Drug use and spending under a formulary informed by cost-effectiveness.

BACKGROUND: The National Academy of Medicine has called for value-based drug formularies to address health plan prescription drug spending while maintaining access to high-value medicines. Thirty employer-sponsored plans implemented a "Value-Based Formulary-essentials" (VBF-e) program that uses cost-effectiveness evidence to inform cost-sharing and coverage exclusion. OBJECTIVE: To evaluate if the VBF-e was associated with changes in medication use and patient out-of-pocket spending and health plan spending on prescription drugs and other health care. METHODS: This was a cohort study using a difference-in-differences design from 2015 through 2019 with 1 year of follow-up after VBF-e implementation at Premera Blue Cross, the largest nonprofit health plan in the Pacific Northwest. The VBF-e exposure group was composed of all individuals aged younger than 65 years and enrolled at least 12 months prior to their employer group's VBF-e implementation date. The contemporaneous control group was composed of propensity score-matched individuals with the same inclusion criteria but their employer group that did not implement VBF-e. We prespecified the following outcomes: days of medication on hand overall and by VBF-e tier (high-value generic, brand, and specialty drugs were in tiers 1 to 3, respectively, and low-value drugs were in tier 4 or excluded from coverage); prescription drug spending; and other health care use (emergency department visits, hospital days, and outpatient visits). RESULTS: Comparing 12,111 exposed (mean age = 36.0; 49.8% female sex) participants with 24,222 control participants (mean age = 34.7; 49.6% female sex), VBF-e reduced use of low-value drugs by 0.3 days per member per month (PMPM) (95% CI = -0.5 to -0.1; 17% decrease) for tier 4 drugs and 0.4 days PMPM (95% CI = -0.5 to -0.4; 83% decrease) for excluded drugs. High-value specialty drug use increased by 0.1 days PMPM (95% CI = 0.0-0.1; 123% increase). Health plan spending decreased by $14 PMPM (95% CI = -26 to -4) and member out-of-pocket spending increased by $1 PMPM (95% CI = 1-2). Other health care use did not change significantly. CONCLUSIONS: An exclusion formulary informed by cost-effectiveness evidence reduced low-value drug use, increased high-value specialty drug use, reduced health plan spending, and increased member out-of-pocket spending without increasing acute care use. DISCLOSURES: This research was supported by a grant from the Patrick and Catherine Weldon Donaghue Medical Research Foundation's Greater Value Portfolio Program. Study Registration Number: NCT04904055.

ICER's Version of HTA Is Positioned to Guide U.S. Health Care Reform.

DISCLOSURES: No funding supported the writing of this letter. The author is an unpaid member of the ICER Methods Advisory Committee and has participated in discussions at ICER meetings and meetings of the New England Comparative Effectiveness Advisory Council (CEPAC).

Evolution of the AMCP Format for Formulary Submissions.

DISCLOSURES: No funding was required for this project. The authors are or have been members of the Format Executive Committee.

Augmenting Cost-Effectiveness Analysis Will Not Improve Affordability.

DISCLOSURES: No outside funding contributed to this article. The authors are employed by Premera Blue Cross and have nothing to disclose.

Decision Making on Medical Innovations in a Changing Health Care Environment: Insights from Accountable Care Organizations and Payers on Personalized Medicine and Other Technologies.

BACKGROUND: New payment and care organization approaches, such as those of accountable care organizations (ACOs), are reshaping accountability and shifting risk, as well as decision making, from payers to providers, within the Triple Aim context of health reform. The Triple Aim calls for improving experience of care, improving health of populations, and reducing health care costs. OBJECTIVES: To understand how the transition to the ACO model impacts decision making on adoption and use of innovative technologies in the era of accelerating scientific advancement of personalized medicine and other innovations. METHODS: We interviewed representatives from 10 private payers and 6 provider institutions involved in implementing the ACO model (i.e., ACOs) to understand changes, challenges, and facilitators of decision making on medical innovations, including personalized medicine. We used the framework approach of qualitative research for study design and thematic analysis. RESULTS: We found that representatives from the participating payer companies and ACOs perceive similar challenges to ACOs' decision making in terms of achieving a balance between the components of the Triple Aim-improving care experience, improving population health, and reducing costs. The challenges include the prevalence of cost over care quality considerations in ACOs' decisions and ACOs' insufficient analytical and technology assessment capacity to evaluate complex innovations such as personalized medicine. Decision-making facilitators included increased competition across ACOs and patients' interest in personalized medicine. CONCLUSIONS: As new payment models evolve, payers, ACOs, and other stakeholders should address challenges and leverage opportunities to arm ACOs with robust, consistent, rigorous, and transparent approaches to decision making on medical innovations.

Impact of a value-based formulary in three chronic disease cohorts.

OBJECTIVES: Value-based insurance design has been suggested as an effective approach to ensure access to highvalue medications in health insurance markets. Premera Blue Cross, a large regional health plan, implemented a value-based formulary (VBF) for pharmaceuticals in 2010 that explicitly used cost-effectiveness analysis to inform medication co-payments. This study assesses the impact of a VBF on adherence and patient and health plan expenditures on 3 chronic disease states: diabetes, hypertension, and hyperlipidemia. STUDY DESIGN: Interrupted time series design of employer-sponsored plans from 2006 to 2013. Beneficiaries exposed to the VBF formed the intervention group, and beneficiaries in similar plans without any changes in pharmacy benefits formed the control group. METHODS: We measured medication expenditures from member, health plan, and member-plus-health plan (overall) perspectives and medication adherence as proportion of days covered. We conducted an exploratory analysis of medication utilization classifying medications according to whether co-payments moved up or down in the year following VBF implementation. RESULTS: For the diabetes cohort, there was a statistically significant reduction in member and overall expenditures of $5 per member per month (PMPM) and $9 PMPM, respectively. For the hypertension cohort, there was a statistically significant reduction in member expenditures of $4 PMPM and an increase in health plan expenditures of $3 PMPM. There were no statistically significant effects on hyperlipidemia cohort expenditures or on medication adherence in any of the 3 disease cohorts. Exploratory analyses suggest that patients in the diabetes and hyperlipidemia cohorts were switching to higher-value medications. CONCLUSIONS: A VBF can ensure access to high-value medications while maintaining affordability.

Impact of a Value-based Formulary on Medication Utilization, Health Services Utilization, and Expenditures.

BACKGROUND: Value-based benefit design has been suggested as an effective approach to managing the high cost of pharmaceuticals in health insurance markets. Premera Blue Cross, a large regional health plan, implemented a value-based formulary (VBF) for pharmaceuticals in 2010 that explicitly used cost-effectiveness analysis (CEA) to inform medication copayments. OBJECTIVE OF THE STUDY: The objective of the study was to determine the impact of the VBF. DESIGN: Interrupted time series of employer-sponsored plans from 2006 to 2013. SUBJECTS: Intervention group: 5235 beneficiaries exposed to the VBF. CONTROL GROUP: 11,171 beneficiaries in plans without any changes in pharmacy benefits. INTERVENTION: The VBF-assigned medications with lower value (estimated by CEA) to higher copayment tiers and assigned medications with higher value to lower copayment tiers. MEASURES: Primary outcome was medication expenditures from member, health plan, and member plus health plan perspectives. Secondary outcomes were medication utilization, emergency department visits, hospitalizations, office visits, and nonmedication expenditures. RESULTS: In the intervention group after VBF implementation, member medication expenditures increased by $2 per member per month (PMPM) [95% confidence interval (CI), $1-$3] or 9%, whereas health plan medication expenditures decreased by $10 PMPM (CI, $18-$2) or 16%, resulting in a net decrease of $8 PMPM (CI, $15-$2) or 10%, which translates to a net savings of $1.1 million. Utilization of medications moved into lower copayment tiers increased by 1.95 days' supply (CI, 1.29-2.62) or 17%. Total medication utilization, health services utilization, and nonmedication expenditures did not change. CONCLUSIONS: Cost-sharing informed by CEA reduced overall medication expenditures without negatively impacting medication utilization, health services utilization, or nonmedication expenditures.

Dichloroacetate alters Warburg metabolism, inhibits cell growth, and increases the X-ray sensitivity of human A549 and H1299 NSC lung cancer cells.

We investigated whether altering Warburg metabolism (aerobic glycolysis) by treatment with the metabolic agent dichloroacetate (DCA) could increase the X-ray-induced cell killing of the radiation-resistant human non-small-cell lung cancer (NSCLC) cell lines A549 and H1299. Treatment with 50mM DCA decreased lactate production and glucose consumption in both A549 and H1299, clear indications of attenuated aerobic glycolysis. In addition, we found that DCA treatment also slowed cell growth, increased population-doubling time, and altered cell cycle distribution. Furthermore, we report that treatment with 50mM DCA significantly increased single and fractionated X-ray-induced cell killing of A549 and H1299 cells. Assay of DNA double-strand break repair by neutral comet assays demonstrated that DCA inhibited both the fast and the slow kinetics of X-ray-induced DSB repair in both A549 and H1299 NSCL cancer cells. Taken together the data suggest a correlation between an attenuated aerobic glycolysis and enhanced cytotoxicity and radiation-induced cell killing in radiation-resistant NSCLC cells.

Design, implementation, and first-year outcomes of a value-based drug formulary.

BACKGROUND: Value-based insurance design attempts to align drug copayment tier with value rather than cost. Previous implementations of value-based insurance design have lowered copayments for drugs indicated for select "high value" conditions and have found modest improvements in medication adherence. However, these implementations have generally not resulted in cost savings to the health plan, suggesting a need for increased copayments for "low value" drugs. Further, previous implementations have assigned equal copayment reductions to all drugs within a therapeutic area without assessing the value of individual drugs. Aligning the individual drug's copayment to its specific value may yield greater clinical and economic benefits. In 2010, Premera Blue Cross, a large not-for-profit health plan in the Pacific Northwest, implemented a value-based drug formulary (VBF) that explicitly uses cost-effectiveness analyses after safety and efficacy reviews to estimate the value of each individual drug. Concurrently, Premera increased copayments for existing tiers. OBJECTIVE: To describe and evaluate the design, implementation, and first-year outcomes of the VBF. METHODS: We compared observed pharmacy cost per member per month in the year following the VBF implementation with 2 comparator groups: (1) observed pharmacy costs in the year prior to implementation, and (2) expected costs if no changes were made to the pharmacy benefits. Expected costs were generated by applying autoregressive integrated moving averages to pharmacy costs over the previous 36 months. We used an interrupted time series analysis to assess drug use and adherence among individuals with diabetes, hypertension, or dyslipidemia compared with a group of members in plans that did not implement a VBF.  RESULTS: Pharmacy costs decreased by 3% compared with the 12 months prior and 11% compared with expected costs. There was no significant decline in medication use or adherence to treatments for patients with diabetes, hypertension, or dyslipidemia. CONCLUSIONS: The VBF and copayment changes enabled pharmacy plan cost savings without negatively affecting utilization in key disease states.

Prioritizing comparative effectiveness research for cancer diagnostics using a regional stakeholder approach.

AIMS: This paper describes our process to engage regional stakeholders for prioritizing comparative effectiveness research (CER) in cancer diagnostics. We also describe a novel methodology for incorporating stakeholder data and input to inform the objectives of selected CER studies. MATERIALS & METHODS: As an integrated component to establishing the infrastructure for community-based CER on diagnostic technologies, we have assembled a regional stakeholder group composed of local payers, clinicians and state healthcare representatives to not only identify and prioritize CER topics most important to the western Washington State region, but also to inform the study design of selected research areas. A landscape analysis process combining literature searches, expert consultations and stakeholder discussions was used to identify possible CER topics in cancer diagnostics. Stakeholders prioritized the top topics using a modified Delphi/group-nominal method and a standardized evaluation criteria framework to determine a final selected CER study area. Implementation of the selected study was immediate due to a unique American Recovery and Reinvestment Act funding structure involving the same researchers and stakeholders in both the prioritization and execution phases of the project. Stakeholder engagement was enhanced after study selection via a rapid analysis of a subset of payers' internal claims, coordinated by the research team, to obtain summary data of imaging patterns of use. Results of this preliminary analysis, which we termed an 'internal analysis,' were used to determine with the stakeholders the most important and feasible study objectives. RESULTS: Stakeholders identified PET and MRI in cancers including breast, lung, lymphoma and colorectal as top priorities. In an internal analysis of breast cancer imaging, summary data from three payers demonstrated utilization rates of advanced imaging increased between 2002 and 2009 in the study population, with a great deal of variability in use between different health plans. Assessing whether breast MRI affects treatment decisions was the top breast cancer study objective selected by the stakeholders. There were other high-priority research areas including whether MRI use improved survival that were not deemed feasible with the length of follow-up time following MRI adoption. CONCLUSION: Continuous stakeholder engagement greatly enhanced their enthusiasm for the project. We believe CER implementation will be more successful when undertaken by regional stakeholders.

Can CER be an effective tool for change in the development and assessment of new drugs and technologies?

BACKGROUND: Comparative effectiveness research (CER) has been proposed in the United States as a way to compare new drugs and technologies with established alternatives and determine not just whether a therapy works, but how well it works compared to other options. OBJECTIVES: To define the current use of CER in the development of new drugs and technologies and explore what is needed for this research approach to reduce or stabilize health care costs in the United States. SUMMARY: In 2010, the Patient-Centered Outcomes Research Institute (PCORI) was established by the Patient Protection and Affordable Care Act (PPACA) to coordinate federally funded CER and recommend research priorities. Hochman and McCormick's (2010) evaluation of 328 randomized trials, observational studies, and meta-analyses involving medications published between June 2008 and September 2009 in 6 key journals showed that most published research did not fulfill the criteria of CER (defined as comparison to active treatment) and that most study design is driven by FDA requirements rather than the need to develop evidence to facilitates election of the most effective therapy. Since PPACA provides alternative funding for CER, it could encourage funding more studies to help determine which treatment delivers the best value per unit of investment from clinical, humanistic, and economic perspectives. Manufacturers may avoid CER because it increases product development costs, but a drug proven more effective is more likely to be accepted by formulary committees, increasing the drug's market share, whereas payers may reject or limit use of a new drug that performs less effectively in comparative studies. CONCLUSIONS: CER may not directly reduce expenditures for drugs and medical technologies. The results may vary widely from case to case; however, despite often significantly higher prices for new drugs, it is important to look beyond product costs to the overall impact on health care costs, including medical cost offsets that may occur through improved health or decreased morbidity. To truly decrease cost and improve quality, cost-effectiveness will have to be integrated into CER with the objective of prioritizing efficient therapies in the real-world health care system. If the methods and output of CER improve, the resulting cost-effectiveness ratios will also be more useful to the payer. CER should ultimately, therefore, be a useful tool to help patients, providers, and decision makers provide the most effective and most cost-effective interventions.

Acceleration of the meckel syndrome by near-infrared light therapy.

BACKGROUND/AIMS: Phototherapy using a narrow-band, near-infrared (NIR) light (using a light-emitting diode, LED) is being used to treat certain medical conditions. This narrow-band red light has been shown to stimulate cytochrome c oxidase (CCO) in mitochondria that would stimulate ATP production and has the ability to stimulate wound healing. LED treatment also decreases chemical-induced oxidative stress in tested systems. As renal cystic diseases are known to have evidence of oxidative stress with reduced antioxidant protection, we hypothesized that NIR light therapy might ameliorate the renal pathology in renal cystic disease. METHODS: Wistar-Wpk/Wpk rats with Meckel syndrome (MKS) were treated with light therapy on days 10-18 at which time disease severity was evaluated. Wpk rats were either treated daily for 80 s with narrow-band red light (640-690 nm wavelength) or sham treated. At termination, renal and cerebral pathology was evaluated, and renal expression and activity of enzymes were assessed to evaluate oxidative stress. Blood was collected for blood urea nitrogen (BUN) determination, the left kidney frozen for biochemical evaluation, and the right kidney and head fixed for morphological evaluation. RESULTS: There were no significant effects of LED treatment on body weight (BW) or total kidney weight in non-cystic rats. Total kidney weight was increased and anephric BW was decreased in cystic versus non-cystic controls. LED reduced BW and total kidney weight in cystic rats compared to non-light-treated cystic (control) rats. BUN was already increased almost 6-fold in cystic rats compared to control rats. BUN was further increased almost 2-fold with NIR treatment in both non-cystic and cystic rats compared to cystic and control rats. The hydrocephalus associated with Wpk/Wpk (ventricular volume expressed as total volume and as percent of anephric BW) was also more severe in NIR-treated cystic rats compared to the normal control rats. Renal glutathione peroxidase and catalase (CAT) were reduced in the cystic kidney while superoxide dismutase and CCO were increased. NIR increased CAT and CCO, marginally decreased glutathione S-transferase and slightly decreased glutathione reductase in cystic rats compared to the normal control rats. The detrimental effects of NIR may be related to reduced renal blood flow associated with progression of cystic pathology. Compression by cysts may not allow sufficient oxygen or nutrient supply necessary to support the increased oxidative phosphorylation-associated cellular activity, and the increased demand induced by NIR-increased CCO may have created further oxidative stress. CONCLUSION: LED phototherapy initiated after the onset of symptoms was detrimental to MKS-induced pathology. NIR stimulates CCO thereby increasing the kidney's need for oxygen. We hypothesize that cystic compression of the vasculature impairs oxygen availability and the enhanced CCO activity produces more radicals, which are not sufficiently detoxified by the increased CAT activity.

Effects of low-level light therapy on streptozotocin-induced diabetic kidney.

Hyperglycemia causes oxidative damage in tissues prone to complications in diabetes. Low-level light therapy (LLLT) in the red to near infrared range (630-1000nm) has been shown to accelerate diabetic wound healing. To test the hypothesis that LLLT would attenuate oxidative renal damage in Type I diabetic rats, male Wistar rats were made diabetic with streptozotocin (50mg/kg, ip), and then exposed to 670nm light at a dose of 9J/cm(2) once per day for 14weeks. The activity and expression of catalase and the activity of Na K-ATPase increased in kidneys of light-treated diabetic rats, whereas the activity and expression of glutathione peroxidase and the expression of Na K-ATPase were unchanged. LLLT lowered the values of serum BUN, serum creatinine, and BUN/creatinine ratio. In addition, LLLT augmented the activity and expression of cytochrome c oxidase, a primary photoacceptor molecule in the mitochondrial respiratory chain, and reduced the formation of the DNA adduct 8-hydroxy-2'-deoxyguanosine in kidney. LLLT improved renal function and antioxidant defense capabilities in the kidney of Type I diabetic rats. Thus, 670nm LLLT may be broadly applicable to the amelioration of renal complications induced by diabetes that disrupt antioxidant defense mechanisms.

Effects of low-level light therapy on hepatic antioxidant defense in acute and chronic diabetic rats.

Diabetes causes oxidative stress in the liver and other tissues prone to complications. Photobiomodulation by near infrared light (670 nm) has been shown to accelerate diabetic wound healing, improve recovery from oxidative injury in the kidney, and attenuate degeneration in retina and optic nerve. The present study tested the hypothesis that 670 nm photobiomodulation, a low-level light therapy, would attenuate oxidative stress and enhance the antioxidant protection system in the liver of a model of type I diabetes. Male Wistar rats were made diabetic with streptozotocin (50 mg/kg, ip) then exposed to 670 nm light (9 J/cm(2)) once per day for 18 days (acute) or 14 weeks (chronic). Livers were harvested, flash frozen, and then assayed for markers of oxidative stress. Light treatment was ineffective as an antioxidant therapy in chronic diabetes, but light treatment for 18 days in acutely diabetic rats resulted in the normalization of hepatic glutathione reductase and superoxide dismutase activities and a significant increase in glutathione peroxidase and glutathione-S transferase activities. The results of this study suggest that 670 nm photobiomodulation may reduce, at least in part, acute hepatic oxidative stress by enhancing the antioxidant defense system in the diabetic rat model.