Exploring the Impact of COVID-19 Restrictions on Nursing Home Residents', Families', and Staff's Perceptions of Bioethical Principles: A Qualitative Study.

In this study, we employed a pre-interview survey and conducted interviews with nursing home staff members and residents/family members to understand their perceptions of whether the COVID-19 restrictions fulfilled obligations to nursing home residents under various principles, including autonomy, beneficence, nonmaleficence, justice, and privacy. We conducted 20 semi-structured interviews with staff members from 14 facilities, and 20 with residents and/or family members from 13 facilities. We used a qualitative descriptive study design and thematic analysis methodology to analyze the interviews. Findings from the pre-interview survey indicated that, compared to nursing home staff, residents and their families perceived lower adherence to bioethics principles during the pandemic. Qualitative analysis themes included specific restrictions, challenges, facility notifications, consequences, communication, and relationships between staff and residents/family members. Our study exposes the struggle to balance infection control with respecting bioethical principles in nursing homes, suggesting avenues for improving processes and policies during public health emergencies.

Factors Associated with Biosimilar Exclusions and Step Therapy Restrictions Among US Commercial Health Plans.

BACKGROUND: Biosimilars have been introduced with the goal of competing with high-priced biologic therapies, yet their adoption has been slower than expected and resulted in limited efficiency gains. We aimed to explore factors associated with biosimilar coverage relative to their reference products by commercial plans in the United States (US). METHODS AND DATA: We identified 1181 coverage decisions for 19 commercially available biosimilars, corresponding to 7 reference products and 28 indications from the Tufts Medical Center Specialty Drug Evidence and Coverage database. We also drew on the Tufts Medical Center Cost-Effectiveness Analysis Registry for cost-effectiveness evidence, and the Merative™ Micromedex® RED BOOK® for list prices. We summarized the coverage restrictiveness as a binary variable based on whether the product is covered by the health plan, and if covered, the difference of payers' line of therapy between the biosimilar and its reference product. We used a multivariate logistic regression to examine the association between coverage restrictiveness and a number of potential drivers of coverage. RESULTS: Compared with reference products, health plans imposed coverage exclusions or step therapy restrictions on biosimilars in 229 (19.4%) decisions. Plans were more likely to restrict biosimilar coverage for the pediatric population (odds ratio [OR] 11.558, 95% confidence interval [CI] 3.906-34.203), in diseases with US prevalence higher than 1,000,000 (OR 2.067, 95% CI 1.060-4.029), and if the plan did not contract with one of the three major pharmacy benefit managers (OR 1.683, 95% CI 1.129-2.507). Compared with the reference product, plans were less likely to impose restrictions on the biosimilar-indication pairs if the biosimilar was indicated for cancer treatments (OR 0.019, 95% CI 0.008-0.041), if the product was the first biosimilar (OR 0.225, 95% CI 0.118-0.429), if the biosimilar had two competitors (reference product included; OR 0.060, 95% CI 0.006-0.586), if the biosimilar could generate annual list price savings of more than $15,000 per patient (OR 0.171, 95% CI 0.057-0.514), if the biosimilar's reference product was restricted by the plan (OR 0.065, 95% CI 0.038-0.109), or if a cost-effectiveness measure was not available (OR 0.066, 95% CI 0.023-0.186). CONCLUSION: Our study offered novel insights on the factors associated with biosimilar coverage by commercial health plans in the US relative to their reference products. Cancer treatment, pediatric population, and coverage restriction of the reference products are some of the most significant factors that are associated with biosimilar coverage decisions.

Macroeconomic consequences of the COVID-19 pandemic.

We estimate the economic impacts of COVID-19 in the U.S. using a disaster economic consequence analysis framework implemented by a dynamic computable general equilibrium (CGE) model. This facilitates identification of relative influences of several causal factors as "shocks" to the model, including mandatory business closures, disease spread trajectories, behavioral responses, resilience, pent-up demand, and government stimulus packages. The analysis is grounded in primary data on avoidance behavior and healthcare parameters. The decomposition of the influence of various causal factors will help policymakers offset the negative influences and reinforce the positive ones during the remainder of this pandemic and future ones.

Cost-effectiveness models for Alzheimer's disease and related dementias: IPECAD modeling workshop cross-comparison challenge.

INTRODUCTION: The credibility of model-based economic evaluations of Alzheimer's disease (AD) interventions is central to appropriate decision-making in a policy context. We report on the International PharmacoEconomic Collaboration on Alzheimer's Disease (IPECAD) Modeling Workshop Challenge. METHODS: Two common benchmark scenarios, for the hypothetical treatment of AD mild cognitive impairment (MCI) and mild dementia, were developed jointly by 29 participants. Model outcomes were summarized, and cross-comparisons were discussed during a structured workshop. RESULTS: A broad concordance was established among participants. Mean 10-year restricted survival and time in MCI in the control group ranged across 10 MCI models from 6.7 to 9.5 years and 3.4 to 5.6 years, respectively; and across 4 mild dementia models from 5.4 to 7.9 years (survival) and 1.5 to 4.2 years (mild dementia). DISCUSSION: The model comparison increased our understanding of methods, data used, and disease progression. We established a collaboration framework to assess cost-effectiveness outcomes, an important step toward transparent and credible AD models.

Access to Disease-Modifying Alzheimer's Therapies: Addressing Possible Challenges Using Innovative Payment Models.

OBJECTIVES: Aduhelm is the first approved disease-modifying therapies (DMT) for Alzheimer disease (AD). Nevertheless, under current payment models, AD DMTs-especially because they treat broader populations-will pose challenges to patient access since costs may accrue sooner than benefits do. New payment approaches may be needed to address this difference in timing. METHODS: We use the Future Elderly Model that draws on nationally representative data sets such as the Health and Retirement Study to estimate the potential benefits because of hypothetical AD DMTs in 4 stylized treatment scenarios for patients with mild cognitive impairment or mild AD, and develop a payment model to estimate the accrual of net costs and benefits to private and public payers. RESULTS: The modeled AD DMTs result in clinical benefit of 0.30 to 0.55 quality-adjusted life-years gained per patient in the baseline treatment scenario and 0.13 to 0.24 quality-adjusted life-years gained per patient in the least optimistic scenario. Private payers may observe a net loss in patients at the age of 61 to 65 years under the status quo (payment upon treatment). Constant and deferred installment payment models resolve this issue. CONCLUSIONS: Innovative payment solutions, such as installment payments, may be required to address misaligned incentives that AD DMTs may create among patients younger than the age of 65 years and may help address concerns about the timing and magnitude of costs and benefits accrued to private payers.

Addressing Challenges to Alternative Payment Models for New Alzheimer's Disease Therapies for US Commercial Payers.

Commercial payers that ultimately decide to cover aducanumab or other Alzheimer's disease therapies may require innovative payment tools to minimize their financial risk given the uncertain benefits and high cost of such treatments. Drawing on the published evidence, we propose two different types of payment models applicable to disease-modifying therapies in Alzheimer's disease, and suggest four strategies to overcome challenges in their implementation. Such strategies range from developing best practices for outcome measurement in Alzheimer's disease, investing in infrastructure to collect real-world data, increasing representativeness of registry data in Alzheimer's disease, and integrating the diagnostic, treatment, and payment landscape. These important steps could make access to emerging therapies in Alzheimer's disease more sustainable in the long term, and could serve as a blueprint for better access to novel therapies in other indications in the future.

Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials.

Introduction: The U.S. Food and Drug Administration (FDA)'s guidances help describe the agency's current thinking on regulatory issues and serve as a means of informal policymaking that is non-binding. This study examines the impact of two guidance documents for Alzheimer's disease (AD) trials. The first guidance in 2013 encouraged the use of cognitive/functional endpoints, while the second in 2018 modified such recommendation. Methods: Using pivotal trial data, we applied a regression discontinuity in time (RDiT) framework to examine trialist response to these guidance documents. Results were stratified by disease-modifying therapy (DMT) status, and controlled for disease staging, FDA registration status, and trial phase. Results: Among AD DMT trials, annual use of cognitive/functional composite endpoints significantly increased after the 2013 guidance (+12.9%, P < .001), and significantly decreased after the 2018 guidance (-19.9%, P = .022). Discussion: Although guidance documents do not set new legal standards or impose binding requirements, our findings indicate they are broadly followed by AD trialists.

Crosswalk between the Mini-Mental State Examination and the Telephone Interview for Cognitive Status (TICS-27/30/40).

BACKGROUND: We develop a crosswalk between the Mini-Mental State Examination (MMSE) and Telephone Interview for Cognitive Status (TICS)-27, TICS-30, and TICS-40 for adults 65 years and older. METHODS: We examined the scores of 1809 participants, with and without cognitive impairment, who completed the MMSE and the TICS assessment in the 2016 Health and Retirement Study and the 2016 Harmonized Cognitive Assessment Protocol study. Crosswalks between MMSE and TICS-27/30/40 were developed via equipercentile equating. RESULTS: We present crosswalks for MMSE and TICS-27/30/40 for the 65+ population representative of the US elderly. While monotonic, the pattern of the TICS-30 to MMSE crosswalk differs from the other two crosswalks (MMSE to TICS-27/40). CONCLUSION: Our analysis offers an empirical crosswalk between two commonly used cognitive measures-the MMSE and TICS. Our findings suggest the need for validated and robust measures that allow for the comparison of scores on different cognitive scales.

Scientists without borders: lessons from Ukraine.

Conflicts and natural disasters affect entire populations of the countries involved and, in addition to the thousands of lives destroyed, have a substantial negative impact on the scientific advances these countries provide. The unprovoked invasion of Ukraine by Russia, the devastating earthquake in Turkey and Syria, and the ongoing conflicts in the Middle East are just a few examples. Millions of people have been killed or displaced, their futures uncertain. These events have resulted in extensive infrastructure collapse, with loss of electricity, transportation, and access to services. Schools, universities, and research centers have been destroyed along with decades' worth of data, samples, and findings. Scholars in disaster areas face short- and long-term problems in terms of what they can accomplish now for obtaining grants and for employment in the long run. In our interconnected world, conflicts and disasters are no longer a local problem but have wide-ranging impacts on the entire world, both now and in the future. Here, we focus on the current and ongoing impact of war on the scientific community within Ukraine and from this draw lessons that can be applied to all affected countries where scientists at risk are facing hardship. We present and classify examples of effective and feasible mechanisms used to support researchers in countries facing hardship and discuss how these can be implemented with help from the international scientific community and what more is desperately needed. Reaching out, providing accessible training opportunities, and developing collaborations should increase inclusion and connectivity, support scientific advancements within affected communities, and expedite postwar and disaster recovery.

Clinical Outcome Measure Crosswalks in Alzheimer's Disease: A Systematic Review.

BACKGROUND: A key challenge in studies that model outcomes, disease progression, and cost-effectiveness of existing and emerging dementia treatments is the lack of conversion criteria to translate, or 'crosswalk', scores on multiple measurement scales. Clinical status in dementia is commonly characterized in the cognitive, functional, and behavioral domains. OBJECTIVE: We conducted a systematic review of peer-reviewed dementia measure crosswalks in the three domains. METHODS: We systematically reviewed published literature for crosswalks between scales used to measure cognitive, functional, or behavioral outcomes in Alzheimer's and related dementias. The search was conducted in PubMed, and additional crosswalks were identified through snowballing and expert input from dementia modelers. RESULTS: Of the reviewed articles, 2,334 were identified through a PubMed search, 842 articles were sourced from backward and forward citation snowballing, and 8 additional articles were recommended through expert input. 31 papers were eligible for inclusion, listing 74 unique crosswalks. Of those, 62 (83.8%) were between endpoints of the cognitive domain and 12 (16.2%) were either between endpoints of the functional domain or were hybrid in nature. Among crosswalks exclusively in the cognitive domain, a majority involved the Mini-Mental State Examination (MMSE) (37 crosswalks) or the Montreal Cognitive Assessment (MoCA) and its variants (25 crosswalks). MMSE was directly compared to MoCA or MoCA variants in 16 crosswalks. CONCLUSION: Existing crosswalks between measures of dementia focus largely on a limited selection of outcome measures, particularly MMSE and MoCA. Few crosswalks exist in the functional domain, and no crosswalks were identified for solely behavioral measures.

The economics of alternative payment models for pharmaceuticals.

Pharmaceuticals are priced uniformly by convention, but vary in their degree of effectiveness for different disease indications. As more high-cost therapies have launched, the demand for alternative payment models (APMs) has been increasing in many advanced markets, despite their well-documented limitations and challenges to implementation. Among policy justifications for such contracts is the maximization of value given scarce resources. We show that while uniform pricing rules can handle variable effectiveness in efficient markets, market inefficiencies of other kinds create a role for different value-based pricing structures. We first present a stylized theoretical model of efficient interaction among drug manufacturers, payers, and beneficiaries. In this stylized setting, uniform pricing works well, even when treatment effects are variable. We then use this framework to define market failures that result in obstacles to uniform pricing. The market failures we identify include: (1) uncertainty of patient distribution, (2) asymmetric beliefs, (3) agency imperfection by payer, (4) agency imperfection by provider, and (5) patient behavior and treatment adherence. We then apply our insights to real-world examples of alternative payment models, and highlight challenges related to contract implementation.

Blood-based biomarkers for Alzheimer's pathology and the diagnostic process for a disease-modifying treatment: Projecting the impact on the cost and wait times.

INTRODUCTION: Concerns have been raised about the limited health system capacity for identification of patients who are eligible for a disease-modifying Alzheimer's treatment (DMT). Blood-based biomarker (BBBM) tests are a promising tool to improve triaging at the primary care level. We projected their impact on cost of and wait times during the diagnostic process. METHODS: We compare four scenarios for triaging patients at the primary care level from the perspective of the U.S. health care system: (1) cognitive test only (Mini Mental State Examination [MMSE]), (2) BBBM test only, (3) MMSE followed by BBBM if positive, and (4) BBBM followed by MMSE if positive. RESULTS: Referring patients to dementa specialists based on MMSE or BBBM results alone would continuously require more specialist appointments than projected to be available until 2050. Combining MMSE and BBBM would eliminate wait lists after the first 3 years and reduce average annual cost by $400 to 700 million, while increasing correctly identified cases by about 120,000 per year. DISCUSSION: The combination BBBM with MMSE is projected to increase the efficiency and value of the triage process for DMT eligibility.

The Potential Benefits of Deferred Payment for a Hypothetical Gene Therapy for Congestive Heart Failure: A Cost-Consequence Analysis.

BACKGROUND: The emergence of potentially curative pharmacologic treatments that deliver long-term clinical benefits with a limited number of doses may create short-term budget challenges for payers as their unit price can be high. OBJECTIVE: This paper tests the clinical and financial properties of a deferred payment model (DPM) in hypothetical therapy for congestive heart failure (CHF) from the perspective of payers, manufacturers, and patients. METHODS: We present an empirical analysis of longitudinal data for cardiovascular admissions and mortality using a Markov transition model for patient progression under different payment scenarios. The model calculates life-years gained and avoided cardiovascular admissions under the status quo and deferred payment and a hypothetical budget constraint. We tracked over 91,000 Medicare fee-for-service beneficiaries over a period of 5 years (2009-2014) using MedPAR 5% data files. RESULTS: We find that a DPM is associated with earlier treatment and a consequent improvement in clinical outcomes. A 25% down-payment is associated with the highest relative improvement and reduces hospital admissions by 0.52% (by 2611 vs. 2071 cases) and mortality by 0.29% (by 799 vs. 648 cases), both relative to the status quo payment. Deferred payment results in limited financial gains for payers or manufacturers, primarily because of the small share of expected cost savings on the total cost of therapy. Our results are robust to changes in relative risk for cardiovascular admissions and a change in the cost of therapy. CONCLUSIONS: A DPM may result in faster access to CHF gene therapy and may thus reduce hospital admissions and mortality in contrast to a status quo payment with the same budget constraint. Although the financial benefits of a DPM in CHF gene therapy are limited, it is possible that deferred payments will show greater promise for treatments with higher cost offsets.

Outcome measures for oncology alternative payment models: practical considerations and recommendations.

OBJECTIVES: This paper aims to synthesize existing scholarship on quality measures in oncology, with a specific focus on outcome-based quality measures, which are often underutilized. We also present a set of "core outcome measures" that may be considered in future oncology alternative payment models (APMs). STUDY DESIGN: Our research consists of a focused literature review, content analysis, and quality measure synthesis and categorization. METHODS: We conducted a focused literature review to generate key evidence on quality measures in oncology. We studied 7 oncology quality assessment frameworks, encompassing 142 quality metrics, and synthesized recommendations using the Center for Medicare and Medicaid Innovation APM toolkit, focusing on outcome measures. RESULTS: We present 34 outcome-based oncology quality measures for consideration, which are classified into 5 domains: clinical care (eg, hospital and emergency department visits, treatment effectiveness, mortality), safety (eg, infections, hospital adverse events), care coordination (for hospital and hospice care), patient and caregiver experience, and population health and prevention. Both general and indication-specific outcome measures should be considered in oncology APMs, as appropriate. Utilizing outcome-based measures will require addressing multiple challenges, ranging from risk adjustment to data quality assurance. CONCLUSIONS: Oncology care will benefit from a more rigorous approach to quality assessment. The success of oncology APMs will require a robust set of quality measures that are relevant to patients, providers, and payers.

The Potential Emergence of Disease-Modifying Treatments for Alzheimer Disease: The Role of Primary Care in Managing the Patient Journey.

Despite recent setbacks, disease-modifying treatments (DMTs) for Alzheimer disease (AD) might become available within a few years. These DMTs are likely to be used in the early stages of AD to avoid the progression to manifest dementia, which implies that a large reservoir of prevalent cases would need to be evaluated when DMTs first become available. Primary care providers (PCPs) would play a vital role in managing the patient flow to specialty care. We review the literature on diagnostic tests that could be used by PCPs and estimate the impact of different testing approaches on demand for specialty care.While many tests have been evaluated, only the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) perform acceptably for detection of early-stage cognitive decline with sensitivities and specificities of 55% to 82% and 72% to 84%, respectively, for the MMSE; and 77% to 96% and 73% to 95%, respectively, for the MoCA. However, neither test is sufficiently specific for the AD pathology and would result in 4 to 5 false positives for each true positive. Blood-based tests for AD biomarkers may soon become available for clinical use. A plasma amyloid-ß (Aß) test has been shown to have a sensitivity of up to 97% and specificity of up to 81%. Adding this test to the MMSE or MoCA could reduce false positives by approximately 80%.These findings suggest a combination of brief cognitive tests and blood-based biomarker tests will allow PCPs to identify patients with potential early stage AD efficiently and triage them for further evaluation.

Assessing the Preparedness of the Health Care System Infrastructure in Six European Countries for an Alzheimer's Treatment.

No disease-modifying therapy is currently available for Alzheimer's disease, but therapies are in development, and one may become available in the near future. Based on results from early-stage clinical trials, therapeutic development has focused on the hypothesis that Alzheimer's dementia must be prevented rather than cured, because candidate treatments have not been able to reverse the course of dementia. Thus, current trials target patients with early-stage Alzheimer's disease. Were a therapy to become available, patients could undergo first screening for signs of early-stage memory loss or mild cognitive impairment (MCI), testing for the Alzheimer's disease pathology, and then treatment with the aim of halting or slowing progression to Alzheimer's dementia. An important health systems challenge will arise if this new treatment paradigm bears out in late-stage clinical trials. In the 28 European Union countries, we estimate that approximately 20 million individuals over age 55 have MCI, although most people have not been tested for disease pathology. Thus, when a therapy first becomes available, there would be a substantial number of existing (or prevalent) MCI patients who would require screening, diagnosis, and then treatment as quickly as possible to prevent the progression to full-blown Alzheimer's dementia. This research analyzes the preparedness of the health care systems in six European countries-France, Germany, Italy, Spain, Sweden, and the United Kingdom-to ensure timely diagnosis and treatment of patients if a disease-modifying therapy for Alzheimer's becomes available.

Biosimilar Cost Savings in the United States: Initial Experience and Future Potential.

The Biologics Price Competition and Innovation Act (BPCIA), enacted as part of the 2010 Patient Protection and Affordable Care Act (ACA), authorized the U.S. Food and Drug Administration (FDA) to create a new regulatory approval pathway for biosimilars, which are biologic drugs that are very similar to already approved "reference" biologics in terms of potency, safety, and efficacy, but are manufactured by different companies. In the seven years since the ACA, many drug manufacturers worked to push new biosimilars through development and FDA review. As of July 2017, there were three marketed biosimilars and two more that were approved by the FDA but not yet marketed. BPCIA's shorter, lower-cost biosimilar approval pathway was designed to introduce competition among biologic manufacturers. This article estimates potential future savings from biosimilars in the United States, summarizes the experience to date with the first marketed biosimilar in the United States, and discusses key policy issues surrounding biosimilars. We estimate that biosimilars will reduce direct spending on biologic drugs by $54 billion from 2017 to 2026, or about 3 percent of total estimated biologic spending over the same period, with a range of $24 to $150 billion. While our estimate uses recent data and transparent assumptions, we caution that actual savings will hinge on industry and regulatory decisions as well as potential policy changes to strengthen the biosimilar market.