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Substitution of brand-name drugs with less expensive, equally effective interchangeable generics is an important strategy for promoting adherence and controlling prescription drug spending. US state laws govern generic substitution, but there is variability among states in how these laws are designed. We aimed to determine how different features of state laws regulating generic substitution are associated with use of generic drugs.Using national claims databases, we studied individuals with commercial insurance or Medicare Advantage plans who newly initiated one of 34 prescription drugs during the year after new generic competition (2017-2018) to determine any association between generic use and 3 different features of state laws. We used multivariable logistic regression to adjust for demographic and clinical characteristics.Of 502 763 individuals who initiated one of the drugs, 409 856 (81.6%) received a generic version. Those in states requiring patient consent or notification had lower use of generics (81.1% vs 82.9%; adjusted odds ratio 0.89; 95% confidence interval 0.87-0.91; Plt; .001). By contrast, mandating versus permitting generic substitution and protecting pharmacists from liability did not appear to have significant effects.In this study of commercially insured and Medicare Advantage patients, patients in states requiring consent or notification for pharmacists to substitute Food and Drug Administration-certified interchangeable generics had lower use of generics. Laws in 39 states plus the District of Columbia could be amended to improve use of inexpensive and equally effective generic drugs.

More than 40 years have passed since the enactment of the Patent and Trademark Amendment (Bayh-Dole) Act, which authorized institutions to patent inventions arising from federally funded research. Although some experts have heralded the Bayh-Dole Act as ushering in a new era of technological advances, others have been less sanguine about its impact. In recent years, the high price of prescription drugs and the patenting of COVID-19 therapeutics and vaccines developed with substantial federal government support have rekindled the debate over whether companies should receive more restricted rights to products originating with government funding. This article traces the history leading to the enactment of the Bayh-Dole Act and critically assesses its strengths and weaknesses as well as unresolved questions concerning its scope. Based on this analysis, the authors propose reforms to better align the Bayh-Dole Act with public values and health outcomes, including clarifying government-use rights, making it easier to invoke march-in rights for failure to meet health and safety needs, increasing transparency in how patents are licensed, and testing different approaches to foster the development and application of inventions.

PURPOSE Generic competition can be delayed if brand-name manufacturers obtain additional patents on supplemental uses. The US Food and Drug Administration allows generic drug manufacturers to market versions with skinny labels that exclude patent-protected indications. This study assessed whether use of generic versions of imatinib varied between indications included and excluded from the skinny labels. METHODS In this cross-sectional study, we identified adult patients covered by commercial insurance or Medicare Advantage plans who initiated imatinib from February 2016 (first generic availability) to September 2020. Generic versions were introduced with skinny labels that included indications covering treatment of chronic myelogenous leukemia (CML) but excluded treatment of gastrointestinal stromal tumors (GISTs) because of remaining patent protections. Logistic regression was used to determine whether use of generic versus brand-name imatinib differed between patients with a diagnosis of CML or GIST, adjusting for demographics, insurance type, prior use of brand-name drugs, and calendar month. RESULTS Among 2,000 initiators, 934 (47%) had CML and 686 (34%) had GIST. Within 3 years after generics entered the market, more than 90% of initiators in both groups used generic imatinib. Initiation of generic imatinib was slightly lower among patients with GIST than among patients with CML (85% v 88%; adjusted odds ratio 0.56; 95% CI, 0.39 to 0.80; P ≤ .001). CONCLUSION Generic versions of imatinib were dispensed frequently for indications both included (CML) and excluded (GIST) from the skinny labeling, although patients with GIST were slightly less likely to receive a generic version. The skinny labeling pathway allowed generics to enter the market before patent protection for treating patients with GIST expired, facilitating lower drug prices.

Gene therapies to treat sickle cell disease are in development and are expected to have high costs. The large eligible population size — by far, the largest for a gene therapy — poses daunting budget challenges and threatens to exacerbate health disparities for Black patients, who make up the vast majority of American sickle cell patients.

High biologic drug prices have placed substantial strain on the US health care system. The Biologics Price Competition and Innovation Act (BPCIA), passed in 2010 as part of the Affordable Care Act, created an abbreviated approval pathway for biosimilars-versions of "originator" biologic drugs made by different manufacturers-to help address this issue. However, a decade after its passage, the BPCIA has spurred only limited competition. We examined the role that litigation has played in this muted success, reviewing all lawsuits related to the BPCIA filed between its enactment and August 1, 2020. Our review identified two key problems: noncompliance with steps in the complex litigation process established by the BPCIA and large numbers of patents enforced by originator manufacturers. Both actions have contributed to frequent confidential settlements between originator and biosimilar manufacturers that have delayed the availability of biosimilars. To facilitate more timely biosimilar entry, policy makers should consider limits on patent prosecution, compulsory public patent listing, and enhanced antitrust enforcement.

Launched in 2002, originator adalimumab (Humira) is the top revenue-generating drug in the United States. Between 2016 and 2019, the US Food and Drug Administration approved 5 adalimumab biosimilars, yet none have been marketed owing to patent dispute settlements. We sought to calculate the cost of this delayed entry to Medicare over this period by estimating the difference between reported spending on originator adalimumab and estimated spending on originator and biosimilar adalimumab products assuming timely biosimilar market entry. Estimates of potential biosimilar spending were calculated based on the following evidence-based projections: (i) market capture of 15% for the first biosimilar and 5.5% for successive biosimilars in their first year on the market, and 5% annually thereafter; (ii) price reductions of 3.5% per year and 2.4% per additional biosimilar entry for originator adalimumab; and (iii) price discounts of 25% at launch, 3.4% per year, and 1.7% per additional biosimilar entry for biosimilar adalimumab. Based on these assumptions, had adalimumab biosimilars launched upon approval, estimated non-rebate spending on them would have been $18.3 million in 2016, $225.7 million in 2017, $436.2 million in 2018, and $727.7 million in 2019, whereas estimated non-rebate spending on originator adalimumab would have been $2.33 billion, $2.04 billion, $1.78 billion, and $1.42 billion. Cumulative spending on adalimumab would have thus been $8.98 billion instead of an observed $12.11 billion. Accounting for estimated rebates, total predicted savings would have been $2.19 billion. Reforms for timely biosimilar availability will be critical in ensuring optimal savings for Medicare after biosimilar approval.

In this commentary, the authors discuss the potential benefits and harms of boosters in response to a boosters-for-all policy for Americans, as well as provide 3 plausible alternative strategies.

List prices for brand-name drugs have risen steeply, often despite the introduction of competition from other brand-name drugs in the same therapeutic class. List prices, however, do not reflect an...

Since 2007, the US Food and Drug Administration has had the authority to require risk evaluation and mitigation strategy (REMS) programs for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Such programs can include requirements for patient monitoring, restrictions on dispensing or administration, and physician and pharmacy training and certification. However, there has been only scattered evidence on the impact of REMS programs on informed decision making, medication access, or patient outcomes. The objective of this article was to describe a study that researchers at Brigham and Women’s Hospital and Harvard Medical School will conduct in partnership with the Food and Drug Administration’s Office of Surveillance and Epidemiology to investigate systematically how REMS programs have operated in practice. Investigations include health insurance claims-based analyses to understand patterns of drug use, adherence to safety requirements, and patient outcomes under REMS programs; surveys and interviews to understand physician and patient experiences with REMS; and REMS program material-based and interview-based analyses to understand the effectiveness of risk communication in REMS programs. These research activities will evaluate the performance of REMS programs, provide information on the benefits and burdens to patients and healthcare providers, and generate recommendations for actionable steps to improve REMS programs overall.

Modified versions of existing drugs can substantially increase costs for patients and the health care system if the new version does not offer meaningful clinical improvement.

ObjectiveTo estimate US public investment in the development of mRNA covid-19 vaccines.DesignRetrospective cohort study.SettingPublicly funded science from January 1985 to March 2022.Data sourcesNational 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 measureDirect 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).Results34 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 (ConclusionsThe 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.

Substantial controversy arose in 2021 when the Food and Drug Administration (FDA) approved the Alzheimer's disease drug aducanumab (Aduhelm) under its accelerated approval program despite a nearly unanimous negative advisory committee vote. Advisory committees are convened before some FDA decisions to provide insight for the agency's decision-making process. To understand the frequency, characteristics, and outcomes of cases in which the FDA authorizes a drug against the recommendations of an advisory committee, we reviewed all FDA advisory committee referrals for new drugs approved during the period 2010-21. The fraction of approved drugs that had been referred to an advisory committee decreased from 55 percent to 6 percent annually, with FDA approvals of negatively reviewed drugs occurring about once a year. Qualitative analysis of committee meetings revealed variability in the substance and wording of key voting questions. Reforms such as transparent criteria for when a drug should be subject to external scrutiny, consistent wording of voting questions, and clear regulatory responses to negative recommendations can better ensure public confidence in the FDA approval process.

Risk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists over whether they consistently accomplish this goal. We aimed to assess how initiation of the erythropoiesis stimulating agents (ESAs) darbepoetin alfa and epoetin alfa changed following implementation and enforcement (following a 1-year post-implementation grace period) of a prominent REMS program warning physicians against use in cancer patients with hemoglobin above 10 g/dL. Using claims data from a large US commercial insurance company, we conducted interrupted time-series analyses of darbepoetin alfa and epoetin alfa initiation among adult cancer patients in the 12 months before REMS program implementation, after REMS program implementation, and after REMS program enforcement. We also evaluated differences in inappropriate initiation (hemoglobin tests all above 10 g/dL in the prior month) between the periods. In total, we identified 3456 darbepoetin alfa initiators and 2632 epoetin alfa initiators. Over the study period, the monthly number of initiators per 100,000 patients with cancer fell from 119 to 32 for darbepoetin alfa and from 82 to 34 for epoetin alfa. However, non-significant post-REMS program implementation level and slope changes per 100,000 adult patients with cancer were observed for darbepoetin alfa (level 0.03 [95% confidence interval (CI) −14.98 to 15.05]; slope 1.94 [95% CI −0.22 to 4.10]) and epoetin alfa (level −4.10 [95% CI −16.85 to 8.65]; slope −0.52 [95% CI −2.35 to 1.32]). Non-significant post-REMS program enforcement level and slope changes were also seen for both drugs (darbepoetin alfa level 1.58 [95% CI −0.58 to 3.74, slope −0.28 [95% CI −15.29 to 14.73]; epoetin alfa level 1.58 (95% CI −0.26 to 3.42], slope 5.74 [95% CI −7.01 to 18.49]). Finally, non-significant changes in inappropriate darbepoetin alfa (60% vs. 53% vs. 57%, p = 0.68) and epoetin alfa (53% vs. 53% vs. 46%, p = 0.41) initiation were observed between the three study periods. REMS program implementation and enforcement were not associated with significant changes in ESA initiation, adding to concerns over the degree to which certain REMS programs enhance patient safety.

In the wake of the withdrawal of the nonsteroidal anti-inflammatory drug rofecoxib, regulators worldwide reconsidered their approach to postmarket safety. Many have since adopted a “life cycle” approach to regulation of medicines, facilitating faster approval of new medicines while planning for potential postmarket safety issues. A crucial aspect of postmarket safety is the effective and timely communication of emerging risk information using postmarket safety advisories, commonly issued as letters to healthcare professionals, drug safety bulletins, media alerts, and website announcements. Yet regulators differ in their use of postmarket safety advisories. We examined the capacity of regulators in the United States, Europe, Canada, and Australia to warn about postmarket safety issues through safety advisories by assessing their governance, legislative authority, risk communication capabilities, and transparency.

Objectives To better understand patients' and pharmacists' preferences for and experiences with changes in pill appearance (size, shape, color, and markings). Study design Cross-sectional. Methods We conducted independent national surveys of patients 50 years and older taking generic drugs for depression, diabetes, epilepsy, HIV, hyperlipidemia, or hypertension and of licensed pharmacists practicing in chain, franchise, or independent pharmacies. Responses were collected between January and April 2016. Results Of 1000 patient respondents (30% response rate), most reported experiencing changes in pill appearance (51%) and preferred to be notified about them (82%), but less than half recalled being notified (verbally: 36%; via sticker: 45%). Among patients who reported experiencing a change, 12% reported stopping their medication or using it less frequently. Of 710 pharmacist respondents (33% response rate), many reported changes in pill appearance occurring frequently in their pharmacies (47% reported that changes occurred 6 or more times per month) and more than three-fourths reported notifying patients about them often (verbally: 88%; via sticker: 77%). Conclusions Our findings reveal opportunities to improve patients' experiences with pill appearance changes through better notification practices and patient education.

This cohort study assesses the frequency of approval and marketing of skinny-label biosimilars and their savings to Medicare.

In response to a sharp rise in opioid-involved overdose deaths in the USA, states have deployed increasingly aggressive strategies to limit the loss of life, including civil commitment—the forcible detention of individuals whose opioid use presents a clear and convincing danger to themselves or others. While civil commitment often succeeds in providing short-term protection from overdose, emerging evidence suggests that it may be associated with long-term harms, including heightened risk of severe withdrawal, relapse and opioid-involved mortality. To better assess and mitigate these harms, states should collect more robust data on long-term health outcomes, decriminalise proceedings and stays, provide access to medications for opioid use disorder and strengthen post-release coordination of community-based treatment.

This cohort study examines the application of a combined reimbursement model to brand-name and generic drugs as well as biologic and biosimilar therapies in the Medicare Part B program., Key Points Question Is generic drug competition associated with prices of physician-administered drugs, and what price changes could occur under increased biosimilar competition? Findings In this cohort study of 50 brand-name drugs and generic versions as well as 28 biologics and biosimilars, generic competition was associated with reduced prices, achieving a nearly 53% price decrease after 3 generic competitors were approved. If biosimilar products were treated similar to generic products in the Medicare Part B program, spending on biologics with their approved biosimilars was estimated to have been nearly 27% lower from 2015 to 2019. Meaning Findings from this study suggest that implementing the bundled biosimilar reimbursement model may be associated with substantially reduced Medicare spending and increased biosimilar market entry., 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.

Importance In response to scrutiny over high drug prices, manufacturers of insulin and direct-acting antiviral agents for treating hepatitis C have recently introduced authorized generic alternatives to their patented brand-name products. These authorized generic drugs have list prices at least 50% lower than the list price of the brand-name drugs, which should result in savings to patients. However, it is unclear whether these authorized generic drugs are offered on Medicare Part D formularies because they may not provide savings to plans or Medicare. Objective To assess Medicare Part D formulary coverage for 4 brand-name formulations of insulin and direct-acting antiviral agents and their authorized generic formulations. Design, Setting, and Participants This cross-sectional study used Medicare Prescription Drug Plan Formulary and Pricing Information Files from quarter 3 of 2020 and Medicare Part D plan enrollment for September 2020. Four patented brand-name drugs (sofosbuvir and velpatasvir fixed-dose combination tablets [Epclusa], ledipasvir and sofosbuvir tablets [Harvoni], insulin lispro [Humalog], and insulin aspart [Novolog]) and their authorized generic formulations for all Part D stand-alone prescription drug plans (n = 959) and Medicare Advantage prescription drug plans (n = 3148) were studied. Main Outcomes and Measures Beneficiary-weighted formulary coverage of brand-name and authorized generic products; beneficiary out-of-pocket costs; and prerebate plan, manufacturer, and Medicare spending on brand-name and authorized generic products. Results In quarter 3 of 2020, 97% of beneficiaries were in plans that covered brand-name drugs only or both brand-name and authorized generic drugs; approximately 3% were in plans that covered authorized generic drugs only. Observed authorized generic drug list prices were 67%, 62%, and 50% lower than list prices for Epclusa, Harvoni, and each brand-name insulin product, respectively. Medicare beneficiaries using authorized generic drugs could save $270 per year for 12 vials of Humalog and $2974 for a full course of Harvoni. Plans, however, have limited incentives to encourage authorized generic drug use because rebates for brands likely exceed savings available with authorized generic drugs, particularly for beneficiaries with spending that reaches the Medicare Part D coverage gap. Conclusions and Relevance The results of this cross-sectional study suggest that authorized generic drugs for insulin and direct-acting antiviral agents may lower out-of-pocket spending for patients but are unlikely to provide savings for Part D plans or Medicare. Instead, these drugs allow manufacturers to offer products at a lower list price without materially lowering net prices or profits.

Neovascular age-related macular degeneration (AMD) is a progressive eye disease and is a leading cause of vision loss in the Western world. Vascular endothelial growth factor inhibitors have become a mainstay of treatment for this disease. Currently, treatment options include three originator biologics with approvals for neovascular AMD (aflibercept, ranibizumab, and brolucizumab-dbll) and one biologic that is commonly used off-label for the condition (bevacizumab). In the USA, Medicare spending on these drugs consistently surpassed $4 billion per year between 2015 and 2019, driven by high prices and varying off-label use of bevacizumab, which is substantially cheaper than the other biologics used to treat neovascular AMD. In this article, we discuss how legal reform can improve market competition for biologic drugs, using AMD therapies as a case study. We chose this group of drugs for their significant contribution to Medicare spending, the price difference between approved therapies and intravitreal bevacizumab, and because there currently exists a large biosimilar pipeline with many drug candidates in the final stage of development. We propose mechanisms for anticipating and facilitating the market introduction of biosimilars, as well as changes to the pricing model in Medicare that can promote use of cost-effective therapies. Reforms such as empowering Medicare to negotiate drug prices may help ensure that introduction of new biologics and biosimilars for AMD will lower spending and increase patient access.

Aims Medicines regulators issue post-market safety warnings to advise of newly uncovered risks, but with mixed impacts. We aimed to identify factors influencing the use of regulatory warnings by primary care and specialist physicians in the US and Australia. Methods Semi-structured qualitative interviews were carried out with 40 primary care physicians, endocrinologists and other generalist specialists in Boston (USA) and Australia. Coding and analysis were performed inductively and iteratively to identify and examine key factors. Analysis centred around four areas: physicians' awareness of drug safety information, preferred information sources, opinion-forming and sharing of information with patients. Results Uncertainty, trust and clinical authority emerged as factors influencing use of advisories. Although regulators were trusted as authoritative institutions, they appeared to lack clinical authority, and physicians validated regulatory information against other trusted sources including evidence, expert opinion and experience. Specialists became aware of drug safety issues through specialised literature, using evidence and clinical consensus to form opinions. Primary care physicians, fielding high volumes of information, relied on convenient, accessible information sources including the media and the "clinical grapevine" for awareness, and on clinical colleagues, specialists and experience for interpretation. Communicating risk to patients was complicated by uncertainty; physicians tailored information to patients' health literacy and information needs. US physicians were more aware of their national regulator's post-market safety role than Australian physicians of theirs. Conclusion Drug safety warnings may not be optimally received or used. Regulators should consider strategies that increase trust, clinical relevance and accessibility, and address physicians' needs in communicating risk to patients.

Biologics are among the most expensive prescription drugs in the United States, posing significant barriers to patient access to necessary treatments. An abbreviated approval pathway for biosimilars, near-identical versions of biologics made by different manufacturers, was created by Congress in 2010 to stimulate competition in hopes of driving down costs and expanding access. However, as of February 2019, only 17 biosimilars have been approved, with only 7 currently on the market. Of the few biosimilars currently available to patients, overall utilization has been limited. This article examines the current landscape of the biosimilar market, characterizes tactics employed by biologics manufacturers to delay market entry and deter prescribing of biosimilars, and assesses ethical issues related to increasing the adoption of biosimilars.

The 2011 German Pharmaceutical Market Restructuring Act subjected brand-name drugs for nonrare diseases to price regulation based on an assessment of their clinical benefit. Indication-specific assessment outcomes range from major added benefit to less benefit than the appropriate comparator(s) and affect price negotiations beyond the first year on the market. Using data on drugs that entered the market in the period 2012-16, we evaluated benefit assessment findings, subsequent drug exits, and their correlates. We considered 171 drug-indication pairs, corresponding to 138 different drugs. Of these, 66 drug-indication pairs (55 different drugs) were found to have added benefit. Almost all drugs with a positive benefit assessment (98 percent) remained on the market, while drugs without a positive benefit assessment were over ten times more likely to exit (25 percent versus 2 percent). US policy makers considering how to address rapidly increasing drug costs may draw valuable lessons from the German experience.

After new prescription drugs reach the market, manufacturers sometimes create modified versions of them. These new formulations can expand patient treatment options, but they may also be protected by later-expiring patents or data exclusivities, which can lead to later generic entry for the new formulations compared with the original product.To quantify how frequently manufacturers introduce new formulations of existing drugs and how often these new formulations earn additional years of market exclusivity beyond that of the original product.Using a cohort design and FDA databases, we assessed how frequently manufacturers introduced new formulations of 17 new small-molecule drugs approved in 2002 and when generic entry for the new formulations and original product occurred.Through 2017, nine (53%) drugs approved in 2002 had been connected to 21 new formulations, most (11/21, 53%) introduced before 2007. Generic entry was observed in 6 of 9 (67%) cases and occurred more than 2 years later for the new formulations in 3 of the cases.Our results suggest that the introduction of new formulations of brand-name drugs occurs in about half of cases and sometimes provides manufacturers with a lengthy period of additional market exclusivity beyond that of the original product.This work was funded by the Laura and John Arnold Foundation. Kesselheim and Sarpatwari also receive support from the Harvard-MIT Center for Regulatory Science and the Engelberg Foundation. Beall has nothing to disclose.

BACKGROUND: Generic versions of a drug can vary in appearance, which can impact adherence. OBJECTIVE: To assess the preferences, perceptions, and responses of patients who experienced a change in the appearance of a generic medication. DESIGN: Cross-sectional survey of patients from a large commercial health plan. PARTICIPANTS: Adults receiving generic versions of lisinopril, fluoxetine, lamotrigine, or simvastatin who experienced a change in the color or shape of their pills between March 2014 and November 2015. MAIN MEASURES: Likert-scale responses to questions concerning perceptions of generic drug safety and effectiveness, reliance on and preferences for pill appearance, and responses to pill appearance changes. Multivariable logistic regression-modeled predictors of seeking advice and adjusting use following a pill appearance change. KEY RESULTS: Of 814 respondents (response rate = 41%), 72% relied on pill appearance to ensure they took the correct medication. A similar percentage wanted their pills to remain the same color (72%), shape (71%), and size (75%) upon refill, but 58% would not have paid a $1 premium on a $5 co-pay to ensure such consistency. Most respondents (86%) wanted their pharmacists to notify them about pill appearance changes, but only 37% recalled such notification; 21% thought they received the wrong medication, and 8% adjusted medication use. Younger respondents (18–33 vs. 50–57 years) were more likely to seek advice (odds ratio [OR] = 1.91; 95% confidence interval [CI],1.02–3.59), and respondents with lower household income ( $100,000) were more likely to adjust medication use (OR = 3.40; 95% CI,1.09–10.67). CONCLUSIONS: Requiring uniform pill appearance may help increase adherence but presents challenges. Standardized pharmacy notification and education policies may be a more feasible short-term solution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-018-4791-1) contains supplementary material, which is available to authorized users.

The COVID-19 pandemic has revealed the vulnerability of the US generic drug supply chain to foreign production. Many policies have been proposed to mitigate this vulnerability. In this article, we argue that nonprofit drug manufacturers have the potential to make important contributions.

List prices for brand-name drugs have risen steeply, often despite the introduction of competition from other brand-name drugs in the same therapeutic class. List prices, however, do not reflect any rebates that manufacturers provide payers. To understand how net prices (after rebates and other discounts) respond to competition, we compared changes in inflation-adjusted, revenue-weighted mean list and net prices of a one-month supply of three classes of diabetes drugs: glucagon-like peptide 1 (GLP1) agonists, dipeptidyl peptidase 4 (DPP4) inhibitors, and sodium glucose cotransporter 2 (SGLT2) inhibitors. These drug classes each had several brand-name products enter the market between 2005 and 2017. The annualized change in list price over this period was $75 (15 percent) for GLP1 agonists, $22 (8 percent) for DPP4 inhibitors, and $41 (11 percent) for SGLT2 inhibitors. In contrast, the annualized change in net price was $38 (10 percent) for GLP1 agonists, -$3 (-2 percent) for DPP4 inhibitors, and -$17 (-9 percent) for SGLT2 inhibitors, suggesting a variable impact of brand-name competition on net prices.

Since 2007, the US Food and Drug Administration has had the authority to require risk evaluation and mitigation strategy (REMS) programs for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Such programs can include requirements for patient monitoring, restrictions on dispensing or administration, and physician and pharmacy training and certification. However, there has been only scattered evidence on the impact of REMS programs on informed decision making, medication access, or patient outcomes.The objective of this article was to describe a study that researchers at Brigham and Women's Hospital and Harvard Medical School will conduct in partnership with the Food and Drug Administration's Office of Surveillance and Epidemiology to investigate systematically how REMS programs have operated in practice.Investigations include health insurance claims-based analyses to understand patterns of drug use, adherence to safety requirements, and patient outcomes under REMS programs; surveys and interviews to understand physician and patient experiences with REMS; and REMS program material-based and interview-based analyses to understand the effectiveness of risk communication in REMS programs.These research activities will evaluate the performance of REMS programs, provide information on the benefits and burdens to patients and healthcare providers, and generate recommendations for actionable steps to improve REMS programs overall.

This cohort study assessed the frequency of approvals of first generic drugs with skinny labels in the US.

This Viewpoint documents the history, value, and success of the 340B Pricing Program, which is under threat from pharmaceutical corporations’ withdrawal and from a pending Supreme Court decision and offers 2 legislative fixes to address the concerns raised by the pharmaceutical companies.

Worldwide spending on prescription drugs has increased dramatically in recent years. Although this increase has been particularly pronounced in the US, it remains largely unaddressed there. In Europe, however, different approaches to regulating drug prices have been implemented. Under the 2011 German Pharmaceutical Market Restructuring Act (Arzneimittelmarktneuordnungsgesetz, or AMNOG), for example, manufacturers freely set the prices of newly authorized drugs during their first year on the market. Benefit assessments are carried out during this year and then used in price negotiations between manufacturers and representatives of the country's statutory health insurers. Using data on fifty-seven anticancer drugs launched in Germany from 2002 to 2017, we found that implementation of AMNOG was associated with drug prices being more closely aligned with clinical benefit. Introducing price negotiations led to a 24.5 percent decrease in negotiated prices relative to launch prices. We did not find evidence that manufacturers responded by setting higher launch prices. AMNOG is an example of how government price negotiation can be designed to better align prices with clinical benefit without delaying patient access.

Our objective was to compare expected and observed biosimilar and generic entry dates for a recent cohort of brand-name drugs. Therefore, we estimated expected biosimilar and generic entry dates for all 328 new drugs approved by the Food and Drug Administration (FDA) between 2000-2012, which we defined as the later of the expiration of the key patent term or statutory exclusivity (12 years for biologics, 5 years for small-molecule drugs not indicated for a rare disease, and 7 years for small-molecule drugs indicated for a rare disease (plus 6 months if a pediatric extension had been granted). For drugs with expected entry prior to 2019, we calculated the proportion with observed biosimilar or generic entry. The expected biosimilar entry dates were estimated to be a median of 12.3 years (interquartile range [IQR]: 12.0-14.0, n=60) after FDA approval. The 12-year biologic statutory exclusivity period comprised 98% of the median expected protection period. By contrast, expected generic entry was estimated to be a median of 12.2 years (IQR: 8.4-14.0, n=268), or 7.2 years after the 5-year small-molecule statutory exclusivity (59% of the total expected market protection period). By 2019, observed biosimilar entry occurred in 12% of cases (3/25) and observed generic entry in 65% (101/155). We concluded that expected US market exclusivity periods are similar for biologic and small-molecule drugs. Statutory exclusivity plays a more substantial role in market exclusivity protection for biologics. Biosimilar competition, currently lagging far behind generic competition, will likely increase as the biosimilar market becomes established.