As we head into the new year, the life-sciences industry can look forward to some long awaited advances in pharmaceutical drug development. Here are our predictions for top trends to look out for in 2015.
1: The Arrival of Adaptive Financing:
Adaptive financing was an idea that was cultivated and nurtured by members and affiliates of Cytel. It is the idea that a financial strategy can be built around outcomes that are observed at certain decision points during clinical development (for example, at interim analyses.) Constructing designs with adaptive financing in mind helps provide potential investors and study sponsors with a monetary ballpark of how much innovation will cost, and how much they have the potential to save. This helps overcome one of the biggest bottlenecks in implementing safer and more efficient adaptive trials, namely the perception by many in the industry that these trials are risky.
2: Increased Use of Multi-Arm Trials to Promote Financial Strategy and Patient Ethics:
Multi-arm trials have become a key piece of the strategic puzzle. As Cytel founder and President Cyrus Mehta once explained, “For many years it was thought that it was incorrect to ask more than one question in a clinical trial. Expensive clinical trials were therefore set up with very particular questions in mind. Multi-arm trials change all of this.” The standard two arm trial is not only inefficient for the trial, but at some level is unfair to patients. Keep in mind that the more we learn from any trial, and the more quickly we can confirm what we learn, the faster we can get effective medicines to those who need it most. Multi-arm trials have immense human impact, and their efficiency promotes sound financial strategy.
3: Focus on Adaptive Early Phase Development:
Phase 1/2a exploratory trials for proof-of-concept and dose-finding allow biotechs and pharmaceuticals to learn about the effects of different doses on their patients, in a way that increases learning while decreasing costs. One of our consultants, Jim Bolognese, recently gave presentations on the use of these combined trials for vaccines and infectious diseases. In light of the terrifying Ebola epidemic in West Africa, such a trial strategy has clear potential to increase benefits to millions of patients, by reducing the time it takes early phase trials to complete, and by increasing the amount of knowledge we have before going into Phase 3.
4: Wider Use of Bayesian Methodology:
Bayesian methods are still not as popular as traditional (frequentist) methods, but we are seeing a rise in the new paradigm. Currently, Bayesian methods are thought to be most useful in the medical devices industry where small changes to technology can lead to significant improvements to the efficacy of medical devices. However, as we saw in 2014, Bayesian methods are also pivotal for efficient and safe exploratory trials in oncology. Many industry speakers at the 2014 East User Group Meeting pointed out innovative uses of Bayesian methods, which will surely take greater root in 2015.
5: Promising Zones Live Up to Their Promise:
This year marks the fifth anniversary of the FDA Guidance on Adaptive Design Clinical Trials for Drugs and Biologics. There is now much more comfort with the idea of an adaptive design than there ever has been before. Many of our customers are currently constructing trials with Promising Zones in mind. A Promising Zone design is one which allows for a sample size re-estimation to take place after the final interim look of a Phase 3 trial (i.e. after the penultimate stage of the trial). The purpose of determining whether or not to re-estimate sample size at this stage is to 'give a boost' to the conditional power. We at Cytel are excited to watch these trials live up to their full promise.
If you have any questions regarding the above, get in touch with a Cytel Consultant:
Related Items of Interest
Mehta, Cyrus R., and Stuart J. Pocock. "Adaptive increase in sample size when interim results are promising: A practical guide with examples." Statistics in medicine 30.28 (2011): 3267-3284.
Schulz, Kraig F., et al. "Drug Development and the Cost of Capital."Optimization of Pharmaceutical R&D Programs and Portfolios. Springer International Publishing, 2015. 35-47.
Bayesian Approaches to Phase 1 Trials in Oncology (Video of Presentation by Satrajit Roychoudhury of Novartis)
Frequentist? Time for an Update! A Blog Post by Pantelis Vlachos, Director of Consulting at Cytel