The Role of Pharmaceutical Innovation in Clinical Practice Guidelines for Chronic Diseases.

Background: Over the last 25 years, clinical practice guidelines have emerged as a means to standardize and improve care. As pharmaceutical innovations develop, guidelines are updated to incorporate new interventions. However, the extent to which pharmacotherapies are represented as treatment options in guideline recommendations has not been well elucidated. This study aimed to quantify the role pharmacotherapy has played in clinical practice guidelines across a range of chronic diseases over the past 20 years. Methods: Clinical practice guidelines published from 2000 to 2021 were identified for five chronic diseases: ischemic heart disease (IHD), non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), Alzheimer's disease (AD), and type 2 diabetes (T2D). Guidelines were reviewed and data on treatment recommendations were collected, including the type of intervention, line of therapy, and, for pharmacotherapies, year of regulatory approval and year of inclusion in guidelines. Results: In total, 92 clinical practice guidelines were reviewed. Among the 184 discrete recommended interventions across the five disease areas, 146 (79.3%) were pharmacotherapies, 21 (11.4%) were behavioral modifications, 6 (3.3%) were surgical interventions, and 11 (6%) were other interventions. Across guidelines, when a line of therapy was specified, behavioral modifications and pharmacotherapies were most frequently recommended as first-line interventions, whereas surgical interventions were more often recommended for subsequent lines of treatment. The time from regulatory approval of novel pharmacotherapies to inclusion in guideline recommendations varied considerably by disease area and geography. Conclusions: Across the reviewed disease areas, behavioral interventions and pharmacotherapies are shown to be critical components of clinical practice. Over the last 20 years, novel pharmaceutical innovations have been incorporated into clinical practice guideline recommendations; however, with varying speeds of adoption. Given the increasing pace of pharmacologic innovation, timely updates of clinical practice guidelines are critical to evolving the standard of care and practicing evidence-based medicine.

Expert Consensus on Comprehensive Early Rhythm Control in Addition to Guideline-Based Care for Atrial Fibrillation: A Modified Delphi Survey.

Atrial fibrillation (AF) practice guidelines recommend a rhythm-control strategy to improve symptoms and quality of life, noting the side effects of antiarrhythmic drugs and catheter ablation. Emerging evidence indicates that comprehensive early rhythm control with antiarrhythmic drugs or catheter ablation is associated with a lower risk of adverse cardiovascular outcomes versus the usual care. Using an online modified Delphi survey approach, perspectives and expert consensus among electrophysiologists were examined through a series of ranking and likelihood questions around treatment decision-making on (1) the use of comprehensive early rhythm-control strategies in patients with AF based on guidelines and emerging research and (2) treatment selection factors. A panel of 17 electrophysiologists reached a consensus on using early rhythm control (median 90, interquartile range 14) based on the view that early intervention improved cardiovascular outcomes (mean rank 1.6 of 3, 82% within 1 SD) and symptoms (1.8 of 3, 41%). AF-related symptoms were identified as the most important in making a treatment initiation decision (1.1 of 7, 88%), followed by AF type (2.5 of 7, 82%). Participants were most likely to initiate treatment at AF symptom onset (median 80; interquartile range 6). In making treatment selection decisions, participants ranked short-term/long-term safety (1.9 of 7, 88%) and efficacy (1.8 of 7, 53%) as the top 2 considerations. In conclusion, experts were in favor of early rhythm control; however, additional research is needed to address the role that early rhythm-control strategies play in current AF treatment management algorithms.

Expert consensus established around flexible, individualized migraine treatment utilizing a modified Delphi panel.

OBJECTIVE: To characterize treatment decision-making processes and formalize consensus regarding key factors headache specialists consider in treatment decisions for patients with migraine, considering novel therapies. BACKGROUND: Migraine therapies have long been subject to binary classification, acute versus preventive, due to limitations of available drugs. The emergence of novel therapies that can be used more flexibly creates an opportunity to rethink this binary classification. To determine the role of these novel therapies in treatment, it is critical to understand whether existing guidelines reflect clinical practice and to establish consensus around factors driving management. METHODS: A three-round modified Delphi process was conducted with migraine clinical experts. Round 1 consisted of an online questionnaire; Round 2 involved an online discussion of aggregated Round 1 results; and Round 3 allowed participants to revise Round 1 responses, incorporating Round 2 insights. Questions elicited likelihood ratings (0 = highly unlikely to 100 = highly likely), rankings, and estimates on treatment decision-making. RESULTS: Nineteen experts completed three Delphi rounds. Experts strongly agreed on definitions for "acute" (median = 100, inter-quartile range [IQR] = 5) and "preventive" treatment (median = 90, IQR = 15), but noted a need for treatment customization for patients (median = 100, IQR = 6). Experts noted certain aspects of guidelines may no longer apply based on established tolerability and efficacy of newer acute and preventive agents (median = 91, IQR = 17). Further, experts agreed on a treatment category referred to as "situational prevention" (or "short-term prevention") for patients with reliable and predictable migraine triggers (median = 100, IQR = 10) or time-limited periods when headache avoidance is important (median = 100, IQR = 12). CONCLUSIONS: Using the modified Delphi method, a panel of migraine experts identified the importance of customizing treatment for people with migraine and the utility of "situational prevention," given the ability of new treatment options to meet this need and the potential to clinically identify patients and time periods when this approach would add value.

Generalized cost-effectiveness analysis to assess treatment value in hepatitis C.

OBJECTIVES: To estimate the comprehensive value of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) compared with peginterferon alfa and ribavirin (PEG/riba) employing a generalized cost-effectiveness analysis (GCEA). STUDY DESIGN: To assess the societal-level cost-effectiveness of DAA treatment for HCV, we extended a previously published discrete-time Markov simulation model of HCV transmission and progression to include market dynamics and broader elements of value. METHODS: We followed a stepwise process to add novel value elements to a traditional CEA model for HCV treatments. For each additional element of value, we estimated incremental cost-effectiveness ratios (ICERs) of DAAs compared with PEG/riba. RESULTS: The health technology assessment (HTA)-style model yielded an ICER value of $64,512 per quality-adjusted life-year (QALY). Adding transmission dynamics resulted in an ICER value of $52,971 per QALY, whereas accounting for transmission dynamics and dynamic price and efficacy further decreased ICER values by 90% to $6406 per QALY. Incorporating genericization, productivity loss, caregiver spillover, and differential valuations of LYs vs quality of life, disease severity, and insurance value further decreased the ICER value to $4487 per QALY, a 93% reduction from the baseline HTA-style CEA to the fully realized GCEA. CONCLUSIONS: Our GCEA study results confirm that DAAs are a cost-effective treatment for HCV compared with PEG/riba even when using conventional cost-effectiveness approaches. Incorporating broader elements of value resulted in more than a 10-fold improvement in cost-effectiveness, emphasizing the substantive impact of a generalized approach and the importance of incorporating GCEAs into decision-making.

The Diagnostic Dilemma of Unseparated Fractures.

Unseparated fractures in teeth without a history of prior endodontic treatment represent a common presentation in clinical practice. Historic heterogeneity in diagnostic terminology and treatment recommendations have produced considerable uncertainty among clinicians regarding how to best treat these teeth. That said, a current review of the literature can provide clinicians with an evidence-grounded framework for managing unseparated fractures. This article reviews the current literature with regard to the epidemiology, diagnosis, and treatment of unseparated fractures.

Cost-effectiveness of genome sequencing for diagnosing patients with undiagnosed rare genetic diseases.

PURPOSE: To estimate the cost-effectiveness of genome sequencing (GS) for diagnosing critically ill infants and noncritically ill pediatric patients (children) with suspected rare genetic diseases from a United States health sector perspective. METHODS: A decision-analytic model was developed to simulate the diagnostic trajectory of patients. Parameter estimates were derived from a targeted literature review and meta-analysis. The model simulated clinical and economic outcomes associated with 3 diagnostic pathways: (1) standard diagnostic care, (2) GS, and (3) standard diagnostic care followed by GS. RESULTS: For children, costs of GS ($7284) were similar to that of standard care ($7355) and lower than that of standard care followed by GS pathways ($12,030). In critically ill infants, when cost estimates were based on the length of stay in the neonatal intensive care unit, the lowest cost pathway was GS ($209,472). When only diagnostic test costs were included, the cost per diagnosis was $17,940 for standard, $17,019 for GS, and $20,255 for standard care followed by GS. CONCLUSION: The results of this economic model suggest that GS may be cost neutral or possibly cost saving as a first line diagnostic tool for children and critically ill infants.

Schizophrenia population health management: perspectives of and lessons learned from population health decision makers.

BACKGROUND: Despite therapeutic advances for patients with schizophrenia, improving patient outcomes and reducing the cost of care continue to challenge formulary decision makers. OBJECTIVES: To (1) understand the perspectives of formulary decision makers on challenges to optimal schizophrenia population management and (2) identify best practices and recommendations for mitigating these challenges. METHODS: This mixed-methods study, conducted in a double-blind manner, comprised in-depth telephone interviews with formulary decision makers from February through May 2020, and a web-based follow-on survey that was sent to all participants in October 2020. US-based formulary decision makers were recruited if they were directly involved in schizophrenia drug formulary or coverage decision making for national or regional payers, health systems, or behavioral health centers. Formulary decision makers' perceptions of challenges, policies, and programs related to schizophrenia population health management were assessed generally and in the context of the COVID-19 pandemic. RESULTS: 19 formulary decision makers participated in the interviews and 18 (95%) completed the survey. Participants reported a spectrum of patient- and payer-driven challenges in schizophrenia population health management, including medication nonadherence, high pharmacy and medical costs, and frequent hospitalizations and emergency department visits. Participants noted that COVID-19 had worsened all identified challenges, although patient unemployment (mean score of 2.00 on a scale of 1 [made much worse] to 5 [made much better]) and reduced access to psychiatric care (mean score, 2.12) were most negatively affected. The most common strategies implemented in order to improve schizophrenia population health management included case management (89%), telemedicine (83%), care coordination programs (72%), strategies to mitigate barriers to accessing medication (61%), and providing nonmedical services to address social determinants of health (56%). Participants noted that, ideally, all treatments for schizophrenia would be available on their formularies without utilization management policies in place in order to increase accessibility to medication, but cost to the health plans made that difficult. Whereas 61% of respondents believed that long-acting injectable antipsychotics (LAIs) were currently underused in their organizations, only 28% represented organizations with open access policies for LAIs. Participants believed that among patients with schizophrenia, LAIs were most beneficial for those with a history of poor or uncertain adherence to oral medications (mean score of 4.50 on a scale of 1 [not at all beneficial] to 5 [extremely beneficial]) and those with recurring emergency department visits and inpatient stays (mean score, 3.94). Study participants reported slightly increased use of LAIs (mean score of 3.17 on a scale of 1 [negatively impacted] to 5 [positively impacted]) among their patients with schizophrenia in response to the COVID-19 pandemic; 29% of participants reported easing access restrictions for LAIs. CONCLUSIONS: Participants described persisting challenges and various approaches intended to improve schizophrenia population health management. They also recommended strategies to optimize future health management for this population, including expanding programs to address social determinants of health and mitigating barriers to accessing treatment. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. Roach, Graf, Pednekar, and Chou are employees of PRECISIONheor, which received financial support from Janssen Scientific Affairs, LLC, to conduct this study. Chou owns equity in Precision Medicine Group, the parent company of PRECISIONheor. Lin and Benson are employees of Janssen Scientific Affairs, LLC. Doshi has served as a consultant, advisory board member, or both, for Acadia, Allergan, Boehringer Ingelheim, Janssen, Merck, Otsuka, and Sage Therapeutics and has received research funding from AbbVie, Biogen, Humana, Janssen, Novartis, Merck, Pfizer, PhRMA, Regeneron, Sanofi, and Valeant.

The value of survival gains from therapeutic innovations for US patients with relapsed/refractory multiple myeloma.

AIMS: This study quantifies the value of survival gains attributable to novel treatments approved since 2003 for United States (US) patients with relapsed/refractory multiple myeloma (RRMM). METHODS: We estimated the increase in survival attributable to lenalidomide and bortezomib for multiple myeloma (MM) patients in the 1983-2013 Surveillance, Epidemiology, and End Results (SEER) registry. To estimate the survival benefit of treatments approved since 2015 (carfilzomib, elotuzomab, daratumumab, used in combination with lenalidomide and dexamethasone) we used clinical trial data to calibrate survival estimated using the SEER data. We then conducted an economic valuation of the estimated shift in survival curves for all therapies. Finally, we estimated the share of the value accruing to patients and manufacturers using treatment costs estimated from MarketScan data. RESULTS: The introduction of bortezomib in combination with dexamethasone (Vd) and lenalidomide in combination with dexamethasone (Rd) resulted in substantial survival gains and societal value for multiple myeloma patients, generating 1.7 additional life-years per RRMM patient. More recently, approved novel treatments have improved survival over effective treatments (i.e. Rd/Vd) by an additional 2.5 life-years - the monetary value of this incremental survival benefit far exceeds the incremental cost of treatment. At the patient level, the incremental benefit of Rd/Vd is $335,500 and with novel treatments is $565,000. Applying this benefit to all future cohorts of US RRMM patients translates into a value of at least $75 billion and $130 billion with Rd/Vd and the novel treatments, respectively. CONCLUSIONS: SEER registry data were only available through 2013. Therefore, survival gains for recently approved treatments were estimated based on clinical trials, rather than observed survival. Our valuation analysis does not capture sources of value aside from survival gains, for example, better quality of life, increased productivity, or the value of surviving until subsequent novel therapies become available. Substantial extensions in life expectancy in RRMM since 2003 translate into real economic value gained by society.

Challenges and opportunities in insomnia disorder.

BACKGROUND: Insomnia disorder is a prevalent, often unrecognized condition that affects millions. This clinical disorder is characterized by difficulty initiating or maintaining sleep over a sustained period. In fact, insomnia disorder affects much more than sleep; it increases the risk of developing serious medical and psychiatric comorbidities and can exacerbate existing conditions. The association between insomnia disorder and serious medical and psychiatric comorbidities are complex and directionality is not yet fully understood. There remain gaps in the treatment landscape for insomnia disorder. METHODS: We performed a narrative review of the published literature to identify challenges, unmet needs, and burden associated with insomnia disorder. RESULTS: In this article, we describe the substantial burden that insomnia disorder poses on patients, the healthcare system, and society in the US. This article explores the factors attributable to this burden including limited provider knowledge, inadequate treatment options, and unknown long-term impacts of off-label treatments. CONCLUSIONS: Several recommendations are proposed to address these challenges and improve patient outcomes through efforts to: (1) establish the societal value of treatment; (2) improve the clinical understanding of insomnia disorder; and (3) prioritize development of and access to effective treatments that do not pose addiction potential or tolerability issues.

Evolution and Regulation of Limb Regeneration in Arthropods.

Regeneration has fascinated both scientists and non-scientists for centuries. Many organisms can regenerate, and arthropod limbs are no exception although their ability to regenerate is a product shaped by natural and sexual selection. Recent studies have begun to uncover cellular and molecular processes underlying limb regeneration in several arthropod species. Here we argue that an evo-devo approach to the study of arthropod limb regeneration is needed to understand aspects of limb regeneration that are conserved and divergent. In particular, we argue that limbs of different species are comprised of cells at distinct stages of differentiation at the time of limb loss and therefore provide insights into regeneration involving both stem cell-like cells/precursor cells and differentiated cells. In addition, we review recent studies that demonstrate how limb regeneration impacts the development of the whole organism and argue that studies on the link between local tissue damage and the rest of the body should provide insights into the integrative nature of development. Molecular studies on limb regeneration are only beginning to take off, but comparative studies on the mechanisms of limb regeneration across various taxa should not only yield interesting insights into development but also answer how this remarkable ability evolved across arthropods and beyond.

Roles of Polycomb group proteins Enhancer of zeste (E(z)) and Polycomb (Pc) during metamorphosis and larval leg regeneration in the flour beetle Tribolium castaneum.

Many organisms both undergo dramatic morphological changes during post-embryonic development and also regenerate lost structures, but the roles of epigenetic regulators in such processes are only beginning to be understood. In the present study, the functions of two histone modifiers were examined during metamorphosis and larval limb regeneration in the red flour beetle Tribolium castaneum. Polycomb (Pc), a member of Polycomb repressive complex 1 (PRC1), and Enhancer of zeste (E(z)), a member of Polycomb repressive complex 2 (PRC2), were silenced in larvae using RNA interference. In the absence of Pc, the head appendages of adults transformed into a leg-like morphology, and the legs and wings assumed a metathoracic identity, indicating that Pc acts to specify proper segmental identity. Similarly, silencing of E(z) led to homeotic transformation of legs and wings. Additional defects were also observed in limb patterning as well as eye morphogenesis, indicating that PcG proteins play critical roles in imaginal precursor cells. In addition, larval legs and antennae failed to re-differentiate when either Pc or E(z) was knocked down, indicating that histone modification is necessary for proper blastema growth and differentiation. These findings indicate that PcG proteins play extensive roles in postembryonic plasticity of imaginal precursor cells.

Short-term budget affordability of hepatitis C treatments for state Medicaid programs.

BACKGROUND: With some Medicaid state programs still restricting patient access to hepatitis C (HCV) treatment, it is important to demonstrate how states could expand treatment access to a broader Medicaid population and balance short-term budget concerns. METHODS: We used the HCV Transmission and Progression (TaP) Markov model to quantify the impact of removing restrictions to HCV treatment access on the infected populations, expenditures, and net social value for the North Carolina (NC), Oregon (OR), and Wisconsin (WI) Medicaid programs. Four HCV treatment access scenarios were modeled: 1) Baseline: Patients were treated according to Medicaid disease severity and sobriety requirements in 2015; 2) Remove Sobriety Restrictions: Disease severity restrictions were maintained, but people who inject drugs (PWID) were given access to treatment; 3) Treat Early: All patients, except for PWIDs, regardless of disease severity, were eligible for treatment and the diagnosis rate increased from 50 to 66%; and 4) Remove Access Restrictions: all patients, regardless of disease severity and sobriety, were eligible for treatment. Our key model outputs were: number of infected Medicaid beneficiaries, HCV-related medical and treatment expenditures, total social value, and state Medicaid spending over 10 years. RESULTS: Across all three states, removing access restrictions resulted in the greatest benefits over 10 years (net social value relative to baseline = $408 M in NC; $408 M in OR; $271 M in WI) and the smallest infected population (5200 in NC; 2000 in OR; 614 in WI). Reduced disease transmission resulted in lower health care expenditures (-$66 M in NC; -$50 M in OR; -$54 M in WI). All of the expanded treatment access policies achieved break-even costs-where total treatment and health care expenditures fell below those of Baseline-in 4 to 8 years. Removing access restrictions yielded the greatest improvement in social value (net of medical expenditures and treatment costs, QALYs valued at $150 K per QALY). CONCLUSIONS: While increasing treatment access in Medicaid will raise short-term costs, it will also provide clear benefits relatively quickly by saving money and improving health within a 10-year window. Patients and taxpayers would benefit by considering these gains and taking a more expansive and long-term view of HCV treatment policies.

Understanding and improving value frameworks with real-world patient outcomes.

OBJECTIVES: To provide recommendations that will improve approaches to measuring the value of new medical technologies to patients. STUDY DESIGN: Informed discussion by experts after literature review. METHODS: A working group was formed, and participants discussed how value frameworks should incorporate key features important to patients in evaluating new medical technologies, particularly for chronic diseases. RESULTS: The working group suggests that new value frameworks should integrate real-world evidence to complement randomized controlled trials, incorporate the ways in which real-world behavior mediates outcomes, and explicitly discuss how therapies affect real-world equity and disparities in care. CONCLUSIONS: Collective stakeholders that include key decision makers within our healthcare system need to recognize the importance of implementing real-world evidence and devote resources to further research into the chronic disease areas in which the impact of human behavior is amplified by the duration of disease and treatment.

Unintended consequences of the potential phase-out of gamma irradiation.

The radioisotope cobalt-60 (Co-60) is important for commercial, medical, and agricultural applications. Its widespread use has meant that Co-60 can be found in less secured facilities, leading to the fear that unauthorized persons could obtain and use it to produce a "dirty bomb". This potential security concern has led to government calls for phasing-out Co-60 and other radiation sources, despite ongoing safety and security regulations for handling, transport and use of radioactive sealed sources. This paper explores potential implications of phasing out radioisotopic technologies, including unintended safety and cost consequences for healthcare and food in the US and globally. The use of Co-60 for healthcare and agricultural applications is well-documented. Co-60 is used to sterilize single-use medical devices, tissue allografts, and a range of consumer products. Co-60 is used in Gamma Knife treatment of brain tumors in over 70,000 patients annually. Co-60 is also used to preserve food and kill insects and pathogens that cause food-borne illness. Co-60 is effective, reliable, and predictable. Limitations of alternative sterilization technologies include complex equipment, toxicities, incompatibilities with plastic, and physical hazards. Alternative ionizing radiation sources for wide-reaching applications, including e-beam and x-ray radiation, have advantages and drawbacks related to commercial scale capacity, penetrability, complexity and reliability. Identifying acceptable alternatives would require time, costs and lengthy regulatory review. FDA testing requirements and other hurdles would delay replacement of existing technologies and slow medical innovation, even delaying access to life-saving therapies.  A phase-out would raise manufacturing costs, and reduce supply-chain efficiencies, potentially increasing consumer prices, and reducing supply. These consequences are poorly understood and merit additional research. Given Co-60's importance across medical and non-medical fields, restrictions on Co-60 warrant careful consideration and evaluation before adoption.

The effect of medication nonadherence on progression-free survival among patients with renal cell carcinoma.

OBJECTIVE: To examine how observed medication nonadherence to 2 second-line, oral anticancer medications (axitinib and everolimus) affects progression-free survival (PFS) among patients with renal cell carcinoma. METHODS: We used an adherence-exposure-outcome model to simulate the impact of adherence on PFS. Using a pharmacokinetic/pharmacodynamic (PK/PD) population model, we simulated drug exposure measured by area under the plasma concentration-time curve (AUC) and minimum blood or trough concentration (Cmin) under 2 scenarios: 1) optimal adherence and 2) real-world adherence. Real-world adherence was measured using the medication possession ratios as calculated from health insurance claims data. A population PK/PD model was simulated on individuals drawn from the Medical Expenditure Panel Survey (MEPS), a large survey broadly representative of the US population. Finally, we used previously published PK/PD models to estimate the effect of drug exposure (i.e., Cmin and AUC) on PFS outcomes under optimal and real-world adherence scenarios. RESULTS: Average adherence measured using medication possession ratios was 76%. After applying our simulation model to 2164 individuals in MEPS, drug exposure was significantly higher among adherent patients compared with nonadherent patients for axitinib (AUC: 249.5 vs. 159.8 ng×h/mL, P<0.001) and everolimus (AUC: 185.4 vs. 118.0 µg×h/L, P<0.001). Patient nonadherence in the real world decreased the expected PFS from an optimally adherent population by 29% for axitinib (8.4 months with optimal adherence vs. 6.0 months using real-world adherence, P<0.001) and by 5% (5.5 vs. 5.2 months, P<0.001) for everolimus. CONCLUSION: Nonadherence by renal cell carcinoma patients to second-line oral therapies significantly decreased the expected PFS.

The role of imperfect surrogate endpoint information in drug approval and reimbursement decisions.

Approval of new drugs is increasingly reliant on "surrogate endpoints," which correlate with but imperfectly predict clinical benefits. Proponents argue surrogate endpoints allow for faster approval, but critics charge they provide inadequate evidence. We develop an economic framework that addresses the value of improvement in the predictive power, or "quality," of surrogate endpoints, and clarifies how quality can influence decisions by regulators, payers, and manufacturers. For example, the framework shows how lower-quality surrogates lead to greater misalignment of incentives between payers and regulators, resulting in more drugs that are approved for use but not covered by payers. Efficient price-negotiation in the marketplace can help align payer incentives for granting access based on surrogates. Higher-quality surrogates increase manufacturer profits and social surplus from early access to new drugs. Since the return on better quality is shared between manufacturers and payers, private incentives to invest in higher-quality surrogates are inefficiently low.

Hospital Readmission Rates Among Patients With Schizophrenia Treated With Long-Acting Injectables or Oral Antipsychotics.

OBJECTIVE: This study analyzed hospital readmission rates of patients with schizophrenia who were treated with long-acting injectable antipsychotics (LAIs) or with oral antipsychotics after being discharged from a hospitalization. METHODS: Medical claims of patients with schizophrenia who were ages 18-64 and had a first hospitalization for a serious mental illness (index hospitalization, October 2007 through September 2012) and at least one prescription for a first- or second-generation antipsychotic were analyzed from the Truven Health MarketScan Multi-State Medicaid Database. Analyses were conducted for patients with a sole diagnosis of schizophrenia (N=1,450) and for all patients with schizophrenia (N=15,556), which added patients with a codiagnosis of bipolar disorder or major depressive disorder. Probability of rehospitalization for any cause at 30 and 60 days after the initial hospitalization was assessed with multivariate logistic regression and propensity score matching (PSM) methods. The PSM model matched age, preindex use of LAIs or short-acting injectables, and select comorbidities between the LAI and the oral antipsychotics groups. RESULTS: LAIs were associated with significantly lower probability of rehospitalization compared with oral antipsychotics at 60 days for schizophrenia-only patients (adjusted odds ratio [AOR]=.60, 95% confidence interval [CI]=.41-.90) and for all patients (AOR=.70, CI=.52-.95). The absolute difference in probability of rehospitalization for all patients was significantly lower by 5.0% at 60 days in the LAI group compared with the oral antipsychotics group. CONCLUSIONS: Compared with use of oral antipsychotics, use of LAIs was associated with fewer readmissions of Medicaid patients with schizophrenia within 60 days after an index hospitalization.

Value of improved lipid control in patients at high risk for adverse cardiac events.

OBJECTIVES: Lipid-lowering therapy (LLT) is suboptimally used in patients with hyperlipidemia in the 2 highest statin benefit groups (SBGs), as categorized by the American College of Cardiology and the American Heart Association. This study estimated the social value of reducing low-density lipoprotein cholesterol (LDL-C) levels by 50% for patients in SBGs 1 and 2 who have been treated with standard LLT but have not reached LDL-C goal, as well as the potential value of PCSK9 inhibitors for patients in these groups. STUDY DESIGN: Simulation model. METHODS: We used National Health and Nutrition Examination Surveys (NHANES) and US Census data to project the population of SBGs 1 and 2 in the time period 2015 to 2035. We used insurance claims data to estimate incidence rates of major adverse cardiac events (MACEs), and NHANES with National Vital Statistics data to estimate cardiovascular disease mortality rates. Using established associations between LDL-C and MACE risk, we estimated the value of reducing LDL-C levels by 50%. We incorporated results from a meta-analysis to estimate the value of PSCK9 inhibitors. RESULTS: Among those treated with LLT with LDL-C > 70 mg/dL in SBGs 1 and 2, the cumulative value of reducing LDL-C levels by 50% would be $2.9 trillion from 2015 to 2035, resulting primarily from 1.6 million deaths averted. The cumulative value of PCSK9 inhibitors would range from $3.4 trillion to $5.1 trillion (1.9-2.8 million deaths averted), or $12,000 to $17,000 per patient-year of treatment. CONCLUSIONS: Lowering LDL-C in high-risk patients with hyperlipidemia has enormous potential social value. For patients in these high-risk groups, PCSK9 inhibitors may have considerable net value depending on the final prices payers ultimately select.

Broad Hepatitis C Treatment Scenarios Return Substantial Health Gains, But Capacity Is A Concern.

Treatment of hepatitis C virus, the most common chronic viral infection in the United States, has historically suffered from challenges including serious side effects, low efficacy, and ongoing transmission and reinfection. Recent innovations have produced breakthrough therapies that are effective in more than 90 percent of patients. These treatments could dramatically reduce the virus's prevalence but are costly. To quantify the benefit of these treatments to society, including the value of reduced transmission, we estimated the effects of several hepatitis C treatment strategies on cost and population health. Treating patients at all disease stages could generate $610-$1,221 billion in additional quality-adjusted life-years, plus an additional $139 billion in saved medical expenditures over fifty years, and minimize the disease burden, but up-front treatment costs would exceed $150 billion. An intermediate scenario--treating 5 percent of the infected population annually, regardless of patients' disease stages--would also return substantial benefits and would be much more affordable under current financing schemes.