The pharmaceutical R&D environment has become increasingly challenging due to rising costs, inefficient and complex drug development, high attrition and long regulatory review cycles. The success rate in bringing new drugs to market is rather low, with only about 11.3% of drugs that enter human trials receiving marketing approval, according to the Center for the Study of Drug Development (CSDD) at Tufts University. Furthermore, it costs approximately $2.6 billion to develop and obtain FDA approval for a new prescription drug, a $1 billion increase from a decade ago, according to data from CSDD. Pharmaceutical scientist, inventor, and biotech entrepreneur Dr. Najib Babul explains how following a popular baseball strategy of data-inspired solutions called “The Shift” might speed up the process that brings new medicines to market.
The idea was memorialized in Michael Lewis’s bestseller, Moneyball: The Art of Winning an Unfair Game about the Oakland A’s and its contrarian GM, Billy Beane, who used an evidence-based statistical approach to field a winning baseball team, despite a limited budget and decades-old baseball orthodoxy. A movie based on the book starring Brad Pitt and Jonah Hill was nominated for six Academy Awards.
According to Dr. Babul, there are many ways to apply the lessons of Lewis’s Moneyball to drug development. One idea is a move towards more adaptive clinical trials in place of traditional randomized controlled clinical trials, the current gold standard in drug development. Adaptive clinical trial designs evaluate treatments by observing participant efficacy and safety outcomes, and then respond with modifications to the ongoing study. Such adaptations have the potential to reduce R&D costs and time to market. While adaptive trial design must not undermine the scientific validity of the research, mid-study changes may include revisions in overall sample size, subject allocation to treatment groups, and real time reductions or increases in dosages. Adaptive trials also have the potential to protect subjects from needless experimental risk by requiring fewer subject exposures to ineffective or potentially toxic doses, or fewer subjects treated overall to provide statistically significant results.
This new paradigm in thinking is not unlike the defensive tactic known as “The Shift” in the sport of baseball where statistics collected throughout the season influence where players position themselves on the field to better prepare for each batter’s hitting tendencies. “The benefits of The Shift have been demonstrated by the effectiveness of various data-inspired defensive alignments – exactly what researchers are aiming for as well,” notes Dr. Najib Babul.
Although the central premise of adaptive clinical trial design is sound, many pharmaceutical companies are reticent to go into uncharted territory without the simultaneous and robust embrace of drug regulators. Notwithstanding ongoing pharma and regulator trepidation, the march towards more efficient clinical trial design is inexorable since companies must eventually contain overall R&D costs to improve profitability. Furthermore, there is growing demand for precision medicine, medicines to treat narrow target populations and medicines for rare diseases, populations ideally suited to adaptive clinical trial design.
The benefit of adaptive designs for clinical trials may ultimately lie in the prospect that the data for future adaptive clinical trials would be shared, overcoming the inherent competitive nature of pharmaceutical companies. Dr. Babul cites a successful example of this in the precompetitive collaboration between AstraZeneca and Merck on a combination therapy for cancer in 2007, which despite the complexity of the treatment, was accomplished quickly. Increasing data sharing and incorporating more adaptive trials would quicken the pace of medicine development and potentially deliver results faster and with greater safety.
A graduate of the University of British Columbia, the State University of New York at Buffalo and the California Institute of Advanced Management, Dr. Najib Babul, PharmD, MBA is currently a drug development consultant to pharmaceutical companies and investment banks, and Director of Medical and Pharmaceutical Consulting at the California Institute of Advanced Management. The author of more than 170 abstracts and manuscripts, Dr. Babul is an accomplished pharmaceutical scientist, inventor, biotech entrepreneur and drug developer with more than 20 years of experience bringing new and repurposed drugs to market.
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