Evolving knowledge of the unmet needs in dry eye disease.

Dry eye disease is a common but underdiagnosed disorder in the United States, and its prevalence is likely to increase as the nation's population ages. Although still regarded as little more than a nuisance by many clinicians and payers alike, dry eye disease is known to have both clinical consequences for ocular health and effects on vision-related quality of life in many people, impairing their ability to function well in vocational and social settings. Pharmaceutical treatments consist mainly of over-the-counter ocular lubricants ("artificial tears") and a few prescription drugs that address the inflammatory component of dry eye disease through immunomodulation and/or inhibition of T-cell activity. In September 2020, Oyster Point Pharma, Inc (Oyster Point Pharma), convened a panel-consisting of 7 managed care executives with experience in management of dry eye disease treatments and 2 eye care practitioners with expertise in dry eye disease-to discuss how the growth of knowledge about dry eye disease in the past 2 decades has altered their thinking about and approach to dry eye disease, as well as how they would like to see the field advance. They pointed to an existing unmet need in knowledge and therapeutics that can address the underlying causes of dry eye disease. Oyster Point Pharma supported the authorship of this article; the authors were members of the panel, and all panelists were compensated by Oyster Point Pharma. This article provides an overview of dry eye disease and summarizes the panel discussion.

Correction to: Cost-Effectiveness Analysis of Patiromer and Spironolactone Therapy in Heart Failure Patients with Hyperkalemia.

Correction to Bounthavong M, Butler J, Dolan CM, Dunn JD, Fisher KA, Oestreicher N, Pitt B, Hauptman PJ, Veenstra DL.

Major Comorbidities of Atopic Dermatitis: Beyond Allergic Disorders.

The consequences of atopic dermatitis reach beyond the skin and past childhood. Patients with atopic dermatitis are at risk of developing allergic comorbidities, but less is known about the associations between atopic dermatitis and non-allergic conditions. Understanding these non-allergic comorbidities has the potential to improve patient outcomes and to help mitigate the cost and burdens associated with these conditions. Atopic dermatitis is associated with cutaneous bacterial infections, more severe forms/courses of cutaneous viral infections, and extra-cutaneous infections. Atopic dermatitis is also associated with several mental health comorbidities particularly attention-deficit hyperactivity disorder, anxiety, and depression. Data are largely inconsistent for specific cancers, but atopic dermatitis appears to protect against malignancy overall; severe long-term atopic dermatitis is associated with adult lymphomas. Atopic dermatitis may also be associated with obesity, cardiovascular disease, and autoimmune disease, particularly alopecia areata and gastrointestinal immune-mediated disorders. Although the causative mechanisms underlying these associations are poorly understood, treating physicians should be aware of associations in seeking to alleviate the burden for patients with atopic dermatitis.

Cost-Effectiveness Analysis of Patiromer and Spironolactone Therapy in Heart Failure Patients with Hyperkalemia.

BACKGROUND AND OBJECTIVE: Certain patients with heart failure (HF) are unable to tolerate spironolactone therapy due to hyperkalemia. Patiromer is a novel agent used to treat hyperkalemia and has been shown to be efficacious, safe, and well-tolerated. The potential clinical outcomes and economic value of using patiromer and spironolactone in patients with HF unable to otherwise tolerate spironolactone due to hyperkalemia are unclear. The objective of this analysis was to model the potential pharmacoeconomic value of using patiromer and spironolactone in patients with a history of hyperkalemia that prevents them from utilizing spironolactone. METHODS: We performed a cost-effectiveness analysis of treatment with patiromer, spironolactone, and an angiotensin-converting enzyme inhibitor (ACEI) in patients with New York Heart Association (NYHA) class III-IV HF compared with ACEI alone. A Markov model was constructed to simulate a cohort of 65-year-old patients diagnosed with HF from the payer perspective across the lifetime horizon. Clinical inputs were derived from the RALES and OPAL-HK randomized trials of spironolactone and patiromer, respectively. Utility estimates and costs were derived from the literature and list prices. Outcomes assessed included hospitalization, life expectancy, and quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were performed to test the robustness of the model findings. RESULTS: Treatment with patiromer-spironolactone-ACEI was projected to increase longevity compared with ACEI alone (5.29 vs. 4.62 life-years gained, respectively), greater QALYs (2.79 vs. 2.60), and costs (US$28,200 vs. US$18,200), giving an ICER of US$52,700 per QALY gained. The ICERs ranged from US$40,000 to US$85,800 per QALY gained in 1-way sensitivity analyses. CONCLUSION: Our results suggest that the use of spironolactone-patiromer-ACEI may provide clinical benefit and good economic value in patients with NYHA class III-IV HF unable to tolerate spironolactone due to hyperkalemia.

Considerations for optimal management of patients with pulmonary arterial hypertension: a multi-stakeholder roundtable discussion.

A roundtable panel of national and regional managed care decision makers and providers met to discuss pulmonary arterial hypertension (PAH) and strategies for management. As a rare, complex disease with high economic costs and potentially devastating outcomes, PAH necessitates that managed care providers balance optimal care with efficient use of healthcare resources. PAH specialists are recognized by health plans as knowledgeable experts and integral partners in managing patients and resources. The diagnosis of PAH must be confirmed by a right heart catheterization. Available therapies are indicated almost exclusively for patients with PAH (riociguat is also indicated in chronic thromboembolic pulmonary hypertension) and target 1 of 3 pathways: endothelin receptor antagonists for the endothelin pathway; phosphodiesterase type-5 inhibitors and soluble guanylate cyclase stimulators for the nitric oxide pathway; and prostanoids as well as a prostacyclin receptor agonist for the prostacyclin pathway, with combination therapy becoming more common. Even in the modern treatment era, as shown in the REVEAL and French registries, PAH is often diagnosed years after symptoms first appear, which leads to a poor prognosis and increased burden on the healthcare system. Facilitating treatment of patients with PAH through centers of excellence, and coordinating care management between health plans and providers with evidence-based approaches can lead to both better results for patients and lower healthcare costs. When PAH experts have access to the right treatments for the right patients at the right time, they can work with insurers to improve the health of patients with PAH while helping to reduce the impact on the healthcare system.

AMCP Format for Formulary Submissions, Version 4.0.

DISCLOSURES: Pannier is a member of the AMCP Format Executive Committee. The authors report no financial or other conflicts of interest related to the subject of this letter.

How drug life-cycle management patent strategies may impact formulary management.

Drug manufacturers may employ various life-cycle management patent strategies, which may impact managed care decision making regarding formulary planning and management strategies when single-source, branded oral pharmaceutical products move to generic status. Passage of the Hatch-Waxman Act enabled more rapid access to generic medications through the abbreviated new drug application process. Patent expirations of small-molecule medications and approvals of generic versions have led to substantial cost savings for health plans, government programs, insurers, pharmacy benefits managers, and their customers. However, considering that the cost of developing a single medication is estimated at $2.6 billion (2013 dollars), pharmaceutical patent protection enables companies to recoup investments, creating an incentive for innovation. Under current law, patent protection holds for 20 years from time of patent filing, although much of this time is spent in product development and regulatory review, leaving an effective remaining patent life of 7 to 10 years at the time of approval. To extend the product life cycle, drug manufacturers may develop variations of originator products and file for patents on isomers, metabolites, prodrugs, new drug formulations (eg, extended-release versions), and fixed-dose combinations. These additional patents and the complexities surrounding the timing of generic availability create challenges for managed care stakeholders attempting to gauge when generics may enter the market. An understanding of pharmaceutical patents and how intellectual property protection may be extended would benefit managed care stakeholders and help inform decisions regarding benefit management.

Translating Atopic Dermatitis Management Guidelines Into Practice for Primary Care Providers.

Atopic dermatitis affects a substantial number of children, many of whom seek initial treatment from their pediatrician or other primary care provider. Approximately two-thirds of these patients have mild disease and can be adequately managed at the primary care level. However, recent treatment guidelines are written primarily for use by specialists and lack certain elements that would make them more useful to primary care providers. This article evaluates these recent treatment guidelines in terms of evaluation criteria, treatment recommendations, usability, accessibility, and applicability to nonspecialists and integrates them with clinical evidence to present a streamlined severity-based treatment model for the management of a majority of atopic dermatitis cases. Because each patient's situation is unique, individualization of treatment plans is critical as is efficient communication and implementation of the plan with patients and caregivers. Specifically, practical suggestions for individualizing, optimizing, implementing, and communicating treatment plans such as choosing a moisturizer formulation, avoiding common triggers, educating patients/caregivers, providing written treatment plans, and scheduling physician follow-up are provided along with a discussion of available resources for patients/caregivers and providers.

The burden of hyperkalemia in patients with cardiovascular and renal disease.

Hyperkalemia is a potentially serious condition that can result in life-threatening cardiac arrhythmias and is associated with an increased mortality risk. Patients older than 65 years who have an advanced stage of chronic kidney disease (stage 3 or higher), diabetes, and/or chronic heart failure are at higher risk for hyperkalemia. To reduce disease progression and improve outcomes in these groups of patients, modulation of the renin-angiotensin-aldosterone system (RAAS) is recommended by guidelines. One limiting factor of RAAS inhibitors at proven doses is the increased risk for hyperkalemia associated with their use. Although there are effective therapeutic options for the short-term, acute management of hyperkalemia, the available strategies for chronic control of high potassium levels have limited effectiveness. The management of high potassium in the long term often requires withdrawing or reducing the doses of drugs proven to reduce cardiovascular and renal outcomes (eg, RAAS inhibitors) or implementing excessive and often intolerable dietary restrictions. Furthermore, withholding RAAS inhibitors may lead to incremental healthcare costs associated with poor outcomes, such as end-stage renal disease, hospitalizations due to cardiovascular causes, and cardiovascular mortality. As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for hyperkalemia. Potential therapies in development may change the treatment landscape in the near future.

Anaphylaxis: a payor's perspective on epinephrine autoinjectors.

The scope of expenditures due to anaphylaxis likely is underestimated by health care payors because anaphylaxis is underdiagnosed and, when reported, most costs of anaphylaxis borne by payors relate to direct medical expenses. Direct costs of anaphylaxis have been estimated at $1.2 billion per year, with direct expenditures of $294 million for epinephrine, and indirect costs of $609 million. More accurate diagnostic coding will allow payors to improve their understanding of the full impact of anaphylaxis on health care plans, employers, patients, and their families. Similarly, more accurate diagnosis and treatment of anaphylaxis should have a direct effect on overall cost savings achieved in this disease state. This includes savings in both direct costs, such as emergency department visits, and indirect costs, such as lost productivity of patients and caregivers. Educating medical personnel on treatment guidelines regarding the specific use of appropriate epinephrine autoinjectors will contribute to cost savings. Even though the cost of autoinjectors has been increasing, evidence indicates that the cost of improper response to, and treatment of, anaphylaxis outweighs that increase. At this time, there are several branded epinephrine autoinjectors and one generic equivalent for one of these branded products available on the US market; the branded autoinjectors are not considered equivalents for substitution. Barriers to coverage and access, such as managed care organization tier classification, medication copay, and socioeconomic status of specific patients, need to be examined more closely and addressed. Education in the proper use of epinephrine autoinjectors, including regular checking of medication expiration dates, is critical for proper management of anaphylaxis and minimizing the costs of anaphylactic events. Managed care organizations can play a role in educational initiatives.

Translating clinical guidelines into practice: the effective and appropriate use of human growth hormone.

There are 9 recombinant human growth hormone (rhGH) products currently available for 10 US Food and Drug Administration-approved indications; each rhGH product is approved for 1 or more indications. Adult and pediatric patients with the various conditions for which rhGH is indicated, from idiopathic short stature (ISS) and growth hormone (GH) deficiency to short bowel syndrome and HIV/AIDS wasting, may benefit from rhGH treatment. In clinical practice, pediatric patients with GH deficiency or ISS make up the majority of the population receiving treatment with rhGH. Most rhGH products are provided through specialty pharmacies that often have to balance the needs of the patient, their own utilization objectives, and the availability of the rhGH on formulary from a particular payer. Often, a payer will prefer only 2 or 3 rhGH products to cover all 10 indications. As such, managed care professionals need to be more informed about the options available and should be familiar with the different indications to help educate patients about treatment. Additionally, healthcare providers should endeavor to identify and manage the care of appropriate patients who would potentially benefit from rhGH therapy, and should be aware of formulary options. Because many of the patients are children and young adults, adherence to treatment is a concern; patient education on the importance of treatment adherence should be ongoing. Various mechanisms are in place (eg, prior authorization requirements and case manager follow-up) to help ensure that rhGH products are used, and used appropriately. This publication includes highlights from a roundtable discussion by key opinion leaders (clinicians and managed care professionals) on how managed care policies and clinical guidelines on appropriate use of rhGH translate into real-world practice. Also discussed are the efficacy and safety of rhGH therapy for its pediatric indications, and the role of specialty pharmacies in managing patient access to therapy.

Impact of glycemic control on healthcare resource utilization and costs of type 2 diabetes: current and future pharmacologic approaches to improving outcomes.

BACKGROUND: The incidence and prevalence of type 2 diabetes continue to grow in the United States and worldwide, along with the growing prevalence of obesity. Patients with type 2 diabetes are at greater risk for comorbid cardiovascular (CV) disease (CVD), which dramatically affects overall healthcare costs. OBJECTIVES: To review the impact of glycemic control and medication adherence on morbidity, mortality, and healthcare costs of patients with type 2 diabetes, and to highlight the need for new drug therapies to improve outcomes in this patient population. METHODS: This comprehensive literature search was conducted for the period between 2000 and 2013, using MEDLINE, to identify published articles that report the associations between glycemic control, medication adherence, CV morbidity and mortality, and healthcare utilization and costs. Search terms included "type 2 diabetes," "adherence," "compliance," "nonadherence," "drug therapy," "resource use," "cost," and "cost-effectiveness." DISCUSSION: Despite improvements in the management of CV risk factors in patients with type 2 diabetes, outcomes remain poor. The costs associated with the management of type 2 diabetes are increasing dramatically as the prevalence of the disease increases. Medication adherence to long-term drug therapy remains poor in patients with type 2 diabetes and contributes to poor glycemic control in this patient population, increased healthcare resource utilization and increased costs, as well as increased rates of comorbid CVD and mortality. Furthermore, poor adherence to established evidence-based guidelines for type 2 diabetes, including underdiagnosis and undertreatment, contributes to poor outcomes. New approaches to the treatment of patients with type 2 diabetes currently in development have the potential to improve medication adherence and consequently glycemic control, which in turn will help to reduce associated costs and healthcare utilization. CONCLUSIONS: As the prevalence of type 2 diabetes and its associated comorbidities grows, healthcare costs will continue to increase, indicating a need for better approaches to achieve glycemic control and manage comorbid conditions. Drug therapies are needed that enhance patient adherence and persistence levels far above levels reported with currently available drugs. Improvements in adherence to treatment guidelines and greater rates of lifestyle modifications also are needed. A serious unmet need exists for greatly improved patient outcomes, more effective and more tolerable drugs, as well as marked improvements in adherence to treatment guidelines and drug therapy to positively impact healthcare costs and resource use.

Implementing CER: what will it take?

BACKGROUND: Comparative effectiveness research (CER) is undeniably changing how drugs are developed, launched, priced, and reimbursed in the United States. But most organizations are still evaluating what CER can do for them and how and when they can utilize the data. A roundtable of stakeholders, including formulary decision makers, evaluated CER's possible effects on managed care organizations (MCOs) and what it may take to fully integrate CER into decision making. OBJECTIVES: To examine the role of CER in current formulary decision making, compare CER to modeling, discuss ways CER may be used in the future, and describe CER funding sources. SUMMARY: While decision makers from different types of organizations, such as pharmacy benefit management (PBM) companies and MCOs, may have varying definitions and expectations of CER, most thought leaders from a roundtable of stakeholders, including formulary decision makers, see value in CER's ability to enhance their formulary decision making. Formulary decision makers may be able to use CER to better inform their coverage decisions in areas such as benefit design, contracting, conditional reimbursement, pay for performance, and other alternative pricing arrangements. Real-world CER will require improvement in the health information technology infrastructure to better capture value-related information. The federal government is viewed as a key driver and funding source behind CER, especially for infrastructure and methods development, while industry will adapt the clinical development and create increasing CER evidence. CER then needs to be applied to determining value (or cost efficacy). CONCLUSIONS: It is expected that CER will continue to grow as a valuable component of formulary decision making. Future integration of CER into formulary decision making will require federal government and academic leadership, improvements in the health information technology infrastructure, ongoing funding, and improved and more consistent methodologies.

Economic considerations for the treatment of opioid and alcohol dependence: a managed care perspective.

This supplement to The American Journal of Managed Care reports the results of several studies analyzing the economic impact of treating opioid or alcohol dependence. While there is a clear need to address and treat substance abuse, effective management with limited resources is a common challenge for managed care professionals and individual practitioners. The information in this supplement may help those who are charged with administering benefit design or disease management programs identify treatment options that can improve outcomes and reduce costs.

Indications for recombinant human growth hormone and evaluation of available recombinant human growth hormone devices: implications for managed care organizations.

There are now many recombinant human growth hormone (rhGH) products and delivery devices available for rhGH therapy. Not all products are approved to treat both children and adults, and they vary with respect to indications approved by the US Food and Drug Administration. Dosing of rhGH is based on weight, and a higher dose (per kg) is recommended in children than adults. This approximates the normal difference in growth hormone (GH) secretion between these 2 patient populations. Patient adherence to treatment is influenced by a number of factors, and patient inclusion in treatment decisions, such as the choice of delivery device, appears to be important. Unmet expectations are a key issue for many patients and families who decide to discontinue treatment. Counseling patients and families about predicted adult height with rhGH therapy should be based on realistic expectations. Managed care organizations face several challenges in providing rhGH therapy, including deciding who is most likely to benefit from treatment and when to discontinue treatment if the benefits appear to level off.

Issues related to recombinant human growth hormone utilization and optimization in a health plan setting.

Healthcare expenditures in the United States are high and continue to increase; as a result, providers and managed care organizations have to evaluate the impact of specialty drugs such as recombinant human growth hormone (rhGH) therapy. As the number of approved indications for rhGH therapy has increased, so too have questions about the appropriate allocation of resources for such therapy. This is particularly true for the recent rhGH indications in children with idiopathic short stature and those short for gestational age who fail to attain normal growth percentiles. With a large increase in the number of children eligible for rhGH therapy, questions arise as to whether all eligible children should be treated with rhGH, and what are the appropriate length of treatment and optimal treatment outcomes. These are important questions for managed care organizations who must determine the treatment parameters that produce the best outcomes in children. The primary disease burdens of growth hormone deficiency (GHD) in adults are the changes in body composition and metabolic parameters, and reduced quality of life, all of which are associated with improvements following rhGH therapy. In adults, the primary economic burden of GHD is healthcare-related costs such as increased hospital days and clinic visits.

Diabetes pharmacy management: balancing safety, cost, and outcomes.

Medication nonadherence, clinical inertia, and contradictory clinical evidence on aggressive disease management contribute to poor outcomes in diabetes management, leading to increased healthcare utilization and costs. As plans increase their focus on the management of type 2 diabetes as an area of high healthcare resource utilization, the importance of appropriate antihyperglycemic agent selection is receiving more attention. The selection process is further complicated by the crowded diabetes drug category, which features several agents with diverse mechanisms of action and routes of administration. The choice of specific antihyperglycemic agents should be predicated on their effectiveness in lowering glucose levels, extraglycemic effects that may reduce long-term complications, safety profiles, tolerability, ease of use, and expense. Beyond appropriate drug selection, pharmacy benefit design also represents an important public health tool for improving treatment adherence and outcomes. Value-based benefit design, in particular, emphasizes high-value medical services by lowering patient copays to encourage plan member use. Essentially, this innovative form of benefit design dictates that the more clinically beneficial the therapy, the lower patients' cost share will be. Other interventions, such as motivational interviewing, pay-for-performance, and medication therapy management, are also being applied to improve treatment adherence and outcomes in the managed care environment, with varying levels of success. Regardless of the specific inventions applied at health plans for improving treatment success in type 2 diabetes, pharmacy director leadership and involvement can contribute to the success of these efforts.

Description of the outcomes of prior authorization of palivizumab for prevention of respiratory syncytial virus infection in a managed care organization.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of upper and lower respiratory tract infections in infants and young children. Most children are exposed to the virus before they are 2 years old and experience such symptoms as cough, fever, and irritability. In a select population of infants, the virus can cause hypoxemia and hospitalization. To avoid hospitalization, good infection control practices should be employed, and for those infants at high risk, prophylaxis with palivizumab is indicated. Palivizumab has been shown to reduce hospitalization rates in high-risk infants by 50%. Because of the high cost of palivizumab, it is prudent to use this medication in the population in which it will be most effective. The American Academy of Pediatrics (AAP) established the criteria for those infants who would benefit the most from palivizumab prophylaxis, and these criteria were the foundation for a prior authorization (PA) program to determine coverage of palivizumab in a health plan of approximately 500,000 members. OBJECTIVE: To (a) analyze the appropriateness of this PA program for palivizumab used prophylactically for RSV, and (b) determine the financial cost associated with the medication and disease for this health plan. METHODS: A 3-year, retrospective study was conducted from the 2005- 2006 RSV season through the 2007-2008 season. The primary endpoint outcome was the hospitalization rate associated with RSV infection. Secondary endpoints included the cost of palivizumab and RSV-related emergency room (ER) utilization. Infants were placed into 2 groups: those who received PA approval for use of palivizumab and those who were denied coverage in the PA process. Disease-related hospitalization and ER visits were identified by at least 1 administrative claim containing either a primary or secondary ICD-9-CM code for any of the following: RSV (079.6), acute bronchiolitis caused by RSV (466.11), or pneumonia caused by RSV (480.1). Drug cost was defined as the health plan's allowed amount, which is based on a predefined fee schedule for the Current Procedural Terminology (CPT) code 90378 for palivizumab. Hospital and ER costs are the health plan allowed amounts (health plan plus member cost) based on the reimbursement rates determined by diagnosis related group (DRG) and other coding, and the plan-allowed amount based on DRGs includes all services and drugs provided in the specific encounter. Drug cost avoided was calculated as the average cost of palivizumab treatment per episode multiplied by the number of infants denied coverage of palivizumab over the 3-year study period. RESULTS: Over 3 RSV seasons through May 2008, the PA program received 1,090 requests for coverage of palivizumab, of which 348 (31.9%) were denied. Of 742 PA-approved infants, 629 received at least 1 dose of palivizumab. The mean (SD) gestational age of the PA-denied group was 34.4 (2.5) weeks versus 32.5 (4.0) weeks for the PA-approved group (P < 0.001). In the PA-denied group, 14 infants (4.0%) were subsequently hospitalized with an RSV infection, and 5 (1.4%) had an RSV-related ER visit versus 40 (6.4%) hospitalized and 14 (2.2%) with ER visits for infants in the PA-approved group (P = 0.055 and P = 0.019, respectively); 15 (4.3%) of the PA-denied group had either a hospitalization or an ER visit versus 42 (6.6%) in the PA-approved group (P = 0.060). One patient in the palivizumab PA-approved group died. Over the 3 RSV seasons, the mean number of palivizumab doses and mean allowed palivizumab cost per treatment episode (per infant per season) were 3.64 and $6,950, respectively, and the average allowed palivizumab cost was $7,702 per utilizing infant. Total per infant costs for palivizumab, RSV hospitalizations, and RSV-related ER visits were $8,534 for infants receiving palivizumab compared with $223 for those denied palivizumab coverage (P = 0.002). Drug cost avoidance associated with the PA program was estimated to be $2,418,600 (348 infants times $6,950 palivizumab cost per episode) over the 3 RSV seasons. CONCLUSION: In a 500,000-member health plan, a PA program to restrict palivizumab use in accordance with AAP recommendations was associated with estimated palivizumab drug cost avoidance of more than $2.4 million over 3 years. There was no significant difference in the RSV-related hospitalization rate for the PA-denied versus the PA-approved groups, but the PA-denied group had a slightly lower rate of RSV-related ER visits.