The Cytel blog keeps you up to speed with the latest developments in biostatistics and clinical biometrics.
Cytel's team of oncology trial design and advanced analytics experts are hosting a series of complimentary webinars covering a range of innovative topics and solutions. On April 28, 2020, Cytel conducted a webinar with Professor Martin Fey, Medical Oncologist, “A Clinician’s Perspective on Cancer Drugs Development”. Our previous blog features an interview with Professor Fey where he talks about his experience of over forty years in medical oncology, the evolution of clinical cancer trials, the difference between clinically meaningful and statistically significant results, the debate around patient perspectives and other important topics around cancer drugs development.
In his webinar, Professor Fey provides us an overview of drug development for cancer treatments, clinician’s perspective on endpoints, importance of patient reported outcomes and patient perspective, and the significance of biomarkers. Continue reading this post for key highlights from the webinar.
Access webinar slides and recording by clicking on the button below.
Cytel is hosting a webinar, “A Clinician’s Perspective on Cancer Drugs Development”, on April 28, 2020. Our speaker, Professor Martin Fey, Medical Oncologist from Switzerland, will brief us on treatment evolution and give us a deep dive into clinician perspective on endpoints, PRO and patients perspectives, and importance of biomarkers in oncology.
In this interview, we speak to Professor Fey about his experience of over forty years in medical oncology, the evolution of clinical cancer trials, the difference between clinically meaningful and statistically significant results, the debate around patient perspectives and other important topics around cancer drugs development.
It is often necessary to pool safety data from late phase studies, in preparation for regulatory submission. Some of our clients have also begun to add Phase 1 safety data to this pool. On some occasions this is required by regulators. In many cases, however, these Phase 1 data simply provide further evidence that a new therapeutic lives up to the promise of safety across patient populations.
Fulyzaq® from Napo/Salix was the first drug ever to be approved using an adaptive two-stage "seamless" clinical trial design. However, when Napo Pharmaceuticals sought orphan drug status for Crofelemer (made from the croton lechleri plant, pictured above left), it received a short window from the FDA in which to complete a Phase 3 trial for safety and efficacy. Aiming to diminish both time and cost, Napo submitted an adaptive design for a Crofelemer trial to the FDA. Initially, the design was rejected on grounds that it would not demonstrate strong control of the type-1 error rate.
Napo then approached Cytel consultants which advised it to consider a seamless adaptive trial. A seamless adaptive trial combines 2 phases of a study into one trial, thereby allowing a trial to complete within a short window. Using appropriate techniques, it is possible to conduct such studies while maintaining strong control of type-1 error.
A seamless adaptive design may be operationally seamless or inferentially seamless. An operationally seamless design is one in which a confirmatory trial proceeds after an exploratory one, but the data from the two are kept distinct. By contrast, an inferentially seamless trial combines data from both phases to make the final inference. Due to these two varieties of seamless adaptive designs, Napo/Salix had the following 3 trial designs from which to choose:
A key stage of exploratory drug development is implementing a proof-of-concept study to demonstrate the safety of a drug. Given the importance of accurate dose-finding for Phase 3 success, methodological improvements to proof-of-concept studies in Phase 2 can translate into greater likelihood of getting a drug to market.
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.