Learning important common data elements from shared study data: The All of Us program analysis.

There are many initiatives attempting to harmonize data collection across human clinical studies using common data elements (CDEs). The increased use of CDEs in large prior studies can guide researchers planning new studies. For that purpose, we analyzed the All of Us (AoU) program, an ongoing US study intending to enroll one million participants and serve as a platform for numerous observational analyses. AoU adopted the OMOP Common Data Model to standardize both research (Case Report Form [CRF]) and real-world (imported from Electronic Health Records [EHRs]) data. AoU standardized specific data elements and values by including CDEs from terminologies such as LOINC and SNOMED CT. For this study, we defined all elements from established terminologies as CDEs and all custom concepts created in the Participant Provided Information (PPI) terminology as unique data elements (UDEs). We found 1 033 research elements, 4 592 element-value combinations and 932 distinct values. Most elements were UDEs (869, 84.1%), while most CDEs were from LOINC (103 elements, 10.0%) or SNOMED CT (60, 5.8%). Of the LOINC CDEs, 87 (53.1% of 164 CDEs) originated from previous data collection initiatives, such as PhenX (17 CDEs) and PROMIS (15 CDEs). On a CRF level, The Basics (12 of 21 elements, 57.1%) and Lifestyle (10 of 14, 71.4%) were the only CRFs with multiple CDEs. On a value level, 61.7% of distinct values are from an established terminology. AoU demonstrates the use of the OMOP model for integrating research and routine healthcare data (64 elements in both contexts), which allows for monitoring lifestyle and health changes outside the research setting. The increased inclusion of CDEs in large studies (like AoU) is important in facilitating the use of existing tools and improving the ease of understanding and analyzing the data collected, which is more challenging when using study specific formats.

regCOVID: Tracking publications of registered COVID-19 studies.

BACKGROUND: In response to the COVID-19 pandemic many clinical studies have been initiated leading to the need for efficient ways to track and analyze study results. We expanded our previous project that tracked registered COVID-19 clinical studies to also track result articles generated from these studies. Our objective was to develop a data science approach to identify and analyze all publications linked to COVID-19 clinical studies and generate a prioritized list of publications for efficient understanding of the state of COVID-19 clinical research. METHODS: We conducted searches of ClinicalTrials.gov and PubMed to identify articles linked to COVID-19 studies, and developed criteria based on the trial phase, intervention, location, and record recency to develop a prioritized list of result publications. RESULTS: The performed searchers resulted in 1 022 articles linked to 565 interventional trials (17.8% of all 3 167 COVID-19 interventional trials as of 31 January 2022). 609 publications were identified via abstract-link in PubMed and 413 via registry-link in ClinicalTrials.gov, with 27 articles linked from both sources. Of the 565 trials publishing at least one article, 197 (34.9%) had multiple linked publications. An attention score was assigned to each publication to develop a prioritized list of all publications linked to COVID-19 trials and 83 publications were identified that are result articles from late phase (Phase 3) trials with at least one US site and multiple study record updates. For COVID-19 vaccine trials, 108 linked result articles for 64 trials (14.7% of 436 total COVID-19 vaccine trials) were found. CONCLUSIONS: Our method allows for the efficient identification of important COVID-19 articles that report results of registered clinical trials and are connected via a structured article-trial link. Our data science methodology also allows for consistent and as needed data updates and is generalizable to other conditions of interest.

Harmonization of Measurement Codes for Concept-Oriented Lab Data Retrieval.

Measurement concepts are essential to observational healthcare research; however, a lack of concept harmonization limits the quality of research that can be done on multisite research networks. We developed five methods that used a combination of automated, semi-automated and manual approaches for generating measurement concept sets. We validated our concept sets by calculating their frequencies in cohorts from the Columbia University Irving Medical Center (CUIMC) database. For heart transplant patients, the preoperative frequencies of basic metabolic panel concept sets, which we generated by a semi-automated approach, were greater than 99%. We also made concept sets for lumbar puncture and coagulation panels, by automated and manual methods respectively.

Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients.

BACKGROUND: Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. METHODS: Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dual-eligibility status, and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), statins, warfarin, direct factor Xa inhibitors, P2Y12 inhibitors, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator, and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. RESULTS: Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 278,912 (74.6%) were on at least one study drug. The three most common study drugs among COVID-19 patients were statins 187,374 (50.1%), ACEI 97,843 (26.2%) and ARB 83,290 (22.3%). For all three outcomes (diagnosis, hospitalization and death), current users of ACEI, ARB, statins, warfarin, direct factor Xa inhibitors and P2Y12 inhibitors were associated with reduced risks, compared to never users. Famotidine did not show consistent significant effects. Hydroxychloroquine did not show significant effects after censoring of recent starters. CONCLUSION: Maintenance use of ACEI, ARB, warfarin, statins, direct factor Xa inhibitors and P2Y12 inhibitors was associated with reduction in risk of acquiring COVID-19 and dying from it.

regCOVID: Tracking publications of registered COVID-19 studies.

In response to the COVID-19 pandemic many clinical studies have been initiated leading to the need for efficient ways to track and analyze study results. We expanded our previous project that tracked registered COVID-19 clinical studies to also track result articles generated from these studies. We conducted searches of ClinicalTrials.gov and PubMed to identify articles linked to COVID-19 studies, and developed criteria based on the trial phase, intervention, location, and record recency to develop a prioritized list of result publications. We found 760 articles linked to 419 interventional trials (15.7% of all 2 669 COVID-19 interventional trials as of 15 August 2021), with 418 identified via abstract-link in PubMed and 342 via registry-link in ClinicalTrials.gov. Of the 419 trials publishing at least one article, 123 (29.4%) have multiple linked publications. We used an attention score to develop a prioritized list of all publications linked to COVID-19 trials and identified 58 publications that are result articles from late phase (Phase 3) trials with at least one US site and multiple study record updates. For COVID-19 vaccine trials, we found 69 linked result articles for 40 trials (13.9% of 290 total COVID-19 vaccine trials). Our method allows for the efficient identification of important COVID-19 articles that report results of registered clinical trials and are connected via a structured article-trial link.

CONSIDER Statement: Consolidated Recommendations for Sharing Individual Participant Data from Human Clinical Studies.

Many research sponsors require sharing of data from human clinical trials. We created the CONSIDER statement, a set of recommendations to improve data sharing practices and increase the availability and re-usability of individual participant data from clinical trials. We developed the recommendations by reviewing shared individual participant data and study artifacts from a set of completed studies, as well as study data deposited on ClinicalTrials.gov and on several data sharing platforms. The CONSIDER statement is comprised of seven sections including: format, data sharing, study design, case report forms, data dictionary, data de-identification and choice of data sharing platform. We developed several different forms of CONSIDER which includes a brief form (the checklist), a full form (detailed descriptions and examples), and a scoring methodology. The checklist can be used to evaluate adherence to various progressive data sharing recommendations. We are currently in Phase 2 of collecting feedback on the CONSIDER statement.

Data Characterization of Medicaid: Legacy and New Data Formats in the CMS Virtual Research Data Center.

Medicaid is a significant health insurance plan providing healthcare coverage to up to a third of the population of the United Sates. We describe two different formats of Medicaid data within Center for Medicare and Medicaid Services Virtual Research Data Center. We analyze record length, age and enrollment justification among patients for both data formats. As of December 2016, the total size of Medicaid population available from CMS is 92,953,389; 45% of patients are aged 0 to 18, 26.6% are aged 19-35 and 23.2% are aged 36-64. In terms of Medicaid eligibility, 35.6% qualify due to (child) age and 26.8% qualify due to income. We also compare the volume of Medicaid to Medicare for year 2016. We conclude that Medicaid data includes patients with significant record lengths and relatively well documented enrollment justification, which are high value assets for data reuse researchers that are willing to balance known data limitations with careful analysis design and interpretation.

Linking Provider Specialty and Outpatient Diagnoses in Medicare Claims Data: Data Quality Implications.

BACKGROUND: With increasing use of real world data in observational health care research, data quality assessment of these data is equally gaining in importance. Electronic health record (EHR) or claims datasets can differ significantly in the spectrum of care covered by the data. OBJECTIVE: In our study, we link provider specialty with diagnoses (encoded in International Classification of Diseases) with a motivation to characterize data completeness. METHODS: We develop a set of measures that determine diagnostic span of a specialty (how many distinct diagnosis codes are generated by a specialty) and specialty span of a diagnosis (how many specialties diagnose a given condition). We also analyze ranked lists for both measures. As use case, we apply these measures to outpatient Medicare claims data from 2016 (3.5 billion diagnosis-specialty pairs). We analyze 82 distinct specialties present in Medicare claims (using Medicare list of specialties derived from level III Healthcare Provider Taxonomy Codes). RESULTS: A typical specialty diagnoses on average 4,046 distinct diagnosis codes. It can range from 33 codes for medical toxicology to 25,475 codes for internal medicine. Specialties with large visit volume tend to have large diagnostic span. Median specialty span of a diagnosis code is 8 specialties with a range from 1 to 82 specialties. In total, 13.5% of all observed diagnoses are generated exclusively by a single specialty. Quantitative cumulative rankings reveal that some diagnosis codes can be dominated by few specialties. Using such diagnoses in cohort or outcome definitions may thus be vulnerable to incomplete specialty coverage of a given dataset. CONCLUSION: We propose specialty fingerprinting as a method to assess data completeness component of data quality. Datasets covering a full spectrum of care can be used to generate reference benchmark data that can quantify relative importance of a specialty in constructing diagnostic history elements of computable phenotype definitions.

Discoverability of information on clinical trial data-sharing platforms.

OBJECTIVE: This study was intended to (1) provide clinical trial data-sharing platform designers with insight into users' experiences when attempting to evaluate and access datasets, (2) spark conversations about improving the transparency and discoverability of clinical trial data, and (3) provide a partial view of the current information-sharing landscape for clinical trials. METHODS: We evaluated preview information provided for 10 datasets in each of 7 clinical trial data-sharing platforms between February and April 2019. Specifically, we evaluated the platforms in terms of the extent to which we found (1) preview information about the dataset, (2) trial information on ClinicalTrials.gov and other external websites, and (3) evidence of the existence of trial protocols and data dictionaries. RESULTS: All seven platforms provided data previews. Three platforms provided information on data file format (e.g., CSV, SAS file). Three allowed batch downloads of datasets (i.e., downloading multiple datasets with a single request), whereas four required separate requests for each dataset. All but one platform linked to ClinicalTrials.gov records, but only one platform had ClinicalTrails.gov records that linked back to the platform. Three platforms consistently linked to external websites and primary publications. Four platforms provided evidence of the presence of a protocol, and six platforms provided evidence of the presence of data dictionaries. CONCLUSIONS: More work is needed to improve the discoverability, transparency, and utility of information on clinical trial data-sharing platforms. Increasing the amount of dataset preview information available to users could considerably improve the discoverability and utility of clinical trial data.

Thirty-Day Outcomes of Children and Adolescents With COVID-19: An International Experience.

OBJECTIVES: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018. METHODS: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death. RESULTS: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%-7.6%), famotidine (9.0%-28.1%), and antithrombotics such as aspirin (2.0%-21.4%), heparin (2.2%-18.1%), and enoxaparin (2.8%-14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable (n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza. CONCLUSIONS: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19.

The changing patterns of comorbidities associated with human immunodeficiency virus infection, a longitudinal retrospective cohort study of Medicare patients.

ABSTRACT: The objective of this paper is to determine the temporal trend of the association of 66 comorbidities with human immunodeficiency virus (HIV) infection status among Medicare beneficiaries from 2000 through 2016.We harvested patient level encounter claims from a 17-year long 100% sample of Medicare records. We used the chronic conditions warehouse comorbidity flags to determine HIV infection status and presence of comorbidities. We prepared 1 data set per year for analysis. Our 17 study data sets are retrospective annualized patient level case histories where the comorbidity status reflects if the patient has ever met the comorbidity case definition from the start of the study to the analysis year.We implemented one logistic binary regression model per study year to discover the maximum likelihood estimate (MLE) of a comorbidity belonging to our binary classes of HIV+ or HIV- study populations. We report MLE and odds ratios by comorbidity and year.Of the 66 assessed comorbidities, 35 remained associated with HIV- across all model years, 19 remained associated with HIV+ across all model years. Three comorbidities changed association from HIV+ to HIV- and 9 comorbidities changed association from HIV- to HIV+.The prevalence of comorbidities associated with HIV infection changed over time due to clinical, social, and epidemiological reasons. Comorbidity surveillance can provide important insights into the understanding and management of HIV infection and its consequences.

Association between tendon ruptures and use of fluoroquinolone, and other oral antibiotics: a 10-year retrospective study of 1 million US senior Medicare beneficiaries.

OBJECTIVES: To assess the association of fluoroquinolone use with tendon ruptures compared with no fluoroquinolone and that of the four most commonly prescribed non-fluoroquinolone antibiotics in the USA. DESIGN: Retrospective observational study. SETTING: US seniors enrolled in the federal old-age, survivor's insurance programme. PARTICIPANTS: 1 009 925 Medicare fee-for-service beneficiaries and their inpatient, outpatient, prescription drug records were used. INTERVENTIONS: Seven oral antibiotics, fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) and amoxicillin, amoxicillin-clavulanate, azithromycin and cephalexin. PRIMARY AND SECONDARY OUTCOME MEASURES: All tendon ruptures combined, and three types of tendon ruptures by anatomic site, Achilles tendon rupture, rupture of rotator cuff and other tendon ruptures occurred in 2007-2016. RESULTS: Of three fluoroquinolones, only levofloxacin exhibited a significant increased risk of tendon ruptures-16% (HR=1.16; 95% CI 1.06 to 1.28), and 120% (HR=2.20; 95% CI 1.50 to 3.24) for rotator cuff and Achilles tendon rupture, respectively, in the ≤30 days window. Ciprofloxacin (HR=0.96; 95% CI 0.89 to 1.03) and moxifloxacin (HR=0.59; 95% CI 0.37 to 0.93) exhibited no increased risk of tendon ruptures combined.Among the non-fluoroquinolone antibiotics, cephalexin exhibited increased risk of combined tendon ruptures (HR=1.31; 95% CI 1.22 to 1.41) and modest to large risks across all anatomic rupture sites (HRs 1.19-1.93) at ≤30 days window. Notably, the risk of levofloxacin never exceeded the risk of the non-fluoroquinolone, cephalexin in any comparison. CONCLUSIONS: In our study, fluoroquinolones as a class were not associated with the increased risk of tendon ruptures. Neither ciprofloxacin nor moxifloxacin exhibited any risk for tendon ruptures. Levofloxacin did exhibit significant increased risk. Cephalexin with no reported effect on metalloprotease activity had an equal or greater risk than levofloxacin; so we question whether metalloprotease activity has any relevance to observed associations with tendon rupture. Confounding by indication bias may be more relevant and should be given more consideration as explanation for significant associations in observational studies of tendon rupture.

Computerized monitoring of COVID-19 trials, studies and registries in ClinicalTrials.gov registry.

Clinical trial registries can provide important information about relevant studies for a given condition to other researchers and the public. We developed a computerized informatics based approach to provide an overview and analysis of COVID-19 studies registered on ClinicalTrials.gov registry. Using the perspective of analyzing active or completed COVID-19 studies, we identified 401 interventional clinical trials, 287 observational studies and 64 registries. We analyzed features of each study type separately such as location, design, interventions and update history. Our results show that the United States had the most COVID-19 interventional trials, France had the most COVID-19 observational studies and France and the United States tied for the most COVID-19 registries on ClinicalTrials.gov. The majority of studies in all three study types had a single study site. For update history "Study Status" is the most updated information and we found that studies located in Canada (2.70 updates per study) and the United States (1.76 updates per study) update their studies more often than studies in any other country. Using normalization and mapping techniques, we identified Hydroxychloroquine (92 studies) as the most common drug intervention, while convalescent plasma (20 studies) is the most common biological intervention. The primary purpose of most interventional trials is for treatment with 298 studies (74.3%). For COVID-19 registries we found the most common proposed follow-up time is 1 year (15 studies). Of specific importance and interest is COVID-19 vaccine trials, of which 12 were identified. Our informatics based approach allows for constant monitoring and updating as well as multiple applications to other conditions and interests.

Baseline phenotype and 30-day outcomes of people tested for COVID-19: an international network cohort including >3.32 million people tested with real-time PCR and >219,000 tested positive for SARS-CoV-2 in South Korea, Spain and the United States.

Early identification of symptoms and comorbidities most predictive of COVID-19 is critical to identify infection, guide policies to effectively contain the pandemic, and improve health systems' response. Here, we characterised socio-demographics and comorbidity in 3,316,107persons tested and 219,072 persons tested positive for SARS-CoV-2 since January 2020, and their key health outcomes in the month following the first positive test. Routine care data from primary care electronic health records (EHR) from Spain, hospital EHR from the United States (US), and claims data from South Korea and the US were used. The majority of study participants were women aged 18-65 years old. Positive/tested ratio varied greatly geographically (2.2:100 to 31.2:100) and over time (from 50:100 in February-April to 6.8:100 in May-June). Fever, cough and dyspnoea were the most common symptoms at presentation. Between 4%-38% required admission and 1-10.5% died within a month from their first positive test. Observed disparity in testing practices led to variable baseline characteristics and outcomes, both nationally (US) and internationally. Our findings highlight the importance of large scale characterization of COVID-19 international cohorts to inform planning and resource allocation including testing as countries face a second wave.

Baseline characteristics, management, and outcomes of 55,270 children and adolescents diagnosed with COVID-19 and 1,952,693 with influenza in France, Germany, Spain, South Korea and the United States: an international network cohort study.

Objectives To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children/adolescents diagnosed or hospitalized with COVID-19. Secondly, to describe health outcomes amongst children/adolescents diagnosed with previous seasonal influenza. Design International network cohort. Setting Real-world data from European primary care records (France/Germany/Spain), South Korean claims and US claims and hospital databases. Participants Diagnosed and/or hospitalized children/adolescents with COVID-19 at age <18 between January and June 2020; diagnosed with influenza in 2017-2018. Main outcome measures Baseline demographics and comorbidities, symptoms, 30-day in-hospital treatments and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome (ARDS), multi-system inflammatory syndrome (MIS-C), and death. Results A total of 55,270 children/adolescents diagnosed and 3,693 hospitalized with COVID-19 and 1,952,693 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were all more common among those hospitalized vs diagnosed with COVID-19. The most common COVID-19 symptom was fever. Dyspnea, bronchiolitis, anosmia and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital treatments for COVID-19 included repurposed medications (<10%), and adjunctive therapies: systemic corticosteroids (6.8% to 37.6%), famotidine (9.0% to 28.1%), and antithrombotics such as aspirin (2.0% to 21.4%), heparin (2.2% to 18.1%), and enoxaparin (2.8% to 14.8%). Hospitalization was observed in 0.3% to 1.3% of the COVID-19 diagnosed cohort, with undetectable (N<5 per database) 30-day fatality. Thirty-day outcomes including pneumonia, ARDS, and MIS-C were more frequent in COVID-19 than influenza. Conclusions Despite negligible fatality, complications including pneumonia, ARDS and MIS-C were more frequent in children/adolescents with COVID-19 than with influenza. Dyspnea, anosmia and gastrointestinal symptoms could help differential diagnosis. A wide range of medications were used for the inpatient management of pediatric COVID-19.

Analysis of data dictionary formats of HIV clinical trials.

BACKGROUND: Efforts to define research Common Data Elements try to harmonize data collection across clinical studies. OBJECTIVE: Our goal was to analyze the quality and usability of data dictionaries of HIV studies. METHODS: For the clinical domain of HIV, we searched data sharing platforms and acquired a set of 18 HIV related studies from which we analyzed 26 328 data elements. We identified existing standards for creating a data dictionary and reviewed their use. To facilitate aggregation across studies, we defined three types of data dictionary (data element, forms, and permissible values) and created a simple information model for each type. RESULTS: An average study had 427 data elements (ranging from 46 elements to 9 945 elements). In terms of data type, 48.6% of data elements were string, 47.8% were numeric, 3.0% were date and 0.6% were date-time. No study in our sample explicitly declared a data element as a categorical variable and rather considered them either strings or numeric. Only for 61% of studies were we able to obtain permissible values. The majority of studies used CSV files to share a data dictionary while 22% of the studies used a non-computable, PDF format. All studies grouped their data elements. The average number of groups or forms per study was 24 (ranging between 2 and 124 groups/forms). An accurate and well formatted data dictionary facilitates error-free secondary analysis and can help with data de-identification. CONCLUSION: We saw features of data dictionaries that made them difficult to use and understand. This included multiple data dictionary files or non-machine-readable documents, data elements included in data but not in the dictionary or missing data types or descriptions. Building on experience with aggregating data elements across a large set of studies, we created a set of recommendations (called CONSIDER statement) that can guide optimal data sharing of future studies.

Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.

Comparative safety and effectiveness of alendronate versus raloxifene in women with osteoporosis.

Alendronate and raloxifene are among the most popular anti-osteoporosis medications. However, there is a lack of head-to-head comparative effectiveness studies comparing the two treatments. We conducted a retrospective large-scale multicenter study encompassing over 300 million patients across nine databases encoded in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The primary outcome was the incidence of osteoporotic hip fracture, while secondary outcomes were vertebral fracture, atypical femoral fracture (AFF), osteonecrosis of the jaw (ONJ), and esophageal cancer. We used propensity score trimming and stratification based on an expansive propensity score model with all pre-treatment patient characteritistcs. We accounted for unmeasured confounding using negative control outcomes to estimate and adjust for residual systematic bias in each data source. We identified 283,586 alendronate patients and 40,463 raloxifene patients. There were 7.48 hip fracture, 8.18 vertebral fracture, 1.14 AFF, 0.21 esophageal cancer and 0.09 ONJ events per 1,000 person-years in the alendronate cohort and 6.62, 7.36, 0.69, 0.22 and 0.06 events per 1,000 person-years, respectively, in the raloxifene cohort. Alendronate and raloxifene have a similar hip fracture risk (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.94-1.13), but alendronate users are more likely to have vertebral fractures (HR 1.07, 95% CI 1.01-1.14). Alendronate has higher risk for AFF (HR 1.51, 95% CI 1.23-1.84) but similar risk for esophageal cancer (HR 0.95, 95% CI 0.53-1.70), and ONJ (HR 1.62, 95% CI 0.78-3.34). We demonstrated substantial control of measured confounding by propensity score adjustment, and minimal residual systematic bias through negative control experiments, lending credibility to our effect estimates. Raloxifene is as effective as alendronate and may remain an option in the prevention of osteoporotic fracture.

Deep phenotyping of 34,128 patients hospitalised with COVID-19 and a comparison with 81,596 influenza patients in America, Europe and Asia: an international network study.

Background In this study we phenotyped individuals hospitalised with coronavirus disease 2019 (COVID-19) in depth, summarising entire medical histories, including medications, as captured in routinely collected data drawn from databases across three continents. We then compared individuals hospitalised with COVID-19 to those previously hospitalised with influenza. Methods We report demographics, previously recorded conditions and medication use of patients hospitalised with COVID-19 in the US (Columbia University Irving Medical Center [CUIMC], Premier Healthcare Database [PHD], UCHealth System Health Data Compass Database [UC HDC], and the Department of Veterans Affairs [VA OMOP]), in South Korea (Health Insurance Review & Assessment [HIRA]), and Spain (The Information System for Research in Primary Care [SIDIAP] and HM Hospitales [HM]). These patients were then compared with patients hospitalised with influenza in 2014-19. Results 34,128 (US: 8,362, South Korea: 7,341, Spain: 18,425) individuals hospitalised with COVID-19 were included. Between 4,811 (HM) and 11,643 (CUIMC) unique aggregate characteristics were extracted per patient, with all summarised in an accompanying interactive website (http://evidence.ohdsi.org/Covid19CharacterizationHospitalization/). Patients were majority male in the US (CUIMC: 52%, PHD: 52%, UC HDC: 54%, VA OMOP: 94%,) and Spain (SIDIAP: 54%, HM: 60%), but were predominantly female in South Korea (HIRA: 60%). Age profiles varied across data sources. Prevalence of asthma ranged from 4% to 15%, diabetes from 13% to 43%, and hypertensive disorder from 24% to 70% across data sources. Between 14% and 33% were taking drugs acting on the renin-angiotensin system in the 30 days prior to hospitalisation. Compared to 81,596 individuals hospitalised with influenza in 2014-19, patients admitted with COVID-19 were more typically male, younger, and healthier, with fewer comorbidities and lower medication use. Conclusions We provide a detailed characterisation of patients hospitalised with COVID-19. Protecting groups known to be vulnerable to influenza is a useful starting point to minimize the number of hospital admissions needed for COVID-19. However, such strategies will also likely need to be broadened so as to reflect the particular characteristics of individuals hospitalised with COVID-19.

Identification of Common Data Elements from Pivotal FDA Trials.

It is difficult to arrive at an efficient and widely acceptable set of common data elements (CDEs). Trial outcomes, as defined in a clinical trial registry, offer a large set of elements to analyze. However, all clinical trial outcomes is an overwhelming amount of information. One way to reduce this amount of data to a usable volume is to only use a subset of trials. Our method uses a subset of trials by considering trials that support drug approval (pivotal trials) by Food and Drug Administration. We identified a set of pivotal trials from FDA drug approval documents and used primary outcomes data for these trials to identify a set of important CDEs. We identified 76 CDEs out of a set of 172 data elements from 192 pivotal trials for 100 drugs. This set of CDEs, grouped by medical condition, can be considered as containing the most significant data elements.