Leah Burns - Academia.edu (original) (raw)

Papers by Leah Burns

Advances in Therapy

Real-world evidence (RWE) is increasingly used to complement clinical trial data for regulatory d... more Real-world evidence (RWE) is increasingly used to complement clinical trial data for regulatory decision-making and in certain cases utilized to establish the clinical effectiveness of a therapy. However, the use of RWE is not applicable for all regulatory submissions, and it can be challenging to identify appropriate use cases. An interactive tool was developed (''Decision Aid,'' https://sn.pub/TpDjZx) to assist researchers, industry, and other stakeholders in identifying regulatory situations that can benefit from leveraging RWE by organizing precedent cases based on a given regulatory objective (new product approval, labeling expansion for new indication or additional clinical data, postmarketing requirement) and type of RWE study design (external control, observational study, pragmatic trial). Key success factors ensuring fitfor-purpose data and rigorous methods (e.g., clear endpoints, minimizing bias, data completeness) are also described. The tool allows the user to navigate through the precedent cases by selecting certain regulatory objectives and/or study designs. The Decision Aid supports regulatory activities in the RWE space and encourages further use of RWE in regulatory decisionmaking.

Value in Health, Oct 1, 2017

Annals of the Rheumatic Diseases, 2016

Poster Presentations, 2017

ordered ordinal regression with outcome treatment change and variables joints (66/68 count), skin... more ordered ordinal regression with outcome treatment change and variables joints (66/68 count), skin (PASI), entheses (LEI and MASES), dactylitis (LDI) and axial disease (BASDAI) Results: 323 patients had had baseline assessment in March 2016. Their average age was 50.0 years (SD 13.8) and 49% were male. 80% patients had arthritis (19% monoarthritis, 39% oligoarthritis and 23%polyarthritis), 9% had an enthesitis subtype, 2% axial disease and 9% dactylitis. Initial treatment consisted of methotrexate (MTX) (52%), in 7% of other synthetic disease modifying antirheumatic drugs (sDMARDs) and due to treatment of psoriasis 3% biologicals. Within the different phenotypes MTX was most frequently started in polyarthritis (84%) followed by oligoarthritis (63%), monoarthritis (33%) and other phenotypes (5%). At 12 months 70% (n=148) stayed on the initial drug. Of those switched, 9 started MTX, within the initial MTX users (n=74) almost equal percentages stopped, switched to metoject or biological (4%). A smaller percentage (2%) switch to leflunomide. Changes in medication were driven by swollen joint count and the presence of dactylitis (Table 1) Conclusions: MTX was initiated in about half of the early PsA patients. The majority of patients were kept on the initial treatment strategy in first year. Failure on initial drug led to variation in subsequent drugs with additional start of other sdmards, switch subcutaneuous MTX, to other sdmards or to biological dmards. Treatment change was driven by Swollen Joint Count and presence of Dactylitis. Skin, Enthesis and Axial disease did not play a role in escalating treatment.

Epidemiological studies increasingly inform Alzheimer’s disease (AD) public health impact, preven... more Epidemiological studies increasingly inform Alzheimer’s disease (AD) public health impact, prevention strategies,drugtargets,therapeutic interventions,and clinicaltrial design. For this reason, the Alzheimer’s Association Research Roundtable convened an international group of AD experts with experience in conducting both observational and clinical trials for a meeting on October 19 and 20, 2010, in Washington, DC, to discuss the role of epidemiologic studies in AD research and therapeutic advances. Topicsincluded wellness markers and risk factors, with a focus on specialpopulations such as those at elevated risk, super agers, and underserved populations. Discussions also highlighted lessons learned from observational studies of aging, cardiovascular disease, and other disease areas, as well as how new technologies have enabled the gathering of data relevant to drug development and clinical trial conduct. 2012 The Alzheimer’s Association. All rights reserved.

Diabetes Care

OBJECTIVE Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver d... more OBJECTIVE Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) and is strongly associated with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NASH have increased risk for adverse clinical outcomes, leading to higher risk for mortality and morbidity. We built a Markov model with 1-year cycles and 20-year horizon to estimate the economic burden of NASH with T2DM in the U.S. RESEARCH DESIGN AND METHODS Cohort size was determined by population size, prevalence of T2DM, and prevalence and incidence of NASH in 2017. The model includes 10 health states—NAFL, NASH fibrosis stages F0 through F3, compensated and decompensated cirrhosis, hepatocellular carcinoma, 1 year post–liver transplant, and post–liver transplant—as well as liver-related, cardiovascular, and background mortality. Transition probabilities were calculated from meta-analyses and literature. Annual costs for NASH and T2DM were taken from literature and billing cod...

Blood

Background: Metabolic changes such as Type II Diabetes Mellitus (T2DM) and hyperlipidemia (HLD) h... more Background: Metabolic changes such as Type II Diabetes Mellitus (T2DM) and hyperlipidemia (HLD) have been reported in patients receiving BCR-ABL tyrosine kinase inhibitor (TKI) therapy. Incidence of metabolic outcomes in this population has not been evaluated in large, real-world studies. The purpose of this study was to determine incidence and risk for T2DM and HLD in commercially and Medicare insured US patients prescribed dasatinib or nilotinib as first or second line therapy for CML. Methods: A retrospective cohort study using the MarketScan healthcare claims was conducted. Patients ≥18 years with ≥2 inpatient or outpatient claims for CML (ICD-9 205.10-205.12) separated by at least 30 days and ≥1 prescription for dasatinib or nilotinib from July 2006- December 2014 were eligible. Patients were required to have continuous enrollment for ≥6 months prior to the first TKI prescription (index date) and no exposure to a TKI other than imatinib during the pre-index period. No minimum f...

Journal of Clinical Oncology

e18108Background: Lipid metabolism is affected to varying levels in patients receiving BCR-ABL ty... more e18108Background: Lipid metabolism is affected to varying levels in patients receiving BCR-ABL tyrosine kinase inhibitor (TKI) therapy. Resultant hyperlipidemia (HLD) is not well documented in larg...

Journal of Hepatology

BACKGROUND AND AIMS Although Non-alcoholic fatty liver disease (NAFLD), Non-alcoholic steatohepat... more BACKGROUND AND AIMS Although Non-alcoholic fatty liver disease (NAFLD), Non-alcoholic steatohepatitis (NASH) and NASH with advanced fibrosis are closely associated with type 2 diabetes mellitus (T2DM), their global prevalence rates have not been not well described. Our aim was to estimate the prevalence of NAFLD, NASH, and advanced fibrosis among T2DM patients by regions of the world. METHODS PubMed, Ovid-Medline, EMBASE and Web of Science were searched from January 1989 to September 2018 for terms involving NAFLD, NASH, and T2DM. Strict exclusion criteria were applied. Regional and global mean prevalence weighted by population size in each country were estimated and pooled using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS Among 80 studies from 20 countries that met our inclusion criteria, there were 49,419 subjects with T2DM (mean age 58.5 years, mean BMI 27.9 kg/m2, and males 52.9%). The global prevalence of NAFLD among T2DM patients was 55.5% (95% CI: 47.3-63.7). Studies from Europe reported the highest prevalence (68.0% [62.1-73.0]). Among 10 studies that estimated the prevalence of NASH, the global prevalence of NASH among subjects with T2DM was 37.3% (95% CI: 24.7-50.0). Seven studies estimated the prevalence of advanced fibrosis in patients with NAFLD and T2DM to be 17.0% (95% CI: 7.2-34.8). Meta-regression models showed that geographic region and mean age (p<.05) were associated with the prevalence of NAFLD, jointly accounting for 63.9% of the heterogeneity. CONCLUSIONS This study provides the global prevalence rates for NAFLD, NASH, and advanced fibrosis in patients with T2DM. These data can be used to estimate the clinical and economic burden of NASH in patients with T2DM around the world. LAY SUMMARY Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is an important risk factor for NAFLD. Additionally, T2DM seems to accelerate the progression of liver disease in NAFLD. Despite the high prevalence and serious clinical implications of NAFLD in patients with T2DM,it is usually overlooked in clinical practice. This meta-analysis provides evidence supporting high prevalence of NAFLD and NASH in patients with T2DM. In this context, increasing awareness about the importance of NAFLD in patients with T2DM among all important stakeholders (primary care physicians, specialists, and health policy makers) must be prioritized.

Thrombosis and Haemostasis

In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin... more In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin ...

Current medical research and opinion, Jan 2, 2017

Evaluate the incidence of Type 2 Diabetes Mellitus (T2DM) and hyperlipidemia (HLD) in CML patient... more Evaluate the incidence of Type 2 Diabetes Mellitus (T2DM) and hyperlipidemia (HLD) in CML patients initiating therapy with dasatinib or nilotinib. Retrospective study using MarketScan claims from 1/2006-12/2014. The first analysis evaluated occurrence of T2DM, defined as ≥2 claims with a T2DM ICD-9 code or 1 diagnosis claim and an anti-diabetic medication. The second analysis evaluated occurrence of HLD, defined as ≥2 claims with an HLD ICD-9 code, or 1 diagnosis claim and an anti-HLD medication. Incidence rates were computed as number of events divided by sum of person years (PY) at risk for all subjects. Multivariate Cox proportional hazards models estimated hazard ratios (HR) for T2DM or HLD. 2,004 and 1,280 patients met criteria for the T2DM analysis (n = 1,272 dasatinib, n = 732 nilotinib) and HLD analysis (n = 845 dasatinib, n = 435 nilotinib). Incidence rate of T2DM was 40.4 per 1,000 PY for nilotinib (95% CI: 27.60, 56.98), and 17.6 per 1,000 PY (95% CI: 11.14, 26.38) for da...

Journal of the American College of Cardiology

Background: Heart failure (HF) clinical heterogeneity constitutes a dilemma for risk stratificati... more Background: Heart failure (HF) clinical heterogeneity constitutes a dilemma for risk stratification and treatment. Unsupervised phenotyping techniques might help in characterizing HF subpopulations and improving risk stratification. Methods: Electronic medical records (EMRs) for chronic stable HF

Journal of the American College of Cardiology, 2016

Limited information is available about safety and resource utilization among non-valvular atrial ... more Limited information is available about safety and resource utilization among non-valvular atrial fibrillation (NVAF) patients treated with oral anticoagulants in the real-world setting. This study assessed incidence of all-cause and major bleeding (MB)-related hospitalization and length of stay (LOS

Neurobiology of Aging, 2012

Value in Health, 2013

Disease etiology may be regarded as a consequence of both genotypic and biochemical phenomena, wh... more Disease etiology may be regarded as a consequence of both genotypic and biochemical phenomena, which impact individual patients in different ways. Disease prognosis, beneficial treatment response, and susceptibility to adverse drug effects are often intimately tied to individual biology. Clinical and genetic biomarkers applied individually or in concert are increasingly used to stratify patient populations in terms of prognosis, therapeutic benefit, or safety. As a result, clinical trialists are challenged to design studies that reflect these determinants of outcome, to optimize the patient's eventual clinical course both in the trial and in actual practice. These designs are informed both by preclinical studies and by real-world research that can establish proof of concept for a novel biomarker and provide a basic understanding of the relationship between biomarker and clinical outcome. As clinical and real-world studies unfold, a deeper understanding of the nature of the biomarker and its potential uses in drug development is gained. Specifically, one can eventually define the biomarker as prognostic (i.e., predicts disease progression), predictive (predicts treatment response or adverse outcome(s)), or exhibiting both prognostic and predictive properties. One must further validate the performance of these emerging biomarkers, again in both the trial and real-world environments. The eventual adoption of the biomarker as a useful pharmacodiagnostic test is premised upon this early translational research. In this article, the development and validation of predictive and prognostic biomarkers is discussed by using selected examples that highlight factors contributing to the valuation of biomarkers and their application to personalized medicine in the real world.

Neurology, 2013

Objective: Data from the Einstein Aging Study (EAS) were used to prospectively evaluate the free ... more Objective: Data from the Einstein Aging Study (EAS) were used to prospectively evaluate the free recall score from the Free and Cued Selective Reminding Test (FCSRT-FR) and Logical Memory I immediate recall (LM-IR) subtest of the Wechsler Memory Scale-Revised for prediction of incident Alzheimer disease (AD) dementia among individuals from a community-based cohort with memory complaints. Methods: Analyses included 854 participants, age $70 years, who initially had no dementia, and had memory complaints. Clinic evaluations were completed annually and AD dementia was diagnosed using standard criteria (n 5 86 cases; average follow-up 4.1 years). Time-dependent receiver operating characteristic analysis was used to evaluate the prognostic ability of FCSRT-FR and LM-IR for incident AD over various durations of follow-up. Results: For identifying those with memory complaints who will develop incident AD dementia over 2-4 years, the FCSRT-FR had better operating characteristics than LM-IR. APOE e4 status, age, and education did not affect cut points; however, positive predictive values were higher among APOE e4-positive individuals. Conclusions: For follow-up intervals of 2-4 years, the FCSRT-FR is more predictive than the LM-IR for identifying individuals with memory complaints who will develop incident AD. APOE e4 status improves positive predictive value, but does not affect the choice of optimal cuts. Neurology â 2013;80:1307-1314 GLOSSARY AD 5 Alzheimer disease; AUC 5 area under the receiver operating characteristic curve; CDR 5 Clinical Dementia Rating; CERAD 5 Consortium to Establish A Registry for Alzheimer's Disease; CI 5 confidence interval; DSM-IV 5 Diagnostic and Statistical Manual of Mental Disorders, 4th edition; EAS 5 Einstein Aging Study; FCSRT-FR 5 free recall score from the Free and Cued Selective Reminding Test; HSA 5 Health Self-Assessment Form; LM-IR 5 Logical Memory I immediate recall; MCI 5 mild cognitive impairment; PPV 5 positive predictive value; ROC 5 receiver operating characteristic.

Neurobiology of Aging, 2013

Our aim was to compare the predictive accuracy of 4 different medial temporal lobe measurements f... more Our aim was to compare the predictive accuracy of 4 different medial temporal lobe measurements for Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Manual hippocampal measurement, automated atlas-based hippocampal measurement, a visual rating scale (MTA-score), and lateral ventricle measurement were compared. Predictive accuracy for AD 2 years after baseline was assessed by receiver operating characteristics analyses with area under the curve as outcome. Annual cognitive decline was assessed by slope analyses up to 5 years after baseline. Correlations with biomarkers in cerebrospinal fluid (CSF) were investigated. Subjects with MCI were selected from the Development of Screening Guidelines and Clinical Criteria for Predementia AD (DESCRIPA) multicenter study (n ¼ 156) and the single-center VU medical center (n ¼ 172). At follow-up, area under the curve was highest for automated atlas-based hippocampal measurement (0.71) and manual hippocampal measurement (0.71), and lower for MTA-score (0.65) and lateral ventricle (0.60). Slope analysis yielded similar results. Hippocampal measurements correlated with CSF total tau and phosphorylated tau, not with beta-amyloid 1e42. MTAscore and lateral ventricle volume correlated with CSF beta-amyloid 1e42. We can conclude that volumetric hippocampal measurements are the best predictors of AD conversion in subjects with MCI.