Are Payers Ready, Willing, and Able to Provide Access to New Durable Gene Therapies?

OBJECTIVE: To explore payer feedback regarding awareness of new gene therapies, sustainability of current financing mechanisms, unique challenges by payer segment, and need and preference for new financial models. STUDY DESIGN: Qualitative interview with standardized interview guide. METHODS: Sixty-minute telephone interviews were conducted with financial decision makers from 15 US payers between August and September 2017. RESULTS: One-third of payers interviewed (n = 5) were newly aware and learning about new gene therapies, 40% (n = 6) described watchful waiting, whereas 26.7% (n = 4) were engaged in active management. New payment models-specifically, performance-based agreements and risk-pooling-were supported by 47% (n = 7) of payers, whereas the current payment model was supported by 53% (n = 8). Major challenges included uncertainty related to utilization, cost, and duration of cure. Payers cited regulation, plan turnover, and ability to track long-term outcomes as barriers to implementation of new models. CONCLUSIONS: Access to new gene therapies may be impacted by payer ability to absorb the cost of coverage. Variation exists in awareness of new gene therapies and level of incorporation of new costs into future plan coverage. The sustainability of current financing mechanisms varies by payer segment, profitability, and size; smaller plans and Medicaid are likely to be impacted first. Government reinsurance, commercial reinsurance, and stop-loss insurance backstop current reimbursement models, dampening the need for urgent action. The tipping point for action may be severe premium inflation in stop loss and reinsurance. Payers are open to innovative financing models that improve financial predictability and reward clinical performance.

Fair, just and compassionate: A pilot for making allocation decisions for patients requesting experimental drugs outside of clinical trials.

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or 'preapproval', access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients' best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee (CompAC). Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice.

From Atoms, Molecules, and Numbers to Literature, Art, and Performance.

I argue that the humanities have an important role in pharmacy education. I came to this view after believing the humanities to be useless and superfluous when I was in pharmacy school and during the earlier phases of my career. I eventually learned that the humanities can teach us a lot that the biomedical sciences can not, and that the humanities can expand on a lot of what the biomedical sciences do teach us. My argument derives from a model that makes a distinction between the disease and illness components of health problems, which makes it possible to see how biomedical sciences focus on disease and how the humanities focus on illness. Because medical schools have adopted the humanities into their education and training programs, I also argue that pharmacists will need a similar grounding if they are to collaborate with physicians on the same terms.

When People with Opioid-Induced Constipation Speak: A Patient Survey.

INTRODUCTION: Opioid-induced constipation (OIC) is a common consequence of opioid use for chronic pain. OIC creates problems for patients independent of their pain syndromes, in addition to threatening pain treatment effectiveness. Healthcare practitioners need to be alert to how patients talk about OIC so that it is not missed. Using a survey mechanism, we sought patient expressions of the personal impact OIC imposes on how they are able to live their lives and on meanings that symptom relief would produce. METHODS: We used an online survey asking adults with OIC about quality of life implications of OIC and focused on open-ended text responses to questions about personal impacts of straining and meanings attached to OIC symptom relief. Participants were from the US, Canada, UK, Germany, Sweden, and Norway. RESULTS: A survey of 513 people with OIC produced 280 text responses concerning the impacts of straining on quality of life and 469 text responses on the meaning OIC symptom relief would confer. Text responses about the quality of life impacts of straining often included explicit descriptions conveying physical, psychological, or practical problems. Text responses about the meaning conferred from OIC symptom relief primarily concentrated around freedom from the constraints that OIC can impose. CONCLUSIONS: Patients are willing and able to comment on the problems OIC cause them, using a variety of terms and phrases. Their comments concerning impacts on their lives will often refer to physical consequences, psychological effects, or practical implications. These insights provide healthcare practitioners guidance on how to engage patients about OIC.

European and Russian physician awareness of best management approaches for infections due to antibiotic-resistant Gram-negative bacteria.

OBJECTIVES: The rapid spread of infections due to antibiotic-resistant, Gram-negative bacteria in Europe and surrounding regions requires a heightened level of awareness among physicians within their practice settings. METHODS: We surveyed 800 physicians who treat these infections across France, Germany, Spain, Italy, and Russia to assess their awareness of best management approaches. RESULTS: We found that more than two-thirds do not consider themselves highly aware of best management practices. The respondents are facing these resistant infections as evidenced by the antibiotics they report using and their stated interest in newer agents. Respondents indicated that precious time is lost waiting for culture results, but also said they will need more information about accuracy, use, and costs for adopting rapid molecular testing. CONCLUSIONS: The survey further identified the need for treatment guidelines and clinical decision support tools that can be applied at the bedside.

Dispensing error rate in a highly automated mail-service pharmacy practice.

STUDY OBJECTIVE: To measure the rate of dispensing errors and to identify the types and sources of dispensing errors in a highly automated mail-service pharmacy practice. DESIGN: Descriptive analysis of a random sample of completed prescriptions. SETTING: A high-volume mail-service pharmacy practice comprising a network of prescription processing and dispensing pharmacies in the United States. MEASUREMENTS AND MAIN RESULTS: During September and October 2003, new and refill prescriptions were retrieved before shipping and evaluated for dispensing accuracy. Container contents were compared against the container label, and the label record was compared against the original prescription order. The overall dispensing error rate was 0.075% (16 dispensing errors among 21,252 prescriptions, 95% confidence interval 0.043-0.122). Fourteen errors involved incomplete or incorrect directions on the final label. All dispensing errors were associated with the initial stages of prescription processing (including order entry); no errors were associated with the mechanical stages of product dispensing. CONCLUSION: A highly automated mail-service pharmacy can achieve a dispensing error rate of less than 1 error/1000 prescriptions, which is substantially lower than the rates reported for retail pharmacies. A high degree of automation in the mechanical aspects of dispensing appears to be a key factor in achieving this high dispensing accuracy.

Clinical Trial Design for Alpha-1 Antitrypsin Deficiency: A Model for Rare Diseases.

Clinical research in rare diseases, including alpha-1 antitrypsin deficiency (AATD), faces challenges not shared by common disease research. These challenges may include the limited number of patient volunteers available for research, lack of natural history studies on which to base many clinical trial interventions, an urgency for the development of drug therapies given the often poor prognosis of rare diseases and uncertainties about appropriate biomarkers and clinical outcomes critical to clinical trial design. To address these challenges and initiate formal discussions among key stakeholders-patients, researchers, industry, federal regulators-the Alpha-1 Foundation hosted the Clinical Trial Design for Alpha-1 Antitrypsin Deficiency: A Model for Rare Diseases conference February 3-4, 2014 in Bethesda, Maryland. Discussions at the conference led to the conclusions that 1) adaptive designs should be considered for rare disease clinical trials yet more dialogue and study is needed to make these designs feasible for smaller trials and to address current limitations; 2) natural history studies, including the identification of appropriate biomarkers are critically needed and precompetitive collaborations may offer a means of creating these costly studies; and 3) patient registries and databases within the rare disease community need to be more publicly available and integrated, particularly for AATD. This report summarizes the discussions leading to these conclusions.

An ethical template for pharmacy benefits.

We propose an ethical template for pharmacy benefits and a fair process for using it. The template delineates four levels of decisions about pharmacy coverage, connecting ethically acceptable types of rationales for limits with decisions made at each level. It provides a framework for organizing ethically relevant reasons for coverage (or the tiered copayments). The process for using the template assures accountability for the reasonableness of benefit decisions. It requires transparency and relevance of rationales for limit setting and revisability of decisions, including through fair procedures for appeals. The template and the process facilitate broader public learning about fair limit setting.

Managing heterogeneity in prescription drug coverage policies.

Necessity and fairness require that health plans limit the products and services they cover. The basis for these decisions refers to population averages and related population parameters. However, individuals vary and may not be accurately represented by the parameters used to establish coverage policies. Health plans, therefore, are obligated to anticipate and manage heterogeneity among their member groups. This commentary offers considerations for managing heterogeneity in prescription drug benefits.

An early examination of access to select orphan drugs treating rare diseases in health insurance exchange plans.

BACKGROUND: Patients with rare diseases often face significant health care access challenges, particularly since the number of available treatment options for rare diseases is limited. The implementation of health insurance exchanges promises improved access to health care. However, when purchasing a plan, patients with rare diseases need to consider multiple factors, such as insurance premium, access to providers, coverage of a specific medication or treatment, tier placement of drug, and out-of-pocket costs.  OBJECTIVE: To provide an early snapshot of the exchange plan landscape from the perspective of patients with select rare diseases by evaluating the degree of access to medications in a subset of exchange plans based on coverage, tier placement, associated cost sharing, and utilization management (UM) applied.  METHODS: The selection of drugs for this analysis began by identifying rare diseases with FDA-approved treatment options using the National Institutes of Health Office of Rare Diseases' webpage and further identification of a subset of drugs based on select criteria to ensure a varied sample, including the characteristics and prevalence of the condition. The medications were categorized based on whether alternative therapies have FDA approval for the same indication and whether there are comparators based on class or therapeutic area. The list was narrowed to 11 medications across 7 diseases, and the analysis was based on how these drugs are listed in exchange plan outpatient pharmacy benefit formularies. This analysis focused on 84 plans in 15 states with the highest expected exchange enrollment and included a variety of plan types to ensure that variability in the marketplace was represented. To best approximate plans that will have the greatest enrollment, the analysis focused on silver and bronze plan formularies because consumers in this market are expected to be sensitive to premiums. Data on drug coverage, tier placement, cost, and UM were collected from these plans beginning October 1, 2013, with the launch of the open enrollment period. RESULTS: Coverage and use of UM for selected medications vary within and across states. This study found that bronze plans were far less likely than silver plans to cover the 11 products included in this analysis. Results also showed that select drugs identified as the only FDA-approved product indicated for a certain rare disease experienced relatively robust coverage (at least 65% of plans) but often included some form of UM. However, coverage of selected rare disease therapies also is complicated by the fact that plans cover certain products under the medical benefit versus the pharmacy benefit. At the time of this analysis, transparency of medical benefit coverage for these products in exchange plans was limited.Selected medications are most likely to appear on the highest tiers of 4-tier formularies or are not covered at all. Although there are no requirements to designate certain tiers as "specialty tiers," more than 70% of plans in this study use coinsurance for the highest tiers of their formularies. Rates of coinsurance for medications on highest tiers range from 10% to 50% in silver plans and 15% to 50% in bronze plans. Among those plans utilizing copayments rather than coinsurance, ranges of copayments for these select products vary between $20 and $250 per prescription across both silver plans and bronze plans. CONCLUSIONS: This preliminary analysis of access to treatments for patients with select rare diseases revealed the complexities involved for patients with specific needs when selecting a plan with appropriate coverage. For patients with rare diseases, the process of identifying and selecting a plan centers on understanding if and how the plan covers a specific treatment or set of treatments. Access factors will likely vary substantially across plans, as demonstrated by the findings from this analysis. With limited treatment options and the potential for cost sharing and UM barriers, increased data transparency to assist patients in navigating formularies will be a critical step for patients to fully understand their access to needed therapies in each plan.

Well connected: pharmacy education and the humanities.

Traditional pharmacy education emphasizes the biological processes of diseases and their pharmacological treatments. While the intense focus on biomedical aspects of disease is vital to educating pharmacy students, this focus is often insufficient in conveying what patients experience. The humanities, however, offer powerful characterizations of the disease experience for individuals as well as its impact on the human condition more generally. In this essay, I describe how using literary texts with pharmacy students provides them with a fuller appreciation of what patients face with their diseases. The goal of this endeavor is to make students more effective as pharmacists in detecting and responding to their patients' problems and needs by connecting their biomedical knowledge to depictions and meanings of illness experiences.

Greater adherence to diabetes drugs is linked to less hospital use and could save nearly $5 billion annually.

Improving adherence to medication offers the possibility of both reducing costs and improving care for patients with chronic illness. We examined a national sample of diabetes patients from 2005 to 2008 and found that improved adherence to diabetes medications was associated with 13 percent lower odds of subsequent hospitalizations or emergency department visits. Similarly, losing adherence was associated with 15 percent higher odds of these outcomes. Based on these and other effects, we project that improved adherence to diabetes medication could avert 699,000 emergency department visits and 341,000 hospitalizations annually, for a saving of $4.7 billion. Eliminating the loss of adherence (which occurred in one out of every four patients in our sample) would lead to another $3.6 billion in savings, for a combined potential savings of $8.3 billion. These benefits were particularly pronounced among poor and minority patients. Our analysis suggests that improved adherence among patients with diabetes should be a key goal for the health care system and policy makers. Strategies might include reducing copayments for certain medications or providing feedback about adherence to patients and providers through electronic health records.

Comparative effectiveness and personalized medicine: evolving together or apart?

Comparative effectiveness research and personalized medicine can at first appear to be at odds with each other. This research initially compares the overall benefits of one therapeutic approach with those of another for the majority of patients, while personalized medicine identifies the subsets of patients who could benefit based on personal characteristics such as genetics. But because comparative effectiveness research typically enrolls heterogeneous patient populations, it can uncover subpopulations that might benefit most from particular treatments. Thus, comparative effectiveness research can help discern the appropriate role of personalized medicine in improving health care outcomes and rationalizing costs.

Comparative effectiveness research and personalized medicine: catalyzing or colliding?

Comparative effectiveness research (CER) is generating intense attention as interest grows in finding new and better drug technology assessment processes. The federal government is supporting the expansion of CER through funding made available in the American Recovery and Reinvestment Act of 2009 (ARRA) and by establishing the Patient-Centered Outcomes Research Institute through the Patient Protection and Affordable Care Act of 2010. At the same time, personalized medicine is generating debate about its place in clinical medicine, and so, naturally, how CER can or cannot play a role in personalized medicine is part of these debates. At the heart of the debate around the role of CER in personalized medicine is the nature of personalized medicine and how it fits within contemporary clinical research concepts. We maintain in this article that CER can serve to catalyze personalized medicine, but we recognize that, for this to happen, researchers will need to embrace new data sources and new analytic approaches. We also recognize that drug technology assessment processes will have to undergo necessary adaptations to accommodate CER as configured for personalized medicine, and that clinicians will need to be educated appropriately and provided access to decision-support systems through health information technology to use the information coming from this research. To illustrate our argument, we describe two ongoing CER studies funded and managed in the private sector evaluating personalized medicine interventions that have important clinical and financial implications. One of the studies investigates the clinical and financial effects of pharmacogenomic testing for warfarin as prescribed in conditions of typical practice settings. The other study is also set in community practice settings and compares cardiovascular outcomes of patients receiving clopidogrel who are extensive metabolizer phenotypes for the cytochrome P450 2C19 hepatic isoenzyme with all patients receiving prasugrel.

Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study).

OBJECTIVES: This study was designed to determine whether genotype testing for patients initiating warfarin treatment will reduce the incidence of hospitalizations, including those due to bleeding or thromboembolism. BACKGROUND: Genotypic variations in CYP2C9 and VKORC1 have been shown to predict warfarin dosing, but no large-scale studies have prospectively evaluated the clinical effectiveness of genotyping in naturalistic settings across the U.S. METHODS: This national, prospective, comparative effectiveness study compared the 6-month incidence of hospitalization in patients receiving warfarin genotyping (n = 896) versus a matched historical control group (n = 2,688). To evaluate for temporal changes in the outcomes of warfarin treatment, a secondary analysis compared outcomes for 2 external control groups drawn from the same 2 time periods. RESULTS: Compared with the historical control group, the genotyped cohort had 31% fewer hospitalizations overall (adjusted hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.58 to 0.82, p < 0.001) and 28% fewer hospitalizations for bleeding or thromboembolism (HR: 0.72, 95% CI: 0.53 to 0.97, p = 0.029) during the 6-month follow-up period. Findings from a per-protocol analysis were even stronger: 33% lower risk of all-cause hospitalization (HR: 0.67, 95% CI: 0.55 to 0.81, p < 0.001) and 43% lower risk of hospitalization for bleeding or thromboembolism (HR: 0.57, 95% CI: 0.39 to 0.83, p = 0.003) in patients who were genotyped. During the same period, there was no difference in outcomes between the 2 external control groups. CONCLUSIONS: Warfarin genotyping reduced the risk of hospitalization in outpatients initiating warfarin. (The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings [MHSMayoWarf1]; NCT00830570).