Measuring lots of little details: Non-Compartmental Analysis and the Early Phase Regulatory Environment.

Posted by Cytel

Jun 28, 2018 6:53:00 AM

 

By Esha Senchaudhuri

With thanks also to Jitendarreddy Seelam and Ramanatha Saralaya for their input.

The fact of the matter is that I now want to recall everything, every trifle, every little detail. I still want to collect my thoughts and - I can't, and now there are these little details, these little details...”
― Fyodor Dostoyevsky, The Meek One

Old Fyodor was hardly talking about clinical trials, but early phase trial sponsors can probably relate to a regulatory environment which requires systematic attention to details, the little details and all these little details. When conducting early phase studies, global regulators require submission of Non -Compartmental Analyses (NCAs) that measure factors such as extent and rate of exposure to a drug, without the complexity of strenuous assumptions or complex models. Through the use of rudimentary methods such as linear trapezoidal rules, NCAs make it relatively easy to measure the concentration of a drug in a body over time. They can capture length of exposure, and time of peak exposure, without the challenges of models that require independent validation [1]. While those other models are also becoming more common in quantitative pharmacometrics, ideally NCAs can complement these other methods.


It may be tempting to assume that due to the ease of measurement, it is unnecessary to invest in statistical expertise and reliable software for NCAs. While the calculations may not be as complex as other forms of pharmacometric modeling, taking shortcuts at this stage can prove problematic later on. 
Widely recognized for being ‘assumption-free’ [1] NCAs are a common subject of regulatory inquiries. Exposure and absorption data is obviously important for early phase trials, so NCAs are required for submission throughout the process. A strong data management system with reliable software can ensure that findings collected at this stage are streamlined across several early phase trials, making such information easy to access and ensuring a rapid response for regulators. Further, NCAs are often required to be submitted with early protocols making it useful to have statistical designers familiar with the NCA findings. As NCAs are an integral part of establishing an early phase audit trail, it is important to use NCA software that streamlines a detailed and complex workflow such as Phoenix WinNonlin. 


Accurate NCAs can combine with other forms of quantitative pharmacometric models like PK/PD analysis to build strong dose-response models for Phase 2. It is common knowledge that unreliable dose-response models in Phase 2 can create headaches for Phase 3 tests. Only 13.2% of Phase 3 trials that are accepted after initial rejection, are rejected on grounds of efficacy. More common reasons are dose selection, choice of endpoints, and other challenges that better Phase 2 modeling can prevent [2]. Working with statistical experts as early as Phase 1 can ensure that knowledge gleaned from NCAs can be employed to build stronger Phase 2 models, thus avoiding Phase 3 pitfalls.


Cytel has a dedicated team that has developed efficiencies and experience in early phase trials, including Non-Compartmental analyses. To learn more about our capabilities in this area, please click on the button below.

NCA
[1] Gabrielsson, J. and Weiner, D., 2012. Non-compartmental analysis. In Computational toxicology (pp. 377-389). Humana Press, Totowa, NJ.
[2] Sacks, L.V., Shamsuddin, H.H., Yasinskaya, Y.I., Bouri, K., Lanthier, M.L. and Sherman, R.E., 2014. Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000-2012. Jama, 311(4), pp.378-384.

 

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Topics: Early Phase Trials, Clinical Development Strategy, pharmacology, clinical trials


The Importance of Standardization in Clinical Outsourcing

Posted by Cytel

Jun 19, 2018 9:30:00 AM

 

At the recent PCMG conference in Malta, Adrian Otte ( Independent Consultant, formerly VP Global Development Operations at Amgen) presented to delegates the strategic choices open to sponsors when  choosing an outsourcing model and the three fundamental issues in play: standardization, flexibility and cost. In Dr. Otte's view, standardization of systems and processes is key, but is often overlooked as a factor by companies of all sizes when deciding how to outsource clinical trial activities. In this blog, Dr Otte joins us to share his insights on this topic, as well as this views on how outsourcing has evolved in recent years, and the future trends that will have most impact. 

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Topics: Clinical Research Services, outsourcing, Clinical Development Strategy, clinical trials


What makes a good data manager?

Posted by Cytel

Jun 14, 2018 10:30:00 AM

In this blog, Paul Fardy, Executive Director of Data Management at Cytel shares his thoughts on how the data manager role has evolved. 

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Topics: big data, Biometrics, real world evidence, clinical data management, clinical trials


Career Perspectives: Interview with Andrea Hita, Biomedical Data Scientist

Posted by Cytel

Jun 7, 2018 8:39:00 AM

Cytel data scientists apply advanced statistical techniques including predictive modelling of biological processes and drug interactions to unlock the potential of big data.

In this blog from our Career Perspectives series, we talk to Andrea Hita, at Data Scientist at Cytel, to find out more about her career path, her current role at Cytel and her interests outside of work.

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Topics: Recruitment, Trial Design, adaptive designs, careers, model-informed-drug-development, clinical trials, data science, CRO, clinical research, R language, genetic algorithm


Career Perspectives: Interview with Omar Sefiani, Principal Statistical Programmer

Posted by Cytel

Apr 28, 2018 9:50:00 AM

Cytel has industry-leading experts in Statistical Programming, our programmers have years of SAS® Programming expertise, combined with in-depth knowledge of the specific clinical subject matter, which allows for competent and on-time completion of tasks.

In this blog, we talk to Omar, who is based in Geneva to find out more about his career path, current role at Cytel and his interests outside of work.

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Topics: Recruitment, Trial Design, Statistical Programming, Statistical Analysis, Phase 3, CDISC, careers, clinical trials, CRO, clinical research


Infographic: Overcoming Data Management Challenges in Immuno-Oncology Trials

Posted by Cytel

Apr 25, 2018 10:13:00 AM

Data management is an essential building block for successful Immuno-Oncology (I-O) trials. At the Immuno-Oncology Clinical Trials operations meeting in New York in earlier this year,  Patti Arsenault, VP Quality Assurance at Cytel discussed with Christopher Lamplugh, AVP, Clinical Data Management, Global Data Operations at Merck, the key challenges for data management in the space, and what’s needed to overcome them. 

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Topics: Oncology, Data Management, Clinical Research Services, Clinical Data, EDC, database build, data manager, big data, clinical trials


Interview with Ken Getz: Exploring Challenges of Clinical Trial Operations Part 2

Posted by Cytel

Apr 13, 2018 7:21:00 AM

We return to our discussion with Ken Getz of the Tufts CSDD for part 2 of our blog post on  key challenges in clinical trial operations. You can find Part 1 of the interview here, or read on to gain his insights on the fundamental problem at the heart of clinical trial operations challenges, and his views on the initiatives and programs that he believes show the most promise for the future. 

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Topics: forecasting, patient enrollment, enforesys, clinical trials


Interview with Ken Getz: Exploring Challenges of Clinical Trial Operations Part 1

Posted by Cytel

Apr 5, 2018 8:30:00 AM

Photo by J. Kelly Brito on Unsplash

Research on clinical trial enrollment makes for sobering reading, characterized by the oft-cited statistic that 11% of active sites fail to enroll a single patient. In this first part of a two part interview, we sit down for a discussion with Ken Getz of the Tufts CSDD. Here, Mr. Getz expands on some of the Center’s more recent research on challenges in clinical trial operations. In the second part, to be published  next week, Mr. Getz will reveal his insights on the key opportunities for the future. 

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Topics: forecasting, patient enrollment, enforesys, clinical trials


Career Perspectives: Interview with Benjamin Esterni, Principal Biostatistician

Posted by Cytel

Mar 16, 2018 7:00:00 AM

At Cytel we believe that expert statistical input has the power to shape the future of clinical development: de-risking portfolios, accelerating timelines, and increasing the probability of success.

In this blog we talk to Benjamin who lives in France, to find out more about his career path, achievements, current role at Cytel and his interests outside of work. 

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Topics: Recruitment, Cytel Strategic Consulting, Statistical Programming, Statistical Analysis, clinical development, biostatistics, adaptive designs, adaptive trials, careers, clinical trials, CRO, clinical research


Developing efficient tools for ADaM dataset creation

Posted by Diganta Bose

Feb 21, 2018 10:00:00 AM

 

By Diganta Bose, Statistical Programming Team Lead at Cytel

Editor's note: This blog is based on work presented at ConSPIC 2017

Innovation within CROs is critical to enhance efficiency, reduce costs, and increase productivity. Importantly, process innovation can also help limit errors, and reduce efforts required by a team to conduct a specific task, so freeing them up for other value-adding activities. The process and technology innovations developed by statistical programmers can make important contributions to improved productivity and aid the industry-wide drive to accelerate new products to market.

In a previous blog, we highlighted an innovative solution developed by Cytel’s Angelo Tinazzi and Dean Shultsto improve efficiency in the Data Monitoring DMC programming process. In this article, I will provide an overview of another programming innovation project, which aims to improve the efficiency of creating ADaM datasets.

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Topics: Statistical Programming, Statistical Analysis, clinical trials


Career Perspectives: Interview with Ursula Garczarek, Associate Director - Strategic Consulting

Posted by Cytel

Feb 13, 2018 9:00:00 AM

Our strategic consulting team work on projects such as: Identifying the best clinical trial design, implementing adaptive designs, developing a regulatory strategy and interacting with regulators.

In this blog we talk to Ursula who is based in Germany, to find out more about her career path, achievements, current role at Cytel and her interests outside of work. 

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Topics: Recruitment, Cytel Strategic Consulting, Statistical Programming, Statistical Analysis, Adaptive Clinical Trials, biostatistics, adaptive designs, careers, clinical trials, CRO, clinical research


Life in Programming: Interview With Ajay Sathe

Posted by Cytel

Feb 6, 2018 4:34:00 AM

 We were excited to learn recently that Ajay Sathe, the CEO of our India Operations, was awarded lifetime honorary membership of PhUSE in recognition of his contributions to the influential statistical programming organization. Ajay is a well-known figure in the global statistical programming community and in this blog we chat with him about his work, the important role of PhUSE in the industry, and what excites him most about work in the biopharma sector.

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Topics: Statistical Programming, Statistical Analysis, clinical trials, CRO, PhUSE


Highlights from PhUSE 2017

Posted by Cytel

Nov 17, 2017 5:00:00 AM

PhUSE 2017 took place in Scotland’s capital city Edinburgh, 8th - 11th October, and brought together a range of experts to tackle the most pressing issues facing statistical programmers today.  We found this year's event informative and well attended. In this blog we share some highlights from the sessions and posters the Cytel team attended.  We will share Cytel's own contributions in a separate article.

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Topics: Statistical Programming, FDA, Interim Analyses, biostatistics, CDISC, R programming, clinical trials


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