Expanding the Catalog of Patient and Caregiver Out-of-Pocket Costs: A Systematic Literature Review.

Out-of-pocket (OOP) health care expenditures in the United States have increased significantly in the past 5 decades. Most research on OOP costs focuses on expenditures related to insurance and cost-sharing payments or on costs related to specific conditions or settings, and does not capture the full picture of the financial burden on patients and unpaid caregivers. The aim for this systematic literature review was to identify and categorize the multitude of OOP costs to patients and unpaid caregivers, aid in the development of a more comprehensive catalog of OOP costs, and highlight potential gaps in the literature. The authors found that OOP costs are multifarious and underestimated. Across 817 included articles, the authors identified 31 subcategories of OOP costs related to direct medical (eg, insurance premiums), direct nonmedical (eg, transportation), and indirect spending (eg, absenteeism). In addition, 42% of articles studied an expenditure that the authors did not label as "OOP." A holistic and comprehensive catalog of OOP costs can inform future research, interventions, and policies related to financial barriers to health care in the United States to ensure the full range of costs for patients and unpaid caregivers are acknowledged and addressed.

Value of Triage Treatment Strategies to Distribute Hepatitis C Direct-Acting Antiviral Agents in an Integrated Healthcare System: A Cost-Effectiveness Analysis.

OBJECTIVES: This study aimed to assess the cost-effectiveness of fibrosis-based direct-acting antiviral treatment policies for patients with chronic hepatitis C virus at the Kaiser Permanente Mid-Atlantic States health system. METHODS: We used a Markov model to compare the lifetime costs and effects of treating patients with chronic hepatitis C virus at different stages of disease severity, or all stages simultaneously, based on a fibrosis score from the US healthcare sector perspective and societal perspective. The initial distribution of patients across fibrosis scores, the effectiveness of direct-acting antiviral therapy, and follow-up and monitoring protocols were specific to the Kaiser Permanente Mid-Atlantic States health system. Direct and indirect costs, transition probabilities, and utilities were derived from the literature. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of our results. RESULTS: The "Treat All" option was dominant from both the societal and healthcare sector perspectives. The conclusion was robust in deterministic sensitivity analysis. The range of incremental costs between the less restrictive policies was small-the difference between the "Treat F1+" and the "Treat All" option was only $111 per person. Probabilistic sensitivity analyses showed, at both the $100 000/quality-adjusted life-year and $150 000/quality-adjusted life-year thresholds, there was a 70% chance that the "Treat All" option was more cost-effective than the "Treat F1+" option. CONCLUSIONS: We found that expanded treatment access is cost-effective and, in many cases, cost saving. Although our results are primarily applicable to a regional integrated healthcare system, it offers some direction to any healthcare setting faced with resource constraints in the face of highly priced drugs.

Stakeholders find that step therapy should be evidence-based, flexible, and transparent: assessing appropriateness using a consensus approach.

BACKGROUND: Step therapy, one approach to utilization management, is used by health plans to ensure safe and clinically appropriate care while managing cost. Several patient and provider groups have each developed principles to guide the appropriate use of step therapy; however, no comprehensive multistakeholder informed set of criteria exist. OBJECTIVE: To assess multistakeholder consensus on criteria for the development and implementation of step therapy for pharmaceutical therapies. Stakeholders were asked to (a) assess the appropriateness of step therapy as a utilization management tool; (b) rate specific criteria across 5 domains (development, implementation, communication, appeals, and evaluation) of step therapy; and (c) categorize these criteria as standards or best practices. METHODS: We conducted a multiphase project culminating in a roundtable of experts representing patient, provider, plan, pharmacy, policy, and ethical perspectives. We first reviewed guiding principles, position statements, and legislative activity to draft criteria regarding step therapy protocol development, implementation, communication, and evaluation. To assess consensus across a convenience sample of experts, we employed an iterative 4-step modified Delphi method. Panelists were asked to (a) rate the overall appropriateness of step therapy, (b) rate the appropriateness of specific criteria, and (c) identify each as a standard or best practice. Appropriateness was rated from 1-9 and categorized in terciles (1-3: not appropriate, 4-6: neither, 7-9: appropriate) to assess quantitative agreement, disagreement, and indeterminate agreement. RESULTS: After the second round of voting, roundtable panelists (n = 16) disagreed on the appropriateness of step therapy for utilization management (50% appropriate, 31.25% neither, and 18.75% inappropriate). Agreement was achieved on 21 criteria across 5 themes (clinical criteria as the foundation for protocol development, implementation of protocols, transparency and communication of processes, navigation of the appeals process, and evaluation of health and administrative impact). Fourteen and seven criteria were categorized as standards and best practices, respectively. CONCLUSIONS: The stakeholders in this panel differed in their assessments of the appropriateness of step therapy but agreed regarding how these protocols should be developed, implemented, communicated, and evaluated. Most criteria were rated as standards that can be used by stakeholders when developing, implementing, and assessing step therapy processes today. DISCLOSURES: This study was funded by the National Pharmaceutical Council. Karmarkar was a fellow at the National Pharmaceutical Council and Duke-Margolis Center for Health Policy at the time this study was conducted. Dubois and Graff are employees of the National Pharmaceutical Council. This work was previously presented as a virtual poster during the AMCP 2020 eLearning Days, April 21-24, 2020.

Characteristics associated with time-to-treatment initiation for chronic Hepatitis C with new direct acting antivirals.

BACKGROUND: Interferon-free direct-acting antivirals (DAAs) were introduced in 2013 and have transformed the therapeutic landscape for chronic Hepatitis C (HCV). Although treatment is recommended for almost all persons infected with HCV, clinical and psychosocial factors may affect treatment initiation. METHODS: We conducted an observational cohort study of Kaiser Permanente Mid-Atlantic States members with prevalent or incident HCV infection identified from November 2013 through May 2016 to identify predictors of DAA initiation. We used Cox regression with time-dependent covariates to compare time to treatment by clinical, demographic and societal factors. RESULTS: Of 2962 patients eligible for DAA therapy, 33% (n = 980) initiated treatment over the study period. The majority of patients (97%) were persistent with therapy and most (95%) tested for sustained virologic response (SVR) achieved cure. We found no effect of race, insurance type or fibrosis stage on treatment initiation. We observed that patients aged 41-60 years (aHR: 2.014, 95% CI: 1.12, 3.60) and 61-80 years (aHR: 2.08, 95% CI: 1.15-3.75) had higher treatment rates compared to younger patients. Incident cases were more likely to be treated than prevalent cases (aHR: 3.05, 95% CI: 2.40-3.89). Patients with a history of substance use disorder (SUD) were less likely (aHR: 0.805, 95% CI: 0.680, 0.953) to be treated. CONCLUSIONS: In the first 3 years of DAA availability, one-third of patients with HCV initiated therapy, and almost all were persistent and achieved cure. While curative, DAAs remain highly priced. Triaging for non-clinical reasons or perceptions about patients will stall our ability to eradicate HCV.

Underestimating the Value of an Intervention: The Case for Including Productivity in Value Assessments and Formulary Design.

BACKGROUND: Value assessment reports are increasingly being considered in health care coverage decisions. The inputs included and analytic methodologies underlying these reports should include all components of value. OBJECTIVE: To determine whether and how productivity was included in a value assessment, compare the incremental cost per quality-adjusted life-year (cost/QALY) estimates with and without productivity, assess if inclusion of productivity changed the value category and estimate the direction and magnitude of change. METHODS: We reviewed pharmaceutical value assessment reports published between March 2017 and July 2019 by the Institute for Clinical and Economic Review (ICER) to determine whether productivity was included and how it was reported (i.e., co-base case or scenario analysis). Within each report, we identified unique treatment comparisons for which modelers estimated an incremental cost/QALY. We categorized the incremental cost/QALY estimates using ICER's willingness-to-pay (WTP) categories and assessed if inclusion of productivity changed the value category (i.e., < $50,000/QALY). For reports that included 2 numerical estimates, we assessed the direction and magnitude of change when productivity was included. RESULTS: Of the 19 reports that evaluated pharmaceutical treatments, 18 (94.7%) included productivity. Two reports (11.1%) incorporated productivity in a co-base case analysis, and 16 included productivity in a scenario analysis. Across these 18 reports, there were 75 unique comparisons of pharmaceutical interventions. Across the 75 comparisons, 4 (5.3%), 3 (4.0%), 8 (10.6%), and 1 (1.3%) of the coverage decisions would change at the $50,000/QALY, $100,000/QALY, $150,000/QALY, and $500,000/QALY threshold, respectively. Sixty comparisons included 2 numerical cost/QALY estimates. The magnitude of change in the cost/QALY, after including productivity, ranged from -80.1% to 6.8%. The estimated value increased for 54 (72%), decreased for 5 (6.6%), and did not change for 1 (1.7%) of the comparisons. CONCLUSIONS: Value assessment should capture the range of costs and benefits of an intervention. The exclusion of productivity costs can alter, often underestimating, the assessment of value. This may affect coverage decisions-inclusion or exclusion from the insurance benefit-based on these assessments. Value assessment reports intended to be used for health care decision making should include productivity and elevate its visibility by using base-case analyses rather than scenario analyses. DISCLOSURES: This study was funded by the National Pharmaceutical Council. Karmarkar is currently a postdoctoral fellow at the National Pharmaceutical Council. Graff and Westrich are employees of the National Pharmaceutical Council, which provides unrestricted research grants to value assessment bodies including ICER and IVI.

Potential Role of Cost and Quality of Life in Treatment Decisions for Arthritis-Related Knee Pain in African American and Latina Women.

OBJECTIVE: The present study was undertaken to investigate whether Latina and African American women with arthritis-related knee pain and primary care providers who treat them believe their treatment decisions would benefit from having more information about the impact of treatment on their quality of life, medical care costs, and work productivity. METHODS: We conducted 4 focus groups of Latina and African American women over age 45 years who had knee pain. We also conducted 2 focus groups with primary care providers who treated Latina and African American women for knee pain. The participants were recruited from the community. They were asked their opinions about a decision tool that presented information on a range of treatment options and their impacts on quality of life, medical care costs, and work productivity. They were asked whether providing this information would help them make better treatment decisions. We analyzed the focus group transcripts using ATLAS.ti. RESULTS: We found that minority women and primary care providers endorsed the use of a decision-making tool that provided information of the impact of treatment on quality of life, medical care costs, and work productivity. Providers felt that patients would benefit from having the additional information but were concerned about its complexity and some patients' ability to comprehend the information. CONCLUSION: Latina and African American women could make more informed treatment decisions for their knee pain using a decision-making tool that provides them with significant information about how various treatment options may impact their quality of life, medical care costs, and workforce productivity.

Fairness in drug prices: do economists think differently from the public?

Using dual-entitlement theory as the guide, we conducted a survey of economists from the National Bureau of Economic Research asking them a series of questions about the fairness of drug prices in the United States. Public opinion surveys have repeatedly shown that the public perceives drug prices to be unfair, but economists trained in laws of supply and demand may have different perceptions. Three hundred and ten senior economists responded to our survey. Forty-five percent agreed that drug prices were unfair when people, specifically low-income individuals, could not afford their prescription medications. Sixty-five percent oppose a dollar threshold, or upper limit, on drug prices. The economists recommend the most promising policy change would be to provide the government additional negotiating power and price controls would moderately impact investment in pharmaceutical research and development.

Efficacy and tolerability of antidepressants in Parkinson's disease: A systematic review and network meta-analysis.

OBJECTIVE: To systematically review and analyze the efficacy and tolerability of different antidepressant pharmacologic treatments for depressive symptoms in Parkinson's disease (PD) METHODS: We searched PubMed, EMBASE, Cochrane database (CENTRAL), clinicaltrials.gov, and bibliographies for randomized controlled trials investigating the efficacy of antidepressant medications versus a non-treatment, placebo, or active treatment groups for depressive symptoms in PD. Twenty of 3191 retrieved studies (1893 patients) were included, but not all could be meta-analyzed. We used a random-effects model meta-analysis to compare depression scores between an active drug and placebo or control group then used a network meta-analysis to compare the effectiveness of different antidepressant classes. The primary outcome was the efficacy of different classes of antidepressant medications in PD patients with depressive symptoms, measured by standardized mean difference (SMD) in depression score from baseline compared with control. RESULTS: Pairwise meta-analysis suggested that type B-selective monoamine oxidase inhibitors (SMD = -1.28, CI = -1.68, -0.88), selective serotonin reuptake inhibitors (SMD = -0.49, CI = -0.93, -0.05), and tricyclics (SMD = -0.83, CI = -1.53, -0.13) are effective antidepressants in PD. Network meta-analysis showed that monoamine oxidase inhibitors had the largest effect on depression in PD (SMD (vs selective serotonin reuptake inhibitors) = -0.78, CI = -1.55, -0.01), but these might not be considered traditional antidepressants given their type B selectivity. CONCLUSIONS: Although limited by few data, this review suggests that multiple antidepressant classes are potentially efficacious in the treatment of depression in PD, but that further comparative efficacy and tolerability research is needed.

Branded prescription drug spending: a framework to evaluate policy options.

BACKGROUND: High drug spending is a concern for policy makers due to limits on access for patients. Numerous policies have been proposed to address high drug spending. The existence of multifarious proposals makes it difficult for policy makers to consider all the alternatives. We developed an approach to select the most viable options to present to policy makers. METHODS: We identified 41 different proposals in the peer-reviewed literature to reduce the level of spending or change the incentives for branded prescription drugs; ten of which we identified as promising proposals. Based on criterion used to assess various legislative proposals regarding branded pharmaceuticals we developed a framework to evaluate the ten promising proposals. We then used a modified Delphi technique to iteratively evaluate these ten proposals starting with the initial criterion. During each iteration, five researchers independently evaluated the ten policies based on available criterion and assessed how to modify the criterion to achieve consensus on what attributes the criterion were intended to measure. We highlight areas of disagreement to show where modifications to existing criterion are needed. RESULTS: We found general agreement for most policy-criterion combinations after three iterations. Areas with the greatest remaining disagreement include possible unintended consequences, the concept of value implied by many of the policies, and secondary effects by the pharmaceutical industry, insurers, and the FDA. CONCLUSIONS: Our analysis provides an approach that can be applied to evaluate policy proposals. It also suggests factors that policy analysts and researchers should consider when they propose policy options and where additional research is needed to assess policy impacts. Developing an objective approach to compare alternatives may facilitate the adoption of policies for branded prescription drugs in the U.S. by allowing policy makers to focus on the most viable options.

A Fresh Perspective on a Familiar Problem: Examining Disparities in Knee Osteoarthritis Using a Markov Model.

BACKGROUND: Disparities in the presentation of knee osteoarthritis (OA) and in the utilization of treatment across sex, racial, and ethnic groups in the United States are well documented. OBJECTIVES: We used a Markov model to calculate lifetime costs of knee OA treatment. We then used the model results to compute costs of disparities in treatment by race, ethnicity, sex, and socioeconomic status. RESEARCH DESIGN: We used the literature to construct a Markov Model of knee OA and publicly available data to create the model parameters and patient populations of interest. An expert panel of physicians, who treated a large number of patients with knee OA, constructed treatment pathways. Direct costs were based on the literature and indirect costs were derived from the Medical Expenditure Panel Survey. RESULTS: We found that failing to obtain effective treatment increased costs and limited benefits for all groups. Delaying treatment imposed a greater cost across all groups and decreased benefits. Lost income because of lower labor market productivity comprised a substantial proportion of the lifetime costs of knee OA. Population simulations demonstrated that as the diversity of the US population increases, the societal costs of racial and ethnic disparities in treatment utilization for knee OA will increase. CONCLUSIONS: Our results show that disparities in treatment of knee OA are costly. All stakeholders involved in treatment decisions for knee OA patients should consider costs associated with delaying and forgoing treatment, especially for disadvantaged populations. Such decisions may lead to higher costs and worse health outcomes.

Reducing Branded Prescription Drug Prices: A Review of Policy Options.

The high prices of specialty pharmaceuticals are causing some public programs to ration care and many private insurers, including Medicare drug plans, to place specialty drugs on high cost-sharing tiers. As a result, access to these drugs is often restricted, and only a small portion of the population with a disease may receive treatment. This concern has generated a wide range of proposed solutions. We conducted a literature review and identified 52 solutions in the peer-reviewed literature that we classified into five broad categories: revising the patent system, encouraging research to increase development of new drugs, altering pharmaceutical regulation, decreasing market demand, and developing innovative pricing strategies. We discuss the rationale for these five approaches and summarize the proposed solutions. We also discuss four empirical issues that are particularly important in any discussion of policy options.

Healthcare utilization and costs in ARDS survivors: a 1-year longitudinal national US multicenter study.

PURPOSE: To evaluate (1) post-discharge healthcare utilization and estimated costs in ARDS survivors, and (2) the association between patient and intensive care-related variables, and 6-month patient status, with subsequent hospitalization and costs. METHODS: Longitudinal cohort study enrolling from four ARDSNet trials in 44 US hospitals. Healthcare utilization was collected via structured interviews at 6 and 12 months post-ARDS, and hospital costs estimated via the Medical Expenditure Panel Survey. Adjusted odds ratios for hospitalization and adjusted relative medians for hospital costs were calculated using marginal two-part regression models. RESULTS: Of 859 consenting survivors, 839 (98%) reported healthcare utilization, with 52% female and a mean age of 49 years old. Over 12 months, 339 (40%) patients reported at least one post-discharge hospitalization, with median estimated hospital costs of US$18,756 (interquartile range $7852-46,174; 90th percentile $101,500). Of 16 patient baseline and ICU variables evaluated, only cardiovascular comorbidity and length of stay were associated with hospitalization, and sepsis was associated with hospital costs. At 6-month assessment, better patient-reported physical activity and quality of life status were associated with fewer hospitalizations and lower hospital costs during subsequent follow-up, and worse psychiatric symptoms were associated with increased hospitalizations. CONCLUSIONS: This multicenter longitudinal study found that 40% of ARDS survivors reported at least one post-discharge hospitalization during 12-month follow-up. Few patient- or ICU-related variables were associated with hospitalization; however, physical, psychiatric, and quality of life measures at 6-month follow-up were associated with subsequent hospitalization. Interventions to reduce post-ARDS morbidity may be important to improve patient outcomes and reduce healthcare utilization.

Sofosbuvir initial therapy abandonment and manufacturer coupons in a commercially insured population.

OBJECTIVES: To describe rates of sofosbuvir initial medication adherence as a function of the insurer-required member cost (ie, out-of-pocket cost) and to determine how manufacturer coupons affect insurer-required member cost. STUDY DESIGN: Observational cross-sectional analysis. METHODS: Administrative pharmacy claims data from 13 million commercially insured members were used to identify sofosbuvir new starts between January 2014 and September 2014. Members were categorized as either sofosbuvir initial adherence or as abandoning therapy. A multivariate logistic regression model adjusting for sociodemographic characteristics, severity of illness, and total drug costs (health insurer plus member amount) for non-sofosbuvir pharmacy claims in 2014 was used to evaluate the association between insurer-required member cost and initial medication adherence. In a sub-analysis, sofosbuvir index claims with coupon data available were analyzed to determine how coupon use impacted insurer-required member cost. RESULTS: A total of 67.3% of members had a pre-coupon member cost of < $250 for their index sofosbuvir claim. Just 201 (5.0%) members were exposed to a member cost of more than $10,000. The logistic regression model demonstrated an association between member cost and abandonment starting at $2500 to < $5000 (odds ratio: 1.9; 95% CI, 1.01-3.43; P = .0393). The average member sofosbuvir index claim cost was $1349 before coupon was applied, and $28 after. Overall, coupons offset the member amounts paid by 98%: $771,593 of the $787,860 member cost requested by the insurer. CONCLUSIONS: These findings indicate that a 30-day supply sofosbuvir member cost of > $2500 was associated with increased initial therapy abandonment, and that manufacturer coupons substantially reduced sofosbuvir insurer-required member cost. Insurers and policy makers should consider the impact of member cost on medication adherence and the impact coupons have on the actual member cost.