Oncology is one of the most dynamic and complex therapeutic areas that a pharma company can be involved in – so considerations for clinical trials are often vastly different and more complicated than for other diseases.
“The oncology space is rapidly evolving,” says Joshua Schultz, CEO of Cytel. “It’s stunning to watch it evolve so rapidly. We’ve got new biomarkers being discovered routinely; we’ve got changes in the standard of care happening along multiple dimensions. We’ve got new treatments being approved all the time.
Cytel is specialised in data and analytics solutions, particularly the more complex types of data analytics that are relevant for oncology studies.
The company has an expanding software group, a large consulting organisation focused on, quantitative strategies to advance the development pathway, and a robust operational statistics, statistical programming, and data management services capability that allows the company to help clients execute against those designs.
Cytel serves an extensive portfolio of oncology developers, making the company particularly well-placed to understand the ever-evolving needs of organisations looking to take on this dynamic therapy area.
Yannis Jemiai, senior vice president of strategic consulting and software solutions says that oncology particularly benefits from some of the complex and innovative trial designs that Cytel has helped to bring into the forefront of drug development.
Adaptive trials, that review accruing data from patients at one or more times as the trial is ongoing and adjust certain parameters of the trial in order to increase the probability of success, have seen a rise in adoption in recent years. Complex and innovative designs represent the next evolution of adaptive trials with more sophisticated approaches such as seamless trial design, use of biomarker enriched populations and adaptive designs that involve multiple adaptations.
Jemiai says that such adaptive and innovative trial designs help researchers adapt to oncology’s rapidly changing standard of care.
“The standard of care changes so fast that it challenges the conclusions that can be drawn from any single long study,” he points out.
A recent example is Merck and Pfizer discontinuing a study for Bavencio (avelumab) in ovarian cancer because patients were no longer being tested against the standard of care following the approval of AstraZeneca’s Lynparza (olaparib).
But despite advanced trial designs and software having existed for some time, Schultz believes that many companies’ trials are not fully harnessing the potential of modern oncology. He says there are several reasons for this.
“A lot of our clients have concerns about regulatory acceptance when trying out new kinds of trials.
“Agencies, and the FDA in particular, have expressed interest in embracing novel designs. They recognise how challenging our landscape is and how the use of more innovative approaches is needed to bring the best medicines to patients in a reasonable timeframe at a reasonable cost.
Nevertheless, Jemiai adds that schemes like the FDA’s recent Complex Innovative Trial Design (CID) Pilot Programme – which aims to facilitate and advance the use of novel clinical trial designs – are an encouraging sign, even if it’s too early to tell exactly what effect they will have.
“The main benefit of the FDA’s pilot scheme is to show that the agency is open to listening, understands the intricacy of these new approaches to trial design, and wants to actively engage with sponsors to optimise development pathways,” he says.
Schultz adds: “We do have to be careful with all of our analytic activities. I don’t think that has changed one bit. However, the changes in the industry – in particular in oncology – are so massive and the potential is so great that people are being pushed to move quickly while retaining focus on quality and patient safety.”
Other concerns can come from the clinical operations sides of businesses, with clients wondering if they have the ability to implement a design that is more complex.
Cytel has software that supports adaptive and complex designs to enable oncology drug and technology developers to account for a variety of factors that can change during the course of a study.
“Right now we provide all of those services and technology to our clients,” Schultz says, “but what is exciting to me is that we’re pushing the frontiers of all of those areas to rise to the increased challenge that our industry faces, in particular in the oncology space.
And Schultz believes that there are other ways technology can help to bridge the gap between where trials are and where they need to be.
“This could be by creating collaboration opportunities for the different stakeholders, or by using cloud computing and simulation to identify the right designs and then translate the output of those designs into value statements that all stakeholders understand. Not just statistical outputs, but also business outputs and clinical operations outputs.
“We are also expanding into different types of consulting. We appreciate that while we have been leaders in statistical consulting and system design consulting for decades, a lot of our clients are trying to understand how to build a whole programme or a project inclusive, not just of statistical disciplines, but also regulatory, market access, manufacturing, clinical operations, medical, etc. It’s our view that a design that doesn’t include all of those perspectives from a very early stage is probably a suboptimal design.”
Lastly, Schultz thinks that real-world analytics is one of the most exciting areas that could really make a big difference to Cytel’s clients and to the company’s ability to execute in the oncology space.
“It’s fundamentally not possible to run randomised clinical trials for every combination of population biomarker, tumour type, etc. that is out there. Real-world data can be used to create historical or synthetic control arms, identify label expansion opportunities, conduct comparative effectiveness or safety research as well as many other types of research that would have traditionally required expensive studies or been infeasible in previous years.
This is not to say that there are no challenges with real-world data. For example, Jemiai says it can often be “like having a hammer and seeing nails everywhere” – whereas traditionally researchers would start with a question and find data that proved or disproved that hypothesis, now they have data that is often not tailored to answer any particular question. Therefore, researchers need to use various kinds of analytics too, such as pseudo-randomisation, to make it more appropriate for the trial in question.
Irving Dark, Cytel’s senior vice president of clinical research services, notes that all these new sources of data create more data complexity, and that Cytel therefore believes it is important to have statisticians and data managers working closely together from the start of the trial and throughout data collection and analysis.
“Traditionally, the statistician would get involved at the beginning with the data manager to look at critical variables and form design,” he says. “He or she had to check things of that nature, and then the statistician would focus on the analysis plan and interim Data Monitoring Committee, etc.
He adds: “In many instances people have treated data management more as a commodity. With the increasing complexity and the number of sources of data that view is shifting and it’s becoming more important to have a different mindset in terms of your approach to data, data collection, cleaning, and analysis.
“The right design and the right data leads to the right decisions. It’s getting that fit-for-purpose data that’s collected specifically based on what your protocol is looking for – not taking a shotgun approach but being much more precise.”
Dark says that streamlining data collection is also becoming increasingly important.
“We need to avoid duplication of effort and duplication of data. We need to ensure that there’s accurate and timely data collection, that there’s collaboration between the CRO and the sponsor company and clarity about how that’s being done.
“Traditionally, you had the sponsor and you had the CRO, and their activities were very segmented. Over time, that has been coming closer and closer together in terms of collaboration and a partnership.
This means that sponsors need to know how to work effectively with CROs such as Cytel, as well as with data monitoring committees (DMCs), the independent group of experts who monitor patient safety and treatment efficacy data while a clinical trial is ongoing. Dark says that proactive communication is key, as well as consulting with each other early and often.
“It’s really a collaborative effort between the sponsor, the DMC and the CRO in making sure that it’s an efficient process.
“It’s important to have a well-run organisational meeting with the DMC early on. There you can identify potential issues, discuss details of future meetings, and think about how the data’s going to be presented in order to ensure efficiency thus minimising the need to go back and ask sites further questions.”
It’s also important to have clean, complete data going to the DMC, because they need to have accurate data in order to make accurate decisions.
“The statistician who is presenting to the DMC really needs to understand the completeness of the data or lack thereof and explain that to the DMC, and make sure that things are explained in a way that’s clear for the clinicians and the statisticians alike,” says Dark.
Companies often struggle with knowing when they are going to achieve enough events in order to have the DMC meeting, he says.
“We’ve developed some easy and predictive probability algorithms in order to predict with high levels of certainty when we expect to reach a certain number of events, which helps significantly for planning.
Looking forward, Schultz predicts even more major changes for trials in the oncology space.
“We believe there will be continuous development with more ‘seamlessness’ between trial phases,” he says. “We believe we’re going to see more platform trials. We’re going to be looking at much more exploratory biomarker-driven development. All of those will lead to profound movement from an innovation perspective, from an investment perspective and from a results perspective.”
As such, Schultz knows that Cytel will have to continually adapt and innovate.
“Cytel is already the leader in data analytics, and for us to retain that mantle and really help our industry unlock the potential of more sophisticated approaches to design, we will continue to invest in next-generation technology.
“We are investing in a much-expanded approach to real-world analytics. We are expanding our consulting capabilities to be able to help our clients not just in statistical design but also in being able to bring other domain experts to the table. This is so that we truly have an integrated approach to project design that incorporates all of the various stakeholders that are required to build a successful research endeavour.”
Schultz says, “It’s an exciting time and we stand right on the cusp with our clients of being able to make full use of the advanced technologies and data assets that have recently become available.”
Joshua Schultz, CEO, Cytel
Joshua Schultz is an accomplished leader with a 20-year track record of success in life sciences and clinical research organisations. Prior to joining Cytel he served as an officer of PAREXEL and senior vice president for PAREXEL’s Access business unit. Joshua has built and led groups for services spanning the development lifecycle, including study start-up, late phase trials and market access. His achievements include the development of novel approaches to building high value strategic partnerships with life science companies and creating innovative operational models that leverage real-world data and related technologies. Prior to joining PAREXEL, he served as Vice President of Corporate Development at Veritas Medicine, which he co-founded. Previously, he worked at Mercer Management Consulting, where he developed growth strategies for Fortune 500 companies.
Joshua holds a B.S.E. in Finance from the Wharton School of Business, a B.A. in International Relations from the University of Pennsylvania, and a Masters of Philosophy in International Relations from the University of Cambridge, UK.
Yannis Jemiai, senior vice president, strategic consulting and software solutions, Cytel
Yannis Jemiai has a pivotal role within Cytel, leading the company’s consulting and software business units. With Cytel Consulting he heads up an elite team of biostatisticians and quantitative strategists, skilled in applying the latest trial techniques and methods, to help our customers accelerate clinical development and mitigate portfolio risks.
Yannis also oversees the development of Cytel’s software product lines, including trial design packages East and Compass, and exact statistics applications StatXact and LogXact. His research has been published in numerous statistical journals. Dr. Jemiai earned his Ph.D. from Harvard University, an M.P.H. from Columbia University, and a B.A. in Molecular and Cellular Biology also from Harvard
Irving Dark, senior vice president, clinical research services, Cytel
Irving Dark brings 25+ years of operations management and business development to his leadership of Cytel’s project-based analytics services business. He has a proven track record of success in guiding drug, biologic and medical device products through the development process, and growing commercial clinical research organisations .
Prior to joining Cytel, Irving was Vice President, Business Development and Operations for Veristat, establishing and overseeing the company’s Data Management, Project Management, and Business Development departments. He was integral to Veristat’s Corporate Compliance activities ensuring regulatory and GCP guideline adherence for programme successes in oncology, influenza, and smallpox vaccine.
Irving’s in-depth clinical development knowledge encompasses biometrics and clinical project management. He is the co-author of numerous published clinical studies and has been a DIA invited speaker. Irving holds an Economics BA from the University of Rhode Island.
As a pioneer in evidence generation, with deep expertise in advanced analytical solutions, Cytel is uniquely equipped to unlock the value from increasingly complex data. Life sciences companies count on Cytel to deliver exceptional insight, minimise trial risk, and accelerate the development of promising new medicines that improve human life. Cytel provides data-focused clinical research services and software solutions for the design and analysis of clinical trials, including industry standards East®, StatXact®, and LogXact®. Cytel recently announced that it is joining forces with Axio Research, a premier provider of data monitoring committee services to create an industry leader in advanced analytics for life sciences. For more information about Cytel, visit www.cytel.com.
Cytel recently announced that it is joining forces with Axio Research, a premier provider of data monitoring committee services to create an industry leader in advanced analytics for life sciences.