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.

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 qualitative exploration of nurse-physician collaboration in intensive care units.

Background: Effective nurse-physician collaboration is associated with superior patient outcomes and improved job satisfaction for both nurses and physicians.

Objectives: This qualitative study explored factors that contribute to nurse-physician collaboration in critical care. Using a qualitative descriptive design, in-depth interviews were conducted with intensive care unit physicians and nurses.

Machine learning applications for therapeutic tasks with genomics data.

Thanks to the increasing availability of genomics and other biomedical data, many machine learning algorithms have been proposed for a wide range of therapeutic discovery and development tasks. In this survey, we review the literature on machine learning applications for genomics through the lens of therapeutic development. We investigate the interplay among genomics, compounds, proteins, electronic health records, cellular images, and clinical texts.

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.

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.

Real-world evidence to support regulatory decision making: New or expanded medical product indications.

There is increasing interest in utilizing real-world data (RWD) to produce real-world evidence (RWE) on the benefits and risks of medical products that could support regulatory approval decisions. The field of pharmacoepidemiology has a long history of focusing on data and evidence that would now be termed "real-world," including evidence from healthcare claims, registries, and electronic health records. However, several emerging trends over the past decade are converging to support the use of these and other RWD sources for approval decisions, and there are several recent examples and ongoing research that demonstrate how RWE may be used to support regulatory approval of new or expanded indications.

Real-world evidence to support regulatory decision-making for medicines: Considerations for external control arms.

Randomized clinical trials (RCTs) are the gold standard in producing clinical evidence of efficacy and safety of medical interventions. More recently, a new paradigm is emerging-specifically within the context of preauthorization regulatory decision-making-for some novel uses of real-world evidence (RWE) from a variety of real-world data (RWD) sources to answer certain clinical questions. Traditionally reserved for rare diseases and other special circumstances, external controls (eg, historical controls) are recognized as a possible type of control arm for single-arm trials.

Predictive values of diagnostic codes for identifying serious hypocalcemia and dermatologic adverse events among women with postmenopausal osteoporosis in a commercial health plan database.

Background: Post-marketing safety studies of medicines often rely on administrative claims databases to identify adverse outcomes following drug exposure. Valid ascertainment of outcomes is essential for accurate results. We aim to quantify the validity of diagnostic codes for serious hypocalcemia and dermatologic adverse events from insurance claims data among women with postmenopausal osteoporosis (PMO).

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.

Sensitivity and specificity of radiographic characteristics in atypical femoral fractures.

Unlabelled: Using the American Society for Bone and Mineral Research Task Force case definition for atypical femoral fractures, sensitivity and specificity of radiographic fracture characteristics were calculated. Fracture pattern was the most sensitive and specific characteristic. This suggests that some characteristics should be weighted more heavily when identifying these fractures.

Comorbidities, bone-sparing agent prescription history and their determinants among postmenopausal women in UK primary care settings: a retrospective database study.

Summary: Distinguishing oral bisphosphonates from other bone-sparing therapies, this retrospective observational study, first, characterized treated osteoporosis patients in the UK, and secondly, explored factors associated with the risk of discontinuation or switching between therapies. The latter should be considered when evaluating real-world data.

Purpose: This retrospective observational study evaluated the characteristics of women with postmenopausal osteoporosis, including comorbidities and determinants of treatment patterns with bone-sparing agents.

Assessment of off-label use of denosumab 60 mg injection during the early postmarketing period using health insurance claims data.

Unlabelled: Off-label use of denosumab 60 milligram (mg) injection was assessed within an administrative claims database. The completeness of claims to assess off-label use was investigated with medical record review. Potential denosumab 60 mg off-label use was observed based on claims, but many had evidence of on-label indications based on medical record review.

The impact of persistence with bisphosphonates on health resource utilization and fracture risk in the UK: a study of patient records from the UK Clinical Practice Research Datalink.

Rationale, Aims And Objectives: Clinical trial data suggest that patients who have received bisphosphonates continue to benefit from them after discontinuation. However, data from real-world clinical practice are inconclusive. We assessed the impact of persistence and discontinuation on health resource utilization (HRU) and fracture rate in women who were prescribed oral bisphosphonates.

Development and evaluation of an algorithm to identify users of Prolia(®) during the early postmarketing period using health insurance claims data.

Purpose: The goal of this study is to develop and validate an algorithm to identify Prolia(®) users within a health insurance claims database.

Methods: Patients with a denosumab-specific or nonspecific administration claim during the early period of Prolia availability in the USA (June 1, 2010 to March 31, 2012) were classified as definite, probable, possible, and nonusers of Prolia using an algorithm consisting of nine different components based on claims patterns consistent with Prolia use. Medical record review confirmed a sample of definite, probable, and possible users and the positive predictive value (PPV) was estimated.

Changing patterns of use of osteoporosis medications in the years after launch: implications for comparative effectiveness research.

Purpose: Newly marketed medications may be used selectively in patients with more severe disease. Changes in patterns of use following a drug's introduction to the market can greatly influence results from non-experimental comparative effectiveness research. We sought to explore this issue by characterizing trends in oral and injectable prescription drug claims for the prevention and treatment of osteoporosis.

Discontinuation and reinitiation patterns of osteoporosis treatment among commercially insured postmenopausal women.

Objective: Poor adherence to chronic medications is common and compromises medication effectiveness. We sought to describe longitudinal patterns of osteoporosis medication use.

Study Design: This was a retrospective observational cohort study using 2005-2009 data from a large, commercially insured population.

Validity of an algorithm to identify osteonecrosis of the jaw in women with postmenopausal osteoporosis in the Danish National Registry of Patients.

Background: Osteonecrosis of the jaw (ONJ) is an adverse effect of drugs that suppress bone turnover - for example, drugs used for the treatment of postmenopausal osteoporosis. The Danish National Registry of Patients (DNRP) is potentially valuable for monitoring ONJ and its prognosis; however, no specific code for ONJ exists in the International Classification of Diseases 10th revision (ICD-10), which is currently used in Denmark. Our aim was to estimate the positive predictive value (PPV) of an algorithm to capture ONJ cases in the DNRP among women with postmenopausal osteoporosis.

Design and methods of a postmarketing pharmacoepidemiology study assessing long-term safety of Prolia® (denosumab) for the treatment of postmenopausal osteoporosis.

Purpose: To describe the rationale and methods for a prospective, open-cohort study assessing the long-term safety of Prolia(®) for treatment of postmenopausal osteoporosis (PMO) in postmarketing settings.

Methods: Data will be derived from United States Medicare, United Healthcare, and Nordic (Denmark, Sweden, Norway) national registries. Observation will begin on the date of first Prolia(®) regulatory approval (May 26, 2010) and continue for 10 years.

Completeness of prescription information in US commercial claims databases.

Purpose: Pharmacy commercial claims databases are widely used for pharmacoepidemiologic research. However, concerns have been raised that these databases may not fully capture claims for generic medications as a result of patients filling outside the context of their insurance. This has implications for many research activities and quality improvement programs.

Accuracy of ICD-9 codes to identify nonunion and malunion and developing algorithms to improve case-finding of nonunion and malunion.

Objective: To evaluate the accuracy of using ICD-9 codes to identify nonunions (NU) and malunions (MU) among adults with a prior fracture code and to explore case-finding algorithms.

Study Design: Medical chart review of potential NU (N=300) and MU (N=288) cases. True NU cases had evidence of NU and no evidence of MU in the chart (and vice versa for MUs) or were confirmed by the study clinician.

Patient-related risk factors for fracture-healing complications in the United Kingdom General Practice Research Database.

Background And Purpose: A variety of risk factors have been hypothesized to contribute to the development of fracture-healing complications; however, population-based estimates of the strength of these risk factors are limited. In this case-control study, we evaluated patient-related risk factors for fracture-healing complications.

Methods: Using the United Kingdom General Practice Research Database, we identified patients with a fracture-healing complication (delayed union, nonunion, or malunion) between 1988 and 2008.

HIV shedding in the oral cavity: an assessment of HIV type, immunovirologic, demographic and oral factors.

Objective: To quantify the prevalence and burden of HIV type 2 (HIV-2) and HIV-1 RNA in the oral cavity of antiretroviral therapy-naive HIV-infected Senegalese individuals and to identify correlates of oral HIV viral loads.

Design: A cross-sectional study of 163 HIV-1 and 27 HIV-2-infected antiretroviral therapy-naive Senegalese adults.

Methods: Participants received clinical and oral exams and provided blood and oral wash samples for viral load and plasma CD4 count ascertainment.

Directed differentiation of progenitor cells towards an islet-cell phenotype.

Exogenous insulin administration and oral anti-diabetic drugs are the primary means of treating diabetes. However, tight glycaemic control, with its inherent risk of hypoglycaemia, is required to prevent the microvascular and macrovascular complications of the disease. While islet or pancreas transplantations offer a longer-term cure, their widespread application is not possible, primarily because of a lack of donor tissue, the burden of life-long immunosuppression, and eventual graft rejection.