Diabetes frequently accompanies heart failure (HF) and HF is observed in up to 15% of patients with type 2 diabetes (T2D). The relationship between diabetes and the heart is, however, complex. It has long been known that diabetes is an important risk factor for coronary artery disease, resultant myocardial ischemia and infarctions leading to HF. But the direct effect of diabetes on the heart muscle is less clear.
The existence of a non-ischemic diabetic cardiomyopathy, disease of the cardiac muscle that is directly related to diabetes and not due to coronary atherosclerosis, has been a longstanding topic for debate. The recent EMPAREG-OUTCOME study in which patient assignment to the sodium-glucose co-transporter-2 (SGLT-2) inhibitor, empagliflozin, was associated with a reduction in HF hospitalizations by 35%1 (for unclear reasons) has reignited this discussion.
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
Covance employees working to support clinical trials recognize that they are helping to move medicine forward and improve healthcare, but sometimes the impact is much closer to home.
“A client of ours was testing a new formulation of a measles, mumps, rubella and varicella (MMRV) vaccine and needed to ensure the end product was safe in pediatric populations,” explained Joshua. The Phase IV study was running smoothly but needed a Clinical Research Associate (CRA). Joshua was thrilled to take on the study and build on his experience. 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.
Immunotherapy agents (IO) are increasingly being used to treat solid tumors due to their dramatic effects on tumor response. However, the assessment of tumor response is not always straightforward given their unique mechanisms of action which include enhancing immune cell infiltration and activation in tumors. Current standard imaging techniques such as fluorinated deoxy-glucose (18F-FDG) PET cannot differentiate between cancer and immune cells. These tumor immune responses can lead to radiographic pseudo-progression whereby there can be an initial “worsening” of radiographic lesions. While IO therapies can be incredibly successful, understanding when a given treatment is successful or if the regimen needs to be augmented, is paramount.1 This confounding, radiographic evidence can lead to patients continuing therapy when no benefit is present or removal of therapy prematurely due to a delay in response time.
Our ongoing “Meet me in 5” series covers 5 people, topics or questions to illustrate how Covance nurtures exceptional people, provides an energized purpose and enables extraordinary potential in its employees’ careers.
In this edition of Meet Me in 5, our leadership team shares their experiences with nurturing careers at Covance.