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December 4, 2014
Biotech and biopharmaceutical companies are familiar with the standard clinical trial processes. They formulate a product, design a clinical trial that includes a wide range of patients whom may all benefit from the product to be evaluated, compare the candidate to a placebo, monitor clinical progress and note any side effects. This process can take years and millions of dollars. Unfortunately, many of these clinical trials end in failure, leaving companies with major losses and patients without treatments for their debilitating diseases.
Phil Birch, D.Phil., vice president of innovation strategy and alliance partnerships at ICON, wrote a column in Genetic Engineering & Biotechnology News in which he discussed how underutilized adaptive trial designs are, despite the distinct advantages they have over standard trial design.
"Simply put, adaptive designs offer mid-study course-correction that fixed trials cannot," Birch said. "Because of this, they produce better insights that inform and improve decision-making. In the eyes of an investor, an adaptive design makes a product asset or portfolio of assets significantly more attractive because the development process has been de-risked. Furthermore, the higher quality clinical evidence collected in an adaptive trial creates a more solid argument for payer reimbursement – an issue becoming more prevalent in the midst of healthcare reform."
FDA requires guidance
Adaptive designs allow researchers to make adjustments to the experimental protocol during a pre-designated point in the middle of the trial based on the data that has accumulated up to that moment. These adjustments may be in dose selection, sample size, trial termination due to futility or success, or population enrichment in cases when patients are selected by biomarker.
The U.S. Food and Drug Administration and European Medicines Agency support the use of adaptive clinical trials, but only with proper guidance. For example, the FDA warns that adaptive trials may increase Type I error rates, or introduce operational and statistical biases. Additionally, adaptive trials require extensive planning so that all potential changes in experimental protocol are accounted for ahead of time.
'There is a disconnect between desire and practice'
Although adaptive designs have certain advantages over standard designs, they are not used as often as they could be. Birch pointed out how more than 60 percent of biotech executives surveyed in 2014 were likely or very likely to want to engage in adaptive clinical trials. However, only 10 percent of executives actually implemented such protocols. Meanwhile, those rates are only slightly higher in the biopharmaceutical industry.
To illustrate the potential success of adaptive design, Birch discussed the drug neratinib, which was part of the ISPY-2 breast cancer trial that continues to evaluate several drug candidates at the same time. I-SPY 2 uses an adaptive design with the overall goals of significantly reducing the amount of time to reach conclusive results, and boosting Phase III trial success rates to 85 percent. In December 2013, neratinib graduated from a Phase II trial to a Phase III experiment, and by July 2014, the drug reached its clinical endpoint. According to the I-SPY 2 researchers, Phase II graduates typically require three years for Phase III study. The company that owns the drug plans to file for FDA approval in 2015, according to Birch.
Ultimately, adaptive design can help companies spend less time and money on drug evaluation, and bring candidates from bench to bedside quickly.