Effectiveness of Sotrovimab in Preventing COVID-19-Related Hospitalizations or Deaths Among US Veterans During Omicron BA.1.

Background: The real-world clinical effectiveness of sotrovimab in preventing coronavirus disease 2019 (COVID-19)-related hospitalization or mortality among high-risk patients diagnosed with COVID-19, particularly after the emergence of the Omicron variant, needs further research. Method: Using data from the US Department of Veterans Affairs (VA) health care system, we adopted a target trial emulation design in our study. Veterans aged ≥18 years, diagnosed with COVID-19 between December 1, 2021, and April 4, 2022, were included. Patients treated with sotrovimab (n = 2816) as part of routine clinical care were compared with all eligible but untreated patients (n = 11,250). Cox proportional hazards modeling estimated the hazard ratios (HRs) and 95% CIs for the association between receipt of sotrovimab and outcomes. Results: Most (90%) sotrovimab recipients were ≥50 years old, and 64% had ≥2 mRNA vaccine doses or ≥1 dose of Ad26.COV2. During the period that BA.1 was dominant, compared with patients not treated, sotrovimab-treated patients had a 70% lower risk of hospitalization or mortality within 30 days (HR, 0.30; 95% CI, 0.23-0.40). During BA.2 dominance, sotrovimab-treated patients had a 71% (HR, 0.29; 95% CI, 0.08-0.98) lower risk of 30-day COVID-19-related hospitalization, emergency room visits, or urgent care visits (defined as severe COVID-19) compared with patients not treated. Conclusions: Using national real-world data from high-risk and predominantly vaccinated veterans, administration of sotrovimab, compared with contemporary standard treatment regimens, was associated with reduced risk of 30-day COVID-19-related hospitalization or all-cause mortality during the Omicron BA.1 period.

Assessing the potential cost-effectiveness of centralised versus point-of-care testing for hepatitis C virus in Pakistan: a model-based comparison.

OBJECTIVES: Pakistan has a hepatitis C virus (HCV) infection prevalence of 6%-9% and aims to achieve World Health Organisation (WHO) targets for elimination of HCV by the year 2030. We aim to evaluate the potential cost-effectiveness of a reference laboratory-based (centralised laboratory testing; CEN) confirmatory testing approach versus a molecular near-patient point-of-care (POC) confirmatory approach to screen the general population for HCV in Pakistan. STUDY DESIGN: We used a decision tree-analytic model from a governmental (formal healthcare sector) perspective. STUDY SETTING: Individuals were assumed to be initially screened with an anti-HCV test at home, followed by POC nucleic acid test (NAT) at nearby district hospitals or followed by NAT at centralised laboratories. PARTICIPANTS: We included the general testing population for chronic HCV in Pakistan. INTERVENTION: Screening with an anti-HCV antibody test (Anti-HCV) followed by either POC NAT (Anti-HCV-POC), or reference laboratory NAT (Anti-HCV-CEN), was compared, using data from published literature and the Pakistan Ministry of Health. MEASURES: Outcome measures included: number of HCV infections identified per year, percentage of individuals correctly classified, total costs, average costs per individual tested, and cost-effectiveness (assessed as cost per additional HCV infection identified). Sensitivity analysis was also performed. RESULTS: At a national level (25 million annual screening tests), the Anti-HCV-CEN strategy would identify 142 406 more HCV infections in 1 year and increase correct classification of individuals by 0.57% compared with the Anti-HCV-POC strategy. The total annual cost of HCV testing was reduced using the Anti-HCV-CEN strategy by US$7.68 million (US$0.31/person). Thus, incrementally, the Anti-HCV-CEN strategy costs less and identifies more HCV infections than Anti-HCV-POC. The incremental difference in HCV infections identified was most sensitive to the probability of loss to follow-up (for POC confirmatory NAT). CONCLUSIONS: Anti-HCV-CEN would provide the best value for money when scaling up HCV testing in Pakistan.

Real-World Effectiveness of Sotrovimab for the Early Treatment of COVID-19 During SARS-CoV-2 Delta and Omicron Waves in the USA.

INTRODUCTION: Sotrovimab, a recombinant human monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had US Food and Drug Administration Emergency Use Authorization for the treatment of high-risk outpatients with mild-to-moderate coronavirus disease 2019 (COVID-19) from 26 May 2021 to 5 April 2022. Real-world clinical effectiveness of sotrovimab in reducing the risk of 30-day all-cause hospitalization and/or mortality was evaluated for the period when the prevalence of circulating SARS-CoV-2 variants changed between Delta and Omicron in the USA. METHODS: A retrospective analysis was conducted of de-identified patients diagnosed with COVID-19 between 1 September 2021 to 30 April 2022 in the FAIR Health National Private Insurance Claims database. Patients meeting high-risk criteria were divided into two cohorts: sotrovimab and not treated with a mAb ("no mAb"). All-cause hospitalizations and facility-reported mortality ≤ 30 days of diagnosis ("30-day hospitalization or mortality") were identified. Multivariable and propensity score-matched Poisson and logistic regressions were conducted to estimate the adjusted relative risk (RR) and odds of 30-day hospitalization or mortality in each cohort. RESULTS: Compared with the no mAb cohort (n = 1,514,868), the sotrovimab cohort (n = 15,633) was older and had a higher proportion of patients with high-risk conditions. In the no mAb cohort, 84,307 (5.57%) patients were hospitalized and 8167 (0.54%) deaths were identified, while in the sotrovimab cohort, 418 (2.67%) patients were hospitalized and 13 (0.08%) deaths were identified. After adjusting for potential confounders, the sotrovimab cohort had a 55% lower risk of 30-day hospitalization or mortality (RR 0.45, 95% CI 0.41-0.49) and an 85% lower risk of 30-day mortality (RR 0.15, 95% CI 0.08-0.29). Monthly, from September 2021 to April 2022, the RR reduction for 30-day hospitalization or mortality in the sotrovimab cohort was maintained, ranging from 46% to 71% compared with the no mAb cohort; the RR estimate in April 2022 was uncertain, with wide confidence intervals due to the small sample size. CONCLUSION: Sotrovimab was associated with reduced risk of 30-day all-cause hospitalization and mortality versus no mAb treatment. Clinical effectiveness persisted during Delta and early Omicron variant waves and among all high-risk subgroups assessed.

Real-world HIV diagnostic testing patterns in the United States.

OBJECTIVES: To understand real-world implementation of the updated CDC HIV diagnostic testing algorithm. STUDY DESIGN: Retrospective database analysis. METHODS: Using data from Quest Diagnostics, we identified patients with at least 1 HIV-1/HIV-2 antibody differentiation test (BioRad Geenius HIV 1/2 Supplemental Assay [Geenius]) between January 1 and December 31, 2017. Study measures included Health Insurance Portability and Accountability Act-compliant patient demographics, test results, test frequency, and sequence relative to the CDC HIV diagnostic algorithm, including HIV-1 RNA Qualitative Assay (Aptima) or HIV-2 nucleic acid test (NAT). RESULTS: A total of 26,319 patients were identified (mean [SD] age, 40.7 [14.3] years; 66.4% male), with 28,954 Geenius tests, 7234 Aptima tests, and 298 HIV-2 NATs. In 26.4% of test sequences, the Geenius results were indeterminate or negative and required subsequent confirmatory NATs. A total of 8.5% of patients had more than 1 Geenius test in 2017, and 11.2% of the time, results of the first and second tests differed. A total of 74.2% of test sequences matched the CDC-recommended algorithm. CONCLUSIONS: Our study findings suggest that the CDC HIV diagnostic algorithm is complex and may pose suboptimal testing efficiency. Opportunities to improve diagnostic efficiency by reducing indeterminate results and repeat tests are warranted.

US cost-effectiveness and budget impact of point-of-care NAAT for streptococcus.

OBJECTIVES: In the United States, approximately 12 million individuals seek medical care for pharyngitis each year, accounting for about 2% of ambulatory care visits. Although the gold standard for diagnosing group A streptococcus (GAS) is culture, it is time intensive. Rapid antigen detection tests (RADT) with or without culture confirmation are commonly used instead. Although RADT provide results quickly, they generally have lower test sensitivity. Recently, point-of-care nucleic acid amplification tests (POC NAAT) have emerged. This study evaluates the cost-effectiveness and budget impact to the US payer of adopting POC NAAT. STUDY DESIGN: This study was a cost-effectiveness analysis, with costs and outcomes calculated via a decision tree. METHODS: A decision-tree model quantified costs and outcomes associated with a GAS diagnostic strategy using POC NAAT compared with RADT + culture confirmation. Model inputs were derived from the published literature. Model outputs included costs and clinical effects: quality-adjusted life-days lost, GAS and antibiotic complications, number of patients appropriately treated, and antibiotic utilization. Sensitivity and scenario analyses were performed. RESULTS: Base-case analysis projected that a POC NAAT strategy would cost $44 per patient compared with $78 for RADT + culture. Compared with RADT + culture, POC NAAT would increase the number of appropriately treated patients and avert unnecessary use of antibiotics. The budget impact of POC NAAT was -0.4% relative to current budget over 5 years. Findings were robust in sensitivity analyses. CONCLUSIONS: Our results suggest that POC NAAT would be less costly and more effective than RADT + culture; POC NAAT adoption may yield cost savings to US third-party payers. Access to POC NAAT is important to optimize GAS diagnosis and treatment decisions in the United States.

Estimated Impact of Public and Private Sector COVID-19 Diagnostics and Treatments on US Healthcare Resource Utilization.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has imposed a considerable burden on the United States (US) health system, with particular concern over healthcare capacity constraints. METHODS: We modeled the impact of public and private sector contributions to developing diagnostic testing and treatments on COVID-19-related healthcare resource use. RESULTS: We estimated that public sector contributions led to at least 30% reductions in COVID-19-related healthcare resource utilization. Private sector contributions to expanded diagnostic testing and treatments led to further reductions in mortality (- 44%), intensive care unit (ICU) and non-ICU hospital beds (- 30% and - 28%, respectively), and ventilator use (- 29%). The combination of lower diagnostic test sensitivity and proportions of patients self-isolating may exacerbate case numbers, and policies that encourage self-isolating should be considered. CONCLUSION: While mechanisms exist to facilitate research, development, and patient access to diagnostic testing, future policies should focus on ensuring equitable patient access to both diagnostic testing and treatments that, in turn, will alleviate COVID-19-related resource constraints.

The Clinical and Economic Impact of Inaccurate EGFR Mutation Tests in the Treatment of Metastatic Non-Small Cell Lung Cancer.

Advances in personalized medicine are supported by companion diagnostic molecular tests. Testing accuracy is critical for selecting patients for optimal therapy and reducing treatment-related toxicity. We assessed the clinical and economic impact of inaccurate test results between laboratory developed tests (LDTs) and a US Food and Drug Administration (FDA)-approved test for detection of epidermal growth factor receptor (EGFR) mutations. Using a hypothetical US cohort of newly diagnosed metastatic non-small cell lung cancer (NSCLC) patients and EURTAC (erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer) clinical trial data, we developed a decision analytic model to estimate the probability of misclassification with LDTs compared to a FDA-approved test. We estimated the clinical and economic impact of inaccurate test results by quantifying progression-free and quality-adjusted progression-free life years (PFLYs, QAPFLYs) lost, and costs due to incorrect treatment. The base-case analysis estimated 2.3% (n = 1422) of 60,502 newly diagnosed metastatic NSCLC patients would be misclassified with LDTs compared to 1% (n = 577) with a FDA-approved test. An average of 477 and 194 PFLYs were lost among the misclassified patients tested with LDTs compared to the FDA-approved test, respectively. Aggregate treatment costs for patients tested with LDTs were approximately $7.3 million more than with the FDA-approved test, due to higher drug and adverse event costs among patients incorrectly treated with targeted therapy or chemotherapy, respectively. Invalid tests contributed to greater probability of patient misclassification and incorrect therapy. In conclusion, risks associated with inaccurate EGFR mutation tests pose marked clinical and economic consequences to society. Utilization of molecular diagnostic tests with demonstrated accuracy could help to maximize the potential of personalized medicine.

A network meta-analysis of therapies for previously untreated chronic lymphocytic leukemia.

BACKGROUND: Several therapy options are available for symptomatic, treatment-naïve chronic lymphocytic leukemia (CLL). Many of these therapies have been compared against chlorambucil, but have not been directly compared against each other. There is currently no agreed upon standard therapeutic regimen for treatment-naïve CLL. METHODS: We performed a systematic literature review to identify randomized controlled trials (RCTs) published prior to November 2011 of therapies for previously untreated CLL. We conducted a network meta-analysis using fixed and random effect statistical models to estimate differences between shape and scale parameters of progression-free survival (PFS) curves for each competing therapy. We used the parameter estimates and a Weibull distribution to project mean PFS for each therapy option. RESULTS: Five RCTs were included in our comparison network. Overall, patients were younger (59-65 years), had good performance status based on the Eastern Cooperative Oncology Group scale (ECOG 0-1), and earlier stage disease (Rai 0-II or Binet A or B). The combination regimen fludarabine with cyclophosphamide and rituximab (FCR) was estimated to yield mean PFS of 76 months (95% CrI: 60, 91), FC 60 months (46, 73), fludarabine 38 months (27, 49), alemtuzumab 24 months (15, 32), and chlorambucil 23 months (15, 32). CONCLUSION: Our results suggest that FCR has relatively higher potential of preventing disease progression in younger, healthier, treatment-naïve CLL patients and should be considered an optimal initial treatment strategy for this patient population. However, because estimates are based on model simulation, additional studies of FCR are necessary to clinically validate its therapeutic potential.

Systematic review of comparative effectiveness data for oncology orphan drugs.

OBJECTIVES: To systematically assess clinical and economic evidence for oncology orphan drugs marketed in the United States and to highlight the challenges and opportunities for evidence development within this pharmaceutical category. STUDY DESIGN: Systematic review. METHODS: We conducted systematic literature searches of the Medline and Embase databases for clinical and cost-effectiveness studies published before June 2010 for all oncology orphan drugs marketed in the United States. We used the Grading of Recommendations Assessment, Development and Evaluation method and the Quality of Health Economic Studies criteria to assess the quality of the selected studies. RESULTS: We identified 60 randomized controlled trials and 21 cost-effectiveness analyses to support 47 oncology orphan drugs. A total of 21 drugs had moderate or high-quality bodies of clinical evidence, 11 had low-quality or very low quality clinical evidence, and 15 drugs could not be evaluated because we were unable to identify clinical evidence that met our inclusion criteria. The Spearman rank correlation coefficient for the level of evidence for oncology orphan drugs and disease prevalence was 0.3 (95% confidence interval, 0.0-0.5). The cost-effectiveness analyses received quality scores between 72 and 100 (range 0-100), with a mean score of 85. CONCLUSIONS: The results of our study show that oncology orphan drugs marketed in the United States have varying levels and quality of clinical evidence and a paucity of evidence regarding economic value. Innovative analytic and policy approaches are needed to develop and implement a decision-making framework for this pharmaceutical category that is consistent with evidence-based medicine and comparative effectiveness research.

The economic value of reducing medication dosing frequency with drug delivery technologies: an evidence assessment.

OBJECTIVE: To critically evaluate published cost-effectiveness studies of novel drug products requiring less-frequent medication dosing compared to conventional formulations of the same drug substance. METHODS: A search was conducted in the Medline and Embase databases for cost-effectiveness studies published before May 2009 that compared two or more drug delivery technologies formulated with the same active drug substance. The Quality of Health Economic Studies (QHES) grading criteria for cost-effectiveness studies was applied to the selected publications. RESULTS: The literature search identified approximately 907 articles of which six cost-effectiveness studies met the inclusion criteria. The studies spanned four chronic conditions, were conducted from various international perspectives and used decision-analytic models to project economic outcomes. The base-case results of all six studies indicated that the drug product with sustained therapeutic efficacy was either more effective and less costly ('dominant') or more cost effective than the conventional formulation of the same drug substance. Quality scores ranging from 70 to 84 (scale 0 to 100) were assigned to the studies, with a mean of 78. LIMITATIONS: This review likely did not capture all relevant drug delivery technologies and drug products. Only one reviewer critically evaluated the cost-effectiveness studies and independently assigned quality scores using the QHES grading criteria, which may be limited in its ability to identify poorly analyzed studies. CONCLUSION: Evaluation of the published literature suggests that drug products with less-frequent medication dosing can be cost effective when compared to conventional formulations, but assessments are challenging because of complex relationships among therapeutic drug levels, dosing frequency, medication adherence, and health outcomes. Additional product-specific, comparative, pragmatic studies in this area are needed.

Optimizing CAD diagnosis in China with CT angiography.

BACKGROUND: Diagnosis of coronary artery disease (CAD) in China with coronary angiography (CA) can be challenging because of high disease prevalence and limited resources. Coronary computed tomography angiography (CTA) may provide an opportunity to minimize invasive diagnostic procedures among intermediate-risk patients indicated for CA and increase patient access to diagnosis of CAD in a cost-effective manner. OBJECTIVE: This study was conducted to evaluate the potential costs and efficiency of using CTA in combination with CA to optimize diagnosis and care of patients with suspected CAD in China. METHODS: We conducted a cost-consequences analysis from the perspective of Fuwai Hospital in Beijing. We developed a decision-analytic model that compared a diagnostic strategy of CA only with a strategy of CTA in combination with CA for patients with intermediate pretest probability of significant CAD and indicated for CA. RESULTS: In the base-case analysis, use of CTA in combination with CA led to a cost-savings of US $597 per patient evaluated compared with the CA-only diagnostic strategy. The hospital cost per angiography-confirmed diagnosis of CAD was US $8,103 for CTA followed by CA compared with US $9,148 for CA only. The unit cost of CA, and CTA sensitivity were the most influential parameters on the results. The range of cost savings associated with use of CTA followed by CA was US $768 - US $461 per patient over a CAD prevalence range of 14% - 59%. CONCLUSION: The results of our study suggest that CTA implementation in China for intermediate-risk patients indicated for CA may optimize the patient population that undergoes invasive CA procedures and may provide cost savings for Chinese hospitals.