Cytel Blog

The past decade has witnessed the rise of simulations-based clinical trial optimization in a manner unimaginable to most only a few years ago. Such optimization has become an integral aspect of strategic clinical trial design. The initial techniques of operationalizing Monte Carlo methods within a study design setting have increased and transformed in the landscape of cloud-powered computing. Nowadays, technology can produce innumerable simulations within a short space of time. Cytel’s Solara, for example, recently ran 1.5 million simulations within a fifteen minute period to identify trial designs optimized over speed, trial cost and probability of success. Why is it then, that some trial sponsors still struggle to make use of such simulations?

Cytel’s COVID-19 Trial Tracker continues to provide real time updates to the status of COVID-19 clinical trials worldwide. Funded by the Gates Foundation, the COVID-19 Trial Tracker uses machine learning technology to ensure that registries across the world feed into the Trial Tracker.

Historically, advances in the statistical design of clinical trials have accompanied progress within the science and practice of computation. The early 1990s witnessed increased exploration of adaptive and group sequential methods, in no small part due to the enhanced calculations made possible by software that had been developed a decade prior. The similar expanse of designs and methods throughout the past two decades, and the novel departures from the traditional two-arm design, have come with the ability to quickly compute more intricate and complex algorithms. By the beginning of the 2010s, the alignment of biostatistics and computation had grown close enough for educators and academics to begin advocating that biostatisticians needed to be well-grounded in computational reasoning, to equip themselves for unchartered terrains of drug discovery ^[1].

One of the most difficult challenges facing Research and Development teams involves determining how to make tradeoffs between the speed, savings and success of a clinical trial. While some sponsors have to forego improved power in order to remain within strict resource limits, others sometimes increase their clinical development budget to accommodate unexpected gains in statistical power.

Complicating the picture is the fact that different members of an R&D team might have differing values that they place on speed, savings and success. While all three of these parameters affect the expected revenue from a trial (sometimes called the expected net present value or eNPV), we often find some members of the R&D team more concerned about completion dates, and others about investments in clinical operations, and so forth.

The rapid pace of technology has opened up numerous avenues for advanced innovative clinical trial design, but how can we use this to propel clinical development goals like maximizing revenue, or ensuring a commercially viable product? When operational constraints are limiting, how do we achieve the best possible trial design? What should we do if a competitor is edging us out of the market?

While we know that the statistical design of clinical trials can shorten trials or set realistic enrollment goals, there is still a growing need to tie these features of trial design directly to commercial revenue. Clinical development teams would ideally know how much they are willing to spend for an incremental gain in statistical power, or the marginal financial gains in waiting a week to unblind data.

The good news is the industry is getting there. Here are 5 Questions to help you begin your journey towards the Re-imagined Clinical Trial:

In April 2020, Cytel launched an open-access global COVID-19 Clinical Trial Tracker to help facilitate greater collaboration between researchers, policymakers, clinicians, journalists, philanthropists, and other critical stakeholders. Funded in part by The Bill and Melinda Gates Foundation, a leader in global health solutions, this live dashboard offers an overview of all the clinical trials taking place in the international effort to tackle the pandemic.

We have been posting regular updates on the clinical development of COVID-19 therapy and vaccines, on Cytel’s Blog page. The following details are based on an updated data search accessed on January 11.

Cytel has recently designed and implemented the TOGETHER Trials, funded by the Bill & Melinda Gates Foundation to generate knowledge to help fight COVID-19, particularly in low and middle-income countries. The trials, with sites in Brazil and South Africa, test three existing interventions as possible treatments for COVID-19 in high-risk adults who do not require hospitalization, compared to a placebo.

The TOGETHER trials use an adaptive platform design. This type of design is particularly useful for contexts such as COVID-19 response, where there are many unknowns and a need for accelerated and resource-efficient answers, for 5 reasons.

An extraordinary amount of global research is underway as the COVID-19 pandemic continues to evolve and spread throughout the world. There are over 800 registered global clinical trials taking place to develop life-saving treatments and vaccines for patients. The World Health Organization is also facilitating collaboration and accelerated efforts on an unprecedented scale. In these difficult times, sponsors must utilize innovative tools and approaches to design their clinical trials in order to provide promising results for all patient populations as quickly and efficiently as possible. 

A successful virtual panel discussion was conducted by Cytel on the ongoing COVID-19 Trials, on April 15. For the second complimentary virtual panel discussion held on April 23, Cytel partnered with Certara, to present, “COVID-19: Trials, Designs and Tools for Promising Results”. It began with challenges faced by clinicians and drug developers, followed by examples of tools and trial designs currently being used to help sponsors of COVID-19 trials. Continue reading for a summary of the panel discussion.

Get free access to COVID-19 Panel slides and recording.

The Cytel Trial Design Innovations (CTDI) Webinar Series recently hosted a webinar on designing event-based studies. Such studies are essential to designing high-efficiency clinical trials in certain therapeutic areas, but they add a number of challenges to the already complex landscape of adaptive trials.

The webinar was held on January 23rd, featuring Biostatistician and pioneering Bayesian trial-designer Pantelis Vlachos. We had the opportunity to sit down with Dr. Vlachos and speak about innovative trial designs and their benefits, adaptations and interim looks in oncology and cardiovascular, the challenges of designing event-based studies more generally, and how Cytel’s array of software tools, particularly East^®, has enabled trial sponsors to fully consider their options in the design of high-efficiency clinical trials.