Companion Diagnostics: The New Engine
Companion diagnostics’ impact on pharmaceutical development is like dropping a new engine into a classic car. Faster speed. Better performance. More efficiency. Companion diagnostics is changing the way we develop, test and market new therapies—with full-throttle power.
Today, we often have the ability to test a patient to see what drugs will work—or not work—and watch for mutations and triggers down the road. But back up a bit: we can also design drug trials to include subjects with the correct biomarkers for the treatment. And back up a bit more: we can develop drugs and biomarker tests together for the most effective combinations of disease targets, drugs and patients. Continue reading
Despite the growing use of flow cytometry, there are currently no official regulatory guidance documents governing its validation. Having recognized the gap, stakeholders from the pharmaceutical industry and clinical testing laboratories have proactively published recommendations.
Scientists helping scientists with guidelines
In 2005, biomarker research was gaining momentum but the lack of clear validation guidelines made biomarker data difficult to interpret, hampering its usage. Existing validation paradigms applied only to PK data. Scientists from the American Association of Pharmaceutical Scientists (AAPS) realized that one set of rules could not fit all and that new standards were needed. They issued Fit-for-Purpose papers, addressing the need for accuracy, compliance and fitness for intended use and introducing the concept of iterative method validation to track biomarker development phases.
In the effort to reduce attrition rates and improve approval rates of new molecular entities by regulatory agencies, there’s no doubt that biomarkers can make a big impact. But it’s not as simple as tacking on additional studies. Biomarker development requires an insightful strategy and consideration of specific opportunities and needs throughout the drug development pipeline.
A quality biomarker starts at the source—the sample itself. Sample collection and handling protocols must be standardized to specify the minimum volume requirement in the proper container along with the most optimal temperature during transportation and storage. These requirements should be backed and driven by validated processes. To further ensure biomarker stability, it’s equally critical to include the maximum allowed time in transportation. Continue reading
Treatments that are safe and effective for adults may be ineffective or even dangerous for children. But infants and children are often prescribed medications with “off-label” use, where the treatment’s safety, dosage and efficacy are based solely on adult studies. To address this issue, both drug developers and regulators are working to boost clinical trials in children and include this underserved market in their studies.
Challenges with pediatric trials
A number of factors work against studying pediatric populations. As a highly fragmented and dynamic population, children and infants undergo rapid developmental changes over time, complicating study design and interpretation.
In addition, small sample sizes and potentially low incidence rates can make it difficult to find a treatment group—as well as a suitable control group with an approved active control. Finally, ethical considerations, such as informed consent can be more complex in pediatric trials. Continue reading
In 2013, oncology represented the largest segment of the clinical trial market. In 2014, it is estimated to grow by 4.9%,1 reaching nearly $100 billion. The number of oncology clinical trials stands well above those in other therapeutic areas and most major biopharmaceutical companies are involved in oncology to some degree.
Yet, with such compelling numbers, why do only 6.7% of these trials lead to FDA approval from Phase 1?2 Possibly because of difficulties recruiting patients for oncology trials, but more likely due to the complexity of cancer as a disease. Continue reading
Over the past several years, the life science community has gained an improved understanding of the immune system–from B and T cells to molecular pathways. With new, state-of-the-art tools and technologies, immunologists now have the ability to take a holistic approach to understanding the mechanisms of immune response. These applications help us devise methods to treat immune system-related diseases and to design better vaccines to combat infectious agents and cancer.
Currently, one of the most sensitive techniques available for the detection, measurement, and functional analysis of immune cells is the enzyme-linked immunospot (ELISPOT) assay. Covance’s Translational Biomarker Solutions group uses the ELISPOT technique to evaluate test subject responses to our sponsors’ vaccines, drugs, and biological products. ELISPOT is also useful in the pre-clinical space, where Covance can assess the toxicity of investigational compounds and biologics, and evaluate the efficacy of vaccines. Continue reading
As the pace of companion diagnostic innovation continues to accelerate, the drug development industry faces several headwinds. Numerous patent ‘cliffs’ are affecting the sales of blockbuster drugs; competition is increasing for a limited clinical trial population in increasingly global trials; and health outcomes pressures from patients, payers and healthcare providers are transforming the drug development process.
Over the past 10 years, advances in analytical technologies have provided new tools to identify patients who are more likely to positively respond to a certain drug or, conversely, experience a negative reaction to the particular therapy. These tools, known as companion diagnostics, are laboratory tests for biomarkers that, once commercialized, are designed to be an accompaniment to the safe and effective use of a particular therapy. Continue reading
Testing drives drug development. From laboratory tests on patient specimens comes almost all of the clinical data needed for a new drug application. How and where those specimens are collected, transported, stored, and analyzed impacts the quality and usefulness of the data they produce. In the past, most tests were processed by local, academic, and specialized testing laboratories and coordinated by each investigator. However, centralized testing is becoming an accelerated trend – one that uses advanced technology and global operations to concentrate oncology clinical trial tests in a single, central laboratory.
The core value of a central lab is consistency. When local laboratories perform testing, their results will be different and results vary over the course of the trial. Central laboratory testing, on the other hand, offers ‘combinable data.’ The end product is that a result from a central laboratory is similar regardless of the global location where it originated from and the lab location where it is tested. At all of Covance’s central laboratories — in Indianapolis, Geneva, Singapore, Shanghai, and Tokyo — we generate data from the same analytical method platform, SOPs, equipment, reagents, and standards, eliminating variables that affect tests results. Continue reading
Over the last decade, the U.S. Food and Drug Administration (FDA), and other global regulatory agencies, have been placing increased scrutiny on clinical data quality. It has become clear that the traditional paradigms of sample testing management will not be sufficient in the future.
In order to avoid putting clinical trial programs at risk, the pharmaceutical industry will need to place a greater emphasis on meeting the new standards for testing data quality and documentation. The need to do so has become more pronounced with the increase in esoteric testing that has been seen in recent clinical trial programs. For example, the rise in genomics testing, immunohistochemistry (IHC) markers and flow cytometry panels has increased the volume of tests being sent out to referral laboratories. The frequency of warning letters from the U.S. FDA has also increased dramatically in the last few years. Continue reading
The gauntlet of oncology trial planning, investigation, and final approval can be daunting. Oncology is the largest, fastest-growing, and most research-intensive therapeutic area in drug development, yet the need for new agents is urgent. Plus, cancer patients are among the hardest to recruit for clinical trials.
Innovations in personalized medicine are also creating a dynamic environment presenting increased requirements for scientific and operational expertise; access to high-performing investigator sites with the right patients; and global combinable data. Continue reading