Integrating breast cancer polygenic risk scores at scale in the WISDOM Study: a national randomized personalized screening trial.

Background: The Women Informed to Screen Depending On Measures of risk (WISDOM) Study is the first prospective, population-wide application of personalized breast cancer screening. We aim to demonstrate the feasibility of the study's novel use of polygenic risk scores (PRSs) to tailor screening, evaluate our strategy for adapting PRSs to diverse populations, and quantify the impact of incorporating PRS on the study's screening recommendations.

Methods: WISDOM is a randomized, preference-tolerant screening trial in the USA testing the safety and morbidity of risk-based versus annual screening in women aged 40-74 without a prior history of breast cancer.

Mammographic calcifications association with risk of advanced breast cancer.

Purpose: Mammographic calcifications on mammograms with a negative/benign assessment are associated with increased breast cancer risk. Associations with advanced breast cancer risk are unknown. We evaluated whether calcifications recorded on mammography reports are associated with advanced invasive breast cancer risk.

National yearly cost of breast cancer screening in the USA and projected cost of advocated guidelines: a simulation study with life table modelling.

Objective: The aim of this study was to estimate the total national direct cost of breast cancer screening from 2019 to 2022 and project the total national cost and average lifetime cost of screening per woman for three current guidelines.

Design: We estimated the national cost of screening from 2019 to 2022, and per cancer detected in 2022, using real-world data on the number of mammograms performed per year. We also projected the national cost of screening using life table modelling for three guidelines: 2021/2023 American College of Radiology (ACR), 2023 American Cancer Society (ACS) and 2024 United States Preventative Services Task Force (USPSTF).

Incorporating Economic Evidence in Clinical Guidelines: A Framework From the Clinical Guidelines Committee of the American College of Physicians.

In recognition of accelerating health care spending and alignment with the American College of Physicians (ACP) principles of promoting high-value care, the ACP Clinical Guidelines Committee (CGC) developed a framework to standardize its approach to identifying, appraising, and considering economic evidence in the development of ACP clinical guidelines. This article presents the CGC's process for incorporating economic evidence, which encompasses cost-effectiveness analyses, economic outcomes in randomized controlled trials, and resource utilization (intervention cost) data. Economic evidence is one component of ACP recommendations.

A network meta-analysis of KarXT and commonly used pharmacological interventions for schizophrenia.

Background: Dopaminergic antipsychotics for schizophrenia have modest effects on symptoms and can cause important side effects. KarXT is an investigational drug for schizophrenia with a novel mechanism targeting muscarinic receptors that may limit these side effects.

Methods: We conducted a systematic review and Bayesian random-effects network meta-analyses of short-term RCTs (3-8 weeks) that enrolled adults with schizophrenia.

Informing the United States Medicare Drug Price Negotiation for Apixaban and Rivaroxaban: Methodological Considerations for Value Assessments Many Years After Launch.

Objectives: To demonstrate how health technology assessment methods can be used to support Medicare's price negotiations for apixaban and rivaroxaban.

Methods: Following the statutory outline of evidence that will be considered by Medicare, we conducted a systematic literature review, network meta-analyses, and decision analyses to evaluate the health outcomes and costs associated with apixaban and rivaroxaban compared with warfarin and dabigatran for patients with nonvalvular atrial fibrillation. Our methods inform discussions about the therapeutic impact of apixaban and rivaroxaban and suggest price premiums above their therapeutic alternatives over a range of cost-effectiveness thresholds.

The impact of capping health system cost savings on the projected cost-effectiveness of etranacogene dezaparvovec compared with factor IX prophylaxis for the treatment of hemophilia B.

This viewpoint discusses cost-effectiveness estimates for EtranaDez, a gene therapy for hemophilia B, using the Institute for Clinical and Economic Review's (ICER) framework for single and short-term therapies (SSTs). EtranaDez offers long-term benefits from a single administration, in contrast to the high costs and frequent dosing required by current factor IX prophylaxis. However, the projected gains in health from EtranaDez are small relative to the cost implications of the therapy, and consequently, how the cost offsets associated with EtranaDez are counted has a substantial impact on assessing its cost-effectiveness.

Cost-effectiveness of eculizumab and efgartigimod for the treatment of anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

Background: Eculizumab and efgartigimod were approved to treat anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (anti-AChR Ab-positive gMG). These relatively new biological treatments provide a more rapid onset of action and improved efficacy compared with conventional immunosuppressive treatments, but at a higher cost.

Objective: To assess the cost-effectiveness of eculizumab and, separately, efgartigimod, each added to conventional therapy vs conventional therapy alone, among patients with refractory anti-AChR Ab-positive gMG and those with anti-AChR Ab-positive gMG, respectively.

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians.

Description: The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs.

Methods: This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications.

Population Attributable Risk of Advanced-Stage Breast Cancer by Race and Ethnicity.

Importance: Advanced-stage breast cancer rates vary by race and ethnicity, with Black women having a 2-fold higher rate than White women among regular screeners. Clinical risk factors that explain a large proportion of advanced breast cancers by race and ethnicity are unknown.

Objective: To evaluate the population attributable risk proportions (PARPs) for advanced-stage breast cancer (prognostic pathologic stage IIA or higher) associated with clinical risk factors among routinely screened premenopausal and postmenopausal women by race and ethnicity.

Extending the Breast Cancer Surveillance Consortium Model of Invasive Breast Cancer.

Purpose: We extended the Breast Cancer Surveillance Consortium (BCSC) version 2 (v2) model of invasive breast cancer risk to include BMI, extended family history of breast cancer, and age at first live birth (version 3 [v3]) to better inform appropriate breast cancer prevention therapies and risk-based screening.

Methods: We used Cox proportional hazards regression to estimate the age- and race- and ethnicity-specific relative hazards for family history of breast cancer, breast density, history of benign breast biopsy, BMI, and age at first live birth for invasive breast cancer in the BCSC cohort. We evaluated calibration using the ratio of expected-to-observed (E/O) invasive breast cancers in the cohort and discrimination using the area under the receiver operating characteristic curve (AUROC).

Impact of BMI on Prevalence of Dense Breasts by Race and Ethnicity.

Background: Density notification laws require notifying women of dense breasts with dense breast prevalence varying by race/ethnicity. We evaluated whether differences in body mass index (BMI) account for differences in dense breasts prevalence by race/ethnicity.

Methods: Prevalence of dense breasts (heterogeneously or extremely dense) according to Breast Imaging Reporting and Data System and obesity (BMI > 30 kg/m2) were estimated from 2,667,207 mammography examinations among 866,033 women in the Breast Cancer Surveillance Consortium (BCSC) from January 2005 through April 2021.