Most sponsors are well aware of the recent revision (R2) of ICH GCP E6, which outlines recommendations to unify standards across the EU, Japan and the U.S. with defined requirements for sponsors regarding the role of monitoring and risk management, there are many factors to consider for a successful implementation.
This article discusses a variety of challenges sponsors may face when preparing to address these recommendations and also examines opportunities to drive greater efficiencies in today’s complex trial ecosystem.
Addressing varying levels of adoption
According to the latest revision, sponsors are tasked with a requirement to employ an adaptable quality management system and are expected to maintain oversight of CROs. But with various tracking systems, vendor logs, CTMS and monitoring platforms, seeing the complete picture can be an overwhelming, error-prone effort. Continue reading
“Affinity” is defined as, “a spontaneous or natural liking or sympathy for someone or or something.” This concept applies also to the biologics (large molecules) we help to develop. Drugs like monoclonal antibodies (mAb) or bispecific antibodies are ideal drug candidates since they have very high affinity to bind to their target substance or site. Given the variability of the targets, safety profiles, and therapeutic windows, it is important to understand the characteristics of the affinity of the target and how to translate phenomena such as target mediated drug disposition (TMDD). Continue reading
Nonalcoholic fatty liver disease (NAFLD) is the accumulation of fat or lipids in the liver in the absence of significant alcohol uptake or viral infection. Within NAFLD there is a spectrum of disease ranging from excess storage of fat in the liver (NAFL) to fat plus inflammation (called nonalcoholic steatohepatitis or NASH), to liver fibrosis and cirrhosis, or end stage liver disease with loss of liver function. NASH is the most common cause of liver disease in developed countries, largely due to the increased prevalence of obesity and type 2 diabetes. A percentage of patients with NASH and liver fibrosis will progress to liver failure or hepatocellular carcinoma or liver cancer. In fact, NASH is expected to be the number one cause for liver transplantation in a few years, making it critical to identify high-risk patients early. Continue reading
Facing ever-increasing costs of running a clinical trial, sponsors must ensure they are properly directing their budget and resolving the areas of highest risk while maintaining patient safety and data integrity.
How can sponsors implement a robust process to allow earlier identification of emerging risks during the course of a trial? This article covers five tips for defining risk levels, categorizing risk and maintaining oversight to ensure that risks and responses are appropriately identified, documented, tracked and managed throughout the life cycle of a study. Continue reading
Identifying viable study sites presents a challenge in many clinical trials. Biosimilar development is especially challenging as the number of sponsors preparing to broaden access to today’s blockbuster biologics, by providing lower-cost biosimilar alternative, continues to grow. While this flood of research activity will make a significant improvement for patient access to breakthrough treatments, it has also created an increasingly competitive environment for finding suitable, experienced sites.
Compounding the issue, physicians are often less interested in supporting biosimilar studies, preferring to engage in clinical trials involving novel targets and compounds or those being conducted by larger academic institutions. Additionally, the level of education and training regarding the established development process for biosimilars is generally low. To overcome these hurdles, Covance has expanded its strategy to help sponsors find qualified sites and investigators willing to provide reliable clinical evidence. Continue reading
The rise of immunotherapy has been meteoric — there are now well more than 1,000 immuno-oncology (IO) trials ongoing according to clinicaltrials.gov. Finding and enrolling the appropriate patients for these potentially revolutionary treatments has presented a profound challenge, one that was recently covered in the aptly titled New York Times article: A Cancer Conundrum: Too Many Drug Trials, Too Few Patients. Another piece of the puzzle is clinical trial design, which can be especially elaborate when testing combination treatments in IO. Exacerbating these issues, IO trials are an increasingly competitive race to market. There is great value assigned to reducing development times and being the first drug approved within a class or for a specific indication.
This blog article discusses the current state of immuno-oncology studies, strategies for enhancing patient recruitment, the role of companion diagnostics and solutions for dealing with the complexity of IO combination studies. Continue reading
The year I graduated from college was the same year an old family friend was retiring. He had spent the majority of his career designing and deploying farm equipment across the United States. When I asked for advice as I entered the workforce he told me a story.
Three months into retirement, a company in California asked him to fly out and consult with their mechanics on why a piece of equipment wasn’t working. He flew out, spent 5 minutes at the company’s site, drew an “X” in chalk on the equipment, and flew home. They called the next day and asked what they needed to do. He directed them to the “X”. As simple as an “X” is, it represented years of experience and understanding of the intricacies of the machine and what could potentially go wrong.
He said the moral of the story was, “It’s good to know where to put the X”. Continue reading
The accelerated arrival of novel vaccines and immunotherapies into the clinical space spurred the emergence of fields like personalized medicine, immuno-profiling and immuno-monitoring built around increasingly sophisticated testing platforms. Among them, immunoassays in the ELISpot (Enzyme-Linked ImmunoSpot) family are the most frequently used functional assays for single-cell analysis.1
Using 2017 data from Trialtrove (Citeline.com), we found that ELISpot assays were used in more than 160 open clinical trials (Figure 1). The main drivers for this rising clinical usage are:
- The increased prevalence of infectious and chronic diseases as the population ages in developed countries
- Extensive use of immunoassays in oncology new vaccines and immunotherapies
- Technological developments, such as test automation and rapid analysis
- Growth in the biotechnology sector
The majority of today’s approved companion (and complementary) diagnostics (CDx) support personalized medicine efforts in oncology, a testament to researchers’ growing knowledge regarding the genetic pathways impacted in various cancers. That understanding increases our ability to convert such knowledge of biology into treatments that specifically target disease based on a tumor’s genetic makeup. This has led to significantly improved outcomes for many patients.
But can we leverage the knowledge of the biology of other disease states along with the appropriate technical progress into successful CDx expansion beyond oncology? Given that nearly 50% of all compounds in clinical development are dropped for lack of efficacy, CDx may represent a viable approach to improve this statistic and boost the efficiency of drug development efforts. Promising clinical areas where CDx may play an important role include immunology, rare and orphan diseases, and neurodegenerative diseases such as Alzheimer’s disease. Continue reading
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.