Partnership with Neosoma enables faster, more precise tumor assessment in glioblastoma research.

Nottingham, England and Morrisville, NC – November 17, 2022 – Calyx, the eClinical and Regulatory solutions and services provider relied on for solving complex data challenges in clinical research, today announced a strategic partnership with Neosoma, Inc., an innovative medical technology company focused on advancing brain cancer treatment. Through this partnership, Calyx Medical Imaging extends Neosoma HGG (High-Grade Glioma), a novel AI-based neuro-oncology software device to its worldwide customers who are developing treatments for glioblastoma, the most common and challenging, malignant primary brain cancer.

“Neosoma’s expertise in AI imaging development nicely complements Calyx’s two decades of experience in clinical trial imaging and the insights we’ve gleaned from having successfully supported nearly 100 neuro-oncology clinical trials,” said Stephen Bravo, MD, Chief Medical Officer, Calyx. “We’re pleased to extend Neosoma’s innovation to clinical development and give our customers greater confidence that the important imaging data they depend on to evaluate their glioblastoma compounds’ effectiveness is accurate and reliable.”

Clinical trials of glioblastoma treatments are complex, largely because gliomas have highly irregular and infiltrating shapes that are difficult even for experienced neuro-radiologists to delineate. Volumetric tumor assessments – which are becoming commonly used as exploratory endpoints – currently need to be conducted manually by neuroradiologists, which presents a time-consuming and difficult challenge for glioma image analysis in clinical trials. Leveraging advanced artificial intelligence, Neosoma HGG has been shown to achieve 95.5% accuracy in tumor volume measurement as established by consensus reads, which exceeds that of individual neuro-radiology experts and can save time while generating consistent, automated volumetric assessments of tumor change.

“Calyx’s Medical Imaging team is widely recognized as the leader in clinical trial imaging, especially in oncology, where experience and deep therapeutic area expertise are critical,” said Aly Abayazeed, MD, Chief Medical Officer, and Co-founder, Neosoma. ‘We are delighted to provide faster and more precise assessment of high-grade gliomas to their customers to advance glioblastoma trials and ultimately bring improved treatment options to patients with this life-threatening disease.”

This partnership will extend to other AI-based solutions being developed by Neosoma and reflects Calyx’s strategy of partnering with best-in-class technology providers to offer innovative imaging biomarkers required to find new treatments for unmet medical needs.

For more information on Calyx Medical Imaging, visit Calyx.ai/Imaging

About Calyx

Through innovative eClinical and Regulatory solutions and services, Calyx turns the uncertain into the reliable, helping bring new medical treatments to market reliably. With deep expertise in clinical development and 30 years supporting trial sponsors and clinical research organizations, Calyx harnesses its intelligence and experience to solve complex problems, deliver fast insights, and get new drugs to market every day.

Medical Imaging | IRT | CTMS | EDC | RIM

Take your trials further with intelligent insights at Calyx.ai or at LinkedIn, Twitter, or Facebook.

Contact:

Christine Tobin | [email protected] | +1 412-628-8598

A lot has changed in how new treatments are developed for Alzheimer’s Disease (AD). With the 2021 approval of Biogen’s Aduhelm™, the FDA has clearly demonstrated a willingness to use imaging biomarkers as primary endpoints in AD, something that has never occurred before in the CNS space.

Here we talk with Calyx’s Dr. Stephen M. Bravo and Dr. Rohit Sood about how the use of medical imaging is advancing AD research and what we can expect moving forward.

“As the technology and our understanding of AD pathophysiology evolves, we expect to see advanced approaches for assessing treatment effect in clinical development, ultimately enabling more effective Alzheimer’s Disease treatments.”

– Rohit Sood, MD, PhD, VP Scientific & Medical Services, Calyx

How is the research behind AD treatment development evolving?

We as an industry are still trying to understand the pathophysiology of Alzheimer’s. Although we’re continuously updating our knowledge based on new information coming out of the labs, it hasn’t yet been appropriately delineated.

Over the last decade our understanding was that beta amyloid was the primary protein responsible for the underlying pathophysiology of AD. Although the contribution of abnormal protein deposition to AD is widely recognized and currently accepted by the scientific community, the exact pathogenesis of AD is complex, and more effort needs to be put into understanding the pathophysiology of AD for the development of therapeutic agents. Moreover, as pharmaceutical clinical trials tailored toward the removal of beta amyloid have failed to demonstrate significant response, there is increasing interest in the role of Tau protein aggregates and beta amyloid plaque, with an emphasis on anti-Tau antibodies.

In addition, there is a school of thought that neuroinflammation plays a role and today, industry is in the process of developing radioisotope tags so that we can identify neuroinflammation and whether there’s a change in the extent of neuroinflammation with drug intervention.

All of these are important factors for trial sponsors to consider when deciding what to target in their AD development programs. But the decision on how to best assess treatment response is not always clear cut. There is an increasingly complex array of potential digital radiology biomarkers that look at brain perfusion and diffusion changes, and volumetric analysis of the hippocampus and other limbic regions including amygdala and entorhinal cortex.

As the technology and our understanding of AD pathophysiology continues to evolve, we expect to see advanced approaches for assessing AD treatment effect in clinical development, ultimately enabling the availability of more effective Alzheimer’s Disease treatments.

“Sponsors and CROs should partner with a core imaging lab whose scientists are experienced in AD study design and understand the optimal imaging modalities needed to demonstrate drug efficacy efficiently, effectively, and economically.”

– Stephen M. Bravo, MD, Chief Medical Officer, Calyx

Is medical imaging currently required in AD studies?

Neuromaging modalities such as PET and MRI have been used to detect pathological changes associated with AD and have played an important role in the development of noninvasive biomarkers of disease progression and assessment of response to therapy in clinical trials. Detection of early neurodegenerative changes associated with AD has been possible due to the development of neuroimaging measures of brain atrophy and brain structures such as hippocampus and cortex. Novel image analysis algorithms for characterizing and classifying AD and Mild Cognitive Impairment (MCI) have been developed and applied to MR images. MRI is also currently used for safety assessment of AD drug therapies, especially important in the development of monoclonal antibody therapies, which can cause life threatening changes in the brain. But now medical imaging is also going to be a requisite for primary efficacy endpoint data collection in order for FDA to consider new drug approvals.

What’s changing in how we assess drug efficacy in AD clinical trials?

Traditionally, efficacy in AD trials is evaluated via rater analysis by clinical doctors who are considered experts in the field of dementia – as well as geriatric, psychiatric, and neurology experts – using the mini mental status examination or other clinical tools to determine baseline disease level and progression or regression. Because these tools are very subjective and produce tremendous amounts of interobserver variability, rater analysis is becoming outdated and, while it will likely never disappear, will likely become less relevant in future trials.

The utilization of radiology biomarker data removes this subjective analytic bias and is a far more rigorous scientific methodology to determine drug effects. Currently, there are AI/machine learning techniques that are being developed to measure subtle changes that are difficult for the human eye to detect, delivering more perspective and a more scientifically rigorous data set that stands up to statistical scrutiny in determining treatment response.

How can Calyx help sponsors leverage medical imaging to demonstrate AD treatment efficacy?

Calyx’s Medical Imaging scientists have significant experience in Alzheimer’s Disease drug development and broad knowledge of the emerging modalities to improve drug response evaluation. They routinely help AD researchers:

1. Determine the best radiological biomarker to evaluate
2. Identify how the radiology modalities used can help to drive identification of an enriched study subject population yielding greater rates of enrollment/randomization
3. Identify digital radiological biomarkers which can be quantified and tracked longitudinally to provide more scientifically rigorous data supporting drug efficacy to the FDA
4. Produce reliable data to support regulatory submissions through the Blinded Independent Central Review (BICR) of imaging reads

What do you see in the future re: the impact medical imaging will have on AD treatment development?

As our understanding of AD advances, so does the technology that we’ll use to develop more effective treatments for it.  We see medical imaging delivering additional value in two ways:

  • Validating the companion diagnostics required to identify patients who will be best served by treatment of the drug being trialed. This drives the economic rational/model which allows for CMS (Medicare/Medicaid) and commercial US insurance reimbursement decisions.
  • Driving further quantitative analysis of MR and PET/CT images to derive even more sophisticated biomarker analysis to help determine the velocity of drug effects and to predict drug effect on an individual basis (supporting the notion of individualized medicine being applied to the clinical research/life sciences space).

Conclusion

FDA’s recognition of using imaging as an objective, noninvasive biomarker is a big step forward for Alzheimer’s Disease research. Clinical trial sponsors should partner with a core imaging lab whose medical imaging scientists are experienced in AD study design and understand the optimal imaging modalities needed to demonstrate drug efficacy efficiently, effectively, and economically.

Partnership delivers advanced approaches for bringing neurodegenerative disease treatments to market

Nottingham, England, Morrisville, NC, and Boston, MA–July 25, 2022 Calyx, the eClinical and Regulatory solutions and services provider relied on for solving complex data challenges in clinical research, today announced it has entered into a partnership with Qynapse, an Artificial Intelligence (AI) neuroimaging medical technology company. The partnership enables Calyx to adopt and deliver Qynapse’s precise and objective AI-powered neuroimaging analysis solutions, QyScore® and QyPredict® to its global pharmaceutical and biotech customers as they develop new medical treatments for central nervous system (CNS) disorders.

“We’re delighted to add Qynapse’s advanced analysis capabilities to our full suite of proven medical imaging services,” said Stephen M. Bravo, MD, Chief Medical Officer at Calyx. “This groundbreaking services and technology partnership will enable our clients to more confidently assess the full potential of treatments in development for Multiple Sclerosis, Parkinson’s, Alzheimer’s, and Huntington’s disease, as well as other neurodegenerative disorders.”

Qynapse has developed one of the largest datasets of proprietary algorithms designed to rapidly analyze and interpret brain scans, delivering more objectivity and precision for the measurement of drug efficacy and safety during CNS clinical trials. Calyx’s Medical Imaging services have been proven in over 2,600 global clinical trials, delivering reliable data that has supported the approval of over 270 new medical treatments.

“We are excited to partner with Calyx, a Medical Imaging and eClinical solutions powerhouse, in bringing life-changing treatments to patients globally,” said Olivier Courrèges, Chief Executive Officer at Qynapse. “Working together we will further expedite and improve the go-to-market process for CNS drug therapies.”

Click here for more information on Calyx’s expertise in CNS clinical trial imaging.

About Calyx

Through innovative eClinical and Regulatory solutions and services, Calyx turns the uncertain into the reliable, helping bring new medical treatments to market reliably. With deep expertise in clinical development and 30 years supporting trial sponsors and clinical research organizations, Calyx harnesses its intelligence and experience to solve complex problems, deliver fast insights, and get new drugs to market every day.

Medical Imaging | IRT | CTMS | EDC | RIM

Take your trials further with intelligent insights at Calyx.ai or at LinkedIn, Twitter, or Facebook.

About Qynapse

Qynapse is a medical technology company with an AI-powered and proprietary neuroimaging software platform that creates the potential for earlier clinical precision on the frontlines of CNS diseases. Qynapse’s flagship solution, QyScore®, FDA-Cleared and CE marked, combines MRI scans and AI to produce rapid, actionable insights for objective brain scan analysis, enhancing diagnosis precision and drug efficacy assessment. Qynapse’s prognostic AI technology, QyPredict®, available for research use only, has the potential to predict disease trajectory and improve targeted patient selection in clinical trials. Qynapse is headquartered in France, in the United States and in Canada.

Learn more about Qynapse’s AI solutions at https://qynapse.com/, or at LinkedIn, Twitter.

Contact:

Christine Tobin | [email protected] | +1 412-628-8598

Reader fatigue in radiology can lead to high medical errors. Out of more than 11,000 preventable hospital deaths in English NHS acute hospitals each year, over eight thousand deaths are attributed to diagnostic error.

Interpretation of medical images is a challenging task as it is repetitive in nature, and errors (false negatives) are relatively common. Radiologists are also subject to visual fatigue due to continuous and longtime exposure to computer screens for interpreting medical images. It has been found that radiological errors are more likely to occur at the end of shift as compared to the beginning.

Blinded Independent Central Review (BICR) is one method recommended by the FDA for registration oncology trials (1). The objective evaluation of clinical indicators involving radiological images is an important end-point factor in oncology trials. During BICR, readers are routinely monitored using different models to ensure quality reads.

“Reviewer Disagreement Index may be used as an early indicator for potential reader quality and fatigue if a particular reader is concurrently reading on multiple trials.”

– Manish Sharma, MD, VP Medical Imaging, Calyx

Reader Monitoring Approaches

Monitoring of reviewers is not just mandatory from a regulatory viewpoint but also critical for proactive intervention throughout the trial. Monitoring safeguards high quality radiological assessments as well as adherence to specific clinical trial protocols. There is always inherent variability in the BICR process due to the difference in backgrounds, training, and humanity of the reviewers. Despite the existing inherent variability, there is a lack of meaningful methods for tracking and proactively improving reviewer performance.

“Double read with adjudication” is one of the frequently used models in various oncology trials review. This method permits better radiological assessments than a single read model. Double read with adjudication makes the process of BICR robust enough to not let variability and even minor errors impact the study outcome, if monitored properly.

Adjudication Rate (AR) has been used as a metric to track reviewer performance but does not accurately identify reviewer performance issues. It is dependent on many external variables like adjudication trigger, end point, indication, tumor burden etc. Adjudication agreement rate (AAR) is a relative performance indicator for a given reviewer where a higher adjudicator agreement rate suggests better reader performance.

Evaluating Reader Fatigue with Reviewer Disagreement Index

In an earlier blog, we presented how Reviewer disagreement index (RDI) considers the subjects for which adjudicator disagreed with the reviewer and considers adjudicator disagreement relative to the total number of cases read. RDI considers both the overall AR for a study and the individual AAR for each reader. The RDI indicates the percentage of disagreed cases for a given reader across the total number of cases read, as defined in the equation below, where a low RDI value indicates better reader performance and high RDI value indicates poor reader performance.

RDI =
# of cases where adjudicator disagreed with given reader
Total # of all cases read

Not surprisingly, there might be a correlation between the number of studies a reader reads on and how the cases are distributed across all studies. If the cases are distributed across too many studies, it can be a major issue contributing to reader fatigue e.g., if the reader in a reading session of 2 hours reads a few cases each on 10 different trials. The best-case scenario is to have a fine balance that would allow a reader a majority of cases on the same study in a reading session.

The plots below show a weak correlation of decreasing timepoints (Y-axis) to increasing RDI (X-axis). RDI can be used to give an early insight to trends by monitoring the ratio of RDI on each study per week, or per reading session and its interplay with overall and other studies’ RDI.

A recent study suggests that RDI can also be used as a good surrogate for reader fatigue (3). RDI may be used on an effective daily / weekly / monthly basis against read volume for monitoring reader fatigue which affects variability and thus read quality. Increasing RDI trend may be used as an early indicator for potential reader quality and fatigue if a particular reader is concurrently reading on multiple trials.

Reference

1. Guidance for Industry Developing Medical Imaging Drug and Biologic Products. Part 3: Design, Analysis, and Interpretation of Clinical Studies. US Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research. Center for Biologics Evaluation and Research; 2004.

2. Clinical Trial Imaging Endpoints Process Standards Guidance for Industry Draft. US Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research. Center for Biologics Evaluation and Research. March 2015 Revision1.

3. Manish Sharma, Madhuri Madasu, Sree Sudha Kota, Surabhi Bajpai, Yibin Shao, Srinivas Pasupuleti, Michael O’Connor, “Using reader disagreement index as a tool for monitoring impact on read quality due to reader fatigue in central reviewers,” Proc. SPIE 12035, Medical Imaging 2022: Image Perception, Observer Performance, and Technology Assessment, 120350J (4 April 2022); doi: 10.1117/12.2613082

Clinscience extends Calyx’s reliable, expedited imaging services to its global pharmaceutical customers

 Nottingham, England and Morrisville, NC – June 9, 2022 Calyx, the eClinical and Regulatory solutions and services provider relied on for solving complex data challenges in clinical research, today announced it has been named an approved provider of centralized medical imaging services by Clinscience, a full service CRO offering smart, end-to-end clinical trial services to the global pharmaceutical industry. 

“The Clinscience team understands what’s important to pharmaceutical and biotech organizations,” said Elizabeth Dalton, Vice President, Channel Partnerships Solutions, Calyx. “We’re honored to work with Clinscience and to deliver the reliable imaging services their customers need to accelerate and optimize their clinical trials.”

Clinscience joins a long list of global pharmaceutical companies and CROs who repeatedly leverage Calyx’s scientific expertise and experience to assess the safety, efficacy, and effectiveness of their compounds. To date, Calyx Medical Imaging has been used in over 2,600 clinical trials worldwide and has supported the approvals of over 270 medical treatments across a broad range of therapeutic areas.

Click here for more information on how CROs – and their clients – benefit from partnering with Calyx.

About Calyx

Through innovative eClinical and Regulatory solutions and services, Calyx turns the uncertain into the reliable, helping bring new medical treatments to market reliably. With deep expertise in clinical development and 30 years supporting trial sponsors and clinical research organizations, Calyx harnesses its intelligence and experience to solve complex problems, deliver fast insights, and get new drugs to market every day.

Medical Imaging | IRT | CTMS | EDC | RIM

Take your trials further with intelligent insights at Calyx.ai or at LinkedIn, Twitter, or Facebook.

About Clinscience

Clinscience is a global CRO company offering smart CRO Services, from protocol creation to final study report development. The Company has offices in Poland, Spain, Italy, Germany, and the US and provides its services in 6 European countries.  More than 150 Biotechnology companies across Europe and the US trust the Clinscience brand. The Company’s procedures and Data-driven approach, harnessed with the Genius Suite™ technology, work together to give the Clients power and flexibility to address even the most unique needs.  Clinscience is part of a publicly-traded parent company, Neuca Plc, an organization in the pharmaceutical wholesaling and healthcare industry that provides the structure to meet the needs of commercial and non-commercial studies.

Visit www.clinscience.com for more information.

Contact:

Christine Tobin | [email protected] | +1 412-628-8598

The role of the patients who participate in clinical trials cannot be underestimated. Yet, we often don’t think about the value they get from their involvement, and how it impacts their daily lives.

Here we talk to Rob Marshall about his dual perspective on clinical trials – from his role in Calyx’s R&D team and from being a clinical trial patient.

Hear directly from Rob as he tells his complete story here.

 

What clinical trials have you participated in?

I’ve participated in numerous trials for asthma treatments. In fact, in one of those trials, my symptom improvement led my doctor to change my prescription to the treatment being studied. And I’m still benefiting from that treatment today.

I’m also the parent of a child in clinical trials. My daughter was diagnosed with a nut allergy when she was very young and for years, we ran the risk of her falling into a life-threatening anaphylactic shock if she wasn’t careful about what and where she ate.

So, when we had an opportunity to enroll her in a trial, we jumped on it. Even though the investigative site was 100 miles away, causing us to travel at least twice/month, often including overnight stays. We knew that by having her participate in the study she would eventually benefit from new treatments being developed. And we were right. In the past ten years, it’s been a delight to watch her eat a chocolate bar with nuts or order a piece of cake in a restaurant without worrying about what ingredients were used. It’s truly been life changing.

“It’s an honor to be part of the clinical trials industry and I’ve seen firsthand how the eClinical solutions we develop are making a difference.”

– Rob Marshall, Sr. Director, Software Engineering, Calyx

Has the use of eClinical technologies impacted your clinical trial experience?

It’s improved the experience massively. For example, when I first started clinical trials in 2010, I had to go to the investigative site for spirometer tests to evaluate my exhalation levels. They’d cart in a big machine with a monitor, graphs, etc. that I’d have to blow into repeatedly (figure 1). If it wasn’t configured correctly (which was often the case), we’d have to start all over again, which lengthened the amount of time and effort for patients and clinicians involved in each visit.

Spirometer
Figure 1: Asthma patients previously had to visit investigative sites routinely for spirometer tests during clinical trials
Variety of trial data capture devices
Figure 2: eClinical technologies, like handheld spirometers and mobile apps, enable patients to provide important trial data remotely, saving them and the investigative sites time and hassle.

Now, 12 years later, I’m given a hand-held spirometer device that fits in my pocket and connects to an app on a phone. I can easily use the device to test my exhalation levels wherever I am, and the data is automatically uploaded to the study database. It’s remarkable how easy it is and saves a lot of time and hassle that I used to go through when having to go to the investigative site on a regular basis.

How does being a clinical trial participant affect your role as a Calyx Software Engineer?

I manage a couple of software engineering groups at Calyx, and we often have discussions around the features and outcomes of the products we’re developing. I’m in a unique position because I can offer insight into the end user’s experience, for example, what it’s like from the patient side to go through the randomization process. And I’m happy to give that context and to advance the conversation because not only am I helping engineer product technology that supports clinical trials, I’m also a user as well.

What motivates you to continue participating in trials, and in your day-to-day job at Calyx?

The life-changing outcomes my family and I have benefitted from drive my ongoing participation. It makes me proud to know that I’m doing my part, knowing it will benefit others who lives are disrupted by disease, just as mine and my daughter’s lives have been. I highly encourage everyone to get involved in trials for that reason.

As I go about my daily job, I try to challenge myself and my teams with how we can make the trial process better. How can we bridge the gap between developing our solutions and the investigative sites and patients that use them? My thinking is the more we understand what it’s like for our end users to participate in a trial, the better we can be at developing the solutions that will simplify their experiences, and ultimately contribute to the development of new treatment options that so many patients need.

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