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.

Benefits, challenges, and strategies related to using presumptive recommendations for HPV vaccination: A qualitative study with rural and non-rural-serving primary care professionals.

HPV vaccination coverage remains far below the national target of 80% among US adolescents, particularly in rural areas, which have vaccine uptake rates that are 10% points lower than non-rural areas on average. Primary care professionals (PCPs) can increase coverage by using presumptive recommendations to introduce HPV vaccination in a way that assumes parents want to vaccinate. Through semi-structured interviews, we explored PCPs' experiences and perceptions of using presumptive recommendations in rural- and non-rural-serving primary care clinics in North Carolina. Thematic analysis revealed that most PCPs in rural and non-rural contexts used presumptive recommendations and felt the strategy was an effective and concise way to introduce the topic of HPV vaccination to parents. At the same time, some PCPs raised concerns about presumptive recommendations potentially straining relationships with certain parents, including those who had previously declined HPV vaccine or who distrust medical authority due to their past experiences with the healthcare system. PCPs dealt with these challenges by using a more open-ended approach when introducing HPV vaccination to parents. In conclusion, our findings suggest that PCPs in both rural and non-rural settings see value in using presumptive recommendations to introduce HPV vaccination, but to adequately address concerns and ensure increased HPV vaccine uptake, PCPs can use simple and culturally sensitive language to ensure fully informed consent and to maintain parental trust. And to further strengthen HPV vaccine discussions, PCPs can utilize other effective HPV communication techniques, like the Announcement Approach, in discussing HPV vaccinations with hesitant parents.

Inclusion of marginalized populations in HPV vaccine modeling: A systematic review.

OBJECTIVE: Models simulating the potential impacts of Human Papillomavirus (HPV) vaccine have been used globally to guide vaccination policies and programs. We sought to understand how and why marginalized populations have been incorporated into HPV vaccine simulation models. METHODS: We conducted a systematic search of PubMed, CINAHL, Scopus, and Embase to identify studies using simulation models of HPV vaccination incorporating one or more marginalized population through stratification or subgroup analysis. We extracted data on study characteristics and described these overall and by included marginalized groups. RESULTS: We identified 36 studies that met inclusion criteria, which modeled vaccination in 21 countries. Models included men who have sex with men (MSM; k = 16), stratification by HIV status (k = 9), race/ethnicity (k = 6), poverty (k = 5), rurality (k = 4), and female sex workers (k = 1). When evaluating for a marginalized group (k = 10), HPV vaccination was generally found to be cost-effective, including for MSM, individuals living with HIV, and rural populations. In studies evaluating equity in cancer prevention (k = 9), HPV vaccination generally advanced equity, but this was sensitive to differences in HPV vaccine uptake and use of absolute or relative measures of inequities. Only one study assessed the impact of an intervention promoting HPV vaccine uptake. DISCUSSION: Incorporating marginalized populations into decision models can provide valuable insights to guide decision making and improve equity in cancer prevention. More research is needed to understand the equity impact of HPV vaccination on cancer outcomes among marginalized groups. Research should emphasize implementation - including identifying and evaluating specific interventions to increase HPV vaccine uptake.

Identifying Healthcare Professionals With Lower Human Papillomavirus (HPV) Vaccine Recommendation Quality: A Systematic Review.

PURPOSE: Strengthening healthcare professionals' (HCPs) communication is an evidence-based approach to increasing human papillomavirus (HPV) vaccine uptake among adolescents. To better target future interventions, we sought to synthesize evidence on HCP subgroups who most need to improve their HPV vaccine recommendation quality. METHODS: We searched five databases for quantitative studies published from 2012 to 2022 on HPV vaccine recommendation quality, including recommendation consistency and strength, for United States adolescents. Two coders independently abstracted data from each eligible study, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We summarized variation in recommendation quality by clinical and HCP characteristics. RESULTS: The 28 eligible studies indicated that relatively low proportions of HCPs used higher-quality recommendation practices (median: 61% across 30 measures) and that recommendation quality varied across HCP subgroups. The most consistent findings were that more pediatric HCPs used higher-quality recommendations than family medicine HCPs (8 of 11 studies, 2-60 percentage point difference) and that HPV-related knowledge was associated with higher recommendation quality (four of seven studies). Most studies observed no differences in recommendation quality by clinical role (e.g., provider vs. nurse) or HCP demographics (e.g., gender, age, race/ethnicity). DISCUSSION: Studies suggest a substantial need to improve HCPs' recommendation quality, with opportunities for targeting future interventions.

Impact of visit characteristics on intention to recommend HPV vaccine: An experiment with US health care professionals.

OBJECTIVE: Presumptive recommendations that assume parents want to vaccinate can increase human papillomavirus (HPV) vaccine uptake. We sought to examine how visit characteristics affect health care professionals' (HCPs) intention to use this evidence-based recommendation style. METHODS: In 2022, we conducted an online experiment with 2527 HCPs who had a role in adolescent vaccination in the United States. Participants read 1 of 8 randomly assigned vignettes about a well-child visit. Using a 2 × 2 × 2 between-subjects factorial design, the vignettes varied the following visit characteristics: patient age (9 vs. 12-year-old), prior parental vaccine refusal (yes vs. no), and time pressure on the HCP (low vs. high). HCPs reported on their intention to use a presumptive HPV vaccine recommendation, as well as on related attitudes, subjective norms, and self-efficacy. Analyses used 3-way analysis of variance and parallel mediation. RESULTS: Participants were pediatricians (26%), family/general medicine physicians (22%), advanced practitioners (24%), and nursing staff (28%). Overall, about two-thirds of HCPs (64%) intended to use a presumptive recommendation. Intentions were higher for older children (b = 0.23) and parents without prior vaccine refusal (b = 0.39, both p < 0.001). Time pressure had no main effect or interactions. HCPs' attitudes and self-efficacy partially mediated effects of patient age and prior vaccine refusal (range of b = 0.04-0.28, all p < 0.05). CONCLUSION: To better support visits with younger children and parents who have refused vaccines, HCPs may need more training for making presumptive recommendations for HPV vaccine. Reinforcing positive attitudes and self-efficacy can help HCPs adopt this evidence-based recommendation style.

Conceptualizing and Measuring Trust, Mistrust, and Distrust: Implications for Advancing Health Equity and Building Trustworthiness.

Trust is vital to public confidence in health and science, yet there is no consensus on the most useful way to conceptualize, define, measure, or intervene on trust and its related constructs (e.g., mistrust, distrust, and trustworthiness). In this review, we synthesize literature from this wide-ranging field that has conceptual roots in racism, marginalization, and other forms of oppression. We summarize key definitions and conceptual frameworks and offer guidance to scholars aiming to measure these constructs. We also review how trust-related constructs are associated with health outcomes, describe interventions in this field, and provide recommendations for building trust and institutional trustworthiness and advancing health equity. We ultimately call for future efforts to focus on improving the trustworthiness of public health professionals, scientists, health care providers, and systems instead of aiming to increase trust in these entities as they currently exist and behave.

How to increase and maintain high immunization coverage: Vaccination Demand Resilience (VDR) framework.

BACKGROUND: Resilience in vaccination demand is ever more critical as the COVID-19 pandemic has increased our understanding of the importance of vaccines on health and well-being. Yet timid demand for COVID-19 vaccines where available and reduced uptake of routine immunizations globally further raise the urgent need to build vaccination resilience. We demonstrate the complexity of vaccination demand and resilience in a framework where relevant dimensions are intertwined, fluid, and contextual. METHODS: We developed the Vaccination Demand Resilience (VDR) framework based on a literature review on vaccination demand and expert consultation. The matrix framework builds on three main axes: 1) vaccination attitudes and beliefs; 2) vaccination seeking behavior; and 3) vaccination status. The matrix generated eight quadrants, which can help explain people's levels of vaccination demand and resilience. We selected four scenarios as examples to demonstrate different interventions that could move people across quadrants and build vaccination resilience. RESULTS: Incongruence between individuals' attitudes and beliefs, vaccination behavior, and vaccination status can arise. For example, an individual can be vaccinated due to mandates but reject vaccination benefits and otherwise avoid seeking vaccination. Such incongruence could be altered by interventions to build resilience in vaccination demand. These interventions include information, education and communication to change individuals' vaccination attitudes and beliefs, incentive programs and reminder-recalls to facilitate vaccination seeking, or by strengthening healthcare provider communications to reduce missed opportunities. CONCLUSIONS: Vaccination decision-making is complex. Individuals can be vaccinated without necessarily accepting the benefits of vaccination or seeking vaccination, threatening resilience in vaccination demand. The VDR framework can provide a useful lens for program managers and policy makers considering interventions and policies to improve vaccination resilience. This would help build and sustain confidence and demand for vaccinations, and help to continue to prevent disease, disability, and death from vaccine-preventable diseases.

Impact of the COVID-19 Pandemic on Medical Product Procurement, Prices, and Supply Chain in Zimbabwe: Lessons for Supply Chain Resiliency.

BACKGROUND: The COVID-19 pandemic has disrupted global health supply chains including manufacturing, storage, and delivery of essential medicines, testing kits, personal protective equipment, and laboratory reagents. We sought to document how pandemic impacted the procurement, prices, and supply chain of medical products in Zimbabwe. METHODS: We conducted semistructured in-depth key informant interviews with 36 health system stakeholders in Zimbabwe involved in medicine procurement. Respondents included pharmacists, regulatory officers, and procurement and supply chain management professionals from public and private sectors. RESULTS: Before the COVID-19 pandemic, respondents described experiencing long-standing resource constraints, medicine shortages, foreign currency shortages, and supply chain inefficiencies. The pandemic exacerbated this situation due to supply constraints, export restrictions, medicine shortages, and movement restrictions that disrupted logistical and stock management systems. Competitive bidding and tendering processes experienced reduced participation by international suppliers. Significant price increases were initially observed among internationally shipped medicines and for personal protective equipment to cover additional freight costs. COVID-19 pandemic impacts were moderated by reduced patient demand and lower health services utilization, resulting in fewer supply shocks and less price volatility. Further, health system adaptations such as switching treatment regimens, modifying dispensing schedules based on stock availability, redistributing stock of medicines among facilities, and new service delivery models such as integrated outreach services helped ensure continued patient access to medicines. CONCLUSIONS: Our findings highlight the need for policies that ensure continuity in access to health services and medical products, even during a pandemic, by avoiding blanket restrictions on medical product exports and imports. Pooled procurement, especially at regional and global levels, with long-term service agreements may help achieve greater resiliency to supply and price shocks from supply chain disruptions. Interventions across manufacturing, trade, and regulatory policy and service delivery models are also needed for supply chain resiliency.

Impact of the COVID-19 pandemic on the quality of medical products in Zimbabwe: a qualitative study based on key informant interviews with health system stakeholders.

OBJECTIVE: To explore the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the quality of medical products in Zimbabwe, including market risks for substandard and falsified products and impacts on quality assurance activities. DESIGN: Qualitative study based on in-depth key informant interviews. SETTING: Health system stakeholders across the medical product supply chain in Zimbabwe. PARTICIPANTS: 36 key informants were interviewed between April and June 2021. RESULTS: We found that the COVID-19 pandemic disrupted quality assurance and regulatory activities of medical products in Zimbabwe, resulted in observations of poor-quality personal protective equipment (PPE) and other COVID-19-related products and led to increased risks to quality. Risks to quality due to COVID-19-related disruptions included increased layers of agents in the supply chain and an influx of non-traditional suppliers. COVID-19-related movement restrictions reduced access to health facilities and thus may have increased the usage of the informal market where smuggled and unregistered medical products are sold with less oversight by the regulator. Most reports of poor-quality medical products were for PPE, such as masks and infrared thermometers, used for the COVID-19 response. Besides these reports, many participants stated that the quality of essential medicines in the formal sector, not related to COVID-19, had largely been maintained during the pandemic due to the regulator's stringent quality assurance process. Incentives for suppliers to maintain quality to retain large donor-funded contracts, and the need for local wholesalers and distributors to comply with quality-related aspects of distribution agreements with global manufacturers of brand-name medical products, mitigated threats to quality. CONCLUSIONS: The COVID-19 pandemic presented opportunities and market risks for circulation of substandard and falsified medical products in Zimbabwe. There is a need for policymakers to invest in measures to safeguard the quality of medical products during emergencies and to build resiliency against future supply chain shocks.

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.

Variations in global prices of chemotherapy for childhood cancer: a descriptive analysis.

Background: The stark disparity in survival for children with cancer across the world has inspired a global call to expand chemotherapy access in low and middle income countries. Among the numerous barriers to success, a paucity of reliable information regarding chemotherapy pricing hinders the ability of governments and other key stakeholders to make informed budget decisions or negotiate lower medication prices. The aim of this study was to generate comparative price information on both individual chemotherapy agents and comprehensive treatment regimens for common childhood cancers using real-world data. Methods: Chemotherapy agents were selected based on their inclusion in the World Health Organization (WHO) Essential Medicines List for Children (EMLc) and their use in frontline regimens for the tracer cancer types prioritized by the WHO's Global Initiative for Childhood Cancer (GICC). Sources included IQVIA MIDAS data, obtained under license from IQVIA, and publicly available data from Management Sciences for Health (MSH). Data on chemotherapy prices and purchase volumes spanning 2012-2019 were aggregated according to WHO region and World Bank (WB) income classification. Cumulative chemotherapy prices for treatment regimens were compared across WB income classification. Findings: Data representing an estimated 1.1 billion doses of chemotherapy were obtained for 97 countries: 43 high income countries (HICs), 28 upper middle income countries (UMICs), and 26 low and lower middle income countries (LLMICs). Median drug prices in HICs were 0.9-20.4 times those of UMICs and 0.9-15.5 times those of LMICs. Regimen prices were generally higher for HICs, hematologic malignancies, non-adapted protocols, and higher risk stratification or stage, albeit with notable exceptions. Interpretation: This study represents the largest price analysis to date of chemotherapy agents used globally in childhood cancer therapy. The findings of this study form a basis for future cost-effectiveness analysis in pediatric cancer and should inform efforts of governments and stakeholders to negotiate drug prices and develop pooled purchasing strategies. Funding: NB received funding support from the American Lebanese Syrian Associated Charities and Cancer Center Support grant (CA21765) from the National Cancer Institute through the National Institutes of Health. TA received funding through the University of North Carolina Oncology K12 (K12CA120780) and the University Cancer Research Fund from the UNC Lineberger Comprehensive Cancer Center.

Systematic review of community pharmacist administration of long-acting injectable antipsychotic medications.

BACKGROUND: Long-acting injectable antipsychotic (LAIA) medications offer an effective treatment option for patients with serious mental illness. Despite demonstrated clinical safety and efficacy as well as increased adherence and less frequent administration compared with daily oral regimens, LAIAs remain underutilized in clinical practice. With legislation allowing pharmacists to administer injectable medications in 48 U.S. states, community pharmacies are uniquely positioned to serve as an access point for patients with serious mental illnesses to receive LAIA injections. OBJECTIVE: This study aimed to conduct a systematic review of the health and economic benefits and costs of community pharmacist administration of LAIA medications. METHODS: A systematic search of the literature published from January 1996 to April 2022 was conducted across 3 databases (Embase, PubMed, and Scopus Plus). Publications describing pharmacist administration of LAIA medications in outpatient settings were included. Publications that examined the use of LAIAs but did not involve a pharmacist administering the medication were excluded. RESULTS: Of 2261 publications reviewed, we identified 8 publications (4 articles and 4 abstracts) that met our inclusion criteria, of which only 7 included results. Four studies reported high medication adherence achieved by patients receiving pharmacist-administered LAIAs. Two publications surveyed patient satisfaction with pharmacist administration of LAIAs in community pharmacy settings. One study found pharmacists' mixed attitudes regarding LAIA administration and time and safety barriers to offering the service. CONCLUSION: We found very little evidence on the impact of pharmacist administration of LAIAs on patient outcomes. This review highlights the need to generate greater evidence on the health and economic benefits as well as financial models for pharmacists to administer LAIA medications in outpatient and community pharmacy settings. Such evidence could support more community pharmacists to offer LAIA medications and contribute to the shift toward value-based care.

Comparing the return on investment of technologies to detect substandard and falsified amoxicillin: A Kenya case study.

The prevalence of substandard and falsified medicines in low- and middle-income countries (LMICs) is a major global public health concern. Multiple screening technologies for post-market surveillance of medicine quality have been developed but there exists no clear guidance on which technology is optimal for LMICs. This study examined the return on investment (ROI) of implementing a select number of screening technologies for post-market surveillance of amoxicillin quality in a case study of Kenya. An agent-based model, Examining Screening Technologies using Economic Evaluations for Medicines (ESTEEM), was developed to estimate the costs, benefits, and ROI of implementing screening technologies for post-market surveillance of substandard and falsified amoxicillin for treatment of pediatric pneumonia in Kenya. The model simulated sampling, testing, and removal of substandard and falsified amoxicillin from the Kenyan market using five screening technologies: (1) Global Pharma Health Fund's GPHF-Minilab, (2) high-performance liquid chromatography (HPLC), (3) near-infrared spectroscopy (NIR), (4) paper analytical devices / antibiotic paper analytical devices (PADs/aPADs), and (5) Raman spectroscopy. The study team analyzed the population impact of utilizing amoxicillin for the treatment of pneumonia in children under age five in Kenya. We found that the GPHF-Minilab, NIR, and PADs/aPADs were similar in their abilities to rapidly screen for and remove substandard and falsified amoxicillin from the Kenyan market resulting in a higher ROI compared to HPLC. NIR and PADs/aPADs yielded the highest ROI at $21 (90% Uncertainty Range (UR) $5-$51) each, followed by GPHF-Minilab ($16, 90%UR $4 - $38), Raman ($9, 90%UR $2 - $21), and HPLC ($3, 90%UR $0 - $7). This study highlights screening technologies that can be used to reduce costs, speed up the removal of poor-quality medicines, and consequently improve health and economic outcomes in LMICs. National medicine regulatory authorities should adopt these fast, reliable, and low-cost screening technologies to better detect substandard and falsified medicines, reserving HPLC for confirmatory tests.

Processes and perceptions of chemotherapy supply chain in Ethiopia: A mixed-method study.

BACKGROUND: The impact and downstream effects of the chemotherapy supply chain in Ethiopia are not well understood. The purpose of this study was to identify perceived gaps in supply chain and characterize their impact on patient care. METHODS: A concurrent mixed-method study was conducted at a large academic cancer center in Ethiopia. In-depth interviews (IDIs) and surveys were completed in collaboration with external stakeholders with knowledge about chemotherapy supply chain in Ethiopia. Thematic coding was used for qualitative analysis of IDI and descriptive statistics were used to summarize quantitative survey data. RESULTS: Six stakeholders participated in the IDIs and seven completed surveys. IDIs revealed that most chemotherapeutic agents are purchased by the Ethiopian Pharmaceutical Supply Agency (EPSA) and are distributed to cancer treatment centers. A free-market purchasing option also exists, but for chemotherapy obtained outside of government-subsidized channels, the potential for substandard or falsified chemotherapy was a concern. Participants expressed confidence that the correct treatment was administered to patients, but viewpoints on reliability and consistency of medication supply were variable. Quantitative data from the survey showed that participants were not confident that medications are prepared safely and correctly. Improper storage and manipulation of high-risk medications remain a significant risk to staff. CONCLUSIONS: This study provides insight from a healthcare staff perspective on how gaps in the chemotherapy supply chain process impact patient care in a low-income country. Inventory management, disruptions in supply chain, and product integrity were perceived as the largest gaps in the current chemotherapy supply chain structure.

Associations between pharmacy choice and influenza vaccination: Mail order vs community pharmacy users.

BACKGROUND: Despite the effectiveness of vaccines, US adult vaccination rates remain low. This is especially true for the influenza vaccine, which is recommended annually and widely available. The accessibility of community pharmacies as convenient places to receive influenza vaccines has been shown to increase uptake. However, use of mail order pharmacies may reduce in-person pharmacist encounters and reduce the likelihood that users receive annual influenza vaccines. OBJECTIVE: To determine the association between the type of pharmacy a patient uses and their likelihood of receiving an influenza vaccine. METHODS: This cross-sectional cohort study used the 2018 Medical Expenditure Panel Survey to observe noninstitutionalized US adult pharmacy users. Pharmacy type was dichotomized into community use only vs any mail order pharmacy use. Multivariable weighted logistic regression was used to identify associations between the type of pharmacy used and influenza vaccination, adjusting for sociodemographic, health status, and health care access and utilization confounders. All analyses were stratified by age (< 65 and ≥ 65 years). RESULTS: The aged younger than 65 years and aged 65 years and older samples had 8,074 and 4,037 respondents who represented 95,930,349 and 40,163,276 weighted observations, respectively. Compared with community pharmacy users, mail order users were more likely to be aged 65 and older, be White, have high income, and have a usual source of care (P < 0.0001). Adjusted odds ratios (AORs) for influenza vaccination were significantly lower among community pharmacy users than mail order users among individuals aged younger than 65 years (AOR=0.71; 95% CI = 0.580.87) but was not significant among those aged 65 years and older (AOR = 0.87; 95% CI = 0.69-1.09). CONCLUSIONS: Community pharmacy users aged younger than 65 years are less likely to receive the influenza vaccine than their mail order pharmacy user counterparts. These counterintuitive results could be caused by residual confounding due to differences in factors that influence pharmacy use type and vaccination likelihood. Further exploration is needed to account for differences between these populations that independently drive vaccination choice. DISCLOSURES: Dr Burbage was a fellow in the Real World Evidence, Population Health and Quality Research Postdoctoral Fellowship Program in collaboration with University of North Carolina Eshelman School of Pharmacy and Pharmacy Quality Alliance, and supported by Janssen Scientific Affairs at the time of this study. She is now employed by Janssen Scientific Affairs. Dr Parikh is an employee of Pharmacy Quality Alliance. Dr Campbell was employed by Pharmacy Quality Alliance at the time of the study. He is now employed by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Dr Ramachandran has received an unrelated research contract with Pharmacy Quality Alliance. Dr Gatwood has received vaccine-related research grants from Merck & Co. and GlaxoSmithKline unrelated to this project and consulting fees for a vaccine-related expert panel with Merck & Co. unrelated to this manuscript and is an advisory board member with Janssen Scientific Affairs. Dr. Urick was employed by the UNC Eshelman School of Pharmacy at the time of this writing and is currently employed by Prime Therapeutics. He has received community pharmacy-related consulting fees from Cardinal Health and Pharmacy Quality Solutions unrelated to this work. Dr Ozawa has a research grant from Merck & Co. unrelated to this project. This project did not receive funding from any agency in the public, commercial, or not-for-profit sectors.

Modeling the Health and Economic Impact of Substandard and Falsified Medicines: A Review of Existing Models and Approaches.

Substandard and falsified medicines are harmful to patients, causing prolonged illness, side effects, and preventable deaths. Moreover, they have an impact on the health system and society more broadly by leading to additional care, higher disease burden, productivity losses and loss of trust in health care. Models that estimate the health and economic impacts of substandard and falsified medicines can be useful for regulators to contextualize the problem and to make an economic case for solutions. Yet these models have not been systematically catalogued to date. We reviewed existing models that estimate the health and economic impact of substandard and falsified medicines to describe the varying modeling approaches and gaps in knowledge. We compared model characteristics, data sources, assumptions, and limitations. Seven models were identified. The models assessed the impact of antimalarial (n = 5) or antibiotic (n = 2) quality at a national (n = 4), regional (n = 2), or global (n = 1) level. Most models conducted uncertainty analysis and provided ranges around potential outcomes. We found that models are lacking for other medicines, few countries' data have been analyzed, and capturing population heterogeneity remains a challenge. Providing the best estimates of the impact of substandard and falsified medicines on a level that is actionable for decision-makers is important. To enable this, research on the impact of substandard and falsified medicines should be expanded to more medicine types and classes and tailored to more countries that are affected, with greater specificity.

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.

Online Pharmacy Accessibility of Imatinib, An Oral Chemotherapy Medication.

BACKGROUND: Since prices of imatinib (Gleevec) remain high, patients on oral chemotherapy are looking for alternative methods to access this life-saving medication. We assessed the accessibility of imatinib through online pharmacies and analyzed each website for medication safety, price, and marketing tactics. METHODS: We searched the term "buy imatinib online" using 4 commonly used internet search engines (Google, Bing, Yahoo!, and DuckDuckGo) and screened web pages displayed in the first 10 pages. Websites were included if they were published in English, sold imatinib, were free to access, and offered shipping in the United States. Websites were classified using LegitScript's categorization as "certified," "unclassified," "unapproved," or "rogue." We analyzed information on websites' patient safety characteristics, marketing techniques, pricing, domain registration information, and IP addresses. RESULTS: Of the 44 online pharmacies identified, only 3 (7%) were certified, and the remainder were classified as rogue (52%; n=23), unapproved (30%; n=13), or unclassified (11%; n=5). Thirteen online pharmacies (30%; 9 rogue, 4 unclassified) sold imatinib without a prescription. Nearly one-quarter (n=10) of online pharmacies selling imatinib did not include drug-related warnings on their websites, and nearly half (n=21) did not limit the purchasable quantity. More than three-quarters (n=34) of online pharmacies selling imatinib did not offer pharmacist consultations, even though nearly all websites extended offers to speak with sales associates (91%; n=40). Most online pharmacies selling imatinib claimed price discounts (95%; n=42), but fewer provided bulk discounts (23%; n=10) or coupons (34%; n=15). One-third of rogue pharmacies selling imatinib (n=7) claimed to be registered or accredited on their websites. CONCLUSIONS: The lack of safety measures taken by illegitimate online pharmacies endangers patient safety because they allow patients to purchase imatinib without appropriate evaluation for response, drug interactions, and adverse effects. Healthcare providers need to be aware of this practice and should assure patient access to imatinib through safe and legitimate pharmacies.

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.

Development and Validation of the Trust in My Doctor, Trust in Doctors in General, and Trust in the Health Care Team Scales.

RATIONALE: Historic and present-day racism and inequity in the United States (U.S.) have resulted in diminished trust in health care among many populations. A key barrier to improving trust in health care is a dearth of well-validated measures appropriate for diverse populations. Indeed, systematic reviews indicate a need to develop and test updated trust measures that are multidimensional and inclusive of relevant domains (e.g., fairness). OBJECTIVE: We developed three trust measures: the Trust in My Doctor (T-MD), Trust in Doctors in General (T-DiG), and Trust in the Health Care Team (T-HCT) scales. METHODS: After developing an initial item pool, expert reviewers (n = 6) provided feedback on the face validity of each scale. We conducted cognitive interviews (n = 21) with a convenience sample of adults to ensure items were interpreted as intended. In 2020, we administered an online survey to a convenience sample of U.S. adults recruited through the Qualtrics Panel (n = 801) to assess scale reliability and validity. RESULTS: Exploratory and confirmatory factor analyses indicated acceptable model fit for second order latent factor models for each scale (root mean square error of approximation: <0.07, comparative fit index: ≥0.98, and standardized root mean square residual: ≤0.03). The T-MD contained 25 items and six subscales: communication competency, fidelity, systems trust, confidentiality, fairness, and global trust. The T-DiG and T-HCT each contained 29 items and seven subscales (the same subscales in the T-MD plus an additional subscale related to stigma-based discrimination). Each scale was strongly correlated with existing trust measures and perceived racism in health care and was significantly associated with delayed health care seeking and receipt of a routine health exam. CONCLUSIONS: The multidimensional T-MD, T-DiG, and T-HCT scales have sound psychometric properties and may be useful for researchers evaluating trust-related interventions or conducting studies where trust is an important construct or main outcome.