The Cytel blog keeps you up to speed with the latest developments in biostatistics and clinical biometrics.
Professor LJ Wei holds that rules are for lawyers, not (necessarily) clinicians. When designing modern clinical trials, the impetus is often to use “efficient and reliable procedures, to obtain clinically interpretable results with respect to risk-benefit analysis…” Yet these efficient and reliable procedures are often just conventions and rules that provide information that is incomplete or difficult to make clinically interpretable.
In a presentation to the East User Group Meeting, Professor Wei identifies 11 problematic areas that currently challenge trial designers. After giving an overview of the challenges that arise in each, Professor Wei provides a few simple solutions about how to overcome them. All the solutions, however, require moving beyond the comfort zone of conventional procedures.
In the slides attached Wei discusses:
Phase 1 oncology trials typically use either rule-based methods or model-based methods to determine the most acceptable level of dose toxicity with which to move forward in Phase 2. This level of toxicity, called the maximum tolerated dose (or the MTD), is the dose which best balances the medical benefits of a higher dose with the risk of toxicity which comes from subjecting a patient to that same dose. Both rule-based methods and model-based methods determine the MTD by relying on small cohorts of patients who test a set of doses against their dose limiting toxicity.
Every year, the East Users Group Meeting brings together notable experts from industry and academia to discuss the future of biostatistical advances in clinical trials, as well as the role of software in facilitating these breakthroughs. In honor of this year’s event, which will be taking place at the Loews Hotel in Philadelphia on October 22, the Cytel Blog will spend the next couple of weeks providing glimpses into the range of discussion presented at the EUGM table.
One debate that has already received quite some attention, involves the weighting of various morbidities in studies with composite endpoints. In a 2013 editorial in the European Heart Journal of the European Society of Cardiology, EUGM speaker Professor L.J. Wei and his colleagues wrote, "A reported P-value must not be confused with an assessment of the magnitude of a treatment's effect in a way that is meaningful to the patient, the clinician and the regulator." 
A few weeks ago, we posted a synopsis of an event held at ISCB Vienna in which statisticians from Cytel, SAS and Stata spoke about processes for developing software for statisticians. The button below will guide you to a copy of the presentation by Cytel's Vice President of Consulting, Yannis Jemiai.
In the presentation, Yannis talks about the decision-making process behind software development, and how it aligns with a general philosophy to empower, simplify and educate. He explains how software developers choose from a variety of statistical algorithms in putting together a classic software package. "Just because we can," he cautions, "doesn't mean that we should."
Statisticians on Software Development Part I: Statisticians from Cytel, SAS and Stata talk Software Development
During an invited speakers session at the lnternational Society for Clinical Biostatistics, Cytel VP Yannis Jemiai was joined by R.N. Rodriguez from the SAS Institute and IR White (formerly of Stata), to discuss innovations in software for clinical trials.
Beyond Wild Horses: Developing Innovation at Cytel
Photos leaked from JSM 2014 appear to show the Reverend Bayes partying with his entourage at the Cytel Cocktail Hour, held at Boston’s Seaport Hotel on August 4, 2014. Bayes is, of course, one of the stars of Cytel’s East 6.3, a modular software package driving drug development through high quality trial design and simulations. Bayes's contributions to the East ESCALATE and East PREDICT modules are posited to transform early phase dose-escalation and interim decision-making. The Reverend has also made scene-stealing cameo appearances in a number of projects with Cytel Consulting.
A new JAMA study on discontinued randomized trials in Switzerland, Germany and Canada, reports that poor recruitment accounts for 101 out of 253 trials that were eventually discontinued (or about 10% of the 1017 trials which participated in the study). When restricted to industry-sponsored trials with non-healthy volunteers, poor recruitment accounted for the discontinuation of 40 trials out of 119 that were discontinued. Across the board, poor recruitment was the foremost cause of trial discontinuity.