Addressing the Drug-Shortage Crisis in Oncology.

This Viewpoint offers strategies for addressing shortages in essential chemotherapeutic drugs.

Cannabis retailer marketing strategies and regulatory compliance: A surveillance study of retailers in 5 US cities.

As cannabis retail expands in the US, its surveillance is crucial to inform regulations and protect consumers. This study addresses this need by conducting point-of-sale audits examining regulatory compliance (e.g., age verification, signage), advertising/promotional strategies, products, and pricing among 150 randomly-selected cannabis retailers in 5 US cities (30/city: Denver, Colorado; Seattle, Washington; Portland, Oregon; Las Vegas, Nevada; Los Angeles, California) in Summer 2022. Descriptive and bivariate analyses characterized the retailers overall and across cities. Age verification rates were high (>90%). The majority of retailers had signage indicating restricted access (e.g., no minors; 87.3%), onsite consumption (73.3%), and distribution to minors (53.3%). Retailers were likely to post warnings regarding use during pregnancy/breastfeeding (72.0%), followed by health risks (38.0%), impacts on children/youth (18.7%), and DUI (14.0%). Overall, 28.7% posted health claims, 20.7% posted youth-oriented signage, and 18.0% had youth-oriented packaging. Price promotions were prevalent, particularly price specials (75.3%), daily/weekly/monthly specials (66.7%), and membership programs (39.3%). One-fourth had signs/promotions indicating curbside delivery/pick-up (28.0%) and/or online ordering (25.3%); 64.7% promoted their website or social media page. The most potent cannabis products were most often e-liquids (38.0%) or oils (24.7%); the least potent were often edibles (53.0%). The most expensive product was often bud/flower (58.0%); the least was joints (54.0%). The vast majority (≥81%) sold vaporizers, wrapping papers, and hookah/waterpipes/bongs, and 22.6% sold CBD products. Marketing strategies differed across cities, reflecting differences in state-specific regulations and/or gaps in compliance/enforcement. Findings underscore the need for ongoing cannabis retail surveillance to inform future regulatory and enforcement efforts.

Imposing a health insurance surcharge on the unvaccinated.

COVID-19 hospitalizations among unvaccinated individuals cost billions of dollars. More employers are considering imposing a premium surcharge on employees participating in the company's health plan who are not vaccinated against COVID-19. These employers see this approach as similar to health premium surcharges for tobacco use, justifying the higher premiums on the basis that unvaccinated individuals could cause the plan to experience higher hospitalization and related costs. However, imposing a surcharge on unvaccinated employees will require employers to think through legal and policy implications and the interests of their employees and their businesses. Employers should weigh their vaccination goals against these interests and consider whether a legally compliant surcharge would further their goals. Employers should carefully consider the prevailing culture among their employees and assess whether the policy would be effective and noncoercive. Premium surcharges may be effective for some but not all employers.

Process evaluation of an academic-community-government partnership to reduce liver diseases attributable to hepatitis B virus.

BACKGROUND: Racial/ethnic minorities have higher incidence and mortality rates of liver cancer, or hepatocellular carcinoma, than non-Hispanic Whites. As such, the Washington-Baltimore Metropolitan Area Hepatitis B Virus (WB-HBV) Demonstration Project, a community-based participatory research (CBPR)-driven academic-community-government (ACG) partnership, was established in 2019 to address disparities and implement strategies to improve the HBV screening and vaccination infrastructure for at-risk communities. CBPR is a partnership of community members, organizational leaders, and academic researchers with a common aim to collectively share and contribute their input at every phase of the project. Herein, we describe the process evaluation of the WB-HBV Project and extract themes and insights to benefit future ACG partnerships and community-engaged research. The process evaluation has been conducted to determine whether CBPR-driven partnership and programmatic activities have been implemented as intended and have resulted in building expanded research capacity for future ACG partnership HBV community-level initiatives. METHODS: A WB-HBV Project Task Force was convened and comprised of eight organizations: four community organizations, three government organizations, and one academic institution. Through a mixed-methods process evaluation, an online survey and key informant interviews were conducted to provide context for program implementation barriers and facilitators. Descriptive statistics were conducted, and interviews were recorded, transcribed, and thematically coded. RESULTS: The survey was completed by 14 of 20 partnership members (70.0%): two academic, eight community, and four government members. Partnership members showed general agreement across 14 domains: organization and structure of meetings; trust; decisions; impact; general satisfaction; strategic planning; ACG policy impact; community-based participatory research and government; participation in meetings; assessment of participation; partnership operations and capacity; communication; challenges/limitations associated with ACG involvement; and benefits compared to challenges associated with ACG involvement. Qualitative interviews were conducted with 15 of the 20 members (75.0%): two academic, nine community, and four government members. Four themes emerged: partnership involvement, project goals and accomplishments, project challenges and barriers, and partnership involvement in government or policy. CONCLUSIONS: The process evaluation presents insights into developing strategies to enhance partnership functioning and increase the ability of present and future ACG partnerships to improve community health outcomes.

Linkage-to-Care Following Community-Based HBV and HCV Screening Among Immigrants from the Washington-Baltimore Metropolitan Area, 2016-2019.

Understanding characteristics that impact linkage-to-care (LTC) among individuals living with HBV and/or HCV can enhance public health efforts to provide tailored care services to prevent and treat viral hepatitis among immigrants. Using HBV/HCV screening and LTC data from immigrants (2016-2019), descriptive and logistic regression analyses were conducted to assess (1) the relationship between LTC and sociodemographic factors and (2) factors associated with HBV/HCV LTC. About 87% of those positive HBsAg had LTC and 52% had LTC among those with HCVAB and confirmed PCR. Access to care was an important LTC predictor for HBV-LTC: those who had neither health insurance nor primary care provider (PCP) were more likely to have HBV-LTC than those who had either health insurance or PCP (aOR = 2.95, 95% CI = 1.32-6.59). It is essential to equally provide HBV/HCV LTC support to all immigrants from countries with high prevalence regardless of access to care.

Marijuana Use and Increases in Use over Time among Young Adult College Students in the State of Georgia: Analyses of Sociocontexual Predictors.

BACKGROUND: While research has assessed correlates of marijuana use, there has been less focus on predictors of differing levels of changes in use during young adulthood, a critical period for use/escalation. OBJECTIVES: We examined changes in marijuana use and related sociocontextual predictors (e.g., earlier-onset substance use, parental use, college type). METHODS: Using data from Georgia college students (ages 18-25 years) in a 2-year, 6-wave longitudinal study (64.6% female, 63.4% White), 2-part random-effects modeling examined use at any assessment and number of days used. RESULTS: Predictors of use status at any assessment included being male (OR = 1.87, 95%CI = [1.28-2.73]), Black (OR = 1.91, 95%CI = [1.15-3.19]), earlier-onset marijuana (OR = 2.63, 95%CI = [1.70-4.06]), cigarette (OR = 2.04, 95%CI = [1.19-3.48]), and alcohol users (OR = 1.49, 95%CI = 1.00-2.22]), parental tobacco (OR = 2.14, 95%CI = [1.18-3.86]) and/or alcohol use (OR = 1.55, 95%CI = [1.09-2.20]), and attending private (vs. public) institutions (OR = 1.68, 95%CI = [1.10-2.59]). Predictors of lower likelihood of use over time included being male (OR = 0.87, 95%CI = [0.77-0.98]), earlier-onset cigarette use (OR = 0.82, 95%CI = [0.68-0.98]), parental alcohol use (OR = 0.86, 95%CI = [0.77-0.97]), and private institution students (OR = 1.17, 95%CI = [1.02-1.34]). Predictors of more days used at baseline included being male (OR = 1.77, 95%CI = [1.40-2.23]), Black (OR = 1.42, 95%CI = [1.04-1.93]), earlier-onset marijuana (OR = 2.32, 95%CI = [1.78-3.01]) and alcohol users (OR = 1.29, 95%CI = [1.01-1.66]), and parental tobacco use (OR = 1.90, 95%CI = [1.32-2.73]). Predictors of fewer days used over time included being older (OR = 0.98, 95%CI = [0.97-1.00]), parental tobacco use (OR = 0.86, 95%CI = [0.78-0.95]), and attending private institutions (OR = 0.89, 95%CI = [0.83-0.93]). CONCLUSIONS: Intervention efforts can be informed by current findings that correlates of baseline use (e.g., being male, attending private institutions) also predicted less use over time, and one's earlier use and parents' use of various substances impacted young adult use.

Consequences to patients, clinicians, and manufacturers when very serious adverse drug reactions are identified (1997-2019): A qualitative analysis from the Southern Network on Adverse Reactions (SONAR).

BACKGROUND: Adverse drug/device reactions (ADRs) can result in severe patient harm. We define very serious ADRs as being associated with severe toxicity, as measured on the Common Toxicity Criteria Adverse Events (CTCAE)) scale, following use of drugs or devices with large sales, large financial settlements, and large numbers of injured persons. We report on impacts on patients, clinicians, and manufacturers following very serious ADR reporting. METHODS: We reviewed clinician identified very serious ADRs published between 1997 and 2019. Drugs and devices associated with reports of very serious ADRs were identified. Included drugs or devices had market removal discussed at Food and Drug Advisory (FDA) Advisory Committee meetings, were published by clinicians, had sales > $1 billion, were associated with CTCAE Grade 4 or 5 toxicity effects, and had either >$1 billion in settlements or >1,000 injured patients. Data sources included journals, Congressional transcripts, and news reports. We reviewed data on: 1) timing of ADR reports, Boxed warnings, and product withdrawals, and 2) patient, clinician, and manufacturer impacts. Binomial analysis was used to compare sales pre- and post-FDA Advisory Committee meetings. FINDINGS: Twenty very serious ADRs involved fifteen drugs and one device. Legal settlements totaled $38.4 billion for 753,900 injured persons. Eleven of 18 clinicians (61%) reported harms, including verbal threats from manufacturer (five) and loss of a faculty position (one). Annual sales decreased 94% from $29.1 billion pre-FDA meeting to $4.9 billion afterwards (p<0.0018). Manufacturers of four drugs paid $1.7 billion total in criminal fines for failing to inform the FDA and physicians about very serious ADRs. Following FDA approval, the median time to ADR reporting was 7.5 years (Interquartile range 3,13 years). Twelve drugs received Box warnings and one drug received a warning (median, 7.5 years following ADR reporting (IQR 5,11 years). Six drugs and 1 device were withdrawn from marketing (median, 5 years after ADR reporting (IQR 4,6 years)). INTERPRETATION: Because very serious ADRs impacts are so large, policy makers should consider developing independently funded pharmacovigilance centers of excellence to assist with clinician investigations. FUNDING: This work received support from the National Cancer Institute (1R01 CA102713 (CLB), https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci; and two Pilot Project grants from the American Cancer Society's Institutional Grant Award to the University of South Carolina (IRG-13-043-01) https://www.cancer.org/ (SH; BS).

The First 2 Years of Biosimilar Epoetin for Cancer and Chemotherapy-Induced Anemia in the U.S.: A Review from the Southern Network on Adverse Reactions.

Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%-60% of all patients with cancer with chemotherapy-induced anemia to <5% of such patients because of safety concerns. Between 2018 and 2020, biosimilar epoetin use varied, increasing to 81% among one private insurer's patients covered by Medicare whose cancer care is administered with Oncology Analytics and to 41% with the same private insurer's patients with cancer covered by commercial health insurance and administered by the private insurer, to 0% in several Veterans Administration Hospitals, increasing to 100% in one large county hospital in California, and with yet-to-be-reported data from most oncology settings. We conclude that biosimilar epoetin appears to have overcome some barriers since 2015, although current uptake in the U.S. is variable. Pricing and safety considerations for all erythropoiesis-stimulating agents are primary determinants of biosimilar epoetin oncology uptake. IMPLICATIONS FOR PRACTICE: Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists.

Campus tobacco control policies and cessation interventions in college students: a commentary calling for research and action to address tobacco-related health disparities.

Tobacco-related health disparities (TRHDs) have a significant impact on population health in the USA. Effectively preventing and controlling TRHDs among young adult populations require multiple prevention and cessation points, including within college/university contexts. This commentary addresses current campus tobacco control policies and cessation interventions for U.S. college students, with an emphasis on TRHDs and opportunities for research and research translation to reduce these disparities. This commentary is informed by literature published between 2010 and 2020 regarding (a) prevalence and impact of campus tobacco control policies; and/or (b) behavioral outcomes from cessation interventions for young adults attending colleges. Despite a doubling of college campuses adopting tobacco-free policies from 2012 to 2017, roughly two-thirds continue to operate without such policies. Few policies address alternative tobacco products (e.g., e-cigarettes, cigars/cigarillos, and hookah), and communication about and enforcement of existing policies is extremely limited. A broad range of cessation intervention strategies have targeted individuals in this age group, but with little focus on TRHDs and limited intervention dissemination. Importantly, college students representing populations at risk for TRHDs (e.g., racial/ethnic/sexual/gender minorities, low socioeconomic status) are less likely to be exposed to strong tobacco control policies or supports for cessation. There are untapped opportunities for behavioral medicine approaches to reduce TRHDs in college settings. Research findings regarding multilevel (policy, community-level, and individual-level) interventions must be translated to policy/practice in order to address tobacco use, particularly among vulnerable college student populations.

Improving oncology biosimilar launches in the EU, the USA, and Japan: an updated Policy Review from the Southern Network on Adverse Reactions.

The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 [11%] with the EMA, seven of 16 [44%] with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.

End of an era of administering erythropoiesis stimulating agents among Veterans Administration cancer patients with chemotherapy-induced anemia.

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01). Following REMS in 2010, mean hematocrit levels at ESA initiation decreased from 30% to 21% (p<0.01). Black box warnings preceded decreased ESA use among VA cancer patients with CIA. REMS was followed by reduced hematocrit levels at ESA initiation. Our findings contrast with privately- insured and Medicaid insured cancer patient data on chemotherapy-induced anemia where ESA use decreased to 3% to 7% by 2010-2012. By 2012, the era of ESA administration to VA to cancer patients had ended but the warnings remain relevant and significant. In 2019, oncology/hematology national guidelines (ASCO/ASH) recommend that cancer patients with chemotherapy-induced anemia should receive ESAs or red blood cell transfusions after risk-benefit evaluation.

End of an era for erythropoiesis-stimulating agents in oncology.

Erythropoiesis-stimulating agents (ESAs) are available to treat chemotherapy-induced anemia (CIA). In 2007-2008, regulatory notifications advised of venous thromboembolism and mortality risks while the Center for Medicare and Medicaid Services' restricted ESA initiation to patients with hemoglobin <10 g/dl. In 2010, a Risk Evaluation and Mitigation Strategies required consent prior to administration. We evaluated ESA utilization from 2003 to 2012 and obtained private health insurer claims data for persons with lung, colorectal, or breast cancer from 2001 to 2012. ESA use for CIA was determined by an ESA claim after chemotherapy, up to 6 months after treatment. We identified 839,948 commercially insured patients, including 24,785 patients with ESA-treated CIA (3.2%). Darbepoetin use increased 3.9-fold from 2003 to 2007 (12.3% to 48.7%) and then decreased 95% to 2.6% by 2012. Epoetin use decreased 90% from 2003 to 2012 (30.3% to 3.1%). Between 2003 and 2012, mean epoetin dosing decreased 0.8-fold (244,979 in 2003 vs. 196,216 units in 2012), but increased 1.8-fold for darbepoetin-treated CIA (262 in 2003 to 467 µg in 2012). Among CIA patients, transfusions were low (4.5%) in 2002-2007, then increased 2.2-fold between 2008 and 2012. Safety initiatives between 2007 and 2010 facilitated reductions in ESA use combined with changes in coverage. These data show the efficacy of regulatory efforts, publication of adverse events and changes in reimbursement in reducing use of ESAs. Future studies are warranted to optimize deimplementation strategies to improve patient safety.

Caveat Medicus: Clinician experiences in publishing reports of serious oncology-associated adverse drug reactions.

Oncology-associated adverse drug/device reactions can be fatal. Some clinicians who treat single patients with severe oncology-associated toxicities have researched case series and published this information. We investigated motivations and experiences of select individuals leading such efforts. Clinicians treating individual patients who developed oncology-associated serious adverse drug events were asked to participate. Inclusion criteria included having index patient information, reporting case series, and being collaborative with investigators from two National Institutes of Health funded pharmacovigilance networks. Thirty-minute interviews addressed investigational motivation, feedback from pharmaceutical manufacturers, FDA personnel, and academic leadership, and recommendations for improving pharmacovigilance. Responses were analyzed using constant comparative methods of qualitative analysis. Overall, 18 clinicians met inclusion criteria and 14 interviewees are included. Primary motivations were scientific curiosity, expressed by six clinicians. A less common theme was public health related (three clinicians). Six clinicians received feedback characterized as supportive from academic leaders, while four clinicians received feedback characterized as negative. Three clinicians reported that following the case series publication they were invited to speak at academic institutions worldwide. Responses from pharmaceutical manufacturers were characterized as negative by 12 clinicians. One clinician's wife called the post-reporting time the "Maalox month," while another clinician reported that the manufacturer collaboratively offered to identify additional cases of the toxicity. Responses from FDA employees were characterized as collaborative for two clinicians, neutral for five clinicians, unresponsive for negative by six clinicians. Three clinicians endorsed developing improved reporting mechanisms for individual physicians, while 11 clinicians endorsed safety activities that should be undertaken by persons other than a motivated clinician who personally treats a patient with a severe adverse drug/device reaction. Our study provides some of the first reports of clinician motivations and experiences with reporting serious or potentially fatal oncology-associated adverse drug or device reactions. Overall, it appears that negative feedback from pharmaceutical manufacturers and mixed feedback from the academic community and/or the FDA were reported. Big data, registries, Data Safety Monitoring Boards, and pharmacogenetic studies may facilitate improved pharmacovigilance efforts for oncology-associated adverse drug reactions. These initiatives overcome concerns related to complacency, indifference, ignorance, and system-level problems as barriers to documenting and reporting adverse drug events- barriers that have been previously reported for clinician reporting of serious adverse drug reactions.

Regulatory and Clinical Experiences with Biosimilar Filgrastim in the U.S., the European Union, Japan, and Canada.

Biosimilar filgrastims are primarily indicated for chemotherapy-induced neutropenia prevention. They are less expensive formulations of branded filgrastim, and biosimilar filgrastim was the first biosimilar oncology drug administered in European Union (EU) countries, Japan, and the U.S. Fourteen biosimilar filgrastims have been marketed in EU countries, Japan, the U.S., and Canada since 2008, 2012, 2015, and 2016, respectively. We reviewed experiences and policies for biosimilar filgrastim markets in EU countries and Japan, where uptake has been rapid, and in the U.S. and Canada, where experience is rapidly emerging. U.S. regulations for designating biosimilar interchangeability are under development, and such regulations have not been developed in most other countries. Pharmaceutical substitution is allowed for new filgrastim starts in some EU countries and in Canada, but not Japan and the U.S. In EU countries, biosimilar adoption is facilitated with favorable hospital tender offers. U.S. adoption is reportedly 24%, while the second filgrastim biosimilar is priced 30% lower than branded filgrastim and 20% lower than the first biosimilar filgrastim approved by the U.S. Food and Drug Administration. Utilization is about 60% in EU countries, where biosimilar filgrastim is marketed at a 30%-40% discount. In Japan, biosimilar filgrastim utilization is 45%, primarily because of 35% discounts negotiated by Central Insurance and hospital-only markets. Overall, biosimilar filgrastim adoption barriers are small in many EU countries and Japan and are diminishing in Canada in the U.S. Policies facilitating improved U.S. adoption of biosimilar filgrastim, based on positive experiences in EU countries and Japan, including favorable insurance coverage; larger price discount relative to reference filgrastim pricing; closing of the "rebate trap" with transparent pricing information; formal educational efforts of patients, physicians, caregivers, and providers; and allowance of pharmaceutical substitution of biosimilar versus reference filgrastim, should be considered. IMPLICATIONS FOR PRACTICE: We reviewed experiences and policies for biosimilar filgrastims in Europe, Japan, Canada, and the U.S. Postmarketing harmonization of regulatory policies for biosimilar filgrastims has not occurred. Acceptance of biosimilar filgrastims for branded filgrastim, increasing in the U.S. and in Canada, is commonplace in Japan and Europe. In the U.S., some factors, accepted in Europe or Japan, could improve uptake, including acceptance of biosimilars as safe and effective; larger cost savings, decreasing "rebate traps" where pharmaceutical benefit managers support branded filgrastim, decreased use of patent litigation/challenges, and allowing pharmacists to routinely substitute biosimilar for branded filgrastim.

How does the Cox maze procedure compare? Cost-effectiveness analysis of alternative treatments of atrial fibrillation.

OBJECTIVES: Data related to the cost effectiveness of surgical interventions and catheter ablation is sparse. This model-based analysis assessed the clinical and economic trade-offs involved in using catheter ablation or the Cox maze procedure in treating patients with atrial fibrillation. METHODS: A deterministic model was developed to project 1 year and lifetime health-related outcomes, costs, quality-adjusted life years (QALYs) and cost effectiveness of each treatment in patients with atrial fibrillation. Using previously unpublished Inova Heart and Vascular Institute (IHVI) data for patients undergoing either procedure, 1 year cost and clinical efficacy inputs were estimated. This data was supplemented with published literature and used to estimate costs, utilities, mortality and likelihood of patient improvement. Results were reported as cost-effectiveness ratios in $/QALY. Sensitivity analyses were conducted to assess the robustness of results. RESULTS: Patients initially treated with a Cox maze procedure were estimated to have higher costs than those treated with catheter ablation, both after 1 year and over the lifetime. However, patients undergoing the Cox maze procedure also had lower rates of 1 year mortality than catheter ablation patients (3.5% vs. 8.5%) and the highest rate of improvement following treatment, resulting in higher QALYs (12.4 vs. 10.2). Compared to catheter ablation, the lifetime incremental cost-effectiveness ratio for the Cox maze surgical procedure was $12,794 per QALY gained. Without quality adjustment, the ratio was $11,315. Results were most sensitive to the likelihood of improvement following each intervention and the cost of the initial procedure. CONCLUSIONS: At a societal willingness to pay of $100,000/QALY, Cox maze procedure was found to both increase overall and quality-adjusted survival and constitute an effective use of resources in patients with atrial fibrillation.

Why Biologics and Biosimilars Remain So Expensive: Despite Two Wins for Biosimilars, the Supreme Court's Recent Rulings do not Solve Fundamental Barriers to Competition.

Biologics and biosimilars are medicines made from living cells that treat common and serious diseases such as cancer, diabetes, rheumatoid arthritis, and other inflammatory diseases. They are highly targeted, efficacious, and represent an increasingly important part of physicians' armamentaria in the combat against these medical conditions. Yet they are extremely expensive, costing on average $10,000-$30,000 per year and exceed $500,000 for the most expensive biologics. The advent of biosimilar drugs, or high similar copies of biologics, was supposed to help reduce costs, but thus far the cost of treatment with biologics or biosimilars has not fallen sharply in the USA. We argue that a primary hurdle is the extent of patent protection for the reference biologics that impedes greater numbers of biosimilars entering into the market. To date, of the 12 biosimilars approved for marketing by the US Food and Drug Administration (FDA), only five are commercially available. All but one of the remaining biosimilars are withheld from commercialization due to patent disputes. We argue that the market for biologics and biosimilars will become price competitive only if more biosimilars are available to patients. To this end, the process to eliminate marginally inventive patents held by the reference drug makers must be streamlined and improved. In this perspective article, we suggest actions to improve the pre-FDA approval patent resolution process known as the patent dance, the streamlined patent invalidation process known as Inter Partes Reviews, and the process of granting patents.