drug Administration's (FDA) Approved Drug Products With Therapeutic Equivalence Evaluations was used to identify GLP-1 receptor agonists approved from 2005 to 2021 and to record patents and nonpatent statutory exclusivities listed for each product. Google Patents was used to extract additional data on patents, including whether each was obtained on the delivery device or another aspect of the product. The primary outcome was the duration of expected protection from generic competition, defined as the time elapsed from FDA approval until expiration of the last-to-expire patent or regulatory exclusivity. Findings: On the 10 GLP-1 receptor agonists included in the cohort, drug manufacturers listed with the FDA a median of 19.5 patents (IQR, 9.0-25.8) per product, including a median of 17 patents (IQR, 8.3-22.8) filed before FDA approval and 1.5 (IQR, 0-2.8) filed after FDA approval. Fifty-four percent of all patents listed on GLP-1 receptor agonists were on the delivery devices rather than active ingredients. Manufacturers augmented patent protection with a median of 2 regulatory exclusivities (IQR, 0-3) obtained at approval and 1 (IQR, 0.3-4.3) added after approval. The median total duration of expected protection after FDA approval, when accounting for both preapproval and postapproval patents and regulatory exclusivities, was 18.3 years (IQR, 16.0-19.4). No generic firm has successfully challenged patents on GLP-1 receptor agonists to gain FDA approval. Conclusions and Relevance: Patent and regulatory reform is needed to ensure timely generic entry of GLP-1 receptor agonists to the market.

Willingness to pay brand premiums for generic medicines in Kenya: A bidding game experiment.

BACKGROUND: Recent growth in the market share of higher priced branded generic medicines in low- and middle-income countries (LMICs) has raised concerns around affordability and access. We examined consumer willingness to pay (WTP) for branded versus unbranded generic non-communicable disease (NCD) medicines in Kenya. METHODS: We randomly assigned NCD patients to receive a hypothetical offer for either a Novartis Access-branded medicine or for an unbranded generic equivalent. We then analysed WTP data captured using a bidding game methodology. RESULTS: We found that WTP for Novartis Access medicines was on average 23% higher than for unbranded generic equivalents (p = 0.009). The WTP brand premium was driven almost entirely by wealthier patients. CONCLUSIONS: Our findings suggest that the dominance of branded generics in LMICs like Kenya reflect in part consumer preferences for these medicines. Governments and other health sector actors may be justified in intervening to improve access to these medicines and equivalent non-branded generics, particularly for the poorest patients who appear to have no preference for branded medicines.

An empirical study of the impact of generic drug competition on drug market prices in China.

Introduction: Generic substitution is encouraged to reduce pharmaceutical spending in China, and with incentive policies, the market size of the generic drug continues to rise. To find out how the generic competition affects drug price in this area, this study examines how the quantity of generic drug manufacturers can influence average drug price in the Chinese market. Methods: This study uses a rigorous selection of drugs from the 2021 China's National Reimbursement Drug List (NRDL), and uses drug-level fixed effects regressions to estimate the relationship between competition and price within each drug. Results: We note that drug prices decline with increasing competition in the Chinese market, but not in a perfectly linear manner, with marginal price declines decreasing after the fourth entrant and "rebounding" at subsequent entrants, especially the sixth. Discussion: The findings suggest the importance of maintaining effective competition between suppliers to control prices, and that the government needs to further control generic pricing, especially for late entry generics, to ensure effective competition in the Chinese market.

Differential Effects by Mental Health Status of Filling the Medicare Part D Coverage Gap.

OBJECTIVE: The objective of this study was to study how changes in insurance benefit design affect medication use of older adults with mental disorders. DATA SOURCES: US Medicare claims data from 2007 to 2018. STUDY DESIGN: Exploiting the gradual elimination of the Medicare prescription drug coverage gap beginning in 2011, we examine the effects on medication use and out-of-pocket spending by drug type with a difference-in-differences approach. We identify subpopulations by mental disorder and compare the estimates across mental health groups and to the general Medicare population. PRINCIPAL FINDINGS: Closing the gap substantially reduced individuals' out-of-pocket spending, and the reduction was larger for those with more severe mental disorders. The policy led to a statistically significant increase in branded drugs used for the Medicare population (0.91; P<0.01; 12.12% increase), beneficiaries with severe mental disorders (2.71; P<0.01; 11.13% increase), and common mental disorders (2.63; P<0.01; 11.62% increase), whereas such effect for beneficiaries with Alzheimer disease and dementia (AD) is substantially smaller (0.44; P<0.01; 1.83% increase). In contrast, the policy decreased generic drugs used by about 3%-5% for all groups. Overall, beneficiaries without mental health illness have a statistically significant increase in total medication use (2.05%) following the coverage gap closure, while all 3 mental health groups have either no statistically significant changes or a small reduction in total mediation use (AD, -1.26%). CONCLUSIONS: Patients' responses to price changes vary across mental disorders and by drug type. The impact on branded drug utilization among those with AD is particularly small. Our findings suggest that lowering medication costs has differential impacts across diseases and may not be sufficient to improve adherence for all conditions, in particular those with severe mental health disorders such as AD.

Do Cost-Effectiveness Analyses Account for Drug Genericization? A Literature Review and Assessment of Implications.

OBJECTIVES: We investigated how health technology assessment (HTA) organizations around the world have handled drug genericization (an allowance for future generic drug entry and subsequent drug price declines) in their guidelines for cost-effectiveness analyses (CEAs). We also analyzed a large sample of published CEAs to examine prevailing practices in the field. METHODS: We reviewed 43 HTA guidelines to determine whether and how they addressed drug genericization in their CEAs. We also selected a sample of 270 US-based CEAs from the Tufts Medical Center's CEA Registry, restricting the sample to studies on pharmaceuticals published from 1991 to 2019 and to analyses taking a lifetime time horizon. We determined whether each CEA examined genericization (and if so, whether in base case or sensitivity analyses), and how inclusion of genericization influenced the estimated incremental cost-effectiveness ratios. RESULTS: Fourteen (33%) of the 43 HTA guidelines mention genericization for CEAs and 4 (9%) recommend that base case analyses include assumptions about future drug price changes due to genericization. Most published CEAs (95%) do not include assumptions about future generic prices for intervention drugs. Only 2% include such assumptions about comparator drugs. Most studies (72%) conduct sensitivity analyses on drug prices unrelated to genericization. CONCLUSIONS: The omission of assumptions about genericization means that CEAs may misrepresent the long run opportunity costs for drugs. The field needs clearer guidance for when CEAs should account for genericization, and for the inclusion of other price dynamics that might influence a drug's cost-effectiveness.

A comprehensive analysis of selected medicines collected from private drug outlets of Dhaka city, Bangladesh in a simple random survey.

Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of selected medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI 5.7-14.6) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. This study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.

Financial Burden of Drugs Prescribed for Cancer-Associated Symptoms.

PURPOSE: The financial toxicity of anticancer drugs is well-documented, but little is known about the costs of drugs used to manage cancer-associated symptoms. METHODS: We reviewed relevant guidelines and compiled drugs used to manage seven cancer-associated symptoms (anorexia and cachexia, chemotherapy-induced peripheral neuropathy, constipation, diarrhea, exocrine pancreatic insufficiency, cancer-associated fatigue, and chemotherapy-induced nausea and vomiting). Using GoodRx website, we identified the retail price (cash price at retail pharmacies) and lowest price (discounted, best-case scenario of out-of-pocket costs) for patients without insurance for each drug or formulation for a typical fill. We describe lowest prices here. RESULTS: For anorexia and cachexia, costs ranged from $5 US dollars (USD; generic olanzapine or mirtazapine tablets) to $1,156 USD (brand-name dronabinol solution) and varied widely by formulation of the same drug or dosage: for olanzapine 5 mg, $5 USD (generic tablet) to $239 USD (brand-name orally disintegrating tablet). For chemotherapy-induced peripheral neuropathy, costs of duloxetine varied from $12 USD (generic) to $529 USD (brand-name). For constipation, the cost of sennosides or polyethylene glycol was <$15 USD, whereas newer agents such as methylnaltrexone were expensive ($1,001 USD). For diarrhea, the cost of generic loperamide or diphenoxylate-atropine tablets was <$15 USD. For exocrine pancreatic insufficiency, only brand-name formulations were available, range of cost, $1,072 USD-$1,514 USD. For cancer-associated fatigue, the cost of generic dexamethasone or dexmethylphenidate was <$15 USD, whereas brand-name modafinil was more costly ($1,284 USD). For a 4-drug nausea and vomiting prophylaxis regimen, costs ranged from $181 USD to $1,430 USD. CONCLUSION: We highlight the high costs of many symptom control drugs and the wide variation in the costs of these drugs. These findings can guide patient-clinician discussions about cost-effectively managing symptoms, while promoting the use of less expensive formulations when possible.

Evaluating the impact of single exit pricing (SEP) on medicine product withdrawal from the private healthcare market in South Africa.

BACKGROUND: The introduction of medicine pricing policies in South Africa (SA) in the form of single exit pricing (SEP) provided a mechanism to improve medicine price transparency and reduce the medicine price and inflation. However, regulation of medicine prices may have further unforeseen effects on the availability of medicine. This research presents the impact of SEP on discontinuation of medicine products on the private healthcare market in SA. OBJECTIVES: To evaluate the impact of SEP legislation on the availability of medicines in the SA private health sector in terms of withdrawal of medicines from the market. METHODS: A descriptive, quantitative analysis of all registered medicines on the SA market by stock-keeping units (SKUs) was done to establish medicine products that were withdrawn from the market by SKUs during a 14-year period (2001 - 2014). RESULTS: A total of 152 manufacturers discontinued 3 691 SKUs between 2001 and 2014. The mean number of discontinuations per generic manufacturer was 22.34 (standard deviation (SD) 58.11), while innovator manufacturers discontinued a mean of 27.61 (41.89). The largest number of SKUs were commercially withdrawn in 2002 (n=603), followed by discontinuations in 2003 (n=463) and 2004 (n=407). There was a negative correlation between number of discontinued SKUs per year and SEP increase (Pearson's correlation coefficient r ‒0.414; p=0.14). The results showed that SEP and a transparent pricing policy may have had an impact on SKU withdrawal from the market prior to SEP implementation. CONCLUSIONS: The result of reduced product availability on the market and its impact on the cost and quality of healthcare to the patient need to be regularly monitored and evaluated to ascertain if direct price regulations achieve the intended outcomes. Other intended or unintended effects on pharmaceutical market dynamics should also be evaluated.

Trends in Use and Expenditures for Brand-name Statins After Introduction of Generic Statins in the US, 2002-2018.

Importance: The high and increasing expenditures for prescription medications in the US is a national problem. Objective: To explore the association of generic statin competition on relevant use and cost savings and to provide use and expenditure trends for all available statins for private and public payers and for out-of-pocket spending. Design, Setting, and Participants: This survey study evaluated data from the January 1, 2002, to December 31, 2018, Medical Expenditure Panel Survey by using a difference-in-differences analysis. Participants included noninstitutionalized individual statin users. Data were analyzed from November 1, 2020, to March 30, 2021. Exposures: The market entry of 5 generic statin medications (atorvastatin, rosuvastatin, simvastatin, lovastatin, and pravastatin). Main Outcomes and Measures: National- and individual-level reductions in the annual number of statin purchases and total expenditures across private insurance, public insurance (Medicaid and Medicare), and out-of-pocket spending (presented in 2018 US dollars). Results: Between January 1, 2002, and December 31, 2018, an average of 21.35 million statins (95% CI, 16.7-25.5 million) were purchased annually, with an average total annual cost of $24.5 billion (95% CI, $18.2-$28.8 billion). The number of brand-name statin purchases decreased by 90.9% (95% CI, 56%-98%) nationally and 27.4% (95% CI, 13%-40%) individually after the end of market exclusivity. Among major payers, the end of market exclusivity was associated with individual cost savings of $370.00 (95% CI, $430.70-$309.20) for private insurers, $281.00 (95% CI, $346.80-$215.30) for Medicare, $72.34 (95% CI, $95.22-$49.46) for Medicaid, and $211.90 (95% CI, $231.20-$192.50) for out-of-pocket spending. Combining all payers, the decrease translates to $925.60 (95% CI, $1005.00-$846.40) of annual savings per individual and $11.9 billion (95% CI, $10.9-$13.0 billion) for the US. Conclusions and Relevance: Results of this survey study suggest that full generic competition of statins was associated with significant cost savings across all major payers within the US health care system.

Availability, prices and affordability of essential medicines: A cross-sectional survey in Hanam province, Vietnam.

OBJECTIVE: To measure medicines' prices, availability, and affordability in Hanam, Vietnam. METHODS: The standardized methodology developed by the World Health Organization (WHO) and Health Action International was used to survey 30 essential medicines (EMs) in 30 public health facilities and 35 private medicine outlets in 2020. The availability of medicine was computed as the percentage of health facilities in which this medicine was found on the data-collection day. International reference prices (IRPs) from Management Sciences for Health (2015) were used to compute Median Price Ratio (MPR). The affordability of treatments for common diseases was computed as the number of days' wages of the lowest-paid unskilled government worker needed to purchase medicines prescribed at a standard dose. Statistic analysis was done using R software version 4.1.1. RESULTS: The mean availability of originator brands (OBs) and lowest-priced generics (LPGs) was 0.7%, 63.2% in the public sector, and 13.7%, 47.9% in the private sector, respectively. In private medicine outlets, the mean availability of both OBs and LPGs in urban areas was significantly higher than that in rural areas (p = 0.0013 and 0.0306, respectively). In the public sector, LPGs' prices were nearly equal to their IRPs (median MPRs = 0.95). In the private medicine outlets, OBs were generally sold at 6.24 times their IRPs while this figure for LPGs was 1.65. The affordability of LPGs in both sectors was good for all conditions, with standard treatments costing a day's wage or less. CONCLUSION: In both sectors, generic medicines were the predominant product type available. The availability of EMs was fairly high but still lower than WHO's benchmark. A national-scale study should be conducted to provide a comprehensive picture of the availability, prices, and affordability of EMs, thereby helping the government to identify the urgent priorities and improving access to EMs in Vietnam.

Association of Generic Competition With Price Decreases in Physician-Administered Drugs and Estimated Price Decreases for Biosimilar Competition.

Importance: Price decreases of biologic and biosimilar products in Medicare Part B have been minimal, even with biosimilar competition. Medicare reimburses clinicians for biologics and biosimilars differently than for brand-name and generic drugs, which has generated greater price reductions. Objective: To characterize the nature of price competition among brand-name and generic drugs under Medicare Part B and to estimate the cost savings to the program of subjecting biologic and biosimilar therapies to a similar price competition. Design, Setting, and Participants: This cohort study analyzed all brand-name drugs and their approved generic versions as well as biologics and biosimilars that were reimbursed under Medicare Part B from quarter 1 of 2005 to quarter 2 of 2021. Two separate data sets were created: brand-name and generic drugs as well as biologics and biosimilars data sets. Brand-name products with generic versions that were introduced before 2005 were excluded, and so were vaccines. Exposures: Number of generic and biosimilar competitors over time. Main Outcomes and Measures: Price change as a percentage of the brand-name drug or biologic price in the quarter before generic or biosimilar competition. Price change was modeled using a linear, fixed-effects time series regression, with the number of generic or biosimilar competitors as the main covariate. Time was expressed as the number of quarters since the first generic or biosimilar competitor entered the market. Savings were estimated by projecting the regression model of brand-name and generic drug competition to observed biologic and biosimilar competition and by applying the estimated price reduction to actual Medicare spending for those products from 2015 to 2019. Results: Of the 988 Healthcare Common Procedure Coding System codes identified, 50 (5.0%) met the inclusion criteria for the brand-name and generic drug data set and 28 (2.8%) met the criteria for the biologic and biosimilar data set. The first generic competitor was associated with reduced drug prices by 17.0%, the second competitor with a 39.5% decrease, the third competitor with a 52.5% decrease, and the fourth and more competitors with a 70.2% decrease (price decline was measured from brand-name drug price before the first generic competitor rather than from price established with fewer competitors). If biologics and biosimilars were subject to the same Medicare reimbursement framework as brand-name and generic drugs, Medicare spending on these products was estimated to have been 26.6% lower ($1.6 billion) from 2015 to 2019. Conclusions and Relevance: This study found minimal uptake of biosimilars and limited price reductions for biologics and biosimilars under the current Medicare Part B reimbursement policy. Adopting the bundled biosimilar reimbursement structure for biologic and biosimilar therapies may be associated with substantial savings and encourage greater biosimilar market entry.