As our industry approaches the one year anniversary of the implementation of SEND (Standard for the Exchange of Nonclinical Data) datasets as required by the FDA for regulatory submissions, attention is shifting to the next set of requirements. From recent notices to upcoming compliance dates, we’ve compiled five key highlights for your information that will also help you proactively prepare for the changes. Continue reading
A Trial Summary (TS) domain represents an essential part of standardizing study data for electronic submissions. In July 2016, the U.S. FDA issued version 3.1 of the Study Data Technical Conformance Guide, which advised including a TS domain to identify the study start date in the submission. In clinical studies, the study start date is earliest date of informed consent from any subject enrolled in the study, whereas nonclinical studies use the study initiation (protocol finalization) date. This article reviews the importance of the study start date and makes recommendations to help ensure a successful submission for current and legacy studies.
In the last 10 years, the study of medications for type 2 diabetes (T2D) has rapidly expanded its investigational footprint to evaluate cardiovascular (CV) effects, a shift driven largely by regulatory guidance that requires at least a demonstration of CV safety. Clinical investigators are also concerned with the effect diabetes medications have on atherosclerotic vascular outcomes as well as HF.
Working with Covance’s Dr. Jonathan Plehn in the webinar The Diabetic Heart: A Focus On Heart Failure, I recently provided a high-level overview of the clinical outcomes data examining the effect of antihyperglycemic therapies on heart failure (HF).
Only a handful of trials1 have analyzed more versus less-intensive glycemic control with regards to the effects on HF. In the ACCORD trial, there was a trend for increased risk with more intense glucose control (OR 1.23, 95% CI 0.97-1.57). In contrast, the UKPDS, ADVANCE and VADT trials suggested a favorable effect, although these results were not clinically relevant nor statistically significant. Meta-analysis of the totality of these data suggests there is essentially no effect, either positive or negative, on HF events with glycometabolic modulation using the older therapies available for T2D. Below, I review specific therapies in more detail. Continue reading
Both type 2 diabetes (T2D) and heart failure (HF) are on the rise and reaching epidemic proportions. This is no surprise as the two conditions are physiologically related. Both are associated with an aging population, dietary indiscretions and sedentary lifestyles. However, debate continues about whether or not an essential diabetic cardiomyopathy exists or if the HF frequently observed in diabetics is due to common comorbid conditions such as coronary artery disease or hypertension. In any case, the epidemiology of the two conditions runs in parallel. HF is currently the most frequent hospital discharge diagnosis provided in US patients over the age of 65 and the prevalence of T2D is about 25% in this age group.
When disaster strikes, the safety of your en-route patient samples depends upon the contingency planning that was done in anticipation of the emergency. While many emergencies happen in an instant, immediately impacting our logistics infrastructure – earthquakes, tornados or volcanic eruptions, for example – some, such as the recent series of severe hurricanes and typhoons, have longer lead times.”
When events of this nature occur, our global logistics team is behind the scenes preparing for such events. With more than 25 full-time staff, this team monitors shipments, coordinates with couriers, and oversees all of the operations that are critical to ensuring that patient samples are received at our labs within stability. Even factoring in emergencies, transportation failures impact only about 0.1% of all specimens. Continue reading
Rheumatoid arthritis (RA) is an autoimmune disease primarily affecting the musculoskeletal system with typical symptoms including swollen and painful joints, joint
stiffness and loss of function, ultimately leading to disability if untreated. RA also has significant systemic features in many patients that appreciably impact upon their quality of life, including fatigue and depression. Prevalence varies between 0.3 – 1.0% and is more common in women and in developed countries.1
Modern RA treatment paradigms (i.e. “treat to target”) focus on achieving remission/low disease activity to minimize joint damage and disability. Biologic agents targeting key inflammatory mediators (TNF-alpha, IL-1, IL-6), key cells and activation pathways of the adaptive immune system such as B cells and T cell co-stimulation pathways, have revolutionized the treatment of RA and many other immune-mediated inflammatory diseases (IMIDs), and have rapidly been introduced into accepted treatment paradigms2,3 when earlier disease modifying anti rheumatic disease (DMARD) agents such as methotrexate (and others) are insufficient to reach these target goals. Continue reading
Diabetic kidney disease (DKD) patients have an increased cardiovascular (CV) risk in addition to their increased risk of progression to end-stage renal disease. Recognizing that the FDA and other regulatory agencies have great interest in both the CV and renal safety and efficacy of compounds under development, pharmaceutical companies should consider inclusion of an appropriate approach to adjudication of potential CV events early in the course of planning for development of drugs to treat DKD.
Adapting current regulatory perspectives
From the regulatory perspective, there is a lot of emphasis focused on looking at both CV and renal risks during the development of type 2 diabetes treatments.1 However, no specific guidance exists for clinically-evident endpoints in DKD. Continue reading
Rheumatoid arthritis (RA) is an autoimmune disease primarily affecting the musculoskeletal system with typical symptoms including swollen and painful joints, joint stiffness and loss of function, ultimately leading to disability if untreated. RA also produces significant systemic affects such as fatigue and depression that may appreciably impact quality of life for many patients. Prevalence varies between 0.3 – 1.0% and is more common in women and in developed countries.1
The immune system is the body’s main defense against foreign materials and biologic agents such as bacteria, viruses, chemicals, and foreign cells and tissues. The immune response includes specific action of lymphocytes (one type of white blood cell) and is facilitated by other white blood cells, including neutrophils, monocytes, macrophages, eosinophils and basophils. The immune system can be viewed as a system controlled by negative feedback, meaning that normally it must reduce the effects of disturbance or invaders through self-regulation. Continue reading
Identification of new medicines for kidney disease remains an ongoing challenge in drug development. This challenge includes establishing new biochemical measurements (biomarkers) which can sensitively and accurately reflect the status of renal health and any associated changes in renal function. Sponsors are exploring many options to improve the application of biomarkers in preclinical use in order to better inform early phase safety studies and downstream clinical trials.
Katherine Landschulz, PhD, associate director of the translational biomarker solutions laboratory, and veterinarian pathologist Laura Boone, DVM, PhD, recently shared their experiences working on renal disease studies at Covance. They discussed their insights on how biomarkers are being used in preclinical studies to predict safety and advance translational medicine in drug development.