The Cytel blog keeps you up to speed with the latest developments in biostatistics and clinical biometrics.
The Cytel team made its annual trip to the PSI (Statisticians in the Pharmaceutical Industry) conference 2nd to 5th June. Taking place in London, UK, the theme of this year's meeting was Data-driven decision-making in medical research. As ever, the discussions both within the official conference agenda and during the networking breaks were engaging and productive.
In this blog, we share some of the particular highlights from the sessions that our team attended. We look forward to participating again in 2020 when the conference will return to Europe.
This article was originally published as part of a series by pharmaphorum in association with Cytel and is reproduced with their permission. Scott Harris, a four-time biotech Chief Medical Officer, and principal at Middleburg Consultants, a pharmaceutical consulting organization, told pharmaphorum’s Richard Staines that using novel adaptive or seamless clinical trial models can help to cut development costs. In doing so they can reduce the risks of trial failure that can spell the end for those biotech companies without the deep pockets of big pharma behind them.
In case you haven’t noticed, the traditional three-phase clinical development process is changing. While big late-stage trials are still pretty common, it’s also no longer a surprise to see sponsors refer to phase 1/2 trials, or phase 2/3, indicating that a smaller trial can be progressed to the next phase if an interim data readout supports further evaluation.
This is known as a “seamless” trial as the boundaries between each development stage have become less defined, and there are other options too.
Middleburg Consultants’ Scott Harris is a proponent of this new way of working and has personal experience of the approach after using it to steer a gastroenterology drug through the approval process.
Nowadays, it’s difficult to pick up a mainstream newspaper or read an industry publication without seeing reference to Artificial Intelligence or AI and progress towards innovations like autonomous vehicles, or customer behavior prediction. For the biopharma industries specifically, AI represents an opportunity to avert the R&D productivity crisis with paradigm-shifting applications such as in-silico drug design, prediction of trial risks and big data analytics.
However, with every opportunity, there are risks and challenges, and in this blog, I will discuss how pharma needs to address the opacity of AI to ensure trust and credibility with all stakeholders.
In this blog, Alla Muchnik, Senior Clinical Data Manager at Cytel, discusses how specialist CROs can add value and streamline processes by providing oversight of data management services delivered by another CRO. This model helps to fulfill essential regulatory obligations for biopharma companies who may lack their own internal oversight resources.
In this blog, Jonathan Pritchard, Director Business Development at Cytel, draws on his experience in commercial, clinical and technology roles within the biopharmaceutical industry and shares his insights on the primary considerations for sponsors when implementing an ePRO solution.
At the Partnerships in Clinical Trials Conference in Barcelona in November 2018, Strategic Consultant Ursula Garczarek participated in a thought leadership stream tackling various developments in Real World Evidence, Pediatrics, Trial Design & Big Data. As well as participating in a panel discussion on innovations in clinical trial design, she was impressed by the contributions and innovations offered from other stakeholders across the healthcare landscape. One of these exceptional contributions came from from Galina Velikova, Professor of Psycho-social and Medical Oncology at the University of Leeds, and in this blog, we are thrilled to share an interview with Professor Velikova, in which she expands her discussion of the role of Patient Reported Outcomes (PROs) and Quality of Life Measures in trials and clinical practice.
No one plans to have a trial whose data collection needs rescuing. However, lagging enrollment rates, operational struggles, and diminished budgets can leave some trials in need of intervention. A great deal has been written about how to prevent the need for rescues (e.g., more investment in study planning and improved communication between stakeholders). Far less has been said about how to assemble a rescue team – the roles that need to be filled and the process of analysis that ensures the completion of a failing trial.
Quantitative pharmacology encompasses the many strategic advantages of using complex mathematical models to understand biochemical relationships that ultimately improve clinical decision-making. This includes pharmacometric modeling, familiar to those who have used pharmacokinetic/pharmacodynamic (PK/PD) modeling to improve dosage decisions, and the extension of such models to the performance of meta-analyses, the construction of decision rules, and other uses involving a broad array of cases. In this blog we summarize some key areas of opportunity.
In honor of Rare Disease Day 2019 we share a new Cytel podcast featuring Cytel Strategic Consultant Ursula Garczarek discussing how innovative statistical approaches can overcome challenges in rare disease development. Below, you can access the podcast and a summary of some of Ursula's key insights from working in rare diseases and interacting with regulatory agencies for complex and innovative designs.
In 2018, Cytel ran a qualitative survey among biostatisticians and programmers on trends in data science and perceptions about the goals, barriers and future of the field in the biopharma and life science industry. Our analysis and report revealed a range of insights from the respondents including :
Lack of shared understanding of what data science represents with less than 1 in 7 of all respondents suggesting a definition of data science.
Clear trend of investment in data science across organizational types with three-quarters of all respondents saying their organizations had a dedicated data science department.
An opportunity for improved clinical trial design by using data science techniques was recognized by the majority of respondents. In addition, respondents across all functions perceive the key opportunity for data science to be in maximizing the value of real-world data.
In a recently published discussion on The Effective Statistician podcast ( a weekly podcast produced in association with PSI) Ursula Garczarek, Associate Director Strategic Consulting at Cytel sat down with hosts Alexander Schacht and Benjamin Piske to discuss where the biopharma and life science industries are headed with the application of data science.
A 2018 publication in the Biometrical Journal by Cytel’s Cyrus Mehta, Lingyun Liu and Sam Hsiao, ‘Optimal Promising Zone Designs’ (1) marks a new milestone for adaptive sample size re-estimation. Inspired by insights from the team's work with a number of Cytel's strategic consulting clients, it presents an easy to implement and new iteration of the popular promising zone design. The basic principle? That any investment of sample size at an interim analysis should be contingent on a minimal acceptable return on the investment. This return is expressed in terms of guaranteed conditional power, By identifying a minimum rate of return upfront, the new design offers greater efficiency to clinical trial planners. Importantly, the design concept is both easy to communicate, and easily understood among statistical and clinical stakeholders alike.
In this blog, Cytel Co-Founder and Fellow of the American Statistical Association, Cyrus Mehta shares his insights with us on the goals and key takeaways of the publication, and how it adds to the growing toolkit of intuitive adaptive designs available to drug developers today. We also share full access to the publication itself.
Career Perspectives: Interview with Tina Checchio, Associate Director, Quantitative Pharmacology & Pharmacometrics
QPP remains at the heart of model based drug development. Short for Quantitative Pharmacology & Pharmacometrics, it refers to several types of quantitative modeling including meta-analysis, PK/PD, statistical modeling and the modeling of go-no-go decision rules. Cytel’s expert Quantitative Pharmacology and Pharmacometrics group delivers high quality solutions to help our customers get those decisions right.
In this blog we talk to Tina who lives in Stonington, Connecticut, to find out more about her career path, current role at Cytel, and her interests outside of work.
Nand Kishore Rawat is a Director and Head, Early Phase Biostatistics based in the King of Prussia, PA Cytel office. We recently spoke with Nand for the Cytel podcast to gain his thoughts on the unique aspects of Phase 1 development and where innovative approaches supported by thorough planning can meet these challenges head-on. Read on for key insights or listen to the podcast.
Happy New Year! As we look ahead to future successes and the new advancements in drug development that 2019 will bring, we are taking a moment to reflect on the topics that resonated most with our community on the Cytel blog in 2018. While these 6 most popular blogs encompass a variety of topics from across the data science, statistics, and statistical programming space, they all have in common a focus on innovative practices and application of statistical, data management, and data science excellence to achieve better outcomes in drug development.
PhUSE EU Connect 2018 took place in Germany’s financial capital Frankfurt, 4th - 7th November and brought together a range of experts to tackle the most pressing issues facing statistical programmers today. The agenda was superb with 143 presentations in 16 different streams and nearly 30 posters. This year’s event theme ‘Future Forward’ did not disappoint and there were some very thought-provoking talks on the drug development industry's challenges and what we can do in the future to meet these challenges. Additional hot topics were: Analytical Risk Based Monitoring, Machine Learning, and Data Standards and Governance. We found this year's event informative and well attended.
In this blog, we share the contributed posters and presentations from our Statistical Programmers and summarize some of the particular highlights from the sessions and posters that our team members attended.
In this blog, Paul Terrill, Director of Strategic Consulting at Cytel outlines his blueprint for ensuring smooth communication between statistical and clinical stakeholders. Paul draws upon his 20 years of experience working as a statistician and his training background to share his guidelines for success. Whether you are a statistician looking to hone your project communication skills, or a clinician keen to maximize the benefit of statistical input to your trial, this article will provide helpful pointers.
This is the third in our blog series ' The Good Data Submission Doctor' in which Angelo Tinazzi, Director of Standards, Systems and CDISC Consulting at Cytel tackles key issues in preparing data for CDISC submission. In the previous “Good Data Submission Doctor” blog Angelo discussed his top 5 SDTM FAQ; in this article he turns his attention to the top FAQs for ADaM. Read on for Angelo's insights.
In this blog, we talk with Robert Greene, Founder and President of the HungerNDThirst Foundation, about his upcoming presentation at Cytel’s East User Group Meeting on 14th and 15th November at Merck in Darmstadt, Germany. Robert will bring a fresh perspective to the discussion of the role statisticians can play in enhancing the position of patients in clinical trials. Patient-centricity is a key topic in modern drug development, and this session aims to encourage statisticians to question the importance of a more patient-centric approach within their field.
We are excited to announce an upcoming webinar in our Trial Innovations Series. “Basket Trials: Design and Implementation Considerations” on 4th December 2018 at 11am EST. Noted basket trial expert, Robert (Bob) Beckman will share his most recent experiences with Cytel Strategic Consulting Statistician Sam Hsiao on expanding the application of this innovative breed of trials. Bob acts as a trial design consultant to biopharma companies in addition to his role as Professor of Oncology and Biostatistics, Bioinformatics, and Biomathematics at Lombardi Comprehensive Cancer Center and the Innovation Center for Biomedical Informatics, Georgetown University Medical Center.
Data is the most crucial asset in any clinical trial and is used to ultimately drive the decision-making process related to the development candidate. Therefore, for any sponsor, paying close attention to the data management aspects of clinical operations should be paramount. The principles of data management are simple and well-founded. However, the application of these principles needs careful consideration, depending on various scenarios and the size of the organization. When implementing data management for your trial, it is critical to plan ahead and fully understand all the steps and activities involved. Fortunately, both strategic and tactical opportunities are available to help sponsors successfully
implement a data management strategy, and ensure quality and simplicity in data collection to enable subsequent analysis. In this ebook, our experienced global data management team outlines some considerations to help sponsors navigate key decisions that need to be made throughout trial implementation.
Cytel biostatisticians Cyrus Mehta and Lingyun Liu, together with Charles Theuer, CEO of TRACON Pharmaceuticals have recently co-authored a publication in the journal Annals of Oncology: “ An Adaptive Population Enrichment Phase 3 Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients with Advanced Angiosarcoma (TAPPAS Trial)”. The paper explores the features of this innovative population enrichment, adaptive sample size re-estimation trial and how it overcomes some fundamental challenges of clinical development in ultra-orphan oncology indications. The publication is timely, in the context of the August 2018 news that the FDA has launched a complex and innovative designs pilot program to facilitate and advance the use of complex adaptive, Bayesian, and other novel clinical trial designs in late-stage drug development. The initiative seeks to further innovation by allowing the FDA to publicly discuss those trial designs that are being considered through the pilot program. Indeed, the TAPPAS trial incorporated regulatory input from both the FDA and EMA and received a Special Protocol Assessment from the FDA. As of the date of publication, the authors were not aware of any other pivotal population enrichment trial that has been implemented in oncology, and therefore the paper’s deconstruction of the design’s key elements will be invaluable to researchers considering similar innovative approaches.
In this second post of the “Good Data Submission Doctor” ( read my first post The Master Recipe: Quality and Attention to Detail Matter here) I would like to go through some of my favorite SDTM Frequently Asked Questions. These are questions I regularly receive in my capacity as a CDISC Subject Matter Expert, either from my colleagues or from the sponsor. Let’s start by taking a look at five of the most recent.
Cytel data scientists apply advanced statistical techniques including predictive modeling of biological processes and drug interactions to unlock the potential of big data.
In this blog we talk to Munshi Imran, who is based in Pune, India to find out more about his career path, current role at Cytel and his interests outside of work.
In this blog, we talk with Simon Kirby, former Senior Director at Pfizer, about his upcoming presentation at Cytel’s East User Group Meeting on 14th and 15th November at Merck Darmstadt, in Germany. Simon will address the topic of Selection Bias for Treatments with Positive Phase 2 Results and in this blog he explains why this is a key topic of particular relevance for pharmaceutical companies in today’s climate of accelerated development. He also talks with us about his career in statistics, current research, and his book Quantitative Decisions in Drug Development.
The Society for Clinical Data Management (SCDM) conference brought clinical data managers from around the world to Seattle-Bellevue, WA on September 23-26. The conference offered an unmatched opportunity to discover innovative solutions in the clinical data management industry. In this blog, we will share our data management colleagues' experiences, observed trends and contributions to the program.
We are delighted that Stephen Senn will be joining us at the EUGM on November 14th and 15th in Darmstadt, Germany. In this blog, we sit down for a discussion with Stephen about his career in statistics, his advice for early career statisticians, his upcoming research, and the topic of his presentation at the East User Group Meeting “70 Years Old and Still Here: the Randomized Clinical Trial and its Critics”.
The "Master Recipe": Quality and Attention to Details Matter When Submitting CDISC Packages to Authorities
One of my wife’s favorite TV shows is ‘Quattro Ristoranti’ (Four Restaurants). In each episode of the show, 4 restaurants of the same style are assessed and the one getting the best evaluation wins the prize. One of the first things the TV presenter Alessandro Borghese, a famous Italian chef, does while visiting the restaurant is to assess (of course!) the kitchen and how much the kitchen and its tools are cleaned. This assessment could have a big impact on the final outcome regardless of the quality of the food served in the restaurant .... the state of the kitchen and its cleanliness influences Borghese’s faith in the chef’s work.
This is exactly what could happen in a data submission to health authorities such as the FDA: the efficacy and safety of your drug are of course what matter, but lack of traceability, or poor or insufficient documentation might trigger questions and concerns from the reviewer. While this might not impact the overall final outcome of your submission, approval could be delayed if the reviewer starts questioning what you have done by requesting changes, or new deliverables to clarify the aspects that were not sufficiently clear in your original submission.
In this blog, we talk with Heiko Götte, Senior Expert Biostatistician at Merck about his upcoming presentation at Cytel’s East User Group Meeting on 14th and 15th November at Merck Darmstadt, in Germany. The topic Heiko will address is Decision Making in Development Programs with Targeted Therapies and he explains to us why this is a key topic for pharmaceutical companies today as they strive to improve their decision-making, and what delegates can expect to take away from the presentation.
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 Adam who lives in North Carolina United States to find out more about his career path, achievements, current role at Cytel and his interests outside of work.
Immunotherapy has brought us many promises, most notably, of a future where humans are able to harness their body’s own ability to protect them from illness. Immuno-oncology (IO) may be the ultimate frontier of that future reality, with a promise of being able to help our bodies deflect or cure us of any malignancies. Today, these therapies include cell therapies, cancer vaccine, and T-cell–stimulating antibodies, with the field continuously expanding.
While medical science behind immune-oncology (IO) treatments is fascinating and expanding at a rapid pace, so too are the statistical challenges posed by the development of these agents.
The biopharmaceutical and healthcare industries now collect more data than ever before due to advances in the variety of information sources combined with the ability to store vast quantities of diverse data. Sophisticated machine learning (ML) and artificial intelligence (AI) techniques allow us to access
and analyze any combination of a multitude of data sources. The way that traditional controlled sources are viewed is being adapted in light of new evidence that emerges from real-world data. A recent Deloitte survey (1) found that 90 percent of biopharma companies are making significant investments in
real-world evidence capabilities to drive drug development and meet regulatory requirements.
Real-world evidence (RWE) has historically been used for post-marketing endorsement and in pricing and reimbursement negotiations. But could data science offer an opportunity to fundamentally shift this
paradigm, leading to better and more affordable medications being approved on the basis of RWE?
In June 2018, Cytel created and ran a survey asking respondents from our audience about the potential of data science approaches in the sector. We are now excited to share the insights from the survey* ( designed as a qualitative pulse check) which reveal a powerful potential shift in the current drug development and approval paradigm.
On August 29th 2018, the FDA announced (1) that it would be establishing a Complex Innovative Trial Design (CID) Pilot Meeting Program. This follows the release earlier in August of a draft guidance (2) to help advance effective and innovative clinical trial designs early in drug development that can expedite new cancer therapies.
EnForeSys is Cytel’s tool for patient recruitment planning. We have discussed on the blog recently with Tufts University's Center for the Study of Drug Development, Ken Getz, the problem the industry continues to face with patient recruitment, and the fact that most trials significantly exceed their original planned duration. In the face of this problem there's a pressing need to create more realistic plans and scenarios. To achieve this, EnForeSys models the enrollment process and then assigns probabilities for various scenarios.
JSM 2018, ASA’s annual gathering of over 6500 attendees attracted statisticians and data scientists to the beautiful city of Vancouver on July 28 – August 2. The conference offers a one of a kind opportunity for statisticians to exchange ideas and explore opportunities for collaboration. In this blog, we will provide access to our team's slide decks from the event, as well as some of their key takeaways from sessions that they attended.
Cytel has grown significantly over the last 30 years, with operations across North America, Europe, and India. All of our processes, talent, and expertise are applied to maximizing the value of clinical data. At Cytel, quality comes first, and our QA team are committed to ensuring processes are in place to support our services.
In this blog we talk to Meredith who lives in Somerville, Massachusetts, to find out more about her career path, current role at Cytel, and her interests outside of work.
After having spent 15 years in the pharmaceutical industry, in May of 2018, I decided to explore new horizons and took the lead of the newly created Basel statistical programming team at Cytel. Building a new team in an exciting environment and being part of a successful story was the challenge I was looking for. In this blog, I will share my perspectives on what a sponsor programmer might expect when moving into a CRO role, and some of the differences and similarities of working within the two environments.
2018 East User Group Meeting Addresses Multiplicity Themes, with keynotes including Stephen Senn and Meinhard Keiser.
Cytel’s 7th East User Group Meeting (EUGM) will take place on November 14 & 15, 2018 at Merck in Darmstadt, Germany, bringing together industry experts, thought leaders and applied statisticians to discuss the future of clinical trials.
The agenda has been developed collaboratively by the EUGM Scientific Committee, and keynote speakers will include Stephen Senn, Meinhard Kieser, Thomas Burnett, Robert Greene and Simon Kirby.
In this blog, we took the opportunity to talk to one of the speakers, Thomas Burnett, Senior Research Associate in Medical and Pharmaceutical Statistics at Lancaster University, about his presentation topic “Bayesian Optimization of Enrichment Designs” and his perspectives on what EUGM delegates will be able to take away from his talk.
We have written on the blog in the past about the value that a statistical consultant can bring to your team, and to the overall clinical development process. Statistical consultants can be instrumental to the success of your development program, providing a variety of input from creating innovative trial designs that improve information quality and efficiency, to supporting regulatory interactions.
By Gordhan Bagri and Munshi Imran Hossain with H A S Shri Kishore
Shiny (from RStudio) is one of the most popular R packages. The package allows programmers to create applications with interactive user interfaces. These applications can then be deployed for non-programmers to perform analysis. Non-programmers can, therefore, make use of the statistical capabilities of R by means of point and click. This is one of the reasons why its use has been on the rise in the last few years.
In this blog, we share a new infographic based on this popular blog post illustrating some of the critical interactions that need to take place between data management and statistics groups to help ensure efficiency and data quality.
At Cytel our strategic consulting team works on a wide range of projects including: Identifying the best clinical trial design, implementing adaptive designs, developing a regulatory strategy and interacting with regulators.
In this blog we talk to Sam who lives in the Boston area, to find out more about his career path, current role at Cytel, industry experience and his interests outside of work.
A recent article published by Cytel authors Samadhan Ghubade, Sharayu Paranjpe, Kushagra Gupta, Anil Gore and colleague Krishna Asvalayan in the journal Current Science, tackles the topic of adverse drug reactions (ADRs) – a matter of great concern in drug research. The authors focused their research on drugs which had been either banned or withdrawn due to a serious problem of ADRs and applied quantitative modeling techniques to see if a systematic pattern of safety signals could be detected within the ADR count data. In this blog, the publication’s authors share their thoughts on the goals, takeaways and next steps for the research and we also link to the full article.
In this blog we share a case study of how we established and ramped up a functional service outsourcing partnership for biostatistics, programming and data management.
It’s shaping up to be a busy year for Cytel’s software development team with a number of upgrades and planned launches across our range of tools. (Watch this space for announcements soon on new quantitative decision-making software OK GO and an upgrade to EnForeSys). East, our industry leading platform for clinical trial design, simulation, and monitoring will be unveiling version 6.5 in the Fall, and delegates at the PSI conference in early June had the chance to grab a sneak peek of the new functionality in one to one demos.
We’ll also be opening the hood on the new design capabilities you can expect in East 6.5 at a complimentary webinar on Wednesday July 18, 11:00AM - 12:00 US EDT (16:00 UK, 17:00 EU).
Our presenters Pantelis Vlachos and Charles Liu, will introduce the 3 new available modules and share their insights on the supporting methodologies and their practical applications. New developments in the East software are typically derived from two sources: our team’s interaction with our customers, particularly during East training; and from our consulting practice when we help clients design their trials.
The new modules in East 6.5 include:
MCPMod (design with Multiple Comparisons Procedures)
MCPMod allows you to measure the likelihood that particular dose-response curves are the right mathematical model for a given set of data. East MCPMod will allow designing a trial using optimal allocation and then analyze the trial data using various dose/model selection criteria resulting
into a solid base (target dose) for the next phase confirmatory trial.
Population Enrichment (Adaptive designs)
An adaptive enrichment design allows the full population is segmented during interim analyses. Recently, we worked with TRACON Pharmaceuticals to design their TAPPAS trial that incorporated a population enrichment component to help overcome the potential heterogeneity of treatment effect between subpopulations for an angiosarcoma design.
It is important to take a strategic approach to clinical development to minimize the potential for Phase 3 attrition. This new module will help users apply simulations to optimize their clinical trial programs.
Click the button below to secure your place at the webinar.
A number of the Cytel team were in Amsterdam, 3rd- 6th June 2018 for the PSI Conference. This year’s conference was held at the magnificent Beurs Van Berlage, a venue full of history and interesting architectural features. We took the opportunity to give delegates a first look at OK GO, our new clinical trial Go/No-Go decision-making software in this magnificent setting.
In this blog, we'll summarize some of the particular highlights from the sessions that our team members attended.
Measuring lots of little details: Non-Compartmental Analysis and the Early Phase Regulatory Environment.
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 . 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’  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 . 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.
 Gabrielsson, J. and Weiner, D., 2012. Non-compartmental analysis. In Computational toxicology (pp. 377-389). Humana Press, Totowa, NJ.
 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.
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.
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.
By Esha Senchaudhuri
An important trend in clinical development involves integrating strategic pharmacometric analysis with program level decision-making, to make the most use of available data. This can occur in various forms, from leveraging preclinical data for go-no-go decision making , to the need for improved comparative effectiveness frameworks .
Here we have five reasons why you should consider utilizing model-based meta-analyses ( MBMAs) for your program or portfolio development.
Our Industry Voices series showcases our clients’ innovative work and breakthrough therapeutics in oncologic indications and other critical areas of medical unmet need.
In this article, we sit down with Charles Theuer, M.D., CEO of TRACON Pharmaceuticals to discuss
his work, his views on the key advancements in oncology development, the unmet needs yet to be overcome, and the importance of efficient trial design in rare cancers. Click here to download a .pdf of the article, or read on.
At the recent CDISC EU Interchange in Berlin, Angelo Tinazzi, Director of Clinical Data Standards and Submissions at Cytel, showcased a popular poster presentation analyzing the differences between the Pinnacle 21 enterprise (P21e) and community versions. Those working in the field of data standards, will know that Pinnacle 21 is led by the team that created OpenCDISC, and is now the leader in software and services for managing CDISC compliance and clinical data quality. The organization continues to offer a community based software tool, in line with the OpenCDISC model, but now offers an enterprise version to sponsors and CROs, that is also used by the FDA itself.
Our Industry Voices series showcases our clients’ innovative work and breakthrough therapeutics in oncologic indications and other critical areas of medical unmet need.
In this article, we are delighted to share an interview with Kurt Gunter, M.D., Chief Medical Officer of Cell Medica in which he discusses his work, his views on the key advancements in oncology development, the unmet needs yet to be overcome, and the importance of strategic biostatistics input to his organization. Read on, or click here to download a copy of the article to read offline.
PSI is a global member organization dedicated to leading and promoting best practice and industry initiatives for statisticians in the biopharmaceutical industry. The PSI annual conference is going from strength to strength, attracting increasing numbers of delegates from Europe and beyond. With the 2018 conference taking place in Amsterdam in only a month’s time, we took the opportunity to sit down with Lucy Rowell, Senior Principal Statistical Scientist at Roche and the Conference Chair, to learn more about this year’s venue, themes, and new hot topics, along with insights on Lucy’s vision for the future of the PSI organization. We look forward to seeing you in The Netherlands!
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.
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.
Our recent Clinical Biometrics Survey explored the views of respondents from across the statistical programming, biostatistics, and data management functions to learn their top challenges, and most important perceived industry trends and skills development. In this blog, our Ajay Sathe gives his perspectives on the key areas of personal and knowledge development that he believes statistical programmers need to focus on to keep abreast of the evolving drug development landscape.
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.
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.
By Esha Senchaudhuri
In response to its R&D productivity from 2005 – 2010, AstraZeneca took the initiative in 2011 to implement what it has called the 5R Framework to strengthen its capabilities. In a Perspectives article from Nature Reviews Drug Discovery , Paul Morgan and his team provided complex details about the success of this framework from the perspective of every stage of drug development. Between 2005 and 2010, AstraZeneca was behind industry averages in every phase of clinical development except Phase 1. After the implementation of 5R, AstraZeneca success rates improved substantially. Indeed, it was announced by IDEA Pharma in March 2018 that AstraZeneca had topped its 2018 innovation index. Here we examine to what Morgan et al, attribute AstraZeneca’s success.
To mark the occasion of our 30th anniversary, in late 2017 we conducted a brief survey to gain a snapshot of what professionals in data management, statistical programming, and biostatistics feel are the key challenges facing their functions, the top areas for skills development, and the clinical data areas they believe are likely to have the greatest impact on drug development.
We are now able to share our findings- read on for some highlights, and to download your complimentary copy of the report.
East is the industry standard platform for clinical trial design, simulation, and monitoring, improving scientific productivity during the critical planning stages of clinical development. In this blog, our Hrishikesh Kulkarni takes us on a tour of his life as a Cytel software trainer and answers some frequently asked questions about how East training sessions work in practice.
CliPLab (Clinical Professional Laboratory) is Cytel’s premier training initiative for bridging the skills gap in biometrics and analytics within clinical development. Leveraging Cytel’s experience and reputation in biostatistics and clinical biometrics, the organization provides practical learning modules in clinical SAS programming, biostatistics, data management, pharmacovigilance, scientific medical writing, key therapeutic areas and crucial soft skills. With learning programs led by experienced trainers, CliPLab engages both with individual students, and companies (e.g. biopharma, CROs) needing to support and augment their internal training programs.
In this blog we share a case study of how CliPLab supported a pharmaceutical customer with a tailored SAS training program for a cohort of new graduate recruits.
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.
by Natalie Fforde, Senior Director of FSP Services at Cytel
With effective use of outsourcing, sponsors are able to respond to market needs and change course where necessary, while ensuring a pool of highly qualified personnel are available to work on clinical trial projects. At Cytel we work with our clients to tailor the outsourcing model that works best for an organization's particular circumstances.
In this blog, I will take a look the Functional Service Provider ( FSP) outsourcing model and some of the key factors that can help make a partnership ‘tick’ successfully.
By Ivan Navarro, Data Scientist at Cytel
R is an open-source implementation of ‘S’, the statistical programming language. With its open character and ability to extend its functionality using external packages, R allows users to create their own packages that are easily loadable into the core instance.
In essence, R-packages are extensions that contain source-code, documentation, data and examples of personal contributions and can be extremely useful for data scientists, statisticians and programmers alike who need to create custom analysis and visualizations. However, creating your first R-package can be a complex task for non-experienced users.
In this blog, I explain how to create a basic R-package which can be used as template for anyone interested in making a contribution. A previous knowledge on R programming is required, but you will not need to deal with technical aspects of the creation process because the R-Package structure is shared at the end.
Photo by Dose Media on Unsplash
By Charles Liu, Senior Product Manager, Cytel
Several years ago, I was one of few Luddites in my social circle still using a “dumb” phone. Other than calls, and (text only!) messaging, it had no other functionality. Once I made the switch, a whole new magical world unveiled itself. With the tap of a button, I could read my email, listen to a podcast, find a nearby restaurant, order a cab, snap a photo, and so on. What was once considered science fiction seems an indispensable part of life today.
There is a consensus in the industry that data on rare diseases is limited, incomplete, and difficult to find or access. Recently we came across the CoRDS patient registry based at Sanford University and learned that the registry is an effective tool used to gather information useful to researchers studying rare diseases.
We sat down with Benjamin Forred, Project Manager, and Austin Letcher, Senior Research Associate at CoRDS to learn more about the registry and hopes for the future.
We extend our congratulations to Lipopharma and the CLINGLIO project consortium on their recent 6,15M€ grant award by the European Union’s Horizon 2020 program. Led by Lipopharma, the multinational consortium brings together 12 academic and industry organizations from Europe, Israel, and the USA.
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.
Recent Publication: A Gatekeeping Procedure to Test a Primary and a Secondary Endpoint in a Group Sequential Design with Multiple Interim Looks
A recent publication in Biometrics ‘A Gatekeeping Procedure to Test a Primary and a Secondary Endpoint in a Group Sequential Design with Multiple Interim Looks’ greatly extends the results of Glimm et al. ( 2010) and Tamhane et al ( 2010) which studied the problem of testing a primary and secondary endpoint, subject to a gatekeeping constraint, using a group sequential design (GSD) with K = 2 looks. This extends the methodology to provide for multiple (K>2) looks. The methodology is applied to the data from the RALES study (Pitt et al., 1999; Wittes et al., 2001).
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.
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.
The Cytel YouTube Channel hosts a wealth of video presentations from Cytel experts as well as external industry and academic speakers about various aspects of clinical trial designs and their implementation. In this blog, we've gathered 6 popular resources from the channel on topics from quantitative decision-making through to overcoming challenges in management of oncology trials. Read on to learn more and access the videos.
News Medical interviewed Dr. Rajat Mukherjee, Statistician, and Director of Data Science at Cytel to investigate the potential of data science in clinical development.
The problem of feature selection
The explosion in the availability of big data has made complex prediction models a conspicuous reality of our times. Whether in banking, financial services and insurance, telecoms, manufacturing or healthcare, predictive models are increasingly used to derive inference from data.
Most of these models use a set of input variables, called features, to predict the output on a variable of interest. For example, the concentration of characteristic biomarkers in the blood can be used to predict the presence, absence or progress of certain diseases.
The available data can provide a large number of features, but generally, it’s preferable to use a small number of really relevant features in a model. This is because a model with more features has a greater complexity which leads to greater demand on computational resources and time to train the model. Therefore it is desirable to restrict the number of features in a predictive model. Choosing the subset of features that will result in a model with optimum performance is the problem of feature selection. This is essentially a problem of plenty.
Our Career Perspectives' series is back!
Cytel has industry-leading experts in statistical programming with years of SAS® Programming expertise, combined with in-depth knowledge of specific clinical subject matter, which allows for competent and on-time completion of tasks. Our extensive service offering includes CDISC migration, mapping to SDTM and statistical programming.
In the first blog of 2018, we talk to Lisa, who is based in Boston, to find out more on her career path, achievements, current role at Cytel and her interests outside of work.
Health professionals and policy makers want to make healthcare decisions based on the relevant research evidence. The questions in clinical research are typically studied more than once independently by different researchers. Literature review is used for summarizing the results of these studies and strengthening the evidence. Systematic review is a type of literature review that collects and critically analyzes multiple research studies or papers that answer the same question. If the results of these multiple studies are diverse and conflicting then the clinical decision-making becomes difficult. To overcome this problem meta-analysis is used. Meta-analysis is a statistical procedure for combining the results of studies that are included in systematic review. While meta-analysis is a powerful technique, it may give misleading results due to issues like improper selection of studies, publication bias, and heterogeneity among studies. In this blog, we will focus on the problem of heterogeneity.
As we prepare to close the door on 2017, we thought we would take a look back at the topics which have been most popular on the Cytel blog this year. It's an interesting insight on what pain points and opportunities feature highly on our global biopharma audience's radar. Read on to learn which of our 2017 blogs have received the most interest from our audience so far.
Signal management is one of the most audited pharmacovigilance processes. It also generates one of the highest findings from audits. The ability of Marketing Authorisation Holders (MAHs) to make a robust signal management system that is fully audit/inspection ready sometimes falls short of expectations. Happily, technology can be used to make the process more scientific and rigorous.
Technology in the signal management process can be divided into two categories. The first one is the front end i.e. what platform (.Net/JAVA) is being used to develop the system. The second is the back end i.e. what programs/software (R, Python, SAS) are used to process the data. In this blog, we will focus on the second category and discuss how R specifically can help improve the signal management process.
In 2011, Cytel organized its first East User Group Meeting (EUGM) in Paris. Since then, we have held an EUGM almost every year, alternating between locations in Europe and North America. These meetings have been a great success, giving opportunities for customers and industry colleagues to meet each other as well as with key opinion leaders, whilst learning more about our East software and providing critical feedback.
This year, the EUGM was held in Cambridge MA on the 25th and 26th of October. In this blog we are delighted to share the slides from some of the speakers' presentations.
In this blog we turn to some reading matter, and interview Gautier Paux and Alex Dmitrienko about the recent book 'Clinical Trial Optimization with R'. The book explores a unified and broadly applicable framework for optimizing decision making and strategy selection in clinical development, through a series of examples and case studies. To learn more, read on for Paux and Dmitrienko's insights.
Cytel offers a full range of clinical data management services and the team of experts is spread across the globe.
In this blog we talk to Makarand, who is based in India, to find out more about his career path, current role at Cytel and his interests outside of work.
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.
Each year Halloran Consulting Group hosts‘CORE’ (Clinical Operations Retreat for Executives) as a forum for industry executives to discuss pressing challenges in a collaborative environment. This year, our Senior V.P. of Clinical Research Services, Irving Dark, discussed the topic of vendor qualification and posed the question to the group: are there better alternatives to the traditional qualification audit process? In this blog, we present Irving’s proposal for an innovative approach that could improve efficiency and allow sponsors to invest more time evaluating the operational and cultural aspects that have greater potential to ensure the success of a partnership
In this blog we are excited to unveil a new project which we have been hard at work on over the last few months.
2017 marks a very special milestone for Cytel – our 30th anniversary. Cyrus Mehta and Nitin Patel founded Cytel in 1987 with an initial objective to solve a specific problem in computational statistics.
At the Chief Medical Officer Summit earlier this year, Cytel's Director of Quantitative Pharmacology and Pharmacometrics Cecilia Fosser, and Senior Director, Business Development, Chuck Gelb presented on how model-informed drug development (MIDD) techniques can improve decision-making and Probability of Success ( PoS) of clinical trial programs. In this blog, we share some highlights and the informative10-minute video replay of their talk which includes a modeling and simulation case study.
Last month was the eighth American Conference on Pharmacometrics (ACoP8) in Florida, a key event on the calendar for Cytel’s Quantitative Pharmacology and Pharmacometrics subject matter experts.
Cytel was delighted to contribute to the event this year and present two posters. This was excellent opportunity to share our knowledge and innovative research, alongside networking with likeminded industry professionals.
As part of Cytel's new Trial Innovations Webinar Series, Pat Mitchell, Statistical Science Director at AstraZeneca presented the October webinar "Formal Go/No-Go decisions are a key component of risk management in early clinical development."
In this blog, we share the second part of our interview with Bob Beckman, about a design concept for a confirmatory basket trial. Beckman is Professor of Oncology and of Biostatistics, Bioinformatics, and Biomathematics at Lombardi Comprehensive Cancer Center and the Innovation Center of Biomedical Informatics, Georgetown University Medical Center. The first part of the interview, which focuses on the context of the design is available to read here. Otherwise, read on to learn more details about this innovative design which has the potential to drastically increase drug development efficiency. Beckman presented on this topic at Cytel's East User Group Meeting in October.
The ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop is sponsored by the ASA Biopharmaceutical Section in cooperation with the FDA Statistical Association. Each year 800 statistical practitioners come together to absorb new information on statistical practices in all areas regulated by the FDA.
Cytel was honored to be involved in the workshop program, and our subject matter experts added value to the conference by sharing their academic and regulatory experiences.
Don’t worry if you missed the event!
In this blog, we share the full slide set slide from Cytel contributions at the ASA Biopharmaceutical Section Regulatory Industry Statistics Workshop.
Cytel's new Trial Innovations Webinar Series provides a platform for the most promising new statistical approaches helping to bridge the gap from methodology to implementation. Ultimately, our goal is to enable our audience to improve their chances of success in clinical development.
The series got underway in August with a webinar on ‘Phase 2 Trial Designs using Program-level Simulations, and Possible Adaptive Approaches’.
The Society for Clinical Data Management (SCDM) conference landed in Orlando last week providing insights and key trends for clinical data managers from around the world. In this blog we share an infographic of some of the agenda highlights along with a more detailed overview of our Alla Muchnik's contribution to the session Study Medication Compliance: Data Collection Challenges.
Namrata Deshpande, Senior Team Lead will be participating in a round table discussion at the Women in Statistics event in California, October 19-21.
This is the first blog in a new 'Career Perspectives' series and we talk to Namrata to find out more on her career path, achievements, current role at Cytel and her interests outside of work.
In this blog we share a case study of work our strategic consulting team conducted supporting accurate event prediction for a cardiovascular outcomes research trial using the Major Adverse Cardiac Events ( MACE) composite endpoint.
By Ashwini Joshi
For small sample data or rare events data, exact non-parametric tests perform better than asymptotic tests. But they come with the disadvantage of conservativeness. Many corrections have been suggested to reduce this conservativeness but none of them solve the problems entirely. StatXact provides various methods of computing exact p-values. Depending upon the problem at hand, the user can decide which one to use.
Let’s consider a hypothetical example of stratified count data. The example shows two sample data with two strata. Events in Treatment1 are rare as compared to the ones in Treatment0. But the event rates are comparable.
Antibiotic resistance is one of the greatest challenges facing human health today. We are excited to welcome Dr. Scott Evans of the Harvard T.H Chan School of Public Health (HSPH) to the blog to discuss how the novel statistical methods he is developing could help tackle this global crisis.
At the East User Group meeting (EUGM) on 25th and 26th October, we will welcome a number of renowned industry speakers to discuss some of the most promising approaches in innovative trial design. Over the next few weeks, we will profile a number of the speakers and their talks. In this blog, we talk with Bob Beckman M.D in advance of his presentation ‘Design Concept for a Confirmatory Basket Trial'. This, the first part of a two-part interview will reveal Bob’s insights into basket trials and their potential. The second part of the blog will delve more deeply into the design concept itself and will be published after the East User Group Meeting. To learn more, read on.
By Munshi Imran Hossain, Software Affiliate at Cytel
Biomedical signals are electrical signals collected from the body. Some of the most common ones are the electrocardiogram (ECG) and the electroencephalogram (EEG). These signals are of great value because they can be used for diagnostic purposes. Importantly, most of them can be collected using non-invasive methods. These attributes, together with the tremendous recent advances in electronic and digital processing technology, have made biomedical signal data an important source of data used in medical diagnostics.
Last month, Cytel statisticians headed to Baltimore for the Joint Statistical Meetings and shared some of their latest research and insights. In this blog we will summarize our highlights -both from Cytel contributions and the sessions Cytel delegates attended. We also provide access to the valuable slide decks from the Cytel authored presentations.
Model-informed drug development has been defined by Richard Lalonde ( Lalonde, 2007) (1) as “Development and application of pharmaco-statistical models of drug efficacy and safety from preclinical and clinical data to improve drug development knowledge management and decision-making”. It has been identified by the FDA as an important way to help reduce attrition and uncertainty in drug development.
In a recent FDA Voice article,(2) FDA Commissioner Scott Gottlieb noted the critical role which modeling and simulation can play in making clinical development more efficient.
He commented that:
“FDA’s Center for Drug Evaluation and Research (CDER) is currently using modeling and simulation to predict clinical outcomes, inform clinical trial designs, support evidence of effectiveness, optimize dosing, predict product safety, and evaluate potential adverse event mechanisms. We’ll be putting out additional, updated guidance on how aspects of these in silico tools can be advanced and incorporated into different aspects of drug development.”
In this blog, we share a new Cytel infographic highlighting 4 key questions a sponsor can explore to apply these approaches within their development programs.
As a biometrics -focused CRO, Cytel regularly works across a program of studies, providing data consistency, and helping to minimize the oversight burden for the sponsor. In this case study, we describe our work with a client on two Phase 1 studies, and how we were able to carry a number of important efficiencies from the first study to the second.
Sadly, clinical development of anti-cancer therapeutics faces particularly high rates of failure, even in the context of low success in drug development as a whole. Operating costs for oncology trials are also higher than those observed across the spectrum of clinical development. In a recent article produced for the Pink Sheet ( a leading provider of insights and analysis for biopharma leaders) Cytel's Yannis Jemiai explored the key challenges facing oncology development today, and discussed how adaptive designs can help to improve researchers' probability of success. The article tackles the application of adaptive designs in both exploratory and confirmatory development and the potential benefits to stakeholders, including patients.