Using Real-World Data to Inform Value-Based Contracts for Cell and Gene Therapies in Medicaid.

OBJECTIVE: High upfront costs and long-term benefit uncertainties of gene therapies challenge Medicaid budgets, making value-based contracts a potential solution. However, value-based contract design is hindered by cost-offset uncertainty. The aim of this study is to determine actual cost-offsets for valoctocogene roxaparvovec (hemophilia A) and etranacogene dezaparvovec (hemophilia B) from Colorado Medicaid's perspective, defining payback periods and its uncertainty from the perspective of Colorado Medicaid. METHODS: This cost analysis used 2018-2022 data from the Colorado Department of Health Care Policy & Financing to determine standard-of-care costs and employed cost simulation models to estimate the cost of Medicaid if patients switched to gene therapy versus if they did not. Data encompassed medical and pharmacy expenses of Colorado Medicaid enrollees. Identified cohorts were patients aged 18+ with ICD-10-CM codes D66 (hemophilia A) and D67 (hemophilia B). Severe hemophilia A required ≥ 6 claims per year for factor therapies or emicizumab, while moderate/severe hemophilia B necessitated ≥ 4 claims per year for factor therapies. Patients were included in the cohort in the year they first met the criteria and were subsequently retained in the cohort for the duration of the observation period. Standard-of-care included factor VIII replacement therapy/emicizumab for hemophilia A and factor IX replacement therapies for hemophilia B. Simulated patients received valoctocogene roxaparvovec or etranacogene dezaparvovec. Main measures were annual standard-of-care costs, cost offset, and breakeven time when using gene therapies. RESULTS: Colorado Medicaid's standard-of-care costs for hemophilia A and B were $426,000 [standard deviation (SD) $353,000] and $546,000 (SD $542,000) annually, respectively. Substituting standard-of-care with gene therapy for eligible patients yielded 8-year and 6-year average breakeven times, using real-world costs, compared with 5 years with published economic evaluation costs. Substantial variability in real-world standard-of-care costs resulted in a 48% and 59% probability of breakeven within 10 years for hemophilia A and B, respectively. Altering eligibility criteria significantly influenced breakeven time. CONCLUSIONS: Real-world data indicates substantial uncertainty and extended payback periods for gene therapy costs. Utilizing real-world data, Medicaid can negotiate value-based contracts to manage budget fluctuations, share risk with manufacturers, and enhance patient access to innovative treatments.

Association between Substance Misuse and Outcomes in Critically III Patients with Pneumonia.

Rationale: In patients with pneumonia requiring intensive care unit (ICU) admission, alcohol misuse is associated with increased mortality, but the relationship between other commonly misused substances and mortality is unknown. Objectives: We sought to establish whether alcohol misuse, cannabis misuse, opioid misuse, stimulant misuse, or misuse of more than one of these substances was associated with differences in mortality among ICU patients with pneumonia. Methods: This was a retrospective cohort study of hospitals participating in the Premier Healthcare Database between 2010 and 2017. Patients were included if they had a primary or secondary diagnosis of pneumonia and received antibiotics or antivirals within 1 day of admission. Substance misuse related to alcohol, cannabis, stimulants, and opioids, or more than one substance, were identified from the International Classification of Diseases (Ninth and Tenth Editions). The associations between substance misuse and in-hospital mortality were the primary outcomes of interest. Secondary outcomes included the measured associations between substance misuse disorders and mechanical ventilation, as well as vasopressor and continuous paralytic administration. Analyses were conducted with multivariable mixed-effects logistic regression modeling adjusting for age, comorbidities, and hospital characteristics. Results: A total of 167,095 ICU patients met inclusion criteria for pneumonia. Misuse of alcohol was present in 5.0%, cannabis misuse in 0.6%, opioid misuse in 1.5%, stimulant misuse in 0.6%, and misuse of more than one substance in 1.2%. No evidence of substance misuse was found in 91.1% of patients. In unadjusted analyses, alcohol misuse was associated with increased in-hospital mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.19), whereas opioid misuse was associated with decreased in-hospital mortality (OR, 0.46; 95% CI, 0.39-0.53) compared with no substance misuse. These findings persisted in adjusted analyses. Although cannabis, stimulant, and more than one substance misuse (a majority of which were alcohol in combination with another substance) were associated with lower odds for in-hospital mortality in unadjusted analyses, these relationships were not consistently present after adjustment. Conclusions: In this study of ICU patients hospitalized with severe pneumonia, substance misuse subtypes were associated with different effects on mortality. Although administrative data can provide epidemiologic insight regarding substance misuse and pneumonia outcomes, biases inherent to these data should be considered when interpreting results.

Evaluation of safety and efficacy outcomes of direct oral anticoagulants versus warfarin in normal and extreme body weights for the treatment of atrial fibrillation or venous thromboembolism.

Despite evolving evidence, the use of direct oral anticoagulants (DOACs) in patients with extremes of body weight remains controversial. This study aimed to measure the impact of DOACs compared to warfarin on safety and efficacy outcomes in extreme body weight patients. This multi-center, health system, retrospective study examined the outcomes of patients with all body weights and extreme body weights prescribed a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban) or warfarin for atrial fibrillation or venous thromboembolism over a 9-year period. The primary outcome was a composite of thromboembolism, symptomatic recurrent VTE, or severe bleeding; analyzed by pre-determined BMI cutoffs. A total of 19,697 patients were included in the study: 11,604 in the DOAC group and in the 8093 in the warfarin group. 295 patients were underweight and 9108 patients were pre-obese to obese class 3. After adjusting for potential confounders, warfarin patients had higher odds of experiencing the composite outcome compared to DOAC patients (OR 1.337, 95% CI 1.212-1.475). Additionally, obese patients were 24.6% more likely to experience the outcome compared to normal BMI patients. Adjusted modeling showed that warfarin patients experienced higher bleed rates compared to DOAC patients (OR 1.432, 95% CI 1.266-1.620). Obese patients were less likely to be diagnosed with a bleed (OR 0.749, 95% CI 0.658-0.854), and underweight patients were more likely to be diagnosed with a bleed (OR 1.522, 95% CI 1.095-2.115) compared to normal BMI patients. In conclusion, DOACs for atrial fibrillation or VTE in patients with extreme body weights appear safe and effective when compared to warfarin.

Association Between Vasopressin Rebranding and Utilization in Patients With Septic Shock.

OBJECTIVES: Vasopressin is suggested as an adjunct to norepinephrine in patients with septic shock. However, after vasopressin was rebranded in November 2014, its cost exponentially increased. Utilization patterns of vasopressin after its rebranding are unclear. The objective of this study was to determine if there is an association between the rebranding of vasopressin in November 2014 and its utilization in vasopressor-dependent patients with severe sepsis or septic shock. DESIGN: Retrospective, multicenter, database study between January 2010 and March 2017. SETTING: Premier Healthcare Database hospitals. PATIENTS: Adult patients admitted to an ICU with severe sepsis or septic shock, who received at least one vasoactive agent for two or more calendar days were included. INTERVENTIONS: The proportion of patients who received vasopressin and vasopressin cost was assessed before and after rebranding, and evaluated with segmented regression. MEASUREMENTS AND MAIN RESULTS: Among 294,733 patients (mean age, 66 ± 15 yr), 27.8% received vasopressin, and ICU mortality was 26.5%. The proportion of patients receiving vasopressin was higher after rebranding (31.2% postrebranding vs 25.8% prerebranding). Before vasopressin rebranding, the quarterly proportion of patients who received vasopressin had an increasing slope (prerebranding slope 0.41% [95% CI, 0.35-0.46%]), with no difference in slope detected after vasopressin rebranding (postrebranding slope, 0.47% [95% CI, 0.29-0.64%]). After vasopressin rebranding, mean vasopressin cost per patient was higher ($527 ± 1,130 vs $77 ± 160), and the quarterly slope of vasopressin cost was higher (change in slope $77.18 [95% CI, $75.73-78.61]). Total vasopressin billed cost postrebranding continually increased by ~$294,276 per quarter from less than $500,000 in Q4 2014 to over $3,000,000 in Q1 2017. CONCLUSIONS: After vasopressin rebranding, utilization continued to increase quarterly despite a significant increase in vasopressin cost. Vasopressin appeared to have price inelastic demand in septic shock.

Comparison of two different intravenous serotonin antagonists used for chemotherapy-induced nausea and vomiting prophylaxis in patients treated with moderately emetogenic risk regimens: A retrospective analysis from a large academic medical center.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) can be a serious and debilitating adverse effect that is highly feared by cancer patients. For patients receiving moderately emetogenic chemotherapy regimens at our institution in the ambulatory infusion center, palonosetron was selected as the preferred serotonin (5-HT3) antagonist for CINV prophylaxis per the 2016 NCCN Guidelines, when a neurokinin1 antagonist was not included in the prophylactic regimen. The purpose of this study was to evaluate the efficacy of dexamethasone and palonosetron versus granisetron for the prevention of CINV in patients receiving moderately emetogenic chemotherapy regimens. METHODS: This study is an Institutional Review Board-approved, single-center retrospective review of electronic health records including patients who received moderately emetogenic chemotherapy regimens with CINV prophylaxis with dexamethasone and either palonosetron or granisetron. RESULTS: A total of 268 eligible patients were included in the study. Eighty-eight patients received palonosetron and 180 patients received granisetron as their 5-HT3 receptor antagonist between October 31, 2014 and October 31, 2016. There were no statistically significant differences between the two antiemetic groups for the primary outcome of presence of any change in day 1 intravenous prophylactic antiemetics. Nine (10.23%) palonosetron patients and 15 (8.33%) granisetron patients required a change in their day 1 intravenous prophylactic antiemetics (P = 0.610). CONCLUSIONS: Despite palonosetron's better efficacy, longer half-life, and higher binding affinity, the results of this retrospective review demonstrates that the choice of serotonin antagonist, palonosetron or granisetron, did not result in a change in day 1 intravenous prophylactic antiemetics or antiemetic outpatient medications for patients undergoing moderately emetogenic chemotherapy regimens.

Evaluation of Prophylactic Heparin Dosage Strategies and Risk Factors for Venous Thromboembolism in the Critically Ill Patient.

BACKGROUND: Venous thromboembolism (VTE) occurs frequently in critically ill patients without heparin prophylaxis. Although heparin prevents VTE, VTEs occur frequently despite prophylaxis. A higher heparin dosage may be more effective for preventing VTE. METHODS: A retrospective study was conducted using the Premier Incorporated Perspective Database to evaluate comparatively the effects of different heparin prophylaxis dosing strategies in the critically ill patient. Critically ill adult patients who were mechanically ventilated for at least 1 day and had an intensive care unit (ICU) length of stay of at least 2 days were included. Patients received 5000 units of heparin either twice/day or 3 times/day. The primary outcome was development of a new VTE. Key secondary outcomes included clinically important bleeding, thrombocytopenia, and mortality. Patients were propensity matched to control for confounding. Multivariable analysis was conducted for VTE risk factors. RESULTS: The study included 30,800 patients from 374 hospitals who were propensity matched by heparin dosage. New VTE occurred in 6.16% of patients treated with 3 times/day heparin versus 6.23% with twice/day heparin (p=0.8). No significant differences in the incidence of pulmonary embolism (0.91% vs 0.8%, p=0.29) or deep vein thrombosis (5.56% vs 5.70% p=0.59) were observed between the two types of heparin dosing. No differences were observed between the two types of heparin dosing in in-hospital mortality (15.8% vs 15.15%), bleeding (0.23% vs 0.33%), or thrombocytopenia (5.19% vs 5.34%, p>0.08 for all), respectively. Risk factors associated with VTE included intraabdominal and urinary tract infections, loop diuretics, malnutrition, obesity, thrombocytopenia, paralytics, vasopressors, female sex, peripheral vascular disease, sepsis, neutropenia, and end-stage renal disease. Antiplatelet therapy, heart failure, diabetes, and substance abuse were associated with reduced VTE (p<0.05 for all). CONCLUSIONS: In critically ill patients, prophylactic dosing of heparin 3 times/day versus twice/day was not associated with differences in new VTE or safety outcomes. Several modifiable VTE risk factors were identified.

Retrospective review of the use of as-needed hydralazine and labetalol for the treatment of acute hypertension in hospitalized medicine patients.

BACKGROUND: The aim of this study was to evaluate the use of as-needed (PRN) labetalol and hydralazine [intravenous (IV) or oral] in hospitalized medicine patients for the treatment of severe asymptomatic hypertension and to examine the potential negative outcomes associated with their use. METHODS: The electronic health record of 250 medicine patients hospitalized at the University of Colorado Hospital between November 2014 and April 2016 who received at least one dose of PRN IV or oral hydralazine or labetalol were retrospectively reviewed. The primary outcome was to describe the use of PRN antihypertensive medications in this population. RESULTS: A total of 573 PRN doses of antihypertensive medication were administered. Oral hydralazine was the most common (521 doses, 90.9%). A total of 36% of PRN administrations were given for a systolic blood pressure (SBP) <180 mmHg and diastolic blood pressure (DBP) <110 mmHg (cut-point for acute severe hypertension). No serious adverse events were related to PRN antihypertensive administration. Despite receiving at least one PRN antihypertensive medication during hospitalization, 40.8% of patients were not continued on their home antihypertensive medication(s) while hospitalized, and 62.4% of patients did not have their home regimens intensified at discharge. CONCLUSION: As-needed oral hydralazine is frequently prescribed for acute blood pressure lowering with administration thresholds often less than what are used to define acute severe hypertension. Many patients are prescribed PRN antihypertensive medication instead of being continued on their home regimens, and most patients do not have the intensity of their home regimens increased. Providers need to be educated about the use of PRN antihypertensive medication for the management of severe asymptomatic hypertension in the hospital setting.