The Cytel blog keeps you up to speed with the latest developments in biostatistics and clinical biometrics.
Cytel’s New Horizons Webinar Series introduces you to the latest innovations in statistical trial design. This webinar from the series is presented by Dr. Yuan Ji, a consultant for Cytel. Yuan is the founder of Laiya Consulting and currently is the Professor of Biostatistics at The University of Chicago. In his presentation, Professor Ji introduces the U-Design version 1.4, which mainly consists of a new module of dose-finding trial designs with joint efficacy and toxicity outcomes.
Click the button to register for the next webinar in this series, presented by Cytel's Ursula Garczarek. Ursula will be presenting a case study on the value of detailed clinical trial simulations for rare diseases.
TOGETHER trials, and the advantages of adaptive platform designs for investigating COVID-19 therapies
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.
When designing clinical trials, many trial designers are advised to keep the trial simple. Prima facie, the keep it simple principle seems like sound advice. There are various logistical uncertainties that arise when implementing a clinical trial, and the more simple a trial – so conventional wisdom says – the easier it is to respond to these uncertainties.
According to Zoran Antonijevic, a Senior Director at Cytel Consulting, there is reason to doubt such conventional wisdom. After all, flexibility is hardly a virtue of a traditional trial design. Simple designs may seem to make it easier to monitor data and report results. However, a flexible design can better address remaining uncertainties in product development. These uncertainties are related to treatment effect, dose selection, or a sub-population that would experience the best benefit/risk from the treatment.
Here at Cytel we firmly believe that if you don’t get the design of a clinical program right, then nothing else matters. A study recently published by the Journal of the American Medical Association, once again confirms the vital importance of proper trial design for the timely approval of a new drug. The article reports that nearly half of all submitted NME applications fail upon first submission, and only half of those that fail are eventually approved. The median approval delay is a costly 435 days. At least 53.6% of the trials eventually approved would have benefitted from improved study design: 24 of the unsuccessful first-time applications (15.9%) resulted from uncertainties related to dose selection; 20 of the rejections (13.2%) were due to choice of study end points that failed to display a clinically meaningful effect; 20 of the rejections (13.2%) were a consequence of inconsistent results when different end points were tested; and 17 (11.3%) demonstrated inconsistent results when different trials or study sites were compared. Moreover, 89 (58.9 %) showed inadequate efficacy, raising a question about whether the dose had been selected properly.
Cytel has biostatisticians with broad experience in clinical trial and clinical development program design, including adaptive designs and designs for efficient dose-finding. We are eager to collaborate on your clinical programs to enhance their probabilities of success.