The methodological considerations and system requirements necessary to establish an effective, real-time, risk-based data monitoring platform in CNS trials are examined in a paper published in Therapeutic Innovation & Regulatory Science. Dr Cynthia McNamara, Director of Clinical Operations, and colleagues from Cronos co-authored the paper in collaboration with William (Bill) Potter from the National Institute of Mental Health. The article presents specific considerations for CNS studies where endpoints are more subjective, relying on Clinician-Reported Outcomes (ClinROs) and Patient-Reported Outcomes (PROs) to determine efficacy. Key risk indicators are discussed, alongside issues of inadequate rater training, rater drift, and potential fraud, as well as the need for a prospective plan of corrective and preventive actions. When applied correctly, real-time monitoring of clinical ratings in CNS trials has the potential to minimize risk and enhance the quality of clinical trial data.

Using the Rater Applied Performance Scale (RAPS), we reviewed audio recordings of 550 MADRS assessments conducted over the telephone in a global clinical trial of depression to determine if the clinical interview skills of remote raters were related to scoring accuracy. We also evaluated the relationship between the severity of illness and rater performance. Dr. Nina Engelhardt, Director of Clinical Content, presented the results at the International Society for CNS Clinical Trials and Methodology (ISCTM) 14th Annual Scientific Meeting, Washington, DC, USA (February 2018).

Dr. Christian Yavorsky, Chief Scientific Officer, co-authored a review in the current edition of Innovations in Clinical NeuroScience (ICNS) on the challenges and solutions for maintaining the consistency of PANSS ratings in clinical trials. The article brings together leaders in the field from Cronos, MedAvante-ProPhase and Bracket to present the current thinking and future directions. Particularly relevant to the work we do at Cronos is the impact of in-study data monitoring, combining data-based algorithms with expert clinician reviews to mitigate rater drift and reduce the impact of non-informative data throughout the course of a trial.

Dr. Christian Yavorsky, Chief Scientific Officer, and Dr. Nina Engelhardt, Director of Clinical Content, presented data from a double-blind, double-randomization, placebo-controlled study of the efficacy of intravenous esketamine in adults with Treatment-Resistant Depression (TRD). The study, sponsored by Janssen, showed that esketamine has a different response profile to existing classes of antidepressants, and that the Montgomery-Asberg Depression Rating Scale (MADRS) effectively captured the rapid changes in mood. The results were presented at the American College of Neuropsychopharmacology (ACNP) 56th Annual Meeting, Palm Springs, CA, USA.

Cronos CCS, Inc. is delighted to announce the appointment of Brian K. Saxby, PhD, as Vice President of Business Development. Dr. Saxby has worked in the clinical trial industry for almost two decades, and held a number of scientific, business development and management positions. He brings a wealth of knowledge of neurology and psychiatry trials, and has published over 30 papers on topics including depression, dementia, stroke, hypertension and aging. Dr. Saxby has a proven track record of product and service development, and we are excited to welcome him to the Cronos team. His appointment strengthens our ability to help clients meet the logistical and measurement challenges of conducting CNS clinical trials.

The Cronos Integrated Research Platform (CIRP) has been enhanced for use on mobile devices (e.g., smartphones, tablets), and all iOS, Android, and Windows operating systems. CIRP is utilized to proactively eliminate clinical trial protocol violations through implementation of protocol-specific validations and effective management of communication. This latest release maintains the same ease of use, while making the system even more convenient and accessible.

Cronos CCS, Inc. has completed a multi-year study with the prestigious Dutch research institute, The University of Groningen, Neuroimaging Centre, demonstrating the equivalence of Cronos PANSS training to that traditionally taught to medical students. The Cronos e-module, which can be completed in 3 hours, was shown to be equivalent to the traditional two-day group course. The results were presented at the Schizophrenia International Research Society conference, held in Florence, Italy, in 2016 as well as at the Phrenos Psychosecongres, in Zwolle, Netherlands. Cronos e-learning innovations save resources without compromising assessment quality or rater performance.

Dr. Christian Yavorsky, Chief Scientific Officer, presented strong evidence for the value of risked-based monitoring (RBM). In all cases utilizing Risk-Based Data Monitoring, the sample size needed for hypothesis testing was reduced from the original by at least 30%, with the un-blinding sample size re-estimation following Risk-Based Data Monitoring showing the most significant reduction in the number of subjects needed. Using an adequate sample size with high quality data collection through RBM could result in more reliable results, more timely trials and fewer resources.

In 2015, Cronos CCS, Inc. responded to the FDA call for comment regarding the use of electronic devices to gather medical data during clinical trials. Cronos, as a CNS-focused provider of risk-based data monitoring and rater training, advised that the use of these devices must be contingent upon clinical and electronic cross-validation of data and reliability ensured by a rigorous program of psychometric data monitoring.

President Guillermo Di Clemente spoke to Drug Development and Delivery about Cronos CCS, Inc.’s unique approach, its relationship with customers, industry trends, and the importance of focusing on quality clinical data. He noted Cronos to be a global provider of centralized risk-based data monitoring and data visualization solutions for neuroscience clinical trials. Its clients achieve high-impact results from their proprietary technology, proven processes, and scientific expertise to assess and confirm the credibility as well as accuracy of data necessary for approval and labeling of pharmaceutical products. Cronos has focused on Central Nervous System Phase II/III clinical trials and worked throughout the world with many of the top global pharmaceutical companies. The company was founded by Dr. Guillermo Di Clemente as a response to obvious issues with clinical data he was experiencing during his Columbia University days.

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Dr. Nina Engelhardt, Director of Clinical Content, joined a panel of representatives of the pharmaceutical industry, clinical trials sites, and companies that provide data quality monitoring to discuss and critique existing data quality techniques and to recommend future directions for enhancing data quality.