Comparative effectiveness of denosumab vs alendronate among postmenopausal women with osteoporosis.

Although clinical trials have shown that denosumab significantly increases bone mineral density at key skeletal sites more than oral bisphosphonates, evidence is lacking from head-to-head randomized trials evaluating fracture outcomes. This retrospective cohort study uses administrative claims data from Medicare fee-for service beneficiaries to evaluate the comparative effectiveness of denosumab vs alendronate in reducing fracture risk among women with PMO in the US. Women with PMO ≥ 66 yr of age with no prior history of osteoporosis treatment, who initiated denosumab (n = 89 115) or alendronate (n = 389 536) from 2012 to 2018, were followed from treatment initiation until the first of a specific fracture outcome, treatment discontinuation or switch, end of study (December 31, 2019), or other censoring criteria.

Staging and clean room: Constructs designed to facilitate transparency and reduce bias in comparative analyses of real-world data.

Purpose: We describe constructs designed to protect the integrity of the results from comparative analyses using real-world data (RWD): staging and clean room.

Methods: Staging involves performing sequential preliminary analyses and evaluating the population size available and potential bias before conducting comparative analyses. A clean room involves restricted access to data and preliminary results, policies governing exploratory analyses and protocol deviations, and audit trail.

Global Epidemiology of Hip Fractures: Secular Trends in Incidence Rate, Post-Fracture Treatment, and All-Cause Mortality.

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model.

Comparability of Osteoporosis Treatment Groups Among Female Medicare Beneficiaries in the United States.

It is often difficult to obtain valid estimates of comparative treatment effectiveness and safety owing to differences across patient populations taking different medications in the real world. One approach for assessing comparability between treatment groups in effectiveness studies is to use negative control outcomes (NCOs). NCOs share similar sources of bias with the primary outcomes but have no plausible causal relationship to the treatment of interest.

Pragmatic considerations for negative control outcome studies to guide non-randomized comparative analyses: A narrative review.

Purpose: This narrative review describes the application of negative control outcome (NCO) methods to assess potential bias due to unmeasured or mismeasured confounders in non-randomized comparisons of drug effectiveness and safety. An NCO is assumed to have no causal relationship with a treatment under study while subject to the same confounding structure as the treatment and outcome of interest; an association between treatment and NCO then reflects the potential for uncontrolled confounding between treatment and outcome.

Methods: We focus on two recently completed NCO studies that assessed the comparability of outcome risk for patients initiating different osteoporosis medications and lipid-lowering therapies, illustrating several ways in which confounding may result.

Changes in Medication Use During Pregnancy for Women with Chronic Conditions: An Analysis of Claims Data.

Purpose: Evaluation of drug safety during pregnancy is dependent on the number of exposed women during routine clinical practice with data available for analysis. We examined medication fills in pregnant and nonpregnant women within select disease cohorts: general population, migraine, diabetes, and hyperlipidemia to explore the potential use of claims data to assess medication use and safety during pregnancy.

Methods: This cohort study, using IBM MarketScan® Research Databases claims data, included women 10-54 years of age with pregnancy resulting in a liveborn infant between January 2010 and September 2015 and matched nonpregnant women.

Patterns of primary prophylactic granulocyte colony-stimulating factor use in older Medicare patients with cancer receiving myelosuppressive chemotherapy.

Purpose: Guidelines recommend primary prophylactic (PP) granulocyte colony stimulating factor (G-CSF) for prevention of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy with high risk (HR: > 20%), or intermediate risk (IR:10-20%) of FN and ≥ 1 patient risk factor (e.g., age ≥ 65y).

Trends in characteristics and outcomes among US adults hospitalised with COVID-19 throughout 2020: an observational cohort study.

Objectives: To examine the temporal patterns of patient characteristics, treatments used and outcomes associated with COVID-19 in patients who were hospitalised for the disease between January and 15 November 2020.

Design: Observational cohort study.

Setting: COVID-19 subset of the Optum deidentified electronic health records, including more than 1.

A Novel Case Study of the Use of Real-World Evidence to Support the Registration of an Osteoporosis Product in China.

On June 23, 2020, Prolia (denosumab) was approved by the National Medical Products Administration (NMPA) in the People's Republic of China as the first monoclonal antibody for the treatment of postmenopausal women with osteoporosis at high risk of fractures. Its brand name in Chinese is , a transliteration from the English name "Prolia", which has an implied meaning of "to give strength to everyone"- a suitable name for a potent anti-resorptive therapy. The approval was supported by a novel marketing authorization application (MAA) that included data from Prolia's global clinical trial program establishing favorable efficacy and safety, augmented by results from a real-world evidence (RWE) study confirming the effectiveness and safety of Prolia in clinical practice within Taiwan and Hong Kong.

Cinacalcet and gastrointestinal bleeding risk in patients receiving hemodialysis.

Purpose: Secondary hyperparathyroidism (SHPT) is common among dialysis patients, and calcimimetics are a mainstay of treatment. This study assessed whether cinacalcet use is associated with gastrointestinal bleeding in a large hemodialysis cohort.

Methods: A linked database of clinical records and medical claims for patients receiving hemodialysis in a large dialysis organization, 2007-2010, was used.

Characteristics and outcomes of hospitalised adults with COVID-19 in a Global Health Research Network: a cohort study.

Objective: To examine age, gender, and temporal differences in baseline characteristics and clinical outcomes of adult patients hospitalised with COVID-19.

Design: A cohort study using deidentified electronic medical records from a Global Research Network.

Setting/participants: 67 456 adult patients hospitalised with COVID-19 from the USA; 7306 from Europe, Latin America and Asia-Pacific between February 2020 and January 2021.

Duration of short-acting granulocyte colony-stimulating factor for primary prophylaxis and risk of neutropenia-related hospitalization in older patients with cancer.

Purpose: Evaluate the relationship between duration of primary prophylactic short-acting granulocyte colony-stimulating factor (PP-sG-CSF) and risk of neutropenia-related hospitalization (NRH) in older patients receiving myelosuppressive chemotherapy.

Methods: Using the Medicare claims database, we conducted a nested case-control study in a cohort of patients aged ≥66 years with breast, colorectal, lung, ovarian, or prostate cancer, or non-Hodgkin lymphoma who initiated a first cycle of any myelosuppressive chemotherapy January 1, 2008-September 30, 2016, and received PP-sG-CSF. We matched up to four controls to each NRH case by age, cancer type, regimen febrile neutropenia (FN) risk category, and year using incidence density sampling.

Using negative control outcomes to assess the comparability of treatment groups among women with osteoporosis in the United States.

Purpose: In contrast to randomized clinical trials, comparative safety and effectiveness assessments of osteoporosis medications in clinical practice may be subject to confounding by indication. We used negative control outcomes to detect residual confounding when comparing osteoporosis medications.

Methods: Using MarketScan Commercial and Supplemental claims, we identified women aged ≥55 years who initiated an oral bisphosphonate (BP) (risedronate, alendronate, or ibandronate), denosumab (an injected biologic), or intravenous zoledronic acid (ZA) from October 1, 2010 to September 30, 2015.

Patterns of granulocyte colony-stimulating factor prophylaxis in patients with cancer receiving myelosuppressive chemotherapy.

Purpose: To evaluate patterns of primary prophylactic (PP) granulocyte colony-stimulating factor (G-CSF) use following chemotherapy by cancer type and febrile neutropenia (FN) risk.

Methods: Using a commercial administrative database, we identified adult patients diagnosed with breast, colorectal, lung, ovarian cancer, or non-Hodgkin lymphoma (NHL) who initiated chemotherapy with high risk (HR) or intermediate risk (IR) for FN between January 1, 2013, and August 31, 2017. We describe use of PP-G-CSF, proportion completing all their cycles with pegfilgrastim, timing of pegfilgrastim, and duration of short-acting G-CSF.

Association of hospital transfusion use and infection-related rehospitalizations among patients receiving hemodialysis: A retrospective cohort study.

Introduction: Red blood cell transfusions have been associated with infection risk. We investigated whether hospital transfusions are associated with infections in maintenance hemodialysis patients requiring transfusions for chronic anemia.

Methods: In this retrospective cohort study, hemodialysis patients who experienced an incident hospitalization during 2012-2013 were identified from the Medicare end-stage renal disease database.

Combinations of mineral and bone disorder markers and risk of death and hospitalizations in the international Dialysis Outcomes and Practice Patterns Study.

Background: Prior studies have developed a chronic kidney disease-mineral and bone disorder (CKD-MBD) composite score based on combinations of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) that have been shown to be associated with an increased risk of clinical outcomes in the USA. We examined this association in a contemporary, international cohort of hemodialysis patients.

Methods: We studied 19 313 patients surviving ≥12 months in the Dialysis Outcomes and Practice Patterns Study Phases 3-5 (2005-15) from Europe, Canada and the USA.

Methodologic considerations for noninterventional studies of switching from reference biologic to biosimilars.

Purpose: As more biosimilars become available in the United States, postapproval noninterventional studies describing biosimilar switching and comparing effectiveness and/or safety between switchers and nonswitchers will play a key role in generating real-world evidence to inform clinical practices and policy decisions. Ensuring sound methodology is critical for making valid inferences from these studies.

Methods: The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) convened a workgroup consisting of academic researchers, industry scientists, and practicing clinicians to establish best practice recommendations for the conduct of noninterventional studies of biosimilar and reference biologic switching.

Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population.

Background: Morbidity and mortality vary seasonally. Timing and severity of influenza seasons contribute to those patterns, especially among vulnerable populations such as patients with ESRD. However, the extent to which influenza-like illness (ILI), a syndrome comprising a range of potentially serious respiratory tract infections, contributes to mortality in patients with ESRD has not been quantified.

Changes in the use of erythropoiesis-stimulating agents (ESAs) and red blood cell transfusion in patients with cancer amidst regulatory and reimbursement changes.

Purpose: Evaluate changes in use of erythropoiesis-stimulating agents (ESAs) and red blood cell transfusion in cancer patients receiving myelosuppressive chemotherapy following regulatory and reimbursement actions.

Methods: Calendar year patient cohorts (2005-2013) with breast, colorectal, lung, multiple myeloma, non-Hodgkin lymphoma, ovarian, or prostate cancer and receiving myelosuppressive chemotherapy were identified within the Marketscan database. Incidence of ESA treatment and transfusion were estimated in each year, as was median number of ESA administrations.

Use of the Medicare database in epidemiologic and health services research: a valuable source of real-world evidence on the older and disabled populations in the US.

Medicare is the federal health insurance program for individuals in the US who are aged ≥65 years, select individuals with disabilities aged <65 years, and individuals with end-stage renal disease. The Centers for Medicare and Medicaid Services grants researchers access to Medicare administrative claims databases for epidemiologic and health outcomes research. The data cover beneficiaries' encounters with the health care system and receipt of therapeutic interventions, including medications, procedures, and services.

Facility-level CKD-MBD composite score and risk of adverse clinical outcomes among patients on hemodialysis.

Background: Patients receiving hemodialysis with values outside of target levels for parathyroid hormone (PTH: 150-600 pg/mL), calcium (Ca: 8.4-10.2 mg/dL), and phosphate (P: 3.

The association between cinacalcet use and missed in-center hemodialysis treatment rate.

Purpose: Missed in-center hemodialysis treatments (MHT) are a general indicator of health status in hemodialysis patients. This analysis was conducted to estimate the association between cinacalcet use and MHT rate.

Methods: We studied patients receiving hemodialysis and prescription benefits services from a large dialysis organization.

Geovariation in Fracture Risk among Patients Receiving Hemodialysis.

Background And Objectives: Fractures are a major source of morbidity and mortality in patients receiving dialysis. We sought to determine whether rates of fractures and tendon ruptures vary geographically.

Design, Setting, Participants, & Measurements: Data from the US Renal Data System were used to create four yearly cohorts, 2007-2010, including all eligible prevalent patients on hemodialysis in the United States on January 1 of each year.