Using EHR data to identify coronavirus infections in hospitalized patients: Impact of case definitions on disease surveillance.

PURPOSE: To evaluate the number, characteristics, and outcomes of patients identified hospitalized with coronavirus disease 2019 (COVID-19) using two different case definitions. PROCEDURES: Electronic Health Record data were evaluated from patients hospitalized with COVID-19 through May 2020 at 52 health systems across the United States. Characteristics of inpatients with positive laboratory tests for SARS-CoV-2 were compared with those with clinical diagnosis of COVID-19 but without a confirmatory lab result. FINDINGS: Of 14,371 inpatients with COVID-19, 6623 (46.1 %) had a positive laboratory result, and n = 7748 (52.9 %) had only a clinical diagnosis of COVID-19. Compared with clinically diagnosed cases, those with laboratory-confirmed COVID were similar in age and sex, but differed by race, ethnicity, and insurance status. Laboratory-confirmed cases were more likely to receive certain COVID-19 therapies including hydroxychloroquine, anti-IL6 agents and antivirals (p < 0.001). Those with laboratory-confirmed COVID-19 had lower rates of most complications such as myocardial infarction, but higher overall mortality (p < 0.001). CONCLUSION: We observed a two-fold difference in the number of patients hospitalized with COVID-19 depending on whether the case definition required laboratory confirmation. Variations in case definitions also led to differences in cohort characteristics, treatments, and outcomes.

Predictors of Response Outcomes for Research Recruitment Through a Central Cancer Registry: Evidence From 17 Recruitment Efforts for Population-Based Studies.

When recruiting research participants through central cancer registries, high response fractions help ensure population-based representation. We conducted multivariable mixed-effects logistic regression to identify case and study characteristics associated with making contact with and obtaining cooperation of Utah cancer cases using data from 17 unique recruitment efforts undertaken by the Utah Cancer Registry (2007-2016) on behalf of the following studies: A Population-Based Childhood Cancer Survivors Cohort Study in Utah, Comparative Effectiveness Analysis of Surgery and Radiation for Prostate Cancer (CEASAR Study), Costs and Benefits of Follow-up Care for Adolescent and Young Adult Cancers, Study of Exome Sequencing for Head and Neck Cancer Susceptibility Genes, Genetic Epidemiology of Chronic Lymphocytic Leukemia, Impact of Remote Familial Colorectal Cancer Risk Assessment and Counseling (Family CARE Project), Massively Parallel Sequencing for Familial Colon Cancer Genes, Medullary Thyroid Carcinoma (MTC) Surveillance Study, Osteosarcoma Surveillance Study, Prostate Cancer Outcomes Study, Risk Education and Assessment for Cancer Heredity Project (REACH Project), Study of Shared Genomic Segment Analysis and Tumor Subtyping in High-Risk Breast-Cancer Gene Pedigrees, Study of Shared Genomic Segment Analysis for Localizing Multiple Myeloma Genes. Characteristics associated with lower odds of contact included Hispanic ethnicity (odds ratio (OR) = 0.34, 95% confidence interval (CI): 0.27, 0.41), nonwhite race (OR = 0.46, 95% CI: 0.35, 0.60), and younger age at contact. Years since diagnosis was inversely associated with making contact. Nonwhite race and age ≥60 years had lower odds of cooperation. Study features with lower odds of cooperation included longitudinal design (OR = 0.50, 95% CI: 0.41, 0.61) and study brochures (OR = 0.70, 95% CI: 0.54, 0.90). Increased odds of cooperation were associated with including a questionnaire (OR = 3.19, 95% CI: 1.54, 6.59), postage stamps (OR = 1.60, 95% CI: 1.21, 2.12), and incentives (OR = 1.62, 95% CI: 1.02, 2.57). Among cases not responding after the first contact, odds of eventual response were lower when >10 days elapsed before subsequent contact (OR = 0.71, 95% CI: 0.59, 0.85). Obtaining high response is challenging, but study features identified in this analysis support better results when recruiting through central cancer registries.

Monitoring product safety in the postmarketing environment.

The safety profile of a medicinal product may change in the postmarketing environment. Safety issues not identified in clinical development may be seen and need to be evaluated. Methods of evaluating spontaneous adverse experience reports and identifying new safety risks include a review of individual reports, a review of a frequency distribution of a list of the adverse experiences, the development and analysis of a case series, and various ways of examining the database for signals of disproportionality, which may suggest a possible association. Regulatory agencies monitor product safety through a variety of mechanisms including signal detection of the adverse experience safety reports in databases and by requiring and monitoring risk management plans, periodic safety update reports and postauthorization safety studies. The United States Food and Drug Administration is working with public, academic and private entities to develop methods for using large electronic databases to actively monitor product safety. Important identified risks will have to be evaluated through observational studies and registries.

Preparing for safety issues following drug approval: pre-approval risk management considerations.

Risk management plans and risk minimization plans as well as postapproval commitment studies are based on risks identified pre-approval that need to be further characterized or minimized in the postmarketing environment. Although the implementation of these activities are conducted in the postapproval arena, the design of the plans and studies as well as the development of effective postapproval tools and mitigation strategies should be carried out pre-approval. The pre-approval period also provides the opportunity to fully understand the treatment population that is included in the clinical trial program and to determine how the target population for the drug after approval may differ from the clinical trial patient population. When regulators or sponsors have expressed concerns about safety issues identified during clinical development, the result may be a postapproval commitment in the form of a registry or an observational safety study or, in the US, a Risk Evaluation and Mitigation Strategy (REMS) as a condition of approval. Specific examples are given for risk mitigation activities that can be conducted pre-approval.

The art and science of risk management: a US research-based industry perspective.

The research-based pharmaceutical industry in the US strongly supports the concepts of risk management and sees formal risk management as playing a major role in the development of safe medicines for the public, as well as providing a mechanism to ensure that decisions concerning individual drug benefit and risk are made based on scientific evidence. Safe medicines refer to those drugs whose benefits have been found to outweigh their risks when they are used according to the approved labelling. Risk management is the comprehensive and proactive application of scientifically based methodologies to identify, assess, communicate and minimise risk throughout the life cycle of a drug so as to establish and maintain a favourable benefit-risk balance in patients. Although there are certainly a number of global risk management initiatives in place or being undertaken, harmonisation has yet to be achieved. Industry is faced with a variety of different risk management approaches and tools. There is a need to move the focus of risk management from the post-approval arena to earlier in the development process and tools need to be developed to support risk management throughout the lifecycle of a drug. The focus in the US on risk minimalisation strategies will also be an area for methodological development. A key factor in the success of overall risk management is the dialogue between industry and regulators throughout the development, review and marketing of the product. It is through such dialogue that appropriate, efficient and effective risk management strategies will be developed and implemented and the best decisions regarding the safe use of pharmaceutical products will be made.