Modeling the Effects of Formulary Exclusions: How Many Patients Could Be Affected by a Specific Exclusion?

Background: Medication formularies, initially designed to promote the use of cost-effective generic drugs, are now designed to maximize financial benefits for the pharmacy benefit management companies that negotiate purchase prices. In the second-largest pharmacy benefit management formulary that is publicly available, 55% of mandated substitutions are not for generic or biosimilar versions of the same active ingredient and/or formulation and may not be medically or financially beneficial to patients. Methods: We modeled the effect of excluding novel agents for atrial fibrillation/venous thromboembolism, migraine prevention, and psoriasis, which all would require substitution with a different active ingredient. Using population data, market share of the 2 largest US formularies, and 2021 prescription data, we calculated how many people could be affected by such exclusions. Using data from the published literature, we calculated how many of those individuals are likely to discontinue treatment and/or have adverse events due to a formulary exclusion. Results: The number of people likely to have adverse events due to the exclusion could be as high as 1 million for atrial fibrillation/venous thromboembolism, 900 000 for migraine prevention, and 500 000 for psoriasis. The numbers likely to discontinue treatment for their condition are as high as 924 000 for atrial fibrillation/venous thromboembolism, 646 000 for migraine, and 138 000 for psoriasis. Conclusion: Substitution with a nonequivalent treatment is common in formularies currently in use and is not without substantial consequences for hundreds of thousands of patients. Forced medication substitution results in costly increases in morbidity and mortality and should be part of the cost-benefit analysis of any formulary exclusion.

The Relative Contributions of NIH and Private Sector Funding to the Approval of New Biopharmaceuticals.

OBJECTIVES: There remains ongoing debate regarding the relative efficacy of public (NIH) and private sector funding in bringing biopharmaceutical innovations to market. This paper investigates the significance of each party's level of funding for obtaining Food and Drug Administration (FDA) authorization. METHODS: A cohort of research projects linked to 23,230 National Institute of Health grants awarded in the year 2000 was audited to account for patents, where the project led to a product in clinical development and potentially FDA approval. A total of 8126 associated patents led to the identification of 41 therapies that registered clinical trials; 18 of these therapies received FDA approved. RESULTS: NIH funding for the 18 FDA-approved therapies totaled $0.670 billion, whereas private sector funding (excluding post-approval funding) totaled $44.3 billion. A logistic regression relating the levels of public and private funding to the probability of FDA approval indicates a positive and significant relationship between private sector funding and the likelihood of FDA approval (p ≤ 0.0004). The relationship between public funding and the likelihood of FDA approval is found to be negative and not statistically significant. CONCLUSION: Our study results underscore that the development of basic discoveries requires substantial additional investments, partnerships, and the shouldering of financial risk by the private sector if therapies are to materialize as FDA-approved medicine. Our finding of a potentially negative relationship between public funding and the likelihood that a therapy receives FDA approval requires additional study.

Accessibility of adult immunizations in pharmacies compared to physician offices in low-income communities.

BACKGROUND: Expanding access to immunization services is essential for improving low-income communities' access to health care. OBJECTIVE: The purpose of this analysis was to assess whether adults who live in low-income communities, and adults 65 years old and older who live in low-income communities, have greater access to pharmacies for immunization services than to relevant physician offices. METHODS: Databases of the number of physician practices and pharmacy locations were geocoded into ZIP Code tabulation areas (ZCTAs). The ZCTAs where the share of families living at or below the federal poverty threshold exceeded 30% were defined as low-income communities for purposes of the analysis. The raw access comparisons were adjusted to reflect whether physician practices have Medicare Part D billing capability, an access constraint for patients aged 65 years and over, and to reflect the differences in hours of operation. RESULTS: There were 15.1% more pharmacy locations within the low-income communities than the availability of physician practices. After adjusting for the hours of operation, the pharmacy locations offered 95.7% more operating hours than the physician practice sites. Compared to the physician practices that have Medicare Part D billing capability, there were 203.0% more pharmacy locations. CONCLUSION: Based on the results, lower-income families had greater access to pharmacies than to physician practices, which indicates that pharmacies can play a valuable role in expanding immunization access and could warrant considering policy reforms that enhance the authority of pharmacists to administer vaccinations. State-level potential reforms could include expanding and harmonizing laws governing pharmacist authority to deliver such services, creating health enterprise zones, and granting special tax breaks, regulatory exemptions, or public assistance to encourage the establishment of physician offices and pharmacies in low-income communities.

Sowing confusion in the field: the interchangeable use of biosimilar terminology.

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) created an abbreviated licensure pathway in the United States that allows for the development and approval of biologic products shown to be biosimilar to or interchangeable with a US Food and Drug Administration (FDA)-licensed reference product. FDA released the draft guidance for industry on Demonstrating Interchangeability with a Reference Product (hereafter referred to as the Draft Interchangeability Guidance) in January 2017. Despite FDA's efforts, there continues to be a great deal of confusion and misinformation surrounding the topic of interchangeability. Here we discuss interchangeability, as well as substitution of biological products, with a focus on the US. Additionally, the separate topic of physician-mediated switching is covered and distinguished from interchangeability and substitution.

Global Acceptance of Biosimilars: Importance of Regulatory Consistency, Education, and Trust.

Globally, biosimilars are expected to have a key role in improving patient access to biological therapies and addressing concerns regarding the escalating cost of health care. Indeed, in Europe, increased use of biologics and reduced drug prices have been observed after the introduction of biosimilars. Recently, several monoclonal antibody biosimilars of anticancer therapies have been approved, and numerous others are in various stages of clinical development. Biosimilars are authorized via a regulatory pathway separate from that used for generic drugs; they are also regulated separately from novel biologics. Biosimilar approval pathways in many major regulatory regions worldwide are, to a broad degree, scientifically aligned. However, owing to regional differences in health care priorities, policies, and resources, some important regulatory inconsistencies are evident. Acceptance of biosimilars by health care systems, health care professionals, and patients will be a key factor in the uptake of these therapies, and such regulatory variations could contribute to confusion and diminished confidence regarding the quality, efficacy, and reliability of these agents. Furthermore, the need for manufacturers to account for regulatory inconsistencies introduces inefficiencies and delays into biosimilar development programs. These issues should be addressed if biosimilars are to attain their maximal global potential. This review summarizes the evolution of the global biosimilar landscape and provides examples of inconsistencies between regulatory requirements in different regions. In addition, we review ongoing efforts to improve regulatory alignment and highlight the importance of education as a crucial factor in generating trust in, and acceptance of, biosimilars on a worldwide scale. IMPLICATIONS FOR PRACTICE: Biosimilars of monoclonal antibody anticancer therapies are beginning to emerge, and more are likely to become available for clinical use in the near future. The extent to which biosimilars can contribute to cancer care will depend on their level of acceptance by health care systems, health care professionals, and patients. A better understanding of the regulatory basis for the approval of biosimilars may enhance confidence and trust in these agents. In order to have informed discussions about treatment choices with their patients, oncologists should familiarize themselves with the biosimilar paradigm.

Drug tendering: drug supply and shortage implications for the uptake of biosimilars.

Due to the continued increase in global spending on health care, payers have introduced a number of programs, policies, and agreements on pharmaceutical pricing in order to control costs. While incentives to increase generic drug use have achieved significant savings, other cost-containment measures are required. Tendering is a formal procedure to purchase medications using competitive bidding for a particular contract. Although useful for cost containment, tendering can lead to decreased competition in a given market. Consequently, drug shortages can occur, resulting in changes to treatment plans to products that may have lower efficacy and/or an increased risk of adverse effects. Therefore, care must be taken to ensure that tendering does not negatively impact patient care or the health care system. A large and expanding portion of total pharmaceutical expenditure is for biologic therapies. These agents have revolutionized the treatment of many diseases, including cancer and inflammatory conditions; however, patient access to biologic drugs can be limited due to availability, insurance coverage, and cost. As branded biologic therapies reach the end of patent- and data-protection periods, biosimilars are being approved as lower-cost alternatives. Biosimilars are products that are highly similar to the originator product with no clinically meaningful differences in terms of safety, purity, or potency. As more biosimilars receive regulatory approval and adoption increases, these therapies are expected to have an impact on global health care spending and should result in overall savings. However, the use of tendering to maximize the potential benefits of biosimilars has varied across the world. Therefore, the objectives of this review are to examine the drug-tendering process and its implications on drug supply and drug shortages, as well as to describe biosimilars and how tendering may influence their uptake.

Assessing the Value of Biosimilars: A Review of the Role of Budget Impact Analysis.

Biosimilar drugs are highly similar to an originator (reference) biologic, with no clinically meaningful differences in terms of safety or efficacy. As biosimilars offer the potential for lower acquisition costs versus the originator biologic, evaluating the economic implications of the introduction of biosimilars is of interest. Budget impact analysis (BIA) is a commonly used methodology. This review of published BIAs of biosimilar fusion proteins and/or monoclonal antibodies identified 12 unique publications (three full papers and nine congress posters). When evaluated alongside professional guidance on conducting BIA, the majority of BIAs identified were generally in line with international recommendations. However, a lack of peer-reviewed journal articles and considerable shortcomings in the publications were identified. Deficiencies included a limited range of cost parameters, a reliance on assumptions for parameters such as uptake and drug pricing, a lack of expert validation, and a limited range of sensitivity analyses that were based on arbitrary ranges. The rationale for the methods employed, limitations of the BIA approach, and instructions for local adaptation often were inadequately discussed. To understand fully the potential economic impact and value of biosimilars, the impact of biosimilar supply, manufacturer-provided supporting services, and price competition should be included in BIAs. Alternative approaches, such as cost minimization, which requires evidence demonstrating similarity to the originator biologic, and those that integrate a range of economic assessment methods, are needed to assess the value of biosimilars.

Can biosimilars help achieve the goals of US health care reform?

The US Patient Protection and Affordable Care Act (ACA) aims to expand health care coverage, contain costs, and improve health care quality. Accessibility and affordability of innovative biopharmaceuticals are important to the success of the ACA. As it is substantially more difficult to manufacture them compared with small-molecule drugs, many of which have generic alternatives, biologics may increase drug costs. However, biologics offer demonstrated improvements in patient care that can reduce expensive interventions, thus lowering net health care costs. Biosimilars, which are highly similar to their reference biologics, cost less than the originators, potentially increasing access through reduced prescription drug costs while providing equivalent therapeutic results. This review evaluates 1) the progress made toward enacting health care reform since the passage of the ACA and 2) the role of biosimilars, including the potential impact of expanded biosimilar use on access, health care costs, patient management, and outcomes. Barriers to biosimilar adoption in the USA are noted, including low awareness and financial disincentives relating to reimbursement. The evaluated evidence suggests that the ACA has partly achieved some of its aims; however, the opportunity remains to transform health care to fully achieve reform. Although the future is uncertain, increased use of biosimilars in the US health care system could help achieve expanded access, control costs, and improve the quality of care.

Biosimilars: Practical Considerations for Pharmacists.

OBJECTIVE: To review the scientific and regulatory aspects of biosimilar development and practical considerations for the use of biosimilars that are relevant to pharmacists. DATA SOURCES: Literature searches of PubMed and congress abstracts for publications pertaining to biosimilars were conducted from January 2016 to January 2017. Individual drug company web pages and governmental, regulatory, and other agency websites were also reviewed. STUDY SELECTION/DATA EXTRACTION: Published articles, regulatory guidelines, and other sources covering biologic/biosimilar development and approval, reporting results of biosimilar studies or survey research, and/or identifying biosimilars in development or approved for use in Europe or the United States were reviewed and included. DATA SYNTHESIS: Biologic therapies have revolutionized the treatment of serious diseases, including hematological or autoimmune disorders and cancers. A biosimilar is highly similar to a licensed biologic (ie, reference or originator) and has no clinically meaningful differences in safety, purity, and potency. Unlike small-molecule drugs, biologics are large, complex proteins that cannot be exactly replicated, so the concept of a generic equivalent cannot be applied to biologics. Regulatory agencies have provided a framework for biosimilar approval, but there are many practical considerations for pharmacists, including interchangeability, substitution, naming, indication extrapolation, product labeling, therapeutic drug monitoring, manufacturer attributes, logistics of product use, and reimbursement. CONCLUSIONS: Pharmacists will play a key role in managing the introduction of biosimilars into health care systems. Understanding the principles of biosimilar development and evolving regulatory guidelines relevant to their use will allow pharmacists to make informed decisions regarding formulary inclusion and educate patients and other health care providers about biosimilars.

Awareness, Knowledge, and Perceptions of Biosimilars Among Specialty Physicians.

INTRODUCTION: The Biosimilars Forum conducted a survey through an independent organization from November 20, 2015 to January 4, 2016 in order to assess current levels of awareness, knowledge, and perceptions of biosimilars among US specialty physicians who already prescribe biologics. The survey was intended to provide a baseline level of knowledge about biosimilars and will be repeated in 2-3 years in order to monitor trends over time. METHODS: A 19-question survey was created by the Biosimilars Forum and was administered by an independent third party. RESULTS: Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including dermatologists, gastroenterologists, hematologist-oncologists, medical oncologists, nephrologists, and rheumatologists. CONCLUSIONS: The results of this survey highlight a significant need for evidence-based education about biosimilars for physicians across specialties. Five major knowledge gaps were identified: defining biologics, biosimilars, and biosimilarity; understanding the approval process and the use of "totality of evidence" to evaluate biosimilars; understanding that the safety and immunogenicity of a biosimilar are comparable to the originator biologic; understanding the rationale for extrapolation of indications; and defining interchangeability and the related rules regarding pharmacy-level substitution. FUNDING: Biosimilars Forum.