Adaptive designs are the unsurprising hot topic of this year’s Joint Statistical Meeting, which features over one hundred and thirty sessions on the subject. Statisticians at Cytel look forward to contributing to the dialogue with two papers on adaptive designs, and a workshop for using simulations to benefit from interim data (i.e. for prediction and trial forecasting.) In addition, Cytel Senior Director & Consultant Jim Bolognese has organized a session on making use of adaptive designs to optimize strategy for drug development programs.
In the Ernst & Young 2014 Biotechnology Industry Report, Cytel CTO Nitin Patel writes: "Historically, biotechnology companies haven't fully appreciated the link between trial design and the ability to secure external financing. Yet, adaptive trial designs - which often reduce the risk, time and cost associated with clinical development - can make the math more attractive for investors." [Beyond Borders, p. 20].
One strategy that has proven successful has been to use adaptive designs to improve a trial's risk profile. Sunesis Pharmaceuticals recently used an adaptive promising zone design to secure $25 million dollars in funding for its Phase III VALOR trial. Sunesis had initially planned a conventional trial, but found few willing investors for a large scale Phase III trial in a therapeutic area widely associated with high financial risk (relapsed/refractory acute myeloid leukemia). By designing an adaptive trial with an interim look after 50% enrollment, Sunesis was able to secure funding conditional upon the trial not stopping for futility.
Royalty Pharma agreed to provide Sunesis $25 million in trial funding in return for 3.6% of net sales, only if the trial continued after the interim look. If interim analysis was ‘promising,’ (i.e. revealed that the trial required a sample-size re-estimation,) then Royalty Pharma’s return on net sales would increase to 6.75%. The adaptive design thereby allowed investors to hedge their bets on a trial’s success, based on information provided during an interim look. [Watch Sunesis CMO Adam Craig talk about the Phase III VALOR trial.]
The arrangement was also quite beneficial for Sunesis. In the case of the VALOR trial, the interim look was promising, and encouraged a sample size re-estimation of 225 patients. This meant that while the original, conventional design struggled to receive funding for a sample size of 450, the VALOR trial successfully obtained funding for a well-powered trial of 712.
Techniques for adaptive portfolio optimization are rapidly becoming invaluable for sound clinical investment. The panel at JSM will explore financial de-risking for both Phase IIb and confirmatory trials.
Cytel Abstracts for Adaptive Design talks at the 2014 Joint Statistical Meeting: