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

Circulation ◽  
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

scholarly journals Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

2021 ◽  
Vol 14 (7) ◽  
pp. 700
Author(s):  
Theodoros Mavridis ◽  
Christina I. Deligianni ◽  
Georgios Karagiorgis ◽  
Ariadne Daponte ◽  
Marianthi Breza ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Real World ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Clinical Investigation ◽  
Phase Iii ◽  
Real World Evidence ◽  
Symptomatic Management ◽  
Repurposed Drugs ◽  
Cephalic Pain

Now more than ever is the time of monoclonal antibody use in neurology. In headaches, disease-specific and mechanism-based treatments existed only for symptomatic management of migraines (i.e., triptans), while the standard prophylactic anti-migraine treatments consist of non-specific and repurposed drugs that share limited safety profiles and high risk for interactions with other medications, resulting in rundown adherence rates. Recent advances in headache science have increased our understanding of the role of calcitonin gene relate peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) pathways in cephalic pain neurotransmission and peripheral or central sensitization, leading to the development of monoclonal antibodies (mAbs) or small molecules targeting these neuropeptides or their receptors. Large scale randomized clinical trials confirmed that inhibition of the CGRP system attenuates migraine, while the PACAP mediated nociception is still under scientific and clinical investigation. In this review, we provide the latest clinical evidence for the use of anti-CGRP in migraine prevention with emphasis on efficacy and safety outcomes from Phase III and real-world studies.

scholarly journals Awareness, Knowledge, and Utility of RCT Data vs RWE: Results From a Survey of US Cardiologists: Real-world Evidence in Clinical Decision Making

2020 ◽  
Vol 14 ◽  
pp. 117954682095341 ◽  
Author(s):  
Todd C Villines ◽  
Mark J Cziraky ◽  
Alpesh N Amin
Keyword(s):  
Decision Making ◽  
Clinical Practice ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
The Body ◽  
Representative Sampling ◽  
Real World Evidence ◽  
Wide Range

Real-world evidence (RWE) provides a potential rich source of additional information to the body of data available from randomized clinical trials (RCTs), but there is a need to understand the strengths and limitations of RWE before it can be applied to clinical practice. To gain insight into current thinking in clinical decision making and utility of different data sources, a representative sampling of US cardiologists selected from the current, active Fellows of the American College of Cardiology (ACC) were surveyed to evaluate their perceptions of findings from RCTs and RWE studies and their application in clinical practice. The survey was conducted online via the ACC web portal between 12 July and 11 August 2017. Of the 548 active ACC Fellows invited as panel members, 173 completed the survey (32% response), most of whom were board certified in general cardiology (n = 119, 69%) or interventional cardiology (n = 40, 23%). The survey results indicated a wide range of familiarity with and utilization of RWE amongst cardiologists. Most cardiologists were familiar with RWE and considered RWE in clinical practice at least some of the time. However, a significant minority of survey respondents had rarely or never applied RWE learnings in their clinical practice, and many did not feel confident in the results of RWE other than registry data. These survey findings suggest that additional education on how to assess and interpret RWE could help physicians to integrate data and learnings from RCTs and RWE to best guide clinical decision making.

Real-world evidence of male breast cancer (BC) patients treated with palbociclib (PAL) in combination with endocrine therapy (ET).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1055-1055 ◽  
Author(s):  
Cynthia Huang Bartlett ◽  
Jack Mardekian ◽  
Michelle Yu-Kite ◽  
Matthew James Cotter ◽  
Sindy Kim ◽  
...  
Keyword(s):  
Real World ◽  
Randomized Clinical Trials ◽  
Treatment Guidelines ◽  
Healthcare Providers ◽  
First Line ◽  
Duration Of Treatment ◽  
Real World Data ◽  
The Real ◽  
Real World Evidence ◽  
Line Setting

1055 Background: The rarity of BC in men limits the feasibility of randomized clinical studies in this population. Treatment guidelines recommend that men with BC be treated similarly to postmenopausal women. PAL, a cyclin-dependent kinase 4/6 inhibitor, is used in men with metastatic BC (mBC) in real-world clinical practice, presenting an opportunity to utilize real-world evidence to enable healthcare providers to assess novel agents in this space. Methods: Two parallel approaches were taken. In the first approach, pharmacy and medical claims data from IQVIA Inc were retrospectively analyzed to describe the treatment patterns and duration of PAL + ET (aromatase inhibitor or fulvestrant) compared to ET in men with mBC. The second approach was a retrospective analysis of data derived from electronic health records in the Flatiron Health database to understand real-world clinical response to PAL + ET vs ET alone. Median duration of treatment (mDOT) was estimated by the Kaplan-Meier method. Results: Between Feb 2015 and Apr 2017, 12.9% (147/1139 [IQVIA dataset]) of men receiving treatment for mBC were prescribed PAL + ET for any line of therapy. The mDOT in the first-line setting was numerically longer in the PAL cohort (n=37) compared with the non-PAL cohort (n=214; 8.5 vs 4.3 mo, respectively). In particular, mDOT in the first-line setting was longer with PAL + letrozole (LET; n=26) than with LET alone (n=63; 9.4 vs 3.0 mo, respectively). In the Flatiron Health dataset between Feb 2015 and July 2017, the real-world maximum response rate in the PAL + ET cohort across all lines of therapy in the mBC setting (n=12) was 33.3% (2 complete responses [CR], 2 partial responses [PR]) vs 12.5% (0 CR, 1 PR) for the ET alone cohort (n=8). Conclusions: The real-world data sources used in this study support that men with mBC derive clinical benefit from the addition of PAL to ET. Given the challenges of conducting randomized clinical trials in men with mBC, noninterventional, real-world evidence data appear to be useful to delineate the benefit of such therapies in this setting. Funding: Pfizer.

scholarly journals Atrial fibrillation: Importance of real world data from regional registries. A focus on the BALKAN-AF registry

2020 ◽  
Vol 26 (1) ◽  
pp. 5-9
Author(s):  
Monika Kozieł ◽  
Gregory Y. H. Lip ◽  
Tatjana S. Potpara
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Real World ◽  
Randomized Clinical Trials ◽  
European Population ◽  
Real World Data ◽  
The Balkans ◽  
Real World Evidence ◽  
Patient Groups ◽  
End Stage

Real world registries of patients with atrial fi brillation (AF) have provided important evidence on contemporary AF management and adherence to guidelines in real-world patients across most of regions in Europe. While prospective randomized clinical trials are the ‘gold standard’ of evidence, we recognize that trials have specifi c inclusion/exclusion criteria and many groups of patients can be under-represented. Thus, real world evidence is needed to supplement and augment the evidence, especially for the under-represented patient groups (eg. the very elderly and frail, ethnic minorities, end stage renal failure, those in nursing homes, cognitive impairment, etc) that have been largely under-represented or excluded from clinical trials. The BALKAN-AF survey is the largest prospective, multicenter (a total of 49 centres), observational AF dataset from the Balkans, a European region inhabited by about 10% of the European population that has been under-represented in many prior clinical trials or registries. In BALKAN-AF, data regarding consecutive subjects with electrocardiographically documented non-valvular AF were collected in seven Balkan countries (Albania, Bosnia & Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia) by a cardiologist or an internal medicine specialist where cardiologist was not available. The Serbian Atrial Fibrillation Association created and conducted the BALKAN-AF survey (performed from December 2014 to February 2015).

scholarly journals Real World Evidence: welcome to reality!

2020 ◽  
Vol 23 (1) ◽  
pp. 75
Author(s):  
Pintaudi, B.
Keyword(s):  
Real World ◽  
Randomized Clinical Trials ◽  
Relevant Information ◽  
Administrative Databases ◽  
Real World Data ◽  
World Data ◽  
Real World Evidence ◽  
History Of ◽  
The Times ◽  
Concrete Face

Real World Data (RWD) constitute a set of information sources on which the very current line of research of Real World Evidence (RWE) is based. RWE studies are based on data from observational studies, administrative databases, population or disease registers, insurance registers, electronic medical records, population health surveys and, more recently, social media and data from mobile devices and apps. While Randomized Clinical Trials (RCTs) answer the question “Can it work?” “Is it safe?” RWDs are more interested in answering the question “Does it work?”. We therefore move from a question of “efficacy / safety” to one of “effectiveness”. RWE studies allow to evaluate the safety of a treatment in a longer period than that of the RCTs, verify its quality and cost effectiveness, allow us to trace the natural history of a disease conditioned or not by a treatment, give us relevant information on compliance and on adherence to treatments and allow us to identify service models and patient preferences. Given the exciting perspective that the “real” vision of things outlines, AMD has decided to keep up with the times by forming a Group of work on “Real World Evidence”. The activities that the RWE Working Group is already promoting and carrying out are: 1) support for the publication of clinical cases; 2) support for the drafting of research protocols; 3) analysis of the Annals database. Addressing Real World Evidence in the widest possible way by collaborating with interested AMD Members, aligning with the need to give a concrete face to things, represents the vision of this Group. “Welcome to reality”! KEY WORD Real World Data, Real World Evidence, effectiveness.

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

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 &gt;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 &lt; 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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