Mukul Singhal

Real-World Evidence in Pain Research: A Review of Data Sources

ABSTRACT Outcomes research studies use clinical and administrative data generated in the course of patient care or from patient surveys to examine the effectiveness of treatments. Health care providers need to understand the limitations and strengths of the real-world data sources used in outcomes studies to meaningfully use the results. This paper describes five types of databases commonly used in the United States for outcomes research studies, discusses their strengths and limitations, and provides examples of each within the context of pain treatment. The databases specifically discussed are generated from (1) electronic medical records, which are created from patient-provider interactions; (2) administrative claims, which are generated from providers’ and patients’ transactions with payers; (3) integrated health systems, which are generated by systems that provide both clinical care and insurance benefits and typically represent a combination of electronic medical record and claims data; (4) national surveys, which provide patient-reported responses about their health and behaviors; and (5) patient registries, which are developed to track patients with a given disease or exposure over time for specified purposes, such as population management, safety monitoring, or research.

Assessment of HER2 testing patterns, HER2+ disease, and the utilization of HER2-directed therapy in early breast cancer

Context Determining human epidermal growth factor receptor 2 (HER2) status is critical for the management of early-stage breast cancer (ESBC). An understanding of HER2 testing practices can provide insight into how test results influence the use of HER2-directed therapy. Objective To assess HER2 testing, HER2+ disease, and HER2-directed therapy in ESBC at the Huntsman Cancer Institute before and after the 2007 American Society of Clinical Oncology and College of American Pathologist (ASCO/CAP) guidelines on HER2 testing were published. Methods Patients were identified from an institutional tumor registry. HER2 testing patterns and results were examined using a chart review of pathology and clinical notes. Patient characteristics, HER2+ rate, and trastuzumab use were evaluated descriptively. Discordance rate with reflex testing (immunohistochemistry [IHC]2+ retested by fluorescence in situ hybridization [FISH]) was also evaluated. Results A total of 1,459 women were included (mean age: 57 years). The rate of HER2+ disease was 17% (number [N] =245). The discordance rate between IHC2+ and FISH was 10%. After the 2007 ASCO/CAP guidelines, fewer tumors were classified as IHC3+ (16% post- versus 21.9% pre-2007), more tumors were characterized as IHC2+ (26.4% post- versus 20.7% pre-2007), and the overall HER2+ rate was decreased (18.7% versus 21.9%), but this was not statistically significant (P=0.519). Most patients with HER2+ ESBC received HER2-targeted therapy (N=185). Conclusion The HER2+ rate was 17% and within the range of the reported rates in the literature. Reflex testing identified additional HER2+ tumors by approximately 10%, and should be considered a potential quality indicator. ASCO/CAP HER2 testing guidelines in 2007 appeared to impact the interpretation and classification of HER2+ tumors.

Glycemic Control and Weight Outcomes for Exenatide Once Weekly Versus Liraglutide in Patients with Type 2 Diabetes: A 1-Year Retrospective Cohort Analysis.

PURPOSE Data comparing real-world effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once weekly (QW) and liraglutide in the treatment of type 2 diabetes (T2D) are limited. Furthermore, there is limited information on exenatide QW or liraglutide response by glycemic control and insulin use status. This study identifies 1-year glycosylated hemoglobin (HbA1c) and weight outcomes with exenatide QW and liraglutide in the real-world setting overall and in insulin-naive patients with uncontrolled T2D. METHODS This retrospective cohort study using national electronic medical record data compared 1-year HbA1c and weight outcomes in patients with T2D prescribed exenatide QW or liraglutide. Included patients were adults (≥18 years old) with T2D who were GLP-1RA naive when newly prescribed exenatide QW or liraglutide between January 1, 2012, and March 31, 2013 (index date). Outcomes were reported descriptively overall and in subsets of insulin-naive patients with baseline HbA1c ≥7.0% or ≥9.0%. Multivariable linear regression analyses were performed to estimate adjusted change in HbA1c and weight. FINDINGS The study included 808 exenatide QW and 4333 liraglutide patients. Mean (SD) age was 57 (11) years in both groups. Mean baseline HbA1c was 8.3% (1.5%) in exenatide QW patients and 8.4% (1.6%) in liraglutide patients (P = 0.66); 16 (2%) of the exenatide QW and 1099 (25.4%) of the liraglutide patients were newly prescribed insulin on the index date (P < 0.001). Adjusted mean HbA1c change at 1 year was -0.37% (95% CI, -0.53% to -0.21%) for exenatide QW and -0.37% (95% CI, -0.55% to -0.18%) for liraglutide. Adjusted HbA1c reduction was more pronounced in insulin-naive patients with baseline HbA1c ≥7.0% (-0.71% and -0.80% for the exenatide QW and liraglutide patients, respectively, P > 0.05) and ≥9.0% (-1.73% and -1.57% for exenatide QW and liraglutide patients, respectively, P > 0.05). Mean (adjusted) weight loss was -2.22 kg (95% CI, -3.06 to -1.37 kg) with exenatide QW and -2.21 kg (95% CI, -3.18 to -1.23 kg) with liraglutide. IMPLICATIONS Exenatide QW and liraglutide lead to similar HbA1c and weight reductions at 1 year in the real-world setting. Greater HbA1c reductions occurred in insulin-naive patients with baseline HbA1c ≥7.0%. Both agents are appropriate options for patients needing antidiabetes therapy to lower HbA1c while promoting weight loss.

Real-World Glycemic Control from GLP-1RA Therapy with and Without Concurrent Insulin in Patients with Type 2 Diabetes

BACKGROUND Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended as add-on therapy in patients with uncontrolled type 2 diabetes (T2D), with no specific guidance as to timing versus insulin. Furthermore, real-world data assessing GLP-1RA outcomes with or without concurrent insulin therapy are lacking. OBJECTIVE To identify glycemic response with GLP-1RAs by insulin use in patients with T2D at 1-year follow-up to inform decisions regarding GLP-1RA use with or without insulin. METHODS This uncontrolled retrospective cohort study included adults with T2D in the Quintiles Electronic Medical Records Database who were newly prescribed GLP-1RA therapy with exenatide once weekly or liraglutide once daily between February 1, 2012, and March 31, 2013 (index period). Primary outcomes were change in hemoglobin A1c (A1c) at 1 year and attainment of A1c < 7%, < 8%, and < 9%. Results were stratified by baseline insulin use, which was defined as no insulin use at baseline, insulin initiated with a GLP-1RA on index date, and insulin prescribed before starting GLP-1RA therapy. Secondary outcomes included 1-year weight, low-density lipoprotein cholesterol (LDL-C), and blood pressure outcomes for the study population. Adjusted mean (marginal) change in A1c at 1 year was estimated using multivariate linear regression, and multivariate logistic regression was used to estimate the likelihood of patients attaining A1c < 7% at follow-up, controlling for potential confounders. RESULTS This study included 5,141 patients with a mean (SD) age of 57.0 (10.9) years, 53.5% of whom were females, and with a mean baseline A1c of 8.4% (1.6). Overall, 35.4% had no baseline insulin use, 42.9% were prescribed insulin before starting GLP-1RA therapy, and 21.7% were started on insulin with a GLP-1RA. The adjusted mean A1c reduction at 1 year was 0.75% (95% CI = -0.86 to -0.63) for patients initiating insulin on index date, 0.61% (95% CI = -0.70 to -0.51) for patients with no baseline insulin use, and 0.23% (95% CI = -0.33 to -0.13) for patients prescribed insulin before GLP-1RA therapy. Patients with no baseline insulin or who coinitiated insulin and a GLP-1RA were more likely to attain A1c < 7% at follow-up versus patients prescribed insulin before initiating GLP-1RA therapy (OR = 1.50, 95% CI = 1.08 to 2.09 and OR = 1.85, 95% CI = 1.30 to 2.62, respectively). At 1-year follow-up, significant improvements in weight, LDL-C, and blood pressures were also observed. CONCLUSIONS GLP-1RA therapy was associated with significant improvements in glycemic control when used with or without insulin, as well as reductions in weight and LDL-C overall. However, greater A1c reductions and a higher likelihood of attaining A1c goal levels were observed when a GLP-1RA was initiated alone or with insulin than when a GLP-1RA was added to a regimen that included insulin. GLP-1RA therapy is an effective treatment option when used with or without insulin and may be considered in patients with uncontrolled glycemia. DISCLOSURES The study was funded by a collaborative research grant from AstraZeneca. Employees of AstraZeneca participated in most aspects of the study and in manuscript preparation. Nguyen and Hurd are employed by, and hold stock in, AstraZeneca. McAdam-Marx reports participation in the AMCP Diabetes Partnership and has stock ownership in GlaxoSmithKline. Study concept and design were contributed by Nguyen, McAdam-Marx, and Singhal, along with Unni and Schauerhamer. Singhal, Unni, Nguyen, and McAdam-Marx collected the data, with assistance from Schauerhamer and Hurd, and data interpretation was performed by Unni, Hurd, McAdam-Marx, Singhal, Nguyen, and Schauerhamer. The manuscript was written by Singhal, Schauerhamer, Unni, and McAdam-Marx, along with Nguyen and Hurd, and revised by McAdam-Marx, Singhal, Unni, and Nguyen, along with Schauerhamer and Hurd.