Author Interviews, Baylor College of Medicine Houston, Merck, Rheumatology / 07.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34434" align="alignleft" width="120"]Grace H. Lo MD MSc Department of Medicine, Baylor College of Medicine Medical Care Line and Research Care Line, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety Michael E. DeBakey Medical Center, Houston, TX Dr. Grace H. Lo[/caption] Grace H. Lo MD MSc Department of Medicine, Baylor College of Medicine Medical Care Line and Research Care Line, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety Michael E. DeBakey Medical Center, Houston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: Osteoarthritis is the most common form of arthritis. Many people who have signs of osteoarthritis on x-rays do not necessarily complain of pain. Presently, there are no known strategies for preventing the development of pain in this group of people. This study suggests that if these people have noisy knees (otherwise known as “crepitus”), they are at higher risk for developing pain within the next year compared to the people who do not have noisy knees. Future studies that target people who have x-ray signs of osteoarthritis, who do not complain of pain, but do report noisy knees, hold the promise of identifying interventions that can prevent knee pain.
Author Interviews, Boehringer Ingelheim, Immunotherapy, Pulmonary Disease / 27.04.2017

MedicalResearch.com Interview with: [caption id="attachment_34196" align="alignleft" width="167"]Thomas Leonard, Ph.D. Executive director, Clinical Development and Medical Affairs, Specialty Care Boehringer Ingelheim Pharmaceuticals, Inc. Dr. Thomas Leonard[/caption] Thomas Leonard, Ph.D. Executive director, Clinical Development and Medical Affairs, Specialty Care Boehringer Ingelheim Pharmaceuticals, Inc. MedicalResearch.com: What is the background for this study? Would you tell us a little more about IPF? Response: Boehringer Ingelheim’s Phase III PF-ILD (progressive fibrosing interstitial lung disease) trial will investigate the safety and efficacy of nintedanib, in a range of progressive fibrosing lung conditions other than idiopathic pulmonary fibrosis, or IPF. The PF-ILD trial is the first time that patients with different fibrosing lung diseases will be included in one single clinical trial assessing the efficacy of nintedanib as a potential treatment, and the trial is the first in the field of fibrosing lung diseases to group patients based on the clinical characteristics of their disease, rather than the diagnosis. There are more than 200 conditions that affect the tissue and space around the air sacs of the lungs, or interstitium, and, collectively, these conditions are called interstitial lung diseases -- or ILDs. Based on clinical observations, there is a group of patients with ILD who, independent from the classification of the ILD, exhibit progressive fibrosis. The proposed terminology for describing this group of patients is PF-ILD. In these patients, the disease appears to follow a course similar to IPF with worsening of respiratory symptoms, lung function, quality of life and ability to perform daily activities, as well as early mortality despite treatment. There is currently no efficacious treatment available for PF-ILD. This trial is exploring how fibrosis in the lungs is treated and whether nintedanib is a potential treatment, based on the efficacy and safety of nintedanib in IPF, a rare and serious lung disease that causes permanent scarring of the lungs, making it difficult to breathe. IPF affects as many as 132,000 Americans, typically men over the age of 65. On average, people with IPF live only three to five years after diagnosis, and approximately 40,000 people die from this disease every year.
Author Interviews, Biomarkers, Hepatitis - Liver Disease, Lancet, Merck / 25.04.2017

MedicalResearch.com Interview with: [caption id="attachment_34147" align="alignleft" width="200"]Jason Grebely PhD Associate Professor Senior Research Fellow (UNSW) Viral Hepatitis Clinical Research Program Dr. Grebely[/caption] Jason Grebely PhD Associate Professor Senior Research Fellow (UNSW) Viral Hepatitis Clinical Research Program MedicalResearch.com: What is the background for this study? What are the main findings? Response: Globally, testing and diagnosis of hepatitis C virus infection remain low. Although point of care tests for HCV infection exist, but many of these tests only measure HCV antibodies (previous exposure), not HCV RNA (active infection). Given that 25% of individuals spontaneously clear HCV infection, efforts to enhance diagnosis of chronic HCV infection and improve the HCV care cascade requires enhanced uptake of HCV RNA testing. We conducted the first evaluation of the Xpert HCV Viral Load test (manufactured by Cepheid) - a point-of-care hepatitis C virus test that can detect active infection - from a finger-stick sample of blood. We established that there is good sensitivity and specificity of the Xpert HCV Viral Load point-of-care test using blood samples collected by finger-stick in participants attending drug health and homelessness services in Australia.
Author Interviews, Critical Care - Intensive Care - ICUs, Merck / 24.04.2017

MedicalResearch.com Interview with: [caption id="attachment_34136" align="alignleft" width="150"]Eilish McCann, PhD</strong> Director, Outcomes Research (Center for Observational and Real-World Evidence) Merck Dr. Eilish McCann[/caption] Eilish McCann, PhD Director, Outcomes Research (Center for Observational and Real-World Evidence) Merck MedicalResearch.com: What is the background for this study? Response: One of the most pressing challenges facing medicine today is the emergence of bacterial resistance to antibiotics. One area of high concern is the increasing prevalence of resistance to powerful antibiotics like carbapenems, as patients with infections due to carbapenem-resistant bacteria have very few alternate effective treatment options. In this study we used real-world data from a Becton, Dickinson and Company electronic research data set to analyze over 140,000 bacterial isolates from patients at 342 hospitals across the United States, so that we could investigate where the burden of carbapenem resistance is most acute. Importantly analysis of real-world data in this way allows us to gain insights from a large number of hospitals, giving a broad and nationally representative picture of the resistance burden.
AstraZeneca, Author Interviews, Autism, Boehringer Ingelheim, Depression, Eli Lilly, J&J-Janssen, JAMA, Merck, OBGYNE / 17.04.2017

MedicalResearch.com Interview with: Florence Gressier MD PhD Insermk Department of psychiatry CHU de Bicêtrem Le Kremlin Bicêtre France MedicalResearch.com: What is the background for this study? What are the main findings? Response: Results from recent studies have suggested an increased risk for Autism Spectrum Disorders (ASDs) in children exposed to antidepressants in utero. We performed a systematic review of and a meta-analysis of published studies to assess the association between ASDs and fetal exposure to antidepressants during pregnancy for each trimester of pregnancy and preconception. Our systematic review and meta-analysis suggests a significant association between increased ASD risk and maternal use of antidepressants during pregnancy; however, it appears to be more consistent during the preconception period than during each trimester. In addition, the association was weaker when controlled for past maternal mental illness. Maternal psychiatric disorders in treatment before pregnancy rather than antenatal exposure to antidepressants could have a major role in the risk for Autism Spectrum Disorders.
Author Interviews, Boehringer Ingelheim, Diabetes, JAMA, Ophthalmology / 13.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33673" align="alignleft" width="170"]Marco A Zarbin, MD, PhD, FACS Alfonse Cinotti, MD/Lions Eye Research Professor and Chair Institute of Ophthalmology & Visual Science Rutgers-New Jersey Medical School Rutgers University Newark, NJ 0710 Dr. Zarbin[/caption] Marco A Zarbin, MD, PhD, FACS Alfonse Cinotti, MD/Lions Eye Research Professor and Chair Institute of Ophthalmology & Visual Science Rutgers-New Jersey Medical School Rutgers University Newark, NJ 0710  MedicalResearch.com: What is the background for this study? What are the main findings?
  1. Most large, randomized clinical trials are powered to assess the efficacy of drugs or interventions, but they usually do not enroll enough patients to accurately assess the frequency of uncommon, undesirable side effects.
  2. In order to compensate for this deficiency in trial design, investigators aggregate the results of numerous studies all of which address the same clinical question with the same (or similar) drugs/interventions to increase the power to detect uncommon side effects. These aggregate studies can be meta-analyses.
  3. Unfortunately, most meta-analyses do not have the ability to answer some critical questions such as the timing of an adverse event relative to the last exposure to the drug, nor can they compensate fully for differences among the aggregated studies in trial design, length of patient follow-up, or presence pre-existing risk factors for the side effects in question.
  4. A pooled analysis of combined clinical trials using patient level data, however, allows a more in depth analysis of side effects than study level data, which are usually used for most published meta-analyses, because patient level data allow one to incorporate the per-patient duration of exposure to treatment, adjust for imbalances in predefined baseline risk factors, and adjust for the effect of results of single studies on the overall result.
Author Interviews, Boehringer Ingelheim, Dermatology, Eli Lilly, Immunotherapy, J&J-Janssen, Merck / 30.03.2017

MedicalResearch.com Eric Hughes Global Development Franchise Head Immunology & Dermatology Novartis MedicalResearch.com: What is the background for this study? What are the main findings? Response: Psoriasis is a chronic immune-mediated inflammatory disease that negatively impacts patients’ quality of life (QOL); therefore QOL outcomes are increasingly recognized as an important measure of efficacy in psoriasis, complementing traditional measures of severity such as the Psoriasis Area and Severity Index (PASI). Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), exhibits significant efficacy in the treatment of moderate-to-severe psoriasis, ankylosing spondylitis and psoriatic arthritis, demonstrating a rapid onset of action and a favorable safety profile. Biologic therapies for psoriasis have previously been associated with a fall-off in efficacy over time; accordingly, extended follow-up is required to adequately evaluate novel therapeutic strategies like IL-17A inhibition. Recently, results from the extension of the SCULPTURE secukinumab trial showed that high responses initially achieved with secukinumab at year 1 in the SCULPTURE study were sustained over time up to 3 years with no new or unexpected safety concerns. In this analysis, we examined whether the sustained efficacy observed in SCULPTURE up to 3 years was translated into sustained effect of secukinumab on patient’s QOL measured by the Dermatology Life Quality Index (DLQI) questionnaire. SCULPTURE, a multi-center extension study, was conducted with subjects who completed 52 weeks of treatment. Subjects were randomized into two maintenance dosing regimens; a fixed-interval schedule of secukinumab 300 mg every 4 weeks (Fixed interval dosing regimen (FI) cohort), and secukinumab retreatment-as-needed (Retreatment as needed (RAN) cohort), in which subjects received placebo until start of relapse, at which time secukinumab 300 mg every 4 weeks was re-initiated. The analysis using as-observed data showed that at Year 3, improvements in the total score on DLQI was well sustained in both FI and RAN cohorts. Approximately two-thirds of the subjects in the FI cohort reported no impact of skin disease on QOL (corresponding to a score of 0 or 1 on DLQI). The proportion of patients in the RAN cohort reporting no impact of the disease on their QOL was well sustained through 3 years but remained consistently lower than those observed in the FI cohort. The results for each subscale of the DLQI questionnaire were consistent with those with DLQI total score i.e. showing high and sustained proportions of patients reporting no impact of the disease on different domains of health-related QOL in the two secukinumab cohorts with greater effect in the FI cohort compared to the RAN cohort.
Author Interviews, Boehringer Ingelheim, Dermatology, Immunotherapy / 29.03.2017

MedicalResearch.com Interview with: Eric Hughes, Global Head of Development, Immunology & Dermatology Novartis Pharma AG Basel, Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is well established that psoriasis negatively affects quality of life and work productivity. However, how the treatments affect psoriasis severity (based on skin clearance, itch, pain and scaling symptoms), health-related quality of life (HRQOL), work productivity, and daily activity directly or indirectly (via other factors) are still largely unknown. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), exhibits significant efficacy in the treatment of moderate-to-severe psoriasis, ankylosing spondylitis, and psoriatic arthritis, demonstrating a rapid onset of action and a favorable safety profile. In CLEAR, a Phase 3b head-to-head study versus ustekinumab, secukinumab demonstrated sustained superior efficacy in clearing skin through Week 52, greater improvement in symptoms and HRQOL, greater relief of work and activity limitations, and a comparable safety profile. In this sub-analysis of the CLEAR study, Novartis was interested in examining the relationships among multiple variables that are thought to be important to patients with psoriasis. The direct and indirect (i.e. mediated) effects of treatment (secukinumab or ustekinumab) on psoriasis severity and patients’ HRQOL, work productivity, and daily activity were examined. The evaluation was conducted using structural equation modeling (or path analysis) and compared these relationships for secukinumab versus ustekinumab at 16 and 52 weeks. Structural equation modeling or path analysis is a statistical method that models the direct and indirect relationship between multiple patient-relevant outcomes simultaneously. Goodness-of-fit statistics for all models were excellent confirming the robustness of the results. Results at Week 16 and at Week 52 for different Psoriasis Area and Severity Index (PASI) response categories (e.g. PASI 75, PASI 90, PASI 100) indicated that psoriasis treatment indirectly affected HRQOL and work productivity and daily activity, measured with the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment (WPAI) questionnaires, respectively. Actually, greater effect of secukinumab over ustekinumab on DLQI was mediated by greater improvement of secukinumab in PASI response as well as by greater improvement in psoriasis-related symptoms (itch, pain and scaling). Greater effect of secukinumab over ustekinumab on work productivity and daily activity was mediated by greater improvement of secukinumab in psoriasis-related symptoms.
ASCO, Author Interviews, Boehringer Ingelheim, Journal Clinical Oncology, NYU/NYMC, Prostate Cancer, Testosterone / 16.03.2017

MedicalResearch.com Interview with: [caption id="attachment_15257" align="alignleft" width="199"]Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York Dr. Stacy Loeb[/caption] Dr. Stacy Loeb MD Msc Assistant Professor of Urology and Population Health New York University Langone Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The association between exposure to testosterone replacement therapy and prostate cancer risk is controversial.  The purpose of our study was to examine this issue using national registries from Sweden, with complete records on prescription medications and prostate cancer diagnoses.  Overall, we found no association between testosterone use and overall prostate cancer risk. There was an early increase in favorable cancers which is likely due to a detection bias, but long-term users actually had a significantly reduced risk of aggressive disease.
Author Interviews, Boehringer Ingelheim, Dermatology, Pharmacology / 08.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32763" align="alignleft" width="180"]Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center Dr. Blauvelt[/caption] Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Findings from the Phase 3 VOYAGE 1 study showed that patients with moderate to severe plaque psoriasis receiving guselkumab, an human anti-interleukin (IL)-23 monoclonal antibody, achieved significant improvement in skin clearance and in comparison with Humira® (adalimumab), a TNF blocker.  The Phase 3 study and head-to-head analysis of guselkumab vs. adalimumab showed the significant and durable efficacy of guselkumab as maintained through one year when compared with adalimumab, and the robust efficacy of this novel IL-23 targeted therapy in meeting all primary and major secondary endpoints.
Author Interviews, Boehringer Ingelheim, Dermatology / 05.01.2017

MedicalResearch.com Interview with: [caption id="attachment_30943" align="alignleft" width="180"]Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center Portland, OR 97223 Dr. Andrew Blauvelt[/caption] Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center Portland, OR 97223 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Findings from the guselkumab Phase 3 VOYAGE 1 study showed that patients with moderate to severe plaque psoriasis receiving the anti-interleukin (IL)-23 monoclonal antibody (mAb) achieved significant improvements in skin clearance compared with patients receiving placebo and patients receiving Humira® (adalimumab), a TNF blocker. The Phase 3 study and head-to-head analysis of guselkumab vs. adalimumab in the treatment of moderate to severe plaque psoriasis also showed the significant efficacy of guselkumab maintained through week 48 compared with adalimumab, and the robust efficacy of guselkumab in meeting all primary and major secondary endpoints.
Author Interviews, Boehringer Ingelheim, Cancer Research / 12.12.2016

[caption id="attachment_30468" align="alignleft" width="133"]Professor Giorgio V. Scagliotti Chair of the Department of Oncology University of Torino,Italy Prof. Scagliotti[/caption] MedicalResearch.com Interview with: Professor Giorgio V. Scagliotti Chair of the Department of Oncology University of Torino,Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: LUME-Meso II is an international study designed to evaluate the safety and efficacy of nintedanib plus pemetrexed/cisplatin, followed by nintedanib versus placebo plus pemetrexed/cisplatin, followed by placebo, for the treatment of patients with unresectable malignant pleural mesothelioma (MPM). MPM is a rare cancer that affects the cells that make up the mesothelium of the pleura – the lining or membrane that covers and protects the lungs. It represents less than 1% of all cancers and is often related to long-term asbestos exposure with some suffering from malignant mesothelioma. A significant improvement in progression-free survival (PFS), the study’s primary endpoint, was observed for patients receiving nintedanib plus chemotherapy compared to patients receiving placebo plus chemotherapy.