EXECUTIVE INTERVIEW - Cronos: Innovation in Clinical Trial Services Through Focus on Quality Data

Cronos Clinical Consulting Service is 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. For more than 6 years, 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 Mr. Guillermo DiClemente as a response to obvious issues with clinical data he was experiencing during his Columbia University days. Mr. DiClemente recently spoke to Drug Development & Delivery about the company’s unique approach, its relationship with customers, industry trends, and the importance of focusing on quality clinical data.

Q: What is the concept and focus of Cronos Clinical Consulting?

A: The concept is to mitigate clinical trial risks faced by Sponsors by focusing on clinical data. We do this by determining if there are internal inconsistencies when raters assess a patient from a clinical point of view. For example, one can obtain accurate body temperature with a thermometer or measure blood pressure with a calibrated device. There is no such tool for measuring hallucinations or various aspects of depression. The sensitivity of the raters sometimes comes into play, which is what Cronos targets. We try to minimize the subjectivity of the scoring.

Q: How are you able to do this?

A: We developed a set of algorithms that detect inconsistencies within an instrument or across instruments. The concept here is that you may have a psychologist or psychiatrist assessing a patient, and they understand the symptoms very well, but may not be familiar with the instrument or how to arrive at the best possible scores. At the same time, from a research standpoint, they may not gathering and therapeutic clinical practice. Utilizing our algorithms, we detect and remediate those inconsistencies, and we address those issues by talking to the raters about symptom assessment.

Q: Can you give us an example of what your algorithms would measure so we can get a feel for how it is practical?

A: The algorithms detect potential discrepancies amongst and between instrument items and are able to highlight if raters are misconceptualizing one or more items. By improving signal detection and protocol fidelity, we can measure site and rater performance from a clinical point of view. Regarding how practical it is, it allows the sponsor to know if raters are able to capture change in patients in real time and not after database lockout.

Q: Have doctors been receptive? Do they realize they need additional tools? Are they resistant because somebody is taking over what they know best?

A: One of the aspects we took into careful consideration during the creation of our system was the target population. In our case, Sponsors contract us, but the target populations are professionals who have not requested our services but are obligated to communicate with us. This is a sensitive arena and as such, we are always very respectful and careful during our interactions with the doctors and raters. We focus our conversation on symptom assessment and the use of the instrument. We do not aim to contradict their clinical knowledge, but rather to share with them how other raters are using the instrument in discussion. This is a very novel and well-accepted approach. Most raters are grateful of our feedback and glad to speak with someone about a meaningful assessment and not just boring, generic PowerPoint presentations about general training. That is the big difference with what we are doing – how a respectful approach can change the outcome of an interaction – especially because we do not tell them they are doing anything wrong. We are just sharing our opinion and that is it.

Q: Is all this conducted in real time?

A: Yes, it is done in real time. We receive data via FTP or from any mobile devices, such as tablets, collecting data. We run the data through our algorithms and schedule calls or remediations by email in less than 24 hours from data receipt.

Q: What companies are currently implementing your services?

A: Currently, our clients are biopharma companies, including five of the top-tier big pharmas. We work on global trials, for example, we are currently working on a trial that spans data from 43 countries. We can see our brand of data quality approach be interesting to other industries like the insurance space.

Q: Are there competitors and other equipment available that is able to do what you can?

A: From a strictly surveillance perspective, yes, there is competition because there are other people checking data, offering independent rating and recording, and videotaping or audiotaping assessments and feedback. Our system is unique in that we do not interact with the patient or review the interview; we analyze the data and remediate the raters as needed, and that is something unique to Cronos. We are an independent company that does data review, we do not need to justify why or how a rater was allowed to do scorings. I know others will claim they do something similar, but when we see the results, it is evident there is something different there. One of the most important parts is that Cronos is only data monitoring, and this aligns us with Sponsor objectives. Regardless of which company trains raters or selects raters and sites, we are in the unique position to provide real-time study awareness. There is no other company positioned this way.

Q: What has changed over the years since you have developed the product and it has been in use? What have you learned from the usage that has perhaps caused changes or tweaks to what you have available?

A: We have seen significant changes over the 6 years we have been in business. There is a new array of variables that we take into consideration now. For example, Sponsors have moved studies to lower cost locales, which made us consider cultural differences in our score expectations. As more global raters are used, we must be more careful with their familiarity with the scale instrument. In addition, we have seen a growth in patient knowledge and hence we need to be careful with repeated patients.

Q: How do you reach out to potential clients?

A: We have a sales force that focuses on branding, client relationship management, and prospecting. However, we find our most powerful tools include demos and research. The proof is in the pudding, and as such, we typically invite clients to share data and ad-honorem we present our results. Additionally, our publications, posters, and white papers showing the impact of our interventions have had strong results.

Q: Are people surprised that you are able to do this?

A: I believe they were surprised in 2008 when we started. Now that we are well known, I do not believe they are surprised anymore. The feedback we receive from sponsors is that Cronos is a niche company that takes data very seriously and provides information about things that are happening in clinical trials. Sponsors feel supported and they believe they can trust our findings. Usually, our findings drive CRA interactions. The Sponsor communicates our findings with the CRAs, which are addressed at the appropriate site.

Q: Do you work with patient selection as well for trials?

A: Yes, we have actually been in three trials in which we have given our patient selection opinion. We are developing a system that we believe is approximately 6 months away from market deployment. What we are doing right now is determining if patients are appropriate based on the scores developed either by independent raters or by site raters.

Q: Do you find that you are able to identify much that is missed?

A: I believe there is a wide spectrum of missed items or issues in a clinical trial with a varied level of risk severity. I find that strictly speaking from a clinical perspective, yes, we are able to identify all the important issues that may influence signal detection and go against protocol fidelity. We can tell the Sponsor with certainty when there is a problem with their data, and we provide solutions to those problems. What has been a tenet for us is when someone is doing something wrong; it shows up in the data right away.

Q: Put it together for our readers. Why pay attention to Cronos?

A: In the current economic climate, sponsors cannot afford to continue to have failed or negative studies for reasons unrelated to the compound. Cronos’ services offer Sponsors insight into what is going on in the real world and in real time. We provide situational awareness and institutional memory. We provide sponsors the ability to make decisions on imperative variables: allow a site to recruit more patients, to retrain a rater, curtail enrollment, or even stop the study. Business is going very well. The company has been growing steadily and organically since 2008. Right now, we have 23 full-time employees and more than 35 consultants around the world addressing raters in their native languages. We are excited about the future prospect of our company.

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