Reduction of biologic pricing following biosimilar introduction: Analysis across 57 countries and regions, 2012-19.

OBJECTIVE: To evaluate the impact of the entry of biosimilars on the pricing of eight biologic products in 57 countries and regions. METHODS: We utilized an interrupted time series design and IQVIA MIDAS® data to analyze the annual sales data of eight biologic products (adalimumab, bevacizumab, epoetin, etanercept, filgrastim, infliximab, pegfilgrastim, and trastuzumab) across 57 countries and regions from January 1, 2012, to December 31, 2019. We examined the immediate and long-term changes in biologics ex-manufacturer pricing following the entry of biosimilars to the market. RESULTS: Following the entry of biosimilars, the average price per dose of biologic product was immediately reduced by $438 for trastuzumab, $112 for infliximab, and $110 for bevacizumab. The persistent effect of biosimilars' market entry led to further reductions in price per dose every year: by $49 for adalimumab, $290 for filgrastim, $21 for infliximab, and $189 for trastuzumab. Similarly, we analyzed the impact of biosimilars on four biologics' prices in the US, where the prices of three biologics significantly decreased every year, with filgrastim, pegfilgrastim, and infliximab decreasing by $955, $753, and $104, respectively. CONCLUSIONS: The introduction of biosimilars has significantly reduced the prices of biologics both globally and in the US. These findings not only demonstrate the economic benefits of increasing biosimilar utilization, but also emphasize the importance of biosimilars in controlling healthcare costs. Policies should aim to expand the availability of biosimilars to counteract the exponential growth of medical spending caused by the use of biologics.

Economic and cost-effectiveness aspects of vaccines in combating antibiotic resistance.

Antimicrobial resistance (AMR) is a global public health threat causing substantial morbidity and mortality as well as significant economic costs. Vaccines can contribute to combating antimicrobial resistance by reducing the incidence of resistant disease cases and lowering overall antibiotic use. Greater utilization and investments in vaccines as a tool for combating AMR might be hampered by limited economic evidence demonstrating the AMR-related value of vaccines. We reviewed the existing literature to assess the state of evidence. We found two modeling studies that provided estimates of AMR-related costs averted by pneumococcal vaccination and a few cost-effectiveness studies that exclusively focused on serotype replacement effects on overall vaccine cost-effectiveness. We did not find any cost-effectiveness studies that directly examined the cost-effectiveness of vaccines in slowing the development of AMR. Further evidence on the cost-effectiveness and economic value of vaccines in controlling AMR can help inform resource allocation decisions and guide development priorities.

Characterizing Medicine Quality by Active Pharmaceutical Ingredient Levels: A Systematic Review and Meta-Analysis across Low- and Middle-Income Countries.

Substandard and falsified medicines are often reported jointly, making it difficult to recognize variations in medicine quality. This study characterized medicine quality based on active pharmaceutical ingredient (API) amounts reported among substandard and falsified essential medicines in low- and middle-income countries (LMICs). A systematic review and meta-analysis was conducted using PubMed, supplemented by results from a previous systematic review, and the Medicine Quality Scientific Literature Surveyor. Study quality was assessed using the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). Random-effects models were used to estimate the prevalence of medicines with < 50% API. Among 95,520 medicine samples from 130 studies, 12.4% (95% confidence interval [CI]: 10.2-14.6%) of essential medicines tested in LMICs were considered substandard or falsified, having failed at least one type of quality analysis. We identified 99 studies that reported API content, where 1.8% (95% CI: 0.8-2.8%) of samples reported containing < 50% of stated API. Among all failed samples (N = 9,724), 25.9% (95% CI: 19.3-32.6%) reported having < 80% API. Nearly one in seven (13.8%, 95% CI: 9.0-18.6%) failed samples were likely to be falsified based on reported API amounts of < 50%, whereas the remaining six of seven samples were likely to be substandard. Furthermore, 12.5% (95% CI: 7.7-17.3%) of failed samples reported finding 0% API. Many studies did not present a breakdown of actual API amount of each tested sample. We offer suggested improved guidelines for reporting poor-quality medicines. Consistent data on substandard and falsified medicines and medicine-specific tailored interventions are needed to ensure medicine quality throughout the supply chain.

Beyond refill alignment: Evaluating the impact of appointment-based model.

BACKGROUND: The appointment-based model (ABM) is a framework for medication synchronization (med sync) which allows improved efficiency in pharmacy operations. Refill alignment forms the foundation of med sync programs and has proven to improve medication adherence. However it is uncertain if the remaining four components of ABM including the identification and enrollment of patients, medication review and patient assessment, preparation of medications, and delivery of medications can positively impact adherence. OBJECTIVE: To identify ABM core component(s) that significantly improve medication adherence and evaluate the extent to what prescription volume utilizing ABM impacts adherence. METHODS: A retrospective, cross-sectional analysis was conducted on 68 community pharmacies. Medication adherence rates were collected for antihypertensive, antihyperlipidemic, and oral hypoglycemic agents. Analyses were performed to determine the impact of ABM operations on adherence. RESULTS: Four components of ABM were associated with significant improvement in adherence. The ABM operations related to those components include patient recruitment, medication delivery, flexible payment options, documenting synchronized medications and refill date, assessing patient ability to fill medications prior to refill date, refill timelines, and inquiring about medication changes during the patient outreach call (p < 0.05). While synchronizing at least 16% of a pharmacy's total prescription volume improved adherence, synchronizing at least 31% produced significant improvement across all chronic disease categories (p < 0.05). CONCLUSION: Operationalization of four core components from the ABM process - identifying and enrolling patients, medication review and assessment, alignment of refills and preparation of medications - were all found to significantly improve adherence. Pharmacies wanting to improve adherence rates across chronic disease categories should aim to have a minimum of 31% of their prescription volume synchronized.

Accessibility of Low-cost Insulin From Illegitimate Internet Pharmacies: Cross-sectional Study.

BACKGROUND: There is much public debate regarding the high cost of insulin. With 1-in-4 patients in the United States with type 1 diabetes reporting difficulties affording insulin, there is concern that some of these patients might look for cost savings on the internet, unaware that 96% of internet pharmacies are illegitimate. Patients who purchase insulin from illegitimate internet pharmacies remove themselves from traditional health care systems that ensure safe, quality-assured, and effective medication use. OBJECTIVE: This study aims to determine the accessibility of Humalog and NovoLog insulin from internet pharmacies and characterize how these sites approached patient safety, and priced as well as marketed their products. METHODS: From September to December 2019, we queried the phrases buy insulin online, buy Humalog online, and buy NovoLog online in common search engines. The first 100 search results from Google and Bing, and the first 50 search results from Yahoo! and DuckDuckGo were screened. Websites were included if they claimed to sell Humalog or NovoLog insulin, were active, free access, in the English language, and had a unique URL. The legitimacy of websites was classified using LegitScript. Safety and marketing characteristics were compared across the legitimacy of internet pharmacies. Internet pharmacy prices were compared with the prices offered through brick-and-mortar pharmacies using GoodRx. RESULTS: We found that 59% (n=29) of the 49 internet pharmacies in our analysis were illegitimate, whereas only 14% (n=7) were legitimate and 27% (n=13) were unclassified. Across illegitimate internet pharmacies, Humalog and NovoLog insulin were 2 to 5 times cheaper as compared with both legitimate internet pharmacies and brick-and-mortar stores. Risks associated with the use of illegitimate internet pharmacies by American consumers were evident: 57% (8/14) did not require a prescription, 43% (6/14) did not display medication information or warnings, and only 21% (3/14) offered access to purported pharmacists. This included 9 rogue internet pharmacies that sold Humalog and NovoLog insulin within the United States, where 11% (1/9) required a prescription, 11% (1/9) placed quantity limits per purchase, and none offered pharmacist services. Rogue internet pharmacies often offered bulk discounts (11/18, 61%), assured privacy (14/18, 78%), and promoted other products alongside insulin (13/18, 72%). The marketing language of illegitimate internet pharmacies appealed more to quality, safety, and customer service as compared with legitimate sites. CONCLUSIONS: The ease of access to low-cost insulin through illegitimate internet pharmacies calls for urgent attention. Illegitimate internet pharmacies place patients at risk of poor-quality medications and subpar pharmacy services, resulting in adverse events and poor diabetes control. A multifaceted approach is needed to close illegitimate internet pharmacies through legal and regulatory measures, develop better search engine filters, raise public awareness of the dangers of illegitimate internet pharmacies, and address the high costs of insulin.

Value of pneumococcal vaccination in controlling the development of antimicrobial resistance (AMR): Case study using DREAMR in Ethiopia.

BACKGROUND: Antimicrobial resistance (AMR) poses an imminent threat to global health security. Pneumococcal vaccination reduces disease incidence, prevents antibiotic use, and decreases antibiotic-resistant infections. However, the benefit of vaccination in reducing AMR has been poorly quantified to date. METHODS: We developed an agent-based model, DREAMR (Dynamic Representation of the Economics of AMR) to evaluate the economic value of childhood immunization with the pneumococcal conjugate vaccine (PCV) in mitigating the development of AMR. Our model incorporates vaccination coverage, disease incidence, care seeking, and antibiotic use. Accumulation of AMR is simulated based on antibiotic exposure through pharmacokinetics and resulting pharmacodynamics. The model was applied to Ethiopia. RESULTS: Introduction of PCV vaccination has helped slow the development of AMR by 14.77% for amoxicillin and 0.59% for ceftriaxone in Ethiopia since 2011. In addition to the benefit of reduction in disease incidence, PCV vaccination has averted approximately 718,100 antibiotic treatment failures and 9,520 AMR-related deaths (27.8% reduction) in Ethiopia between 2011 and 2017, resulting in savings of $32.7 million. Maintaining current PCV immunization coverage will contribute an additional $7.67 million in annual AMR cost savings over five years compared to no vaccination scenario, which could increase to $11.43 million by increasing PCV coverage to 85% by 2022. CONCLUSIONS: This study is the first to demonstrate the broader economic value of pneumococcal vaccination in controlling the development of AMR in Africa. Vaccination not only saves lives by preventing illnesses, but also benefits society by reducing antibiotic utilization and treatment failures due to AMR.

Systematic review of the costs for vaccinators to reach vaccination sites: Incremental costs of reaching hard-to-reach populations.

INTRODUCTION: Economic evidence on how much it may cost for vaccinators to reach populations is important to plan vaccination programs. Moreover, knowing the incremental costs to reach populations that have traditionally been undervaccinated, especially those hard-to-reach who are facing supply-side barriers to vaccination, is essential to expanding immunization coverage to these populations. METHODS: We conducted a systematic review to identify estimates of costs associated with getting vaccinators to all vaccination sites. We searched PubMed and the Immunization Delivery Cost Catalogue (IDCC) in 2019 for the following costs to vaccinators: (1) training costs; (2) labor costs, per diems, and incentives; (3) identification of vaccine beneficiary location; and (4) travel costs. We assessed if any of these costs were specific to populations that are hard-to-reach for vaccination, based on a framework for examining supply-side barriers to vaccination. RESULTS: We found 19 studies describing average vaccinator training costs at $0.67/person vaccinated or targeted (SD $0.94) and $0.10/dose delivered (SD $0.07). The average cost for vaccinator labor and incentive costs across 29 studies was $2.15/dose (SD $2.08). We identified 13 studies describing intervention costs for a vaccinator to know the location of a beneficiary, with an average cost of $19.69/person (SD $26.65), and six studies describing vaccinator travel costs, with an average cost of $0.07/dose (SD $0.03). Only eight of these studies described hard-to-reach populations for vaccination; two studies examined incremental costs per dose to reach hard-to-reach populations, which were 1.3-2 times higher than the regular costs. The incremental cost to train vaccinators was $0.02/dose, and incremental labor costs for targeting hard-to-reach populations were $0.16-$1.17/dose. CONCLUSION: Additional comparative costing studies are needed to understand the potential differential costs for vaccinators reaching the vaccination sites that serve hard-to-reach populations. This will help immunization program planners and decision-makers better allocate resources to extend vaccination programs.

Promoting, seeking, and reaching vaccination services: A systematic review of costs to immunization programs, beneficiaries, and caregivers.

INTRODUCTION: Understanding the costs to increase vaccination demand among under-vaccinated populations, as well as costs incurred by beneficiaries and caregivers for reaching vaccination sites, is essential to improving vaccination coverage. However, there have not been systematic analyses documenting such costs for beneficiaries and caregivers seeking vaccination. METHODS: We searched PubMed, Scopus, and the Immunization Delivery Cost Catalogue (IDCC) in 2019 for the costs for beneficiaries and caregivers to 1) seek and know how to access vaccination (i.e., costs to immunization programs for social mobilization and interventions to increase vaccination demand), 2) take time off from work, chores, or school for vaccination (i.e., productivity costs), and 3) travel to vaccination sites. We assessed if these costs were specific to populations that faced other non-cost barriers, based on a framework for defining hard-to-reach and hard-to-vaccinate populations for vaccination. RESULTS: We found 57 studies describing information, education, and communication (IEC) costs, social mobilization costs, and the costs of interventions to increase vaccination demand, with mean costs per dose at $0.41 (standard deviation (SD) $0.83), $18.86 (SD $50.65) and $28.23 (SD $76.09) in low-, middle-, and high-income countries, respectively. Five studies described productivity losses incurred by beneficiaries and caregivers seeking vaccination ($38.33 per person; SD $14.72; n = 3). We identified six studies on travel costs incurred by beneficiaries and caregivers attending vaccination sites ($11.25 per person; SD $9.54; n = 4). Two studies reported social mobilization costs per dose specific to hard-to-reach populations, which were 2-3.5 times higher than costs for the general population. Eight studies described barriers to vaccination among hard-to-reach populations. CONCLUSION: Social mobilization/IEC costs are well-characterized, but evidence is limited on costs incurred by beneficiaries and caregivers getting to vaccination sites. Understanding the potential incremental costs for populations facing barriers to reach vaccination sites is essential to improving vaccine program financing and planning.

Cost savings of paper analytical devices (PADs) to detect substandard and falsified antibiotics: Kenya case study.

BACKGROUND: Over 10% of antibiotics in low- and middle-income countries (LMICs) are substandard or falsified. Detection of poor-quality antibiotics via the gold standard method, high-performance liquid chromatography (HPLC), is slow and costly. Paper analytical devices (PADs) and antibiotic paper analytical devices (aPADs) have been developed as an inexpensive way to estimate antibiotic quality in LMICs. AIM: To model the impact of using a rapid screening tools, PADs/aPADs, to improve the quality of amoxicillin used for treatment of childhood pneumonia in Kenya. METHODS: We developed an agent-based model, ESTEEM (Examining Screening Technologies with Economic Evaluations for Medicines), to estimate the effectiveness and cost savings of incorporating PADs and aPADs in amoxicillin quality surveillance in Kenya. We compared the current testing scenario (batches of entire samples tested by HPLC) with an expedited HPLC scenario (testing smaller batches at a time), as well as a screening scenario using PADs/aPADs to identify poor-quality amoxicillin followed by confirmatory analysis with HPLC. RESULTS: Scenarios using PADs/aPADs or expedited HPLC yielded greater incremental benefits than the current testing scenario by annually averting 586 (90% uncertainty range (UR) 364-874) and 221 (90% UR 126-332) child pneumonia deaths, respectively. The PADs/aPADs screening scenario identified and removed poor-quality antibiotics faster than the expedited or regular HPLC scenarios, and reduced costs significantly. The PADs/aPADs scenario resulted in an incremental return of $14.9 million annually compared with the reference scenario of only using HPLC. CONCLUSION: This analysis shows the significant value of PADs/aPADs as a medicine quality screening and testing tool in LMICs with limited resources.

Health and economic impact of the pneumococcal conjugate vaccine in hindering antimicrobial resistance in China.

Antimicrobial resistance (AMR) poses a serious threat to global public health. However, vaccinations have been largely undervalued as a method to hinder AMR progression. This study examined the AMR impact of increasing pneumococcal conjugate vaccine (PCV) coverage in China. China has one of the world's highest rates of antibiotic use and low PCV coverage. We developed an agent-based DREAMR (Dynamic Representation of the Economics of AMR) model to examine the health and economic benefits of slowing AMR against commonly used antibiotics. We simulated PCV coverage, pneumococcal infections, antibiotic use, and AMR accumulation. Four antibiotics to treat pneumococcal diseases (penicillin, amoxicillin, third-generation cephalosporins, and meropenem) were modeled with antibiotic utilization, pharmacokinetics, and pharmacodynamics factored into predicting AMR accumulation. Three PCV coverage scenarios were simulated over 5 y: 1) status quo with no change in coverage, 2) scaled coverage increase to 99% in 5 y, and 3) accelerated coverage increase to 85% over 2 y followed by 3 y to reach 99% coverage. Compared to the status quo, we found that AMR against penicillin, amoxicillin, and third-generation cephalosporins was significantly reduced by 6.6%, 10.9%, and 9.8% in the scaled scenario and by 10.5%, 17.0%, and 15.4% in the accelerated scenario. Cumulative costs due to AMR, including direct and indirect costs to patients and caretakers, were reduced by $371 million in the scaled and $586 million in the accelerated scenarios compared to the status quo. AMR-reducing benefits of vaccines are essential to quantify in order to drive appropriate investment.

Characteristics of online pharmacies selling Adderall.

OBJECTIVES: Adderall (amphetamine-dextroamphetamine) is a controlled substance with harmful adverse effects if abused or misused. We assessed the availability of Adderall from common search engines, and evaluated the safety and marketing characteristics of online pharmacies selling Adderall. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: From December 2019 to February 2020, the phrase "buy Adderall online" was queried in four search engines: Google (N = 100), Bing (N = 100), Yahoo (N = 50) and DuckDuckGo (N = 50). Online pharmacies that claimed to sell Adderall and had unique Uniform Resource Locators, were active, free-access, and in English language were included. OUTCOME MEASURES: Online pharmacies were categorized as rogue, unclassified, or legitimate on the basis of LegitScript classifications. Safety and marketing characteristics, and costs were collected. RESULTS: Of the 62 online pharmacies found to sell Adderall, 61 were rogue or unclassified. Across all rogue and unclassified online pharmacies, prescriptions were not required (100%), pharmacist services were not offered (100%), and quantity limits were not placed on the number of Adderall purchases (100%). Rogue and unclassified online pharmacies appealed to cost, offering price discounts (61%), bulk discounts (67%), and coupon codes (70%). Contrary to their claims, cheaper prices were available for all formulations and dosages of Adderall from GoodRx than from these online pharmacies. Rogue and unclassified online pharmacies promoted and enabled the illicit purchase of Adderall, appealing to privacy (74%), offering purchase through cryptocurrency (74%), and claiming registration or accreditation of their sites (33%). CONCLUSION: Rogue online pharmacies are pervasive in search engine results, enabling the illicit purchase of Adderall without a prescription. Consumers are at risk of purchasing Adderall, a medication with high abuse potential, from unsafe sources. Law enforcement, regulatory agencies, and search engines should work to further protect consumers from unregistered and illegitimate online pharmacies selling Adderall.

Is the Choice of Cost-Effectiveness Threshold in Cost-Utility Analysis Endogenous to the Resulting Value of Technology? A Systematic Review.

BACKGROUND: Cost-utility analysis (CUA) is widely used for health technology assessment; however, concerns exist that cost-utility analysts may suggest higher cost-effectiveness thresholds (CETs) to compensate for technologies of relatively lower value. OBJECTIVE: We explored whether selection of a CUA study's CET was endogenous to estimated incremental cost-effectiveness ratios (ICERs). METHODS: We systematically reviewed the US cost-effectiveness literature between 2000 and 2017 where studies with explicit CET and ICERs were included. We classified the ratio of studies hypothesized to analyze cost-effective technologies at low CETs (i.e., less than $100,000/quality-adjusted life-year [QALY]) vs higher CETs (i.e., $100,000-$150,000/QALY) relative to their ICER, using a Chi square test to examine whether technologies that were cost effective at high CETs would still be cost effective at lower thresholds. We also performed fixed-effects linear regression exploring the associations between ICERs and reported CETs over time. RESULTS: Among 317 ICERs reviewed: (A) 185 had an ICER < $50,000/QALY; (B) 53 had $50,000 ≤ ICER, < $100,000; (C) 20 had $100,000 ≤ ICER < $150,000; and (D) 59 had an ICER ≥ $150,000. Chi square testing showed a strong association (p < 0.001) between estimated ICER values and chosen CET, illustrating a lack of independence between the two. The regression analysis indicated that CETs have a baseline value of $52,000 and grow by $0.37 for each dollar increase in the estimated ICER. CONCLUSIONS: Cost-effectiveness thresholds represent the hypothesis tests of typical CUAs. Our analysis highlights that most CUAs that cite high CETs also result in greater ICERs for the novel interventions that they investigate; thus, these interventions would otherwise not have been cost effective at lower CETs. Selection of a CET may come after the ICER is calculated to infer value that suits a hypothesis.

Impact of Antibiotic Resistance on Treatment of Pneumococcal Disease in Ethiopia: An Agent-Based Modeling Simulation.

Antimicrobial resistance (AMR) is a growing threat to global health. Although AMR endangers continued effectiveness of antibiotics, the impact of AMR has been poorly estimated in low-income countries. This study sought to quantify the effect of AMR on treatments for pediatric pneumococcal disease in Ethiopia. We developed the DREAMR (Dynamic Representation of the Economics of AMR) model that simulate children younger than 5 years who acquire pneumococcal disease (pneumonia, meningitis, and acute otitis media) and seek treatment from various health facilities in Ethiopia over a year. We examined the AMR levels of three antibiotics (penicillin, amoxicillin, and ceftriaxone), treatment failures, and attributable deaths. We used the cost-of-illness method to assess the resulting economic impact of AMR from a societal perspective by estimating the direct and indirect treatment costs and productivity losses. Findings showed that AMR against antibiotics that were used to treat pneumococcal disease led to 195,763 treatment failures per year, which contributed to 2,925 child deaths annually in Ethiopia. Antimicrobial resistance resulted in a first-line treatment failure rate of 29.4%. In 1 year, the proportion of nonsusceptible Streptococcus pneumoniae bacteria increased by 2.1% and 0.5% for amoxicillin and penicillin, and reduced by 0.3% for less commonly used ceftriaxone. Annual costs of AMR to treat pneumococcal disease were around US$15.8 million, including US$3.3 million for ineffective first-line treatments, US$3.7 million for second-line treatments, and US$8.9 million for long-term productivity losses. Antibiotic stewardship to reduce misuse and overuse of antibiotics is essential to maintain the effectiveness of antibiotics, and lessen the health and economic burden of AMR.

Parents' preferences for interventions to improve childhood immunization uptake in northern Nigeria.

BACKGROUND: Routine childhood immunization coverage has been low in northern Nigeria. While local authorities and international partners have been working hard to improve coverage, population preferences for interventions have not been documented. This study aimed to understand parents' preferences and identify possible interventions to improve uptake of childhood immunization. METHODS: Preferences for immunization interventions were elicited using a best-worst scaling (BWS) instrument among parents with children under five. We explored the value of six program attributes (each varying across three levels) identified through a literature review and engagement with local stakeholders. In each of 18 hypothetical programs identified through a main effect orthogonal design, respondents selected the best and worst attributes that may facilitate vaccination of children. Assuming sequential best-worst responses, we used conditional logit to estimate preferences. We employed latent class analysis (LCA) to categorize and examine respondents' preferences across interventions. RESULTS: 97 men and 101 women in 198 households were surveyed. The most preferred level for each attribute included door-to-door vaccinations, free food supplements, bundling with nutritional support programs, involvement of religious leaders, information dissemination through media campaigns, and strengthening of health services by the government. Three types of preferences were recognized in the LCA. The value-driven group (14%) characterized by youngest age, predominantly female, and lower education perceived bundled services with food and nutritional programs as the most important feature of an intervention. Convenience and information seekers (28%) characterized by oldest age and the lowest employment preferred door-to-door vaccinations and media campaigns. The remaining complacent group (58%), characterized by highest education and highest employment, did not show strong preferences to any intervention compared to the other two groups. CONCLUSIONS: Routine immunization programs should consider joining forces with food and nutritional programs to improve vaccination uptake. Incorporating door-to-door visits and media campaigns to target older and unemployed populations may increase childhood immunization uptake in northern Nigeria.