Self-administration of medications in inpatient postnatal women: an opportunity to empower self-care, improved medicines knowledge and adherence utilising clinical pharmacists and midwifery workforce and use of a midwife formulary.

OBJECTIVES: To assess the impact of self-administration of medicines (facilitated by a midwife formulary) on postnatal women's knowledge of certain post-delivery medications, awareness of the Green Bag Scheme, factors contributing to constipation, pain satisfaction, adherence, and time released to midwives plus feedback from these women and their midwives. METHODS: The study was conducted in consented postnatal women, who self-administered medications from their bedside lockers. The mode of delivery and parity were recorded. Data were compared in women who self-administered to those who did not. Midwives used our established midwife formulary to write their essential unprescribed medications. Direct interview questionnaires were used to obtain their knowledge on chosen post-delivery medicines, pain satisfaction, the Green Bag Scheme and factors contributing to constipation. Regular medicines counts were used to check adherence. Midwives' time not administering these self-administered medications was estimated. Self-reported questionnaires were used to obtain feedback from participants and midwives. Responses were analysed proportionately and where appropriate by simple statistics. RESULTS: Women (n=203) who self-administered were compared with those (n=401) who did not. Greater medicines' knowledge and better (96% vs 79%) pain satisfaction were found in self-administering women. Knowledge of each contributing factor to constipation varied. Mode of delivery and parity had no impact on these outcomes. Adherence seemed high 96% (195/203). Awareness of the Green Bag Scheme was poor (66/604). Most women, 94% (191/203) found the service helpful and 89% (178/200) would take part again. At least 224 hours were released to midwives by these self-administering women. 164/203 (81%) midwives felt the scheme was beneficial. CONCLUSIONS: Self-administering women had better pain satisfaction, medication knowledge and adherence. The need to improve engagement in the Green Bag Scheme was flagged. This service, supported by use of a midwife formulary, can release time to midwives to do other tasks including care for women with more complex issues. A business case for this service is under review.

Assessing Payers' Preferences for Real-World Evidence in the United States: A Discrete Choice Experiment.

OBJECTIVES: To rank the US payers' preferences for attributes of real-world evidence (RWE) studies in the context of chronic disease and to quantify trade-offs among them. METHODS: We conducted a discrete choice experiment in which 180 employees from payer organizations were tasked to choose between 2 RWE studies assuming they were assessing evidence to inform formulary decisions for chronic disease treatment. Each RWE study was characterized by 7 attributes with 3 levels each: very informative, moderately informative, and not measured. We used a D-optimal main-effects design. Survey data were fitted to a conditional logit model to obtain a relative measure of the ranking of importance for each attribute. RESULTS: Clinical outcomes were the most preferred attribute. It was 4.68 times as important as productivity outcomes-the least preferred attribute. It was followed by health-related quality of life (2.78), methodologic rigor (2.09), resource utilization (1.71), and external validity (1.56). CONCLUSIONS: This study provides a quantification of the value payers place on key RWE attributes. Across attributes, payers have higher preferences for clinical and health-related quality of life outcomes than the other attributes. Between attributes' levels, payers prefer high levels of information in clinical outcomes and methodologic rigor but are indifferent in other attributes. Our results bridge the gap between the information that payers seek and the attributes that RWE studies prioritize and effectively guide future research design.

The budget impact of adding pralsetinib to a US health plan formulary for treatment of non-small cell lung cancer and thyroid cancer with RET alterations.

BACKGROUND: Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of all lung cancers. Thyroid cancer, while generally not as lethal as lung cancer, has a large prevalent population and a rapidly increasing incidence in the United States. Pralsetinib is a highly potent, selective rearranged during transfection (RET) inhibitor indicated for the treatment of RET-positive NSCLC and thyroid cancer tumors. OBJECTIVE: To estimate the budget impact of adding pralsetinib to a 1 million-member US health plan formulary for the treatment of patients with metastatic RET fusion-positive NSCLC, advanced or metastatic RET-mutant medullary thyroid cancer (MTC), or advanced or metastatic RET fusion-positive thyroid cancer (non-MTC). METHODS: A budget impact model with a 3-year time horizon was developed in Microsoft Excel to estimate the number of eligible RET-positive NSCLC and thyroid cancer patients in a plan and quantify associated treatment costs (2020 USD). Comparators in the analyses included pralsetinib, selpercatinib, and cabozantinib, as well as indication-specific use of pembrolizumab, pemetrexed/carboplatin combination, vandetanib, lenvatinib, and sorafenib. Drug acquisition, molecular testing, treatment monitoring, and adverse event management costs were included to estimate total annual costs and per-member per-month (PMPM) costs in current (without pralsetinib) and potential future market scenarios, where pralsetinib is assumed to split the projected RET inhibitor market share with selpercatinib. The number of treated patients was based on age- and sex-adjusted incidence of disease, the proportion of patients diagnosed with advanced or metastatic disease, and projected RET testing rates. Treatment duration was based on progression-free survival or duration of response data from clinical trials. Medical resources were monetized using standardized sources such as Medicare reimbursement and wholesale acquisition cost (WAC). RESULTS: The model estimated that there would be approximately 6 new treatment-eligible patients in a 1 million-member plan annually. Monthly WAC is $19,243 for pralsetinib and $20,600 for selpercatinib at the recommended starting dose. Adoption of pralsetinib, with corresponding increases in pralsetinib market share, would be slightly cost saving to a payer, decreasing the overall budget impact to the health plan by $49,985 in year 3 (-$0.0042 PMPM; -$0.0030, -$0.0006, and -$0.0005 for NSCLC, MTC, and thyroid cancer [non-MTC], respectively). In year 3, drug costs were the key driver of total costs (~80%-98%) and cost savings. All other medical resource categories were cost-neutral or nominally cost saving or additive in the budget impact analysis. CONCLUSIONS: Quantifying the budget impact associated with the adoption of new targeted precision therapies is an important consideration for payers. For eligible NSCLC and thyroid cancer patients, our analysis suggests that adoption of pralsetinib is expected to result in modest cost savings for US payers. DISCLOSURES: Support for this study was provided by Blueprint Medicines Corporation. This study was conducted by Veritas Health Economics Consulting, Inc., in collaboration with Blueprint Medicines, which was involved in the design of the study; collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication. Duff is an employee of Veritas Health Economics Consulting, which received research funding from Blueprint Medicines to develop the budget impact model. Norregaard and Sullivan are employees of Blueprint Medicines. Bargiacchi and Brener were employees of Blueprint Medicines at the time of the research study. This study was presented as a poster at the AMCP Virtual Learning Event, April 2021.

AMCP Partnership Forum: Racial health disparities-a closer look at benefit design.

As part of its stand against racial injustice and its commitment to action, AMCP dedicated a partnership forum to discussion of potential sources of racial health disparities and inequities in benefit design because these are primary drivers of medication use. This forum, held virtually March 23-24, 2021, convened more than 40 experts representing key stakeholders from managed care settings. Key principles that emerged from the forum discussion as means to mitigate racial health disparities were to acknowledge that structural racism exists and that it can impact the provision of health care, including but not limited to formulary development and benefit design processes; to integrate proactive strategies to improve equity, beginning with education and training, into all aspects of health care; and to view patients holistically with an understanding of the compounding effect of social determinants of health on their personal wellness. With these principles in mind, participants highlighted several priority considerations including improving existing gaps in data, addressing diversity and equity as they relate to formulary development, evaluating systems such as benefit offerings through a lens of increasing equity, recognizing cost-related factors that affect equity, considering patients' interactions with and their ability to access the system, and committing to patient-centered care. Participants also suggested areas for policy-related focus and noted the need to develop and deploy specific education and training. DISCLOSURES: This forum was sponsored by Amgen, the National Pharmaceutical Council, Pfizer, PhRMA, Sandoz, and Takeda. Their representatives joined the forum as panelists or participants. These proceedings were prepared as a summary of the forum to represent common themes; they are not necessarily endorsed by all attendees nor should they be construed as reflecting group consensus.

Formulary tiers, medication cost sharing, and transparency in bronze and silver qualified health plans in 2014 vs 2018.

BACKGROUND: In 2014, qualified health plans sold in the Affordable Care Act (ACA) marketplaces were accused of providing drug coverage that was too restrictive and costly. After the change in administration in 2016, efforts to repeal portions of the ACA led to increases in premiums, decreases in enrollment, and overall uncertainty. OBJECTIVE: To examine how the number of formulary tiers and medication cost sharing, as well as transparency around these aspects, in qualified bronze and silver health plans in California, Florida, and Illinois changed from 2014 to 2018. METHODS: A search of all bronze and silver qualified health plans in California, Florida, and Illinois was performed in 2014 and in 2018 through the marketplace and issuer websites. RESULTS: From 2014 to 2018, the total number of bronze and silver qualified health plans offered in California, Florida, and Illinois remained relatively stable (36 to 35, 123 to 122, and 60 to 74, respectively). Over the same time period, the median number of formulary tiers remained constant for California and Florida (four and five) and increased from five to seven for Illinois. Of note, most Illinois plans shifted from a formulary with five or fewer tiers (92% of plans) to seven tiers (73% of plans) between 2014 and 2018. There was also an increase in the use of coinsurance instead of copay for each of the four following formulary tiers: generic (19% to 27% of plans), preferred brand (21% to 38%), nonpreferred brand (33% to 52%), and specialty (76% to 91%). Additionally, there was an increase in the median coinsurance rates for each of the aforementioned tiers: 0% to 25%, 0% to 35%, 30% to 40%, and 30% to 40%, respectively. The proportion of plans that provided their formularies on the marketplace website increased from 82% to 97% from 2014 to 2018, with the increase mostly driven by California plans (0% to 80%). There was a small increase in the proportion of plans that reported medication cost sharing through the medical benefit from 2014 (19%) to 2018 (25%). CONCLUSIONS: Between 2014 and 2018, qualified health plans increased their use of formularies with greater numbers of tiers, the use of coinsurance for each tier, and higher coinsurance rates. Availability of formularies on marketplace websites increased, but cost sharing transparency for medications covered by the medical benefit could greatly improve. DISCLOSURES: No funding supported this study. Hung reports past employment by Blue Cross Blue Shield Association, CVS Health, and a grant from PhRMA outside of the submitted work. She was an intern at the Biotechnology Industry Organization when this work began. Sauvageau has no disclosures. This work was presented as a poster at the AMCP 2018 Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Biologic medicine inclusion in 138 national essential medicines lists.

BACKGROUND: Essential medicines lists (EMLs) are intended to reflect the priority health care needs of populations. We hypothesized that biologic disease-modifying antirheumatic drugs (DMARDs) are underrepresented relative to conventional DMARDs in existing national EMLs. We aimed to survey the extent to which biologic DMARDs are included in EMLs, to determine country characteristics contributing to their inclusion or absence, and to contrast this with conventional DMARD therapies. METHODS: We searched 138 national EMLs for 10 conventional and 14 biologic DMARDs used in the treatment of childhood rheumatologic diseases. Via regression modelling, we determined country characteristics accounting for differences in medicine inclusion between national EMLs. RESULTS: Eleven countries (7.97%) included all 10 conventional DMARDs, 115 (83.33%) ≥5, and all countries listed at least one. Gross domestic product (GDP) per capita was associated with the total number of conventional DMARDs included (ß11.02 [95% CI 0.39, 1.66]; P = 0.00279). Among biologic DMARDs, 3 countries (2.2%) listed ≥10, 15 (10.9%) listed ≥5, and 47 (34.1%) listed at least one. Ninety-one (65.9%) of countries listed no biologic DMARDs. European region (ß1 1.30 [95% CI 0.08, 2.52]; P = 0.0367), life expectancy (ß1-0.70 [95% CI -1.22, - 0.18]; P = 0.0085), health expenditure per capita (ß1 1.83 [95% CI 1.24, 2.42]; P < 0.001), and conventional DMARDs listed (ß1 0.70 [95% CI 0.33, 1.07]; P < 0.001) were associated with the total number of biologic DMARDs included. CONCLUSION: Biologic DMARDs are excluded from most national EMLs. By comparison, conventional DMARDs are widely included. Countries with higher health spending and longer life expectancy are more likely to list biologics.

Overcoming barriers to biosimilar adoption: real-world perspectives from a national payer and provider initiative.

In response to a published national payer survey indicating striking needs for multistakeholder initiatives to increase biosimilar adoption, a focus workgroup meeting joining payers and providers was conducted in December 2019 in Boston, MA. Before the focus group meeting, a survey was sent to health care providers to collect perceptions about barriers to biosimilar adoption and gather input on best potential strategies for addressing these barriers. The focus group panel consisted of 5 managed care pharmacists and 3 physician experts in rheumatology, dermatology, and gastroenterology, representing large managed care organizations and health care systems in the Boston area. A clinical moderator facilitated discussions between the payers and providers regarding challenges to biosimilar adoption and potential collaborative strategies to overcome these barriers. The focus group participants identified hurdles to biosimilar adoption in 3 major areas: (1) the lack of confidence in biosimilar interchangeability and a need for education about biosimilars, (2) the lack of financial incentives to switch to biosimilars from the reference biologic product, and (3) administrative burdens that impair the prescription of biologics. Learning from their mutual experiences, the focus group participants formulated action plans to address these barriers. The top strategies recommended by the participants included advancing biosimilar education, facilitating administrative processes related to biosimilar prescriptions, and increasing provider reimbursement while reducing cost sharing to patients receiving biosimilars. DISCLOSURES: The study reported on in this article was part of a continuing education program funded by an independent educational grant that was awarded by Sandoz Inc., a Novartis Division, to PRIME Education, LLC. The grantor had no role in the study design, execution, analysis, or reporting. The Academy of Managed Care Pharmacy (AMCP) received grant funding from PRIME to assist with participant recruitment and content review for the continuing education program. Bandekar, Cheifetz, Edgar, Helfgott, Hoye-Simek, Liu, and Smith received an honorarium from PRIME for serving as faculty for the continuing education program. Cheifetz has received research grants from Inform Diagnostics and consulting fees from AbbVie, Bacainn, BMS, Grifols, Janssen, Pfizer, Prometheus, Samsung, and Takeda unrelated to this work. Smith has received consulting fees from Boehringer-Ingelheim, has served as an investigator on industry-initiated trials for AbbVie and Pfizer, and has served as an investigator on investigator-initiated trials for Novartis and Regeneron. Carter, Fajardo, and Simone have nothing to disclose.

Personal Formularies of Primary Care Physicians Across 4 Health Care Systems.

Importance: More conservative prescribing has the potential to reduce adverse drug events and patient harm and cost; however, no method exists defining the extent to which individual clinicians prescribe conservatively. One potential domain is prescribing a more limited number of drugs. Personal formularies-defined as the number and mix of unique, newly initiated drugs prescribed by a physician-may enable comparisons among clinicians, practices, and institutions. Objectives: To develop a method of defining primary care physicians' personal formularies and examine how they differ among primary care physicians at 4 institutions; evaluate associations between personal formularies and patient, physician, and practice site characteristics; and empirically derive and examine the variability of the top 200 core drugs prescribed at the 4 sites. Design, Setting, and Participants: This retrospective cohort study was conducted at 4 US health care systems among 4655 internal and family medicine physicians and 4 930 707 patients who had at least 1 visit to these physicians between January 1, 2017, and December 31, 2018. Exposures: Personal formulary size was defined as the number of unique, newly initiated drugs. Main Outcomes and Measures: Personal formulary size and drugs used, physician and patient characteristics, core drugs, and analysis of selected drug classes. Results: The study population included 4655 primary care physicians (2274 women [48.9%]; mean [SD] age, 48.5 [4.4] years) and 4 930 707 patients (16.5% women; mean [SD] age, 51.9 [8.3] years). There were 41 378 903 outpatient prescriptions written, of which 9 496 766 (23.0%) were new starts. Institution median personal formulary size ranged from 150 (interquartile range, 82.0-212.0) to 296 (interquartile range, 230.0-347.0) drugs. In multivariable modeling, personal formulary size was significantly associated with panel size (total number of unique patients with face-to-face encounters during the study period; 1.2 medications per 100 patients), physician's total number of encounters (5.7 drugs per 10% increase), and physician's sex (-6.2 drugs per 100 patients for female physicians). There were 1527 unique, newly prescribed drugs across the 4 sites. Fewer than half the drugs (626 [41.0%]) were used at every site. Physicians' prescribing of drugs from a pooled core list varied from 0% to 100% of their prescriptions. Conclusions and Relevance: Personal formularies, measured at the level of individual physicians and institutions, reveal variability in size and mix of drugs. Similarly, defining a list of commonly prescribed core drugs in primary care revealed interphysician and interinstitutional differences. Personal formularies and core medication lists enable comparisons and may identify outliers and opportunities for safer and more appropriate prescribing.

Questionnaire-based Pan-India survey for impact assessment of National Formulary of India.

OBJECTIVES: The National Formulary of India (NFI), a ready reckoner for medicines among healthcare-professionals aims for promoting rational drug use. This needs periodic update based on evidence-based medicines and suggestions from end-users. This study assessed the level of awareness among health-care professionals and sought suggestions for enhancement of utility/content of NFI. MATERIALS AND METHODS: This pan-India cross-sectional, questionnaire-based survey was conducted between November-2020 and March-2021. A Google-doc-based validated questionnaire (20 questions) was circulated through E-mail/social media groups and to 311 medical institutes/hospitals/clinics across India through the adverse drug reaction monitoring centers under the Pharmacovigilance Program of India. RESULTS: A total of 461 participants (39-interns, 167-resident doctors, and the rest practicing physicians/doctors) affiliated to 224 institutes/hospitals/clinics had responded. About 46% respondents consulted NFI for drug-related information and 82.3% stated that NFI provides balanced unbiased information. About 95% respondents were aware of NFI's content and 76% mentioned usefulness of NFI in their clinical practice; however, 34.4% had misconceptions about NFI, 28.7% had a false belief that NFI is a legal document to safeguard health-care providers and 22.2% had never used it. Suggestions to enhance NFI's utility included digital accessibility, incorporation of information like drugs for basic medical emergencies (71.3%), disposal of expired-pharmaceutical products (38.7%), pharmaceutical price control policy (36.3%), and drug-procurement practices in hospitals (35.6%). CONCLUSION: As per the survey findings, NFI is an effective tool for instant access to precise and unbiased drug-related information, and fostering rational use of drugs. Boosting its practical usefulness needs incorporation of suggested information, digital accessibility, and periodic update.

FDA expedited approval and implications for rational formulary and health plan design.

DISCLOSURES: No funding supported this commentary. The authors are employed by Humana, Inc. Shrank reports board of directors work for GetWell Network and NCQA. The other authors have nothing to disclose.

Verifying the value of existing frameworks for formulary review at a large academic health system: assessing inter-rater reliability.

BACKGROUND: The value assessment framework (VAF) is one approach to assessing the evidence and value of medications. VAFs are a way to measure and communicate the value of medications and other health care technologies for decision-making purposes. Given the increasing number of high-cost medications, challenging formulary inquiries, and critiques of currently available tools, health systems need to explore a standardized way to incorporate value assessment into formulary decision making. OBJECTIVES: To (a) evaluate existing VAFs by measuring inter-rater reliability among typical clinicians completing formulary reviews and (b) explore general implications of applying these tools to formulary decision making for all medications at a large academic health system. METHODS: This was a retrospective, observational study at a single health system. A list of medications added, denied, and removed from the system formulary from September 1, 2013, through August 31, 2018, was collected. Published VAFs, such as the American Society of Clinical Oncology (ASCO) Value Framework, European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale, National Comprehensive Cancer Network (NCCN) Evidence Blocks, American College of Cardiology/American Heart Association Value Framework, and the incremental cost-effectiveness ratio (ICER) calculation were applied by 3 different reviewer groups. The primary outcome was inter-rater reliability among the 3 different reviewers for a given framework. Cohen's weighted kappa and the intraclass correlation coefficient (ICC) were used to assess inter-rater reliability. RESULTS: The frameworks were applied to 94 medications. The VAFs with the highest ICCs between all 3 raters were NCCN (0.635; 95% CI = 0.387-0.823) and ASCO (0.634; 95% CI = 0.370-0.832), both indicating moderate inter-rater reliability. The VAFs with the lowest ICCs were ESMO (0.368; 95% CI = 0.126-0.611) and ICER (0.159; 95% = CI -0.018-0.365), with ICCs corresponding to poor reliability. CONCLUSIONS: Because high-cost medications are a challenge to health systems, VAFs may be beneficial to target formulary decision making in this setting. Applying VAFs proactively may improve interrater reliability and usability in formulary decision making. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose.

Financial Implications of Avapritinib for Treatment of Unresectable Gastrointestinal Stromal Tumors in Patients With a PDGFRA Exon 18 Variant or After 3 Previous Therapies in a Hypothetical US Health Plan.

Importance: With the approval of avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 variant, including PDGFRA D842V variants, and National Comprehensive Cancer Network guideline recommendations as an option for patients with GIST after third-line treatment, it is important to estimate the potential financial implications of avapritinib on a payer's budget. Objective: To estimate the budget impact associated with the introduction of avapritinib to a formulary for metastatic or unresectable GISTs in patients with a PDGFRA exon 18 variant or after 3 or more previous treatments from the perspective of a US health plan. Design, Setting, and Participants: For this economic evaluation, a 3-year budget impact model was developed in March 2020, incorporating costs for drug acquisition, testing, monitoring, adverse events, and postprogression treatment. The model assumed that avapritinib introduction would be associated with increased PDGFRA testing rates from the current 49% to 69%. The health plan population was assumed to be mixed 69% commercial, 22% Medicare, and 9% Medicaid. Base case assumptions included a GIST incidence rate of 9.6 diagnoses per million people, a metastatic PDGFRA exon 18 mutation rate of 1.9%, and progression rate from first-line to fourth-line treatment of 17%. Exposures: The model compared scenarios with and without avapritinib in a formulary. Main Outcomes and Measures: Annual, total, and per member per month (PMPM) budget impact. Results: In a hypothetical 1-million member plan, fewer than 0.1 new patients with a PDGFRA exon 18 variant per year and 1.2 patients receiving fourth-line therapy per year were eligible for treatment. With avapritinib available, the total increase in costs in year 3 for all eligible adult patients with a PDGFRA exon 18 variant was $46 875, or $0.004 PMPM. For patients undergoing fourth-line treatment, the total increase in costs in year 3 was $69 182, or $0.006 PMPM. The combined total budget impact in year 3 was $115 604, or $0.010 PMPM, including an offset of $3607 in postprogression costs avoided or delayed. The higher rates of molecular testing resulted in a minimal incremental testing cost of $453 in year 3. Conclusions and Relevance: These results suggest that adoption of avapritinib as a treatment option would have a minimal budget impact to a hypothetical US health plan. This would be primarily attributable to the small eligible patient population and cost offsets from reduced or delayed postprogression costs.

Changes in PBM Business Practices in 2019: True Innovation or More of the Same?

In 2019, pharmacy benefit managers (PBMs) responded to intense public criticism with business model changes described as movements toward full transparency and innovation to reduce costs for benefit plan sponsors. We critically analyze these changes in light of key challenges in specialty drug management: pharmaceutical manufacturer practices (price increases driven by coverage mandates and lack of price control, intensive and sometimes misleading advertising, patent extensions), FDA changes (increased reliance on manufacturer funding, weakened evidentiary base for drug approvals), and provider prescribing patterns (lag from evidence to routine practice, manufacturer influences on the knowledge base, direct manufacturer payments to frequent prescribers). The persistence of controversial PBM practices suggests that business model changes were mostly cosmetic, without altering key marketplace dysfunctions. Examples include "spread" pricing, in which PBMs pay pharmacies less than employer-paid amounts; rebate-influenced formulary development; and shifting of prescription volume to PBM-owned pharmacies. Spread in Medicaid was estimated at $224.8 million in Ohio and $123.5 million in Kentucky in 1-year periods and is the subject of an ongoing federal investigation. Rebate influence on formulary development is suggested by slow biosimilar adoption and a study documenting little association between brand exclusions and clinical or cost-effectiveness. Even in 100% passthrough arrangements, the price differential between rebated products and lower-cost alternatives may far exceed revenues returned to the payer. Shifting of business to PBM-owned pharmacies was identified in Florida managed Medicaid in 2018, where the state's 5 largest specialty pharmacies, all owned by managed care organizations or PBMs, collected 28% of prescription drug profit despite dispensing only 0.4% of claims. Finally, contract provisions and terms typically limit the ability of plan sponsors to monitor PBM performance. These include "offsetting," changes in definitions (e.g., "single-source generic") during the contract term, restrictions on audit rights, and exclusion of some pharmaceutical manufacturer revenues from "100%" passthroughs. We conclude that ostensibly positive changes in PBM practices have been offset by undisclosed business arrangements, shifts to alternative revenue sources, and opaque contractual terms. Establishing and maintaining a sustainable benefit will require fundamental alterations to this dysfunctional market DISCLOSURES: This work was funded solely by Archimedes, with no external funding. Motheral is the CEO of Archimedes, a specialty drug management company, and EpiphanyRx, a PBM that provides alternatives to the business models described in this article. Fairman is a consultant to Archimedes.

Dynamic pharmacy leadership during the COVID-19 crisis: Optimizing patient care through formulary and drug shortage management.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for health systems around the world. We describe our approach to adapting the pharmacy leadership structure to address critical medication shortages through innovative data analysis, procurement strategies, and rapid implementation of medication policy. SUMMARY: Yale New Haven Health deployed a system incident management command structure to effectively respond to the COVID-19 crisis. System pharmacy services adopted a similar framework to enable efficient communication and quick decision-making in key domains, including drug procurement and policy. By refining a model to project health-system medication needs, we were able to anticipate challenges and devise alternative treatment algorithms. By leveraging big data and creating a system knowledge base, we were able to consolidate reporting and coordinate efforts to ensure system success. Various procurement strategies were employed to ensure adequate supply, including frequent communication with our wholesaler, sourcing direct from suppliers, outsourcing of sterile products compounding to registered 503B outsourcing facilities, and acquisition of active pharmaceutical ingredients for compounding of essential medications. Strategic positioning of pharmacists within the health system's incident command response teams and rapid adaption of drug use policy governance fueled accelerated response and nimble implementation. Communication was streamlined and executed via multiple outlets to reach a broad audience across the health system. CONCLUSION: With medication shortages posing a threat to patient care, dynamic pharmacy leadership proved essential to providing patient care at the height of the COVID-19 pandemic. System alignment and the rapid adaption of the existing framework for drug shortage management and medication use policy were crucial to success in crisis response.

Dosing Recommendations for Pediatric Patients With Renal Impairment.

A treatment gap exists for pediatric patients with renal impairment. Alterations in renal clearance and metabolism of drugs render standard dosage regimens inappropriate and may lead to drug toxicity, but these studies are not routinely conducted during drug development. The objective of this study was to examine the clinical evidence behind current renal impairment dosage recommendations for pediatric patients in a standard pediatric dosing handbook. The sources of recommendations and comparisons included the pediatric dosing handbook (Lexicomp), the U.S. Food and Drug Administration-approved manufacturer's labels, and published studies in the literature. One hundred twenty-six drugs in Lexicomp had pediatric renal dosing recommendations. Only 14% (18 of 126) of Lexicomp pediatric renal dosing recommendations referenced a pediatric clinical study, and 15% of manufacturer's labels (19 of 126) described specific dosing regimens for renally impaired pediatric patients. Forty-two products had published information on pediatric renal dosing, but 19 (45%) were case studies. When pediatric clinical studies were not referenced in Lexicomp, the renal dosing recommendations followed the adult and pediatric dosing recommendations on the manufacturer's label. Clinical evidence in pediatric patients does not exist for most renal dosing recommendations in a widely used pediatric dosing handbook, and the adult renal dosing recommendations from the manufacturer's label are currently the primary source of pediatric renal dosing information.

Regulatory approval and public drug plan listing of new drugs for rare disorders in Canada and New Zealand.

A previous assessment of the alignment of health technology assessments and price negotiations for new drugs for rare disorders in Canada completed between 2014 and 2018 demonstrated that it is working for governments but has yet to lead to improved access in a timely manner for all appropriate patients in all provinces. In this analysis, drugs for rare and ultra-rare disorders with a completed price negotiation or no negotiation between 2014 and 2018 in Canada, and their reimbursement recommendations and listings in Canadian public drug programs are compared with their regulatory approval in New Zealand and listing in the New Zealand National Formulary. The results show that pharmaceutical manufacturers generally seek regulatory approval for rare disorder drugs in Canada before New Zealand, and fewer rare disorder medicines receive regulatory approval in New Zealand. One reason for this difference might be New Zealand's smaller population. However, another reason is likely the restrictive drug formulary in New Zealand. Drugs not given coverage in New Zealand are frequently made unavailable by the manufacturer. Planned changes to Canada's pricing regulations and guidelines will significantly diminish the country's attractiveness as a place in which pharmaceutical companies want to do business, which has the potential to negatively impact the health of all Canadians irrespective of whether they have private or public drug coverage.

Essential Medicinal Chemistry of Essential Medicines.

Since 1977, the World Health Organization publishes a list of essential medicines, i.e., those that satisfy the priority health care needs of the population and are selected with regard to disease prevalence and public health relevance, evidence of clinical efficacy, and safety, as well as comparative costs and cost-effectiveness. The Essential Medicines List (EML) is an invaluable tool for all countries to select those medicines that have an excellent risk/benefit ratio and that are reputed to be of pivotal importance to health. In the present perspective, we describe the chemical composition and the main features of the small molecules that are included in the EML, spanning from their origin, to their stereochemistry and measure of drug-likeness. Most and foremost, we wish to disseminate the importance of the EML, which can be both a helpful teaching tool in an ever-expanding world of medicines and an inspiration for those involved in pharmaceutical R&D.