Real world evidence of calcifediol use and mortality rate of COVID-19 hospitalized in a large cohort of 16,401 Andalusian patients

AbstractBackgroundCOVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19.MethodsWe present a retrospective survival study that includes all Andalusian patients hospitalized between January and November 2020 because of COVID-19 infection. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15-30 days before hospitalization were recorded. The effect of treatment with vitamin D metabolites for other indication previous to the hospitalization was studied with respect to patient survival by means of Kaplan-Meyer survival curves and Log Hazard Ratios, using a propensity score to compensate the disbalance of compared classes and the confounding factors. The availability of detailed patient data in the BPS allowed to obtain Real-World Evidence (RWE) of the effects of prior use of vitamin D or its metabolites on the mortality due to COVID-19 infection.FindingsA retrospective cohort of 16.401patients was extracted from the BPS, which includes all the patients hospitalized with COVID-19 diagnosis between January and November 2020 in Andalusia, one of the largest regions in Europe with the size of an average median country. A total of 358 patients were found with cholecalciferol, and 193 with calcifediol, prescriptions 15 days before hospitalization. For a period extended to 30 days before hospitalization, the numbers increase to 416 and 210 and, respectively. Kaplan-Meyer survival curves and hazard ratios support an association between consumption of these metabolites and patient survival. Such association was stronger in calcifediol (Log Hazard Ratio, LHR = -1.27±0.32) than in cholecalciferol (LHR= -0.56±0.15), when prescribed 15 days before hospitalization This effect decreases when a larger 30 days period is considered (calcifediol LHR= -1.01±0.27 and cholecalciferol LHR= -0.27±0.12), suggesting that the closer was the treatment to the hospitalization the stronger the association.ConclusionsA significant reduction in mortality in patients hospitalized with COVID-19 is associated with the prescription of vitamin D, especially calcifediol, within 15-30 days prior to hospitalization.

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Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients

Scientific Reports ◽

10.1038/s41598-021-02701-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Carlos Loucera ◽

María Peña-Chilet ◽

Marina Esteban-Medina ◽

Dolores Muñoyerro-Muñiz ◽

Román Villegas ◽

...

Keyword(s):

Vitamin D ◽

Retrospective Cohort ◽

Patient Survival ◽

Endocrine System ◽

Vitamin D Metabolites ◽

Kaplan Meier ◽

Hazard Ratios ◽

Real World Evidence ◽

Central Registry ◽

Health Database

AbstractCOVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19. We present a survival study on a retrospective cohort of 15,968 patients, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15–30 days before hospitalization were recorded. The effect of prescription of vitamin D (metabolites) for other indication previous to the hospitalization was studied with respect to patient survival. Kaplan–Meier survival curves and hazard ratios support an association between prescription of these metabolites and patient survival. Such association was stronger for calcifediol (Hazard Ratio, HR = 0.67, with 95% confidence interval, CI, of [0.50–0.91]) than for cholecalciferol (HR = 0.75, with 95% CI of [0.61–0.91]), when prescribed 15 days prior hospitalization. Although the relation is maintained, there is a general decrease of this effect when a longer period of 30 days prior hospitalization is considered (calcifediol HR = 0.73, with 95% CI [0.57–0.95] and cholecalciferol HR = 0.88, with 95% CI [0.75, 1.03]), suggesting that association was stronger when the prescription was closer to the hospitalization.

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855. Persistence on F/TAF versus F/TDF for HIV Pre-Exposure Prophylaxis: A Real-World Evidence Analysis in the United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1050 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S518-S519

Author(s):

Li Tao ◽

Valentina Shvachko ◽

Moupali Das ◽

Christoph C Carter ◽

Jared Baeten ◽

...

Keyword(s):

United States ◽

Real World ◽

The United States ◽

Odds Ratios ◽

Preexposure Prophylaxis ◽

Hazard Ratios ◽

Real World Evidence ◽

The Us ◽

Evidence Analysis ◽

Exposure Prophylaxis

Abstract Background Persistence to preexposure prophylaxis (PrEP) is an important determinant of its efficacy, but evidence on real-world persistence is lacking. This study assesses adherence to F/TDF and F/TAF for PrEP both in terms of discontinuation and re-initiation patterns. Methods We identified HIV-negative individuals in the United States who initiated F/TDF or F/TAF for PrEP between October 2019 and December 2020 from a de-identified prescription claims database; users taking generic F/TDF were excluded. Non-persistence was defined as a prescription fill gap of >30 days; discontinuation included switch from F/TDF to F/TAF or F/TAF to F/TDF. We used survival analyses to estimate persistence, Cox regressions to compare the hazard ratios (HR) of discontinuation, and logistic regression to compare the odds ratios of re-initiation after discontinuation. Results Among F/TAF users (N=82,402) median age at PrEP initiation was 35 years (interquartile range [IQR] 28−47) and median PrEP persistence was 4 months (IQR 1.8-8.9), compared to 31 years (IQR 25−40) and 2 months (IQR 1.0-3.8) for F/TDF users (N=48,501). PrEP persistence at 60 and 90 days was higher among F/TAF users than F/TDF users (Figure). F/TDF users were 2.5 times more likely to discontinue than F/TAF users, with more marked differences in older users than that in younger users (p for interaction between discontinuation and age group < 0.01, Table). We also observed a higher rate of discontinuation of F/TDF versus F/TAF if PrEP was prescribed by internal medicine or infectious disease physicians than by family medicine physicians (data not shown). After discontinuation, F/TAF users were 1.7 times more likely than F/TDF users to re-initiate PrEP; the association was not different by age. Persistence rates of F/TAF and F/TDF for PrEP by time of PrEP initiation Hazard ratios (HR) and corresponding 95% confidence intervals (CI) of non-persistence and odds ratios (OR) of re-initiation after discontinuation for users of F/TAF and F/TDF for PrEP in the US, Oct 2019 – Dec 2020 Conclusion In this real-world analysis, the F/TAF for PrEP regimen was associated with higher persistence and re-initiation than F/TDF for PrEP. These findings underscore the dynamic nature of PrEP utilization in the real-world and the importance of interventions aimed at improving PrEP persistence and re-initiation in people who would benefit from PrEP. Disclosures Li Tao, MD, PhD, Gilead Sciences Inc (Employee, Shareholder) Valentina Shvachko, MS, Gilead Sciences Inc (Employee, Shareholder) Moupali Das, MD, Gilead Sciences Inc. (Employee, Shareholder) Christoph C. Carter, MD, Gilead Sciences Inc. (Employee, Shareholder) Jared Baeten, MD, PHD, Gilead Sciences Inc. (Employee, Shareholder) David Magnuson, PharmD, Gilead Sciences Inc (Employee, Shareholder)

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Emulating Randomized Clinical Trials with Nonrandomized Real-World Evidence Studies: First Results from the RCT DUPLICATE Initiative

Circulation ◽

10.1161/circulationaha.120.051718 ◽

2020 ◽

Author(s):

Jessica M. Franklin ◽

Elisabetta Patorno ◽

Rishi J. Desai ◽

Robert J. Glynn ◽

David Martin ◽

...

Keyword(s):

Real World ◽

Randomized Clinical Trials ◽

Cardiovascular Effects ◽

Primary Analysis ◽

Clinical Trial Registration ◽

Use Patterns ◽

Success Criteria ◽

Hazard Ratios ◽

Real World Evidence ◽

First Results

Background: Regulators are evaluating the use of non-interventional real-world evidence (RWE) studies to assess the effectiveness of medical products. The RCT-DUPLICATE initiative uses a structured process to design RWE studies emulating randomized controlled trials (RCTs) and compare results. Here, we report findings of the first 10 trial emulations, evaluating cardiovascular outcomes of antidiabetic or antiplatelet medications. Methods: We selected 3 active-controlled and 7 placebo-controlled RCTs for replication. Using patient-level claims data from US commercial and Medicare payers, we implemented inclusion/exclusion criteria, selected primary endpoints, and comparator populations to emulate those of each corresponding RCT. Within the trial-mimicking populations, we conducted propensity score matching to control for >120 pre-exposure confounders. All study parameters were prospectively defined and protocols registered before hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. Success criteria for the primary analysis were pre-specified for each replication. Results: Despite attempts to emulate RCT design as closely as possible, differences between the RCT and corresponding RWE study populations remained. The regulatory conclusions were equivalent in 6 of 10. The RWE emulations achieved a HR estimate that was within the 95% CI from the corresponding RCT in 8 of 10 studies. In 9 of 10, either the regulatory or estimate agreement success criteria were fulfilled. The largest differences in effect estimates were found for RCTs where second-generation sulfonylureas were used as a proxy for placebo regarding cardiovascular effects. Nine of 10 replications had a standardized difference between effect estimates of <2, which suggests differences within expected random variation. Conclusions: Agreement between RCT and RWE findings varies depending on which agreement metric is used. Interim findings indicate that selection of active comparator therapies with similar indications and use patterns enhances the validity of RWE. Even in the context of active comparators, concordance between RCT and RWE findings is not guaranteed, partially because trials are not emulated exactly. More trial emulations are needed to understand how often and in what contexts RWE findings match RCTs. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifiers: NCT03936049, NCT04215523, NCT04215536, NCT03936010, NCT03936036, NCT03936062, NCT03936023, NCT03648424, NCT04237935, NCT04237922

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103. Persistence on F/TDF for HIV Pre-exposure Prophylaxis: Insights from Real-world Evidence

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.413 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S181-S181

Author(s):

Li Tao ◽

Valentina Shvachko ◽

Robertino Mera ◽

Moupali Das ◽

Christoph Carter ◽

...

Keyword(s):

Renal Dysfunction ◽

Real World ◽

Bone Fracture ◽

Clinical Characteristics ◽

Hazard Ratios ◽

Real World Evidence ◽

Younger Age ◽

History Of ◽

Exposure Prophylaxis ◽

Over Time

Abstract Background Background: Daily F/TDF is highly effective for HIV pre-exposure prophylaxis (PrEP). Prior studies have found that women and people of younger age have lower adherence and lower persistence on PrEP, yet real-world evidence describing persistence associated with other clinical characteristics and the patterns of persistence is limited. Methods Methods: We identified 313,526 HIV-1 negative individuals in the United States who initiated F/TDF for PrEP between January 1, 2012 and December 31, 2019 from a de-identified prescription claims database. PrEP users were defined as non-persistent if a gap in prescription fills >30 days was detected. We used survival analyses to estimate the persistence rate by year of PrEP initiation, and Cox regressions adjusting for multiple demographic and clinical characteristics to determine hazard ratios and corresponding 95% confidence interval of non-persistence for PrEP. Results Results: Among the 313,526 PrEP users with a median age at PrEP initiation of 35 years of age (interquartile range, IQR, 26−43), 88% were men (median days of persistence = 118, IQR 30−316 days) and 12% were women (median 30 days, IQR 30−92 days). PrEP persistence at 30, 60 and 90 days increased over time, reaching the highest levels in 2019 (Figure). In a multivariate analysis, younger age, female sex, and non-white race were associated with higher risk of non-persistence (Table). We also observed associations of a 5% lower rate of non-persistence if PrEP was prescribed by internal medicine or infectious disease physicians than by family medicine physicians, and a 13% lower rate of non-persistence associated prescriptions ordered from mail-order pharmacies than prescriptions of retail pharmacies. Finally, history of bone fracture or renal dysfunction prior to PrEP initiation were associated with a 13% and 9% higher rate of non-persistence, respectively. Figure. F/TDF for PrEP persistence rates over time. Table. Hazard ratios and corresponding 95% confidence intervals of non-persistence on F/TDF PrEP since initiation, 2012–2019 Conclusion This study demonstrates that persistence on F/TDF for PrEP has improved over time, and identifies several characteristics associated with non-persistence, including age, sex, race/ethnicity, prescriber specialty, type of pharmacy, and history of bone fracture or renal dysfunction. These findings can help to inform interventions aimed at improving PrEP persistence in people at risk of HIV. Disclosures Li Tao, MD, PhD, Gilead Sciences Inc (Employee) Valentina Shvachko, n/a, Gilead Sciences Inc (Employee) Robertino Mera, MD, PhD, Gilead Sciences Inc (Employee) Moupali Das, MD, MPH, Gilead Sciences Inc (Employee) Christoph Carter, MD, PhD, Gilead Sciences Inc (Employee) David Magnuson, PharmD, Gilead Sciences Inc (Employee)

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Abstract 13128: Development and Initial Utilization of a Multi-institutional Distributed Data Network Designed to Evaluate Real-world Clinical Outcomes in Patients Presenting for Percutaneous Coronary Intervention (PCI): Results From the Building the Unique Device Identifier (UDI) Into Longitudinal Data for Medical Device Evaluation (BUILD) Network

Circulation ◽

10.1161/circ.142.suppl_3.13128 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Joseph B Muhlestein ◽

Jove Graham ◽

James Tcheng ◽

Andrew McKinnon ◽

Stacey Knight ◽

...

Keyword(s):

Clinical Outcomes ◽

Real World ◽

Coronary Intervention ◽

Common Data Model ◽

Distributed Data ◽

Relevant Evidence ◽

Hazard Ratios ◽

Real World Evidence ◽

Chart Abstraction ◽

Drug Eluting

Introduction: Generating real-world evidence for regulatory and research purposes is a fundamental transformation of healthcare. To develop and demonstrate the operational components, we created the BUILD network, a framework for the longitudinal follow-up of all patients undergoing PCI at three large health systems, Mercy, Geisinger, and Intermountain. It leverages consistent data through a standardized common data model using distributed analyses without site-specific programming or external transfer of clinical data. To demonstrate BUILD’s potential, we evaluated clinical outcomes between two commonly used drug-eluting coronary stents. Methods: We included all patients receiving zotarolimus, or everolimus stents from 2012-19. Data were compiled from registries and electronic health/billing records systems without explicit chart abstraction, and retained at each site in the BUILD analysis database. A common query examined 32 baseline covariates, created propensity-matched cohorts, assessed for balance, and compared 1-year major adverse cardiac event (MACE) rates between groups, with weighted data combined to create event-free survival plots. Results: We identified 11,030 patients (Mercy=4,906, Geisinger=4,109, Intermountain=127; mean age 65±12, 69% males, 23% zotarolimus). Figure 1 shows hazard ratios and survival curves for the composite endpoints in matched cohorts. Differences in subsequent PCI, mortality, and composite MACE were not significantly different between stent types. Conclusions: This large real-world, multicenter demonstration project showed no statistical differences in 1-year clinical outcomes of patients receiving zotarolimus versus everolimus stents—results similar to other studies. More importantly, it demonstrated that multi-institutional data networks can be successfully developed to provide clinically relevant evidence while maintaining the source data locally on-premise at each institution.

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Safety and efficacy of direct acting oral anticoagulants and vitamin K antagonists in nonvalvular atrial fibrillation – a network meta-analysis of real-world data

VASA ◽

10.1024/0301-1526/a000746 ◽

2019 ◽

Vol 48 (2) ◽

pp. 134-147 ◽

Cited By ~ 8

Author(s):

Mirko Hirschl ◽

Michael Kundi

Keyword(s):

Real World ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Efficacy And Safety ◽

Nonvalvular Atrial Fibrillation ◽

Real World Data ◽

Hazard Ratios ◽

Direct Acting ◽

Event Rates

Abstract. Background: In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice. Materials and methods: By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies. Results: For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions. Conclusions: DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.

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