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Importance: For patients with heart failure with reduced ejection fraction (HFrEF), treatment with sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, has become increasingly preferred over angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs). However, sacubitril-valsartan is much more expensive than generic ACE-I/ARBs. It is unknown whether the high cost of sacubitril-valsartan is offset by lower spending on hospitalizations and other treatments., Objective: To compare total and out-of-pocket health care spending among Medicare beneficiaries initiating sacubitril-valsartan vs ACE-I/ARBs for HFrEF., Design, Setting, and Participants: This was a cohort study using data from Medicare fee-for-service claims with propensity score matching of Medicare beneficiaries with HFrEF. Data analysis was performed from November 2022 to December 2023., Exposure: Initiation of sacubitril-valsartan or an ACE-I/ARB. Patients were matched by propensity score based on 104 covariates, including demographic characteristics, comorbidities, baseline annual spending, and baseline use of health care services., Main Outcomes and Measures: Mean total and out-of-pocket health care expenditures during the 365 days after initiating sacubitril-valsartan or an ACE-I/ARB. Censoring for incomplete follow-up was addressed using Kaplan-Meier probability weighting. Cost differences, cost ratios, and 95% CIs were calculated using a nonparametric bootstrapping method with 500 samples drawn with replacement., Results: Among 13 755 matched pairs of Medicare patients with HFrEF (mean [SD] age, 77.5 [7.5] years; 5138 [39%] 80 years or older; 9949 females [36%] and 17 561 males [64%]), mean annual total health care spending per person was similar for sacubitril-valsartan initiators and ACE-I/ARB initiators (difference, $701; 95% CI, -$132 to $1593). Sacubitril-valsartan initiators had higher prescription drug costs (difference, $1911; 95% CI, $1704 to $2113), lower inpatient costs (difference, -$790; 95% CI, -$1468 to -$72), lower outpatient costs (difference, -$330; 95% CI, -$664 to -$11), and higher annual out-of-pocket spending (difference, $109; 95% CI, $13 to $208)., Conclusions and Relevance: This cohort study found that Medicare beneficiaries initiating sacubitril-valsartan to treat HFrEF had similar total health care spending as those initiating ACE-I/ARBs; higher prescription drug spending was offset by lower inpatient and outpatient spending. However, sacubitril-valsartan use was associated with higher patient out-of-pocket costs, which may exacerbate health disparities and limit access and affordability.

Importance: Academic detailing (interactive educational outreach) is a widely used strategy to encourage evidence-based prescribing by clinicians., Objective: To evaluate academic detailing programs targeted at improving prescribing behavior and describe program aspects associated with positive outcomes., Evidence Review: A systematic search of MEDLINE from April 1, 2007, through December 31, 2022, was performed for randomized trials and nonrandomized studies of academic detailing interventions to improve prescribing. Academic detailing was defined as evidence-based medication education outreach delivered interactively to individuals or small groups of prescribers. Only studies that measured prescribing outcomes were included. Two investigators independently assessed studies for risk of bias using validated assessment tools. Among all studies rated as having low risk of bias and randomized trials rated as having moderate risk of bias, the absolute change in the proportion of patients using the targeted medications and the proportion of studies that led to significant changes in 1 or more prescribing outcome were determined. The data analysis was performed between January 25, 2022, and November 4, 2024., Findings: The 118 studies identified varied by setting (eg, inpatient, outpatient) and academic detailing delivery (eg, individual vs groups of prescribers). The most common therapeutic targets were antibiotic overuse (32 studies [27%]), opioid prescribing (24 studies [20%]), and management of mental health conditions (16 studies [14%]) and cardiovascular disease (13 studies [11%]). Most studies (66 [56%]) combined academic detailing with other interventions (eg, audit and feedback, electronic health record reminders). Among 36 studies deemed to have the lowest risk of bias, 18 interventions (50%; 95% CI, 33%-67%) led to significant improvements in all prescribing outcomes, and 7 (19%; 95% CI, 8%-36%) led to significant improvements in 1 or more prescribing outcomes. The median absolute change in the proportion of patients using the targeted medication or medications was 4.0% (IQR, 0.3%-11.3%) in the intended direction., Conclusions and Relevance: In this systematic review of academic detailing interventions addressing evidence-based prescribing, most interventions led to substantial changes in prescribing behavior, although the quality of evidence varied. These findings support the use of academic detailing to bring about more evidence-based prescribing in a variety of clinical settings.

Objective: To determine whether annual changes in prices for clinician-administered drugs are associated with changes in patient out-of-pocket costs., Data Sources and Study Setting: National commercial claims database, 2009 to 2018., Study Design: In a serial, cross-sectional study, we calculated the annual percent change in manufacturer list prices and net prices after rebates. We used two-part generalized linear models to assess the relationship between annual changes in price with (1) the percentage of individuals incurring any out-of-pocket costs and (2) the percent change in median non-zero out-of-pocket costs., Data Collection/extraction Methods: We created annual cohorts of privately insured individuals who used one of 52 brand-name clinician-administered drugs., Principal Findings: List prices increased 4.4%/yr (interquartile range [IQR], 1.1% to 6.0%) and net prices 3.3%/yr (IQR, 0.3% to 5.5%). The median percentage of patients with any out-of-pocket costs increased from 38% in 2009 to 48% in 2018, and median non-zero annual out-of-pocket costs increased by 9.6%/yr (IQR, 4.1% to 15.4%). There was no association between changes in prices and out-of-pocket costs for individual drugs., Conclusions: From 2009 to 2018, prices and out-of-pocket costs for brand-name clinician-administered drugs increased, but these were not directly related for individual drugs. This may be due to changes to insurance benefit design and private insurer drug reimbursement rates., (© 2024 Health Research and Educational Trust.)

Background: Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) that is now preferred over angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin-II-receptor blockers (ARBs) for treating heart failure with reduced ejection fraction (HFrEF). Primary medication adherence to a costly brand-name ARNI, compared to inexpensive generic ACE-Is or ARBs, is unknown., Methods: This cohort study used a linked database of electronic health records and Medicare fee-for-service claims from a large integrated health care system in Boston to compare primary medication adherence among Medicare beneficiaries with HFrEF newly prescribed sacubitril-valsartan, those newly prescribed a generic ACE-I or ARB, and those switching from an ACE-I or ARB to sacubitril-valsartan. The primary outcome was the proportion of individuals who filled their first prescription for any ARNI, ACE-I, or ARB within 90 days; a secondary outcome was the mean number of days to first fill. We used logistic regression to adjust for variations in patient characteristics, including demographics, comorbidities, medication use, and qualification for subsidized out-of-pocket prescription drug costs., Results: Among 50 new sacubitril-valsartan prescription recipients, 33 (66%) demonstrated primary adherence at 90 days, compared to 141 of 231 (61%) new ACE-I or ARB prescription recipients (adjusted odds ratio 1.32, 95% CI, 0.63-2.73, P = .51). The mean time to first fill was 18 days for those prescribed sacubitril-valsartan and 9 days for those prescribed generic ACE-Is or ARBs (P < .001). By contrast, primary adherence at 90 days was higher (329 of 364, 90%) among those who switched from a generic ACE-I or ARB to newly prescribed sacubitril-valsartan., Conclusions: In this small, single-center cohort study of Medicare beneficiaries with HFrEF, there was no difference in primary medication adherence among individuals newly prescribed sacubitril-valsartan and those newly prescribed generic ACE-Is or ARBs, although it took sacubitril-valsartan prescription recipients longer to fill their medication. Adherence was high among patients switching from an ACE-I or ARB to sacubitril-valsartan, suggesting that this switch was not associated with interruptions in renin-angiotensin blockade., (Published by Elsevier Inc.)

Importance: In the US, many patients struggle to afford prescription drugs, leading to adverse health outcomes. To improve cost-related medication nonadherence, prescribers and clinical staff must understand how to assist patients in overcoming high prescription drug costs., Observations: We reviewed the benefits and limitations of 7 strategies to help patients afford prescription drugs: co-payment cards, patient assistance programs, pharmacy coupons, direct-to-consumer pharmacies, public assistance programs, international online pharmacies, and real-time prescription benefit tools. We created an algorithm to help clinicians identify appropriate strategies based on a patient's health insurance and the type of drug (brand-name vs generic). For example, co-payment cards can lower out-of-pocket costs for privately insured patients taking brand-name prescription drugs. For uninsured individuals or those with public insurance like Medicare Part D who meet financial eligibility criteria, patient assistance or public assistance programs may be available. All patients, regardless of health insurance, can forgo insurance and purchase drugs directly using pharmacy coupons or direct-to-consumer pharmacies, which sometimes offer lower prices for generic drugs compared to insurance. For insured patients, such purchases do not count toward insurance deductibles or annual out-of-pocket maximums. Online international pharmacies provide a last resort for patients in need of brand-name drugs who lack affordable domestic options. Increasingly, prescribers can use real-time prescription drug benefit tools to estimate patient out-of-pocket costs and identify alternative lower-cost treatments for insured patients, but these tools can be inaccurate or incomplete., Conclusions and Relevance: The current patchwork of strategies to help patients manage high prescription drug costs highlights the structural and policy challenges within the US prescription drug market that impede affordable access for some patients. While these strategies provide tangible solutions for clinicians to help patients access medically appropriate but costly medications, they do not address the root causes of high drug prices.

Purpose: Research and regulatory approval for pediatric uses of prescription drugs often lag years after adult approvals, during which time substantial off-label use of medications in children can occur. We evaluated whether US Food and Drug Administration (FDA) regulatory actions affected the pediatric use of omalizumab, a biologic drug used to treat asthma., Methods: In this serial cross-sectional study, we identified quarterly cohorts of children (0-18 years) with moderate-to-severe asthma within two large national claims databases of those with commercial insurance and Medicaid from 2003 to 2019. Using an interrupted time-series analysis, we fit segmented linear regression models to identify changes in the incidence of omalizumab use in 6-11-year-old children compared with 12-18-year-olds after two time points: (1) 2009Q3 when an FDA advisory committee voted against use for 6-11-year-old children and (2) 2016Q2 when FDA expanded omalizumab's labeling to include 6-11-year-old children., Results: We identified 9298 new pediatric omalizumab users (84% Medicaid). Among 6-11-year-old children, the incidence of omalizumab use did not change following the FDA's initial review of evidence in 2009 and increased after 2016 Q2 FDA approval for this age group in both Medicaid (58 per 100 000 children with asthma, 95% confidence interval [CI] 27-89, p < 0.001) and commercial insurance (57 per 100 000, 95% CI 21-94, p = 0.003) compared with 12-18-year-old children., Conclusions: The use of omalizumab among asthmatic children aged 6-11 years remained steady after FDA advisory committee concerns in 2009 and increased after FDA expanded the indication to include this population in 2016. Additional market incentives may help to ensure the timely generation of evidence and regulatory approval of medications for children., (© 2024 John Wiley & Sons Ltd.)

Background: Direct-to-consumer (DTC) pharmacies sell generic prescription drugs, often at lower prices than traditional retail pharmacies; however, not all drugs are available, and prices vary., Objective: To determine the availability and cost of generic drugs at DTC pharmacies., Design: Cross-sectional study., Setting: Five national DTC pharmacies in April and May 2023., Participants: Each qualifying form of 100 generic drugs with the highest cost-per-patient (expensive) and the 50 generic drugs with the highest number of patients (common) in Medicare Part D in 2020 MAIN MEASURES: Availability of these drugs and the lowest DTC pharmacy price for a standardized drug strength and supply (e.g., 30 pills), compared to GoodRx retail pharmacy prices., Key Results: Of the 118 expensive generic dosage forms, 94 (80%) were available at 1 or more DTC pharmacies; out of 52 common generic dosage forms, 51 (98%) were available (p < 0.001). Of the 88 expensive generics available in comparable quantities and strengths across pharmacies, 42 (47%) had the lowest cost at Amazon, 23 (26%) at Mark Cuban Cost Plus Drug Company, 13 (14%) at Health Warehouse, and 12 (13%) at Costco; for 51 common generic formulations, 16 (31%) had the lowest cost at Costco, 14 (27%) at Amazon, 10 (20%) at Walmart, 6 (12%) at Health Warehouse, and 5 (10%) at Mark Cuban Cost Plus Drug Company. For the 77 expensive generics with available GoodRx retail pharmacy prices, the median cost savings at DTC pharmacies were $231 (95% CI, $129-$792) or 76% (IQR, 53-91%); for 51 common generics, savings were $19 (95% CI, $10-$34) or 75% (IQR, 67-83%)., Conclusions: Many of the most expensive generic drugs are unavailable at direct-to-consumer pharmacies. Meanwhile, less expensive, commonly used generics are widely available, but drug prices vary by pharmacy and savings are modest, requiring patients to shop around for the lowest cost., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Among 196,766 commercially insured and Medicare Advantage patients who newly initiated biologic drugs with available biosimilar versions, biosimilar initiation increased from 1 percent in 2013 to 34 percent in 2022. Patients were less likely to initiate biosimilars if they were younger than age eighteen or the drug was prescribed by a specialist or administered in a hospital outpatient facility.

Background: Originator drug manufacturers use several strategies to delay generic competition in the USA, but it remains unclear whether this results in longer market exclusivity compared to other countries., Objectives: We sought to understand how drug market exclusivity lengths vary between the USA and two comparable countries., Methods: We focused on drugs approved within 2 years of each other in the USA, France, and Australia from 1995 to 2005, and we compared the lengths of exclusivity from marketing approval through first generic competition or June 2023 using Kaplan-Meier analyses., Results: Among 165 drugs in common between the USA and France, the median length of exclusivity was slightly longer in France (15.0 years, interquartile range [IQR]: 13.0-19.6) than the USA (14.5 years, IQR: 11.7-17.6). Among 100 drugs in common between the USA and Australia, the median length of exclusivity was longer in Australia (16.3 years, IQR: 13.9-22.4) than in the USA (14.4 years, IQR: 12.0-17.1)., Conclusions: Market exclusivity lengths in the USA are not longer than in France and Australia. Potential reasons include the larger US market and incentives that offer transient high generic drug prices in the USA for manufacturers that successfully challenge originator market exclusivity., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Importance: Direct-acting antivirals (DAAs) are safe and highly effective for curing hepatitis C virus (HCV) infection, but their high cost led certain state Medicaid programs to impose coverage restrictions. Since 2015, many of these restrictions have been lifted voluntarily in response to advocacy or because of litigation., Objective: To estimate how the prescribing of DAAs to Medicaid patients changed after states eased access restrictions., Design, Setting, and Participants: This modified difference-in-differences analysis of 39 state Medicaid programs included Medicaid beneficiaries who were prescribed a DAA from January 1, 2015, to December 31, 2019. DAA coverage restrictions were measured based on a series of cross-sectional assessments performed from 2014 through 2022 by the US National Viral Hepatitis Roundtable and the Center for Health Law and Policy Innovation., Exposure: Calendar quarter when states eased or eliminated 3 types of DAA coverage restrictions: limiting treatment to patients with severe liver disease, restricting use among patients with active substance use, and requiring prescriptions to be written by or in consultation with specialists. States with none of these restrictions at baseline were excluded., Main Outcomes and Measures: Quarterly number of HCV DAA treatment courses per 100 000 Medicaid beneficiaries., Results: Of 39 states, 7 (18%) eliminated coverage restrictions, 25 (64%) eased restrictions, and 7 (18%) maintained the same restrictions from 2015 to 2019. During this period, the average quarterly use of DAAs increased from 669 to 3601 treatment courses per 100 000 Medicaid beneficiaries. After states eased or eliminated restrictions, the use of DAAs increased by 966 (95% CI, 409-1523) treatment courses per 100 000 Medicaid beneficiaries each quarter compared with states that did not ease or eliminate restrictions., Conclusions and Relevance: The results of this study suggest that there was greater use of DAAs after states relaxed coverage restrictions related to liver disease severity, sobriety, or prescriber specialty. Further reductions or elimination of these rules may improve access to a highly effective public health intervention for patients with HCV.

Importance: The US lacks a systematic approach for aligning drug prices with clinical benefit, and traditional cost-effectiveness analysis (CEA) faces political obstacles. The efficiency frontier (EF) method offers policymakers an alternative approach., Objective: To assess how the EF approach could align prices and clinical benefits of biologic medications for plaque psoriasis and estimate price reductions in the US vs 4 peer countries: Australia, Canada, France, and Germany., Design and Setting: This health economic evaluation used the EF approach to compare the prices and clinical benefits of 11 biologics and 2 biosimilars for plaque psoriasis in the US, Australia, Canada, France, and Germany. Data were collected from February to March 2023 and analyzed from March to June 2023., Main Outcome Measures: EFs were constructed based on each biologic's efficacy, measured using the Psoriasis Area and Severity Index (PASI) 90 response rate, and annual treatment cost as of January 2023; US costs were net of estimated manufacturer rebates. Prices based on the EF were compared with traditional CEA-based prices calculated by the Institute for Clinical and Economic Review at a threshold of $150 000 per quality-adjusted life-year gained., Results: Among 13 biologics, PASI 90 response rates ranged from 17.9% (etanercept) to 71.6% (risankizumab); US net annual treatment costs ranged from $1664 (infliximab-dyyb) to $79 277 (risankizumab). The median (IQR) net annual treatment cost was higher in the US ($34 965 [$20 493-$48 942]) than prerebate costs in Australia ($9179 [$6691-$12 688]), Canada ($15 556 [$13 017-$16 112]), France ($9478 [$6637-$11 678]), and Germany ($13 829 [$13 231-$15 837]). The US EF included infliximab-dyyb (PASI 90: 57.4%; annual cost: $1664), ixekizumab (PASI 90: 70.8%; annual cost: $33 004), and risankizumab (PASI 90: 71.6%; annual cost: $79 277). US prices for psoriasis biologics would need to be reduced by a median (IQR) of 71% (31%-95%) to align with those estimated using the EF; the same approach would yield smaller price reductions in Canada (41% [6%-57%]), Australia (36% [0%-65%]), France (19% [0%-67%]), and Germany (11% [8%-26%]). Except for risankizumab, the EF-based prices were lower than the prices based on traditional CEA., Conclusions and Relevance: This economic evaluation showed that for plaque psoriasis biologics, using an EF approach to negotiate prices could lead to substantial price reductions and better align prices with clinical benefits. US policymakers might consider using EFs to achieve prices commensurate with comparative clinical benefits, particularly for drug classes with multiple therapeutic alternatives for which differences can be adequately summarized by a single outcome measurement.

Importance: Biologic drugs account for a growing share of US pharmaceutical spending. Competition from follow-on biosimilar products (subsequent versions that have no clinically meaningful differences from the original biologic) has led to modest reductions in US health care spending, but these savings may not translate to lower out-of-pocket (OOP) costs for patients., Objective: To investigate whether biosimilar competition is associated with lower OOP spending for patients using biologics., Design, Setting, and Participants: This cohort study used a national commercial claims database (Optum Clinformatics Data Mart) to identify outpatient claims for 1 of 7 clinician-administered biologics (filgrastim, infliximab, pegfilgrastim, epoetin alfa, bevacizumab, rituximab, and trastuzumab) from January 2009 through March 2022. Claims by commercially insured patients younger than 65 years were included., Exposure: Year relative to first biosimilar availability and use of original or biosimilar version., Main Outcomes and Measures: Patients' annual OOP spending on biologics for each calendar year was determined, and OOP spending per claim between reference biologic and biosimilar versions was compared. Two-part regression models assessed for differences in OOP spending, adjusting for patient and clinical characteristics (age, sex, US Census region, health plan type, diagnosis, and place of service) and year relative to initial biosimilar entry., Results: Over 1.7 million claims from 190 364 individuals (median [IQR] age, 53 [42-59] years; 58.3% females) who used at least 1 of the 7 biologics between 2009 and 2022 were included in the analysis. Over 251 566 patient-years of observation, annual OOP costs increased before and after biosimilar availability. Two years after the start of biosimilar competition, the adjusted odds ratio of nonzero annual OOP spending was 1.08 (95% CI, 1.04-1.12; P < .001) and average nonzero annual spending was 12% higher (95% CI, 10%-14%; P < .001) compared with the year before biosimilar competition. After biosimilars became available, claims for biosimilars were more likely than reference biologics to have nonzero OOP costs (adjusted odds ratio, 1.13 [95% CI, 1.11-1.16]; P < .001) but had 8% lower mean nonzero OOP costs (adjusted mean ratio, 0.92 [95% CI, 0.90-0.93; P < .001). Findings varied by drug., Conclusions and Relevance: Findings of this cohort study suggest that biosimilar competition was not consistently associated with lower OOP costs for commercially insured outpatients, highlighting the need for targeted policy interventions to ensure that the savings generated from biosimilar competition translate into increased affordability for patients who need biologics.

As the Centers for Medicare & Medicaid Services (CMS) navigates the process of negotiating drug prices, it plans to compare the cost, safety, and effectiveness of each drug with its therapeutic alternatives. How CMS selects therapeutic alternatives is a consequential decision, and there remains uncertainty about their methodology. To understand the challenges CMS will face in selecting therapeutic alternatives, we developed a methodology that leverages clinical guidelines by US medical professional associations to identify potential therapeutic alternatives for etanercept, one of the first 10 drugs selected for Medicare price negotiation. For each of etanercept's 5 US Food and Drug Administration-approved indications, we identified all drugs with the same mechanism of action as etanercept and considered drugs with different mechanisms if they were recommended in place of etanercept at the same treatment stage, or if there was no strong comparative safety or effectiveness evidence that the drug differed from etanercept. We identified 22 potential therapeutic alternatives to etanercept, including 4 drugs with the same mechanism, 10 biologics with different mechanisms, and 8 small-molecule drugs. We faced several challenges in selecting therapeutic alternatives using clinical guidelines, such as how to reconcile strong recommendations that were based on weak evidence and how to consider combination therapies. This exercise demonstrates the complex considerations that CMS will face as it negotiates drug prices based on therapies' cost, safety, and effectiveness relative to therapeutic alternatives.

Glucagon-like peptide-1 receptor agonists are effective for treating obesity, but the high cost of these medications endangers the financial viability of our health care system. To ensure that these drugs are available to Medicare beneficiaries, pharmaceutical manufacturers must lower their prices.

Importance: The Inflation Reduction Act (IRA) requires Medicare to negotiate prices for some high-spending drugs but exempts drugs approved solely for the treatment of a single rare disease., Objective: To estimate Medicare spending and global revenues for drugs that might have been exempt from negotiation from 2012 to 2021., Design, Setting, and Participants: This cross-sectional study analyzed drugs that met the IRA threshold for price negotiation (Medicare spending >$200 million/y) in any year from 2012 to 2021 and had an Orphan Drug Act designation. We stratified drugs into 4 mutually exclusive categories: approved for a single rare disease (sole orphan), approved for multiple rare diseases (multiorphan), initially approved for a rare disease and subsequently approved for a nonrare disease (orphan first), and initially approved for a nonrare disease and subsequently approved for a rare disease (non-orphan first)., Outcomes: The primary outcomes were the number of sole orphan drugs, estimated Medicare spending on those drugs from 2012 to 2021, and global revenue since launch., Results: Among 282 drugs, 95 (34%) were approved to treat at least 1 rare disease, including 25 sole orphan drugs (26%), 20 multiorphan drugs (21%), 13 orphan first drugs (14%), and 37 non-orphan first drugs (39%). From 2012 to 2021, Medicare spending on sole orphan drugs increased from $3.4 billion to $10.0 billion. Each year, a median (IQR) of $2.5 ($1.9-$2.6) billion in Medicare spending would have been excluded from price negotiation because of the sole orphan exemption. The cumulative global revenue of the median (IQR) sole orphan drug was $11 ($6.6-$19.2) billion., Conclusions and Relevance: The sole orphan exemption will exclude billions of dollars of Medicare drug spending from price negotiation. The high level of global revenues achieved by these drugs, however, suggests that special exemption is unnecessary for them to achieve financial success. Congress could consider removing the sole orphan exemption to obtain additional savings for patients and taxpayers and to eliminate any potential disincentive for developing additional indications for these drugs.

Importance: Many cancer drugs are approved under the US Food and Drug Administration (FDA) accelerated approval pathway based on preliminary evidence. It is unclear how this limited evidence is integrated into the National Comprehensive Cancer Network (NCCN) guidelines, which are common references for clinicians and are used by public and private payers to determine reimbursement for oncology treatments., Objective: To analyze the NCCN guidelines' assessments for cancer drug indications that received FDA accelerated approval compared with cancer drug indications that received FDA regular approval., Design, Setting, and Participants: This cross-sectional study analyzes FDA-approved indications for cancer drugs that were granted accelerated approval from program inception in 1992 to June 30, 2022. For each drug, the FDA-approved labeling was reviewed to identify all indications. All analyses were performed at the drug-indication level., Exposure: The exposure was FDA regulatory status as of October 2022, including regular approval, accelerated approval, accelerated approval converted to regular approval, and withdrawn accelerated approval., Main Outcomes and Measures: The level of evidence and consensus (category 1, 2A, 2B, and 3) and treatment preference (preferred, alternative preferred, other recommended, and useful in certain circumstances) ratings assigned by NCCN committees as of February 2023., Results: A total of 315 oncology indications for 100 drugs were analyzed. These indications included 156 (50%) with regular approval, 60 (38%) with accelerated approval, 78 (49%) with accelerated approval that was converted to regular approval, and 21 (13%) with withdrawn accelerated approvals. Among all indications, 105 (33%) were rated by the NCCN as having category 1 evidence, 185 (59%) with category 2A, 6 (2%) with category 2B, and 2 (1%) with category 3 evidence. Compared with indications with regular approval, those with accelerated approval were less frequently assigned category 1 evidence (47% vs 3%; P < .001) and were less often listed as preferred treatment options (58% vs 40%; P = .008). Among the 21 withdrawn accelerated approval indications, 8 (38%) remained in the NCCN guidelines, with most having level 2A evidence ratings., Conclusions and Relevance: This study found that cancer drug indications with accelerated approval were less likely to be assigned high-level evidence ratings and preferred status in the NCCN guidelines compared with indications with regular approval; most accelerated and regular approval drugs had low-quality evidence ratings but high levels of consensus among oncologists on NCCN committees. Greater clarity on the thresholds and definitions of evidence levels would make the NCCN guidelines more useful to clinicians, patients, and payers.

Background: During the COVID-19 pandemic, access to in-person care was limited, and regulations requiring in-person dispensing of mifepristone for medical abortions were relaxed. The effect of the pandemic and accompanying regulatory changes on abortion use is unknown., Objective: To estimate changes in the incidence rate of induced medical and procedural abortions., Design: Serial cross-sectional study with interrupted time-series analyses., Setting: Commercially insured persons in the United States., Participants: Reproductive-aged women., Intervention: Onset of the COVID-19 pandemic in March 2020 and subsequent regulatory changes affecting the in-person dispensing requirement for mifepristone., Measurements: Monthly age-adjusted incidence rates of medical and procedural abortions were measured among women aged 15 to 44 years from January 2018 to June 2022. Medical abortions were classified as in-person or telehealth. Linear segmented time-series regression was used to calculate changes in abortion rates after March 2020., Results: In January 2018, the estimated age-adjusted monthly incidence rate of abortions was 151 per million women (95% CI, 142 to 161 per million women), with equal rates of medical and procedural abortions. After March 2020, there was an immediate 14% decrease in the monthly incidence rate of abortions (21 per million women [CI, 7 to 35 per million women]; P  = 0.004), driven by a 31% decline in procedural abortions (22 per million women [CI, 16 to 28 per million women]; P  < 0.001). Fewer than 4% of medical abortions each month were administered via telehealth., Limitation: Only abortions reimbursed by commercial insurance were measured., Conclusion: The incidence rate of procedural abortions declined during the COVID-19 pandemic, and this lower rate persisted after other elective procedures rebounded to prepandemic rates. Despite removal of the in-person dispensing requirement for mifepristone, the use of telehealth for insurance-covered medical abortions remained rare. Amid increasing state restrictions, commercial insurers have the opportunity to increase access to abortion care, particularly via telehealth., Primary Funding Source: Health Resources and Services Administration., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1609.

Objective: To investigate the use and timing of market introduction of authorized generics (AGs), which unlike independent generics are sold by the brand-name drug manufacturer under a generic label., Data Sources: This study used public Medicaid prescription drug use data from 2014 to 2020., Study Design: This cross-sectional study measured the percentage of filled prescriptions for AGs, compared with brand-name and independent generic versions. We also identified the frequency and characteristics of AGs marketed at least 1 year before independent generics., Data Extraction Methods: Drugs were classified based on manufacturer-reported data to Medicaid., Principal Findings: From 2014 to 2020, 1023 AGs accounted for 175 million filled Medicaid prescriptions. These represented 4% of Medicaid prescription drug use, and 16% of medication use among products with AGs available. Among 393 AGs for drugs without generic competition before 2014, 139 (35%) were marketed at least 1 year before independent generics or had no independent generic competition through December 2020., Conclusions: AGs represented a small share of Medicaid prescription drug use from 2014 to 2020, but when AGs were available, they accounted for sizeable market share. Among the minority of cases in which AGs were marketed a year or more before independent generics, manufacturers may be using AGs to bolster brand-name drug prices or to undermine independent generic competition, meriting further attention by regulators., (© 2023 Health Research and Educational Trust.)

State Medicaid programs cover nearly all Food and Drug Administration-approved prescription drugs in exchange for mandatory manufacturer rebates, including rebates that offset price increases beyond inflation. These inflationary rebates originally applied to brand-name drugs only, but in 2017 Congress expanded them to include generics. Using public Medicaid medication spending and utilization data and three different measures of drug prices, we found that nearly half of generic drugs were subject to inflationary rebates during the period 2017-20, offsetting 2-12 percent of the $53.6 billion in generic drug spending during that time. Rebates were larger among non-orally administered drugs and those with the highest prices. Generic inflationary rebates offset substantial Medicaid spending during that period, suggesting that many generic prices increased above inflation despite the new policy. This might change now that inflationary rebates have been expanded to Medicare under the Inflation Reduction Act of 2022, although additional policies that ensure competitive markets would better protect all US patients from rising generic drug prices.

Importance: The Inflation Reduction Act of 2022 authorizes Medicare to negotiate prices of top-selling drugs based on several factors, including therapeutic benefit compared with existing treatment options., Objective: To determine the added therapeutic benefit of the 50 top-selling brand-name drugs in Medicare in 2020, as assessed by health technology assessment (HTA) organizations in Canada, France, and Germany., Design, Setting, and Participants: In this cross-sectional study, publicly available therapeutic benefit ratings, US Food and Drug Administration documents, and the Medicare Part B and Part D prescription drug spending dashboards were used to determine the 50 top-selling single-source drugs used in Medicare in 2020 and to assess their added therapeutic benefit ratings through 2021., Main Outcomes and Measures: Ratings from HTA bodies in Canada, France, and Germany were categorized as high (moderate or greater) or low (minor or no) added benefit. Each drug was rated based on its most favorable rating across countries, indications, subpopulations, and dosage forms. We compared the use and prerebate and postrebate (ie, net) Medicare spending between drugs with high vs low added benefit., Results: Forty-nine drugs (98%) received an HTA rating by at least 1 country; 22 of 36 drugs (61%) received a low added benefit rating in Canada, 34 of 47 in France (72%), and 17 of 29 in Germany (59%). Across countries, 27 drugs (55%) had a low added therapeutic rating, accounting for $19.3 billion in annual estimated net spending, or 35% of Medicare net spending on the 50 top-selling single-source drugs and 11% of total Medicare net prescription drug spending in 2020. Compared with those with high added benefit, drugs with a low added therapeutic rating were used by more Medicare beneficiaries (median 387 149 vs 44 869) and had lower net spending per beneficiary (median $992 vs $32 287)., Conclusions and Relevance: Many top-selling Medicare drugs received low added benefit ratings by the national HTA organizations of Canada, France, and Germany. When negotiating prices for these drugs, Medicare should ensure they are not priced higher than reasonable therapeutic alternatives.

Background: Antiretroviral (ARV) medications to treat human immunodeficiency virus (HIV) are a major contributor to Medicaid prescription drug spending. Despite having been used for over 3 decades, the first generic ARVs only recently became available, and many newer versions continue to be sold at high prices despite within-class competition. We estimated Medicaid spending on ARVs from 2007 through 2019., Methods: Using public Medicaid State Drug Utilization data, we identified trends in ARV spending and use from 2007 through 2019. We estimated net spending and average prices (spending per 30-day supply), accounting for statutory Medicaid rebates, including a 15%-23% base rebate plus additional rebates if a drug's price increased faster than inflation., Results: Among 48 ARVs, estimated net Medicaid spending from 2007 through 2019 was $25 billion for 17 million 30-day supplies. Annual use increased 118%, from 0.7 million 30-day supplies in 2007 to 1.6 million in 2019. During this time, estimated annual net spending increased 178%, from $1.1 billion to $3.0 billion, and average net prices increased 28%, from $1432 to $1830 per 30-day supply., Conclusions: Annual Medicaid net spending on ARVs nearly tripled from 2007 to 2019, due to a combination of expanded use and rising prices. Medicaid did not extract expected benefits from its mandatory inflationary rebates because they were offset by use of newer, more expensive ARVs. To better control spending related to products with incremental innovation, the US government should be authorized to assure that launch prices for new drugs are aligned with the added benefit they offer over existing therapies., Competing Interests: Potential conflicts of interest. This work was conducted and submitted while B. S. W. was a fellow with the Program On Regulation, Therapeutics, And Law (PORTAL). He has since completed the fellowship and now works as an associate at Hogan Lovells US LLP. A. S. K. reports serving as an expert witness on behalf of a class of plaintiffs in a lawsuit against Gilead related to FDA approval of its tenofovir-containing products. B. N. R. reports grants or contracts from Anthem Public Policy Institute (grant to Brigham and Woman's Hospital). The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To estimate US public investment in the development of mRNA covid-19 vaccines., Design: Retrospective cohort study., Setting: Publicly funded science from January 1985 to March 2022., Data Sources: National Institutes of Health (NIH) Report Portfolio Online Reporting Tool Expenditures and Results (RePORTER) and other public databases. Government funded grants were scored as directly, indirectly, or not likely related to four key innovations underlying mRNA covid-19 vaccines-lipid nanoparticle, mRNA synthesis or modification, prefusion spike protein structure, and mRNA vaccine biotechnology-on the basis of principal investigator, project title, and abstract., Main Outcome Measure: Direct public investment in research and vaccine development, stratified by the rationale, government funding agency, and pre-pandemic (1985-2019) versus pandemic (1 January 2020 to 31 March 2022)., Results: 34 NIH funded research grants that were directly related to mRNA covid-19 vaccines were identified. These grants combined with other identified US government grants and contracts totaled $31.9bn (£26.3bn; €29.7bn), of which $337m was invested pre-pandemic. Pre-pandemic, the NIH invested $116m (35%) in basic and translational science related to mRNA vaccine technology, and the Biomedical Advanced Research and Development Authority (BARDA) ($148m; 44%) and the Department of Defense ($72m; 21%) invested in vaccine development. After the pandemic started, $29.2bn (92%) of US public funds purchased vaccines, $2.2bn (7%) supported clinical trials, and $108m (<1%) supported manufacturing plus basic and translational science., Conclusions: The US government invested at least $31.9bn to develop, produce, and purchase mRNA covid-19 vaccines, including sizeable investments in the three decades before the pandemic through March 2022. These public investments translated into millions of lives saved and were crucial in developing the mRNA vaccine technology that also has the potential to tackle future pandemics and to treat diseases beyond covid-19. To maximize overall health impact, policy makers should ensure equitable global access to publicly funded health technologies., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: grant support from Arnold Ventures, Commonwealth Fund, Anthem Public Policy Institute, National Institutes of Health, and Tennessee Department of Mental Health and Substance Abuse Services; HSL is a senior advisor to the Public Good Projects; AS and REB have received consulting fees from the Council for Informed Drug Spending Analysis and Alosa Health, respectively; HSL is a co-founder of ThisIsOurShot and VacunateYa, a national grassroots organization that empowers trusted messengers on social media to spread accurate health information and combat covid-19 vaccine misinformation (unpaid); no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Brand-name drug manufacturers can market or license authorized generics (AGs), which are the same product sold under a generic name. By contrast, independent generics (IGs) are made by other manufacturers. The brand-name manufacturer of entacapone, a treatment for Parkinson's disease, established 4 AGs before IGs emerged. We used this case study to understand how AGs can affect the length of brand-name exclusivity and robustness of generic competition., Methods: Using public Food and Drug Administration and court records, we identified the regulatory and legal history for generic entacapone products marketed through 2021. We used Medicare Part D data to estimate trends in use, prices, and spending on entacapone products from 2011 to 2020, comparing actual spending with projected spending if IG competition had begun after expiration of the key patent protecting entacapone (October 2013) and prices had fallen consistent with levels observed for other generic drugs., Results: From 2012 to 2014, 3 potential entacapone IG manufacturers instead launched AG versions after settlement agreements with the brand-name manufacturer; the brand-name manufacturer additionally introduced its own AG. Four different IG versions were marketed beginning in 2015. From 2011 to 2020, average Medicare prices declined by 62%, less than the projected 74% to 92% price decline expected for a drug with 8 generics. Over this period, Medicare spent $1.1 billion on entacapone products, which could have been reduced by an estimated $137 to $449 million through typical IG competition., Conclusions: The case of entacapone demonstrates how licensing multiple AGs in place of IG competition can increase spending. Government regulators should more rigorously monitor AGs to prevent such strategies., (Copyright © 2022 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)