History of Design Innovation

At the celebration of its 35th Anniversary, Cytel establishes the Cytel Design Institute (CDI). The CDI’s mission is to programmatically capture, illustrate, and develop Cytel’s thought leadership in the innovative application of science and analytics (design science). In so doing, we seek to accelerate development of new therapeutics and improve clinical development success rates, cycle times and cost return on investment efficiency.

Cytel releases Solara, the industry's first-to-market clinical trial strategy platform for simulation-guided clinical study design and selection. It also unveils East Bayes, which includes new Bayesian dose-finding methods curated by Cytel statisticians. It designs the TOGETHER Trial for finding affordable COVID-19 therapies in low and middle-income nations, and is named a finalist in the Edison Awards.    

Cytel acquires Laiya Consulting, strengthening thought-leadership in Bayesian statistics, particularly early phase. It expands its real world solutions and health economics outcomes research by acquiring Ingress Health and Purple Squirrel Economics. It makes forays into platform trials with many new scientists joining Cytel, as well as providing public webinars on the topic. It also publishes one of the earliest industry primers on operationalizing basket and umbrella trials. Once COVID-19 occurs, Cytel publishes several guidelines on how to protect and rescue ongoing clinical trials, as well as builds the COVID-19 Trial Tracker.

Cytel expands into real world data and real world evidence by aquiring Lighthouse and MTEK. This brings more basket and platform trials under its belt. This solidifies capabilities in historical borrowing, trial emulation, Bayesian modeling, single arm trials, natural history of disease, and other innovations. Cytel also makes its first foray into Global Health and epidemiology.

Cytel publishes extensively on Cardiovascular Health and Diabetes, looking more closely at how design considerations and choice of clinical endpoints can build efficiencies in bringing new medicines to market.   

Cytel is acquired by New Mountain Capital. As it consolidates its commitment to adaptive, Bayesian and innovative designs, it also begins to turn to its next phase of growth into real world solutions. 

As a part of the global celebrations of 25 years of adaptive confirmatory designs, Cyrus Mehta publishes seminal paper reviewing the leading clinical trials with Adaptive Designs.  The EXAMINE Trial, a trial for cardiovascular outcomes in patients with diabetes, was the first to change an endpoint as a part of the interim adaptation. Read more in the published results. 

Cytel releases Enforesys, which applies advanced knowledge of Monte Carlo methods to enrollment and feasibility forecasting.  In doing so it presents a way to utilize simulations-based solutions to reduce enrollment uncertainty, which according to JAMA was the foremost reason for trial discontinuity at the time .

These simulations enabled sponsors to: forecast enrollment while accounting for variability at the site level; model fluctuations in enrollment rate for improved targeting; and build a more accurate, data-driven feasibility strategy with Monte Carlo modeling.

To learn more click here: https://www.cytel.com/whitepaper-enforesys

In this era innovative trials became more widespread, available to biotechs for the first time. Cytel designs a number of trials including  a promising zone design for the VALOR trial in relapsed/refractory Acute Myeloid Leukemia, and the endpoint adaptation for EXAMINE a trial for cardiovascular outcomes in patients with diabetes. Cytel also began to build the bridge between design and strategy with key publications in Bayesian decision-making.

East(R) releases a number of modules to empower statisticians to create complex, innovative and novel designs. This includes East Enrichment to create population enrichment designs for biomarker driven trials;  as well as East Escalate for improved dose-finding; and Multi-arm Multi-stage trials that facilitate seamless Phase II/III designs.

The second wave of adaptive designs to take shape in the industry included sample size re-estimation designs, enrichment designs, seamless phase designs, and more. Adaptations began to include changes to endpoint, changes to the number of trial arms carried forward, and the earliest attempts to tie design to decision sciences.

This era also included the development of the Promising Zone design. Invented by founder Cyrus Mehta and colleagues, this simple design ensures that new medicines do not fail to receive regulatory approval simply because the study is underpowered. 

Cytel consolidates its position in adaptive and group sequential trials with dozens of publications. It also expands its biometrics services with offices in South Asia (Pune & Hyderabad), Switzerland (Geneva), and Western Europe (Paris, Barcelona and Lyon). 

In the early 1990s, Cytel's thought leadership focused on making small sample designs widely available in industry to expedite clinical trials. Wider access to software meant products like East, StatXact and LogXact hit the market and created the first generation of technology-enabled clinical trials.

At the same time, Cytel's scientists and statisticians continued to publish in innovative methodologies including Bayesian, Group Sequential and exact small sample methods.  

Cytel is founded in 1987 with an SBIR grant to bring StatXact to market. StatXact continues to be used for calculations of small samples, and is now the most expansive toolkit for small sample methods available in the industry. 

StatXact came to market in 1989 (click to learn more about the story of early Cytel).

Professors Cyrus Mehta, Nitin Patel and a number of their students were challenged by renowned statistician Marvin Zelen, to see if they could  design clinical trials with smaller population samples. Two innovations spearheaded this initiative: the wider use of early computing technology, and the methodological innovations in Operations Research and Combinatorics that this opened up. Cytel's early scholars began to publish in small sample methods (exact methods), Bayesian methods and other operations research, and eventually received SBIR grants to operationalize their research for the industry.