Biopharmaceutical companies are targeting improvements in clinical trial design as a critical factor in pipeline portfolio
success. One major driver of change is adaptive trial design, which has been shown to improve the quality and relevance of
clinical data, enhancing in turn the likelihood of a faster, more predictable path to market authorization. Draft FDA guidelines
on adaptive trial design, issued in 2010, have bolstered the appeal of this tool in maintaining productive relationships with
The high visibility given to a major breast cancer trial based on adaptive design principles—known as the I-SPY 2 program—promises
to continue the industry's evolution toward endorsement of the adaptive approach. The I-SPY 2 trial represents a significant
reengineering of the clinical trial design process with the aim to rapidly evaluate the potential of new drugs in the treatment
of breast cancer while reducing cost, compressing time, and lowering the number of study volunteers.
The trial incorporates several innovative features, including an adaptive design that enables researchers to use data from
patients early in the trial to guide decisions about which treatments, and doses of a particular treatment, might be more
useful for patients who enter the trial later. It provides a scientific basis for eliminating treatments that are ineffective
and for selecting treatment that show promising efficacy more quickly. One of the other key I-SPY 2 design features is the
collaborative nature of the trial in that the multiple drug candidates developed by multiple companies are evaluated. New
candidates are added as others either progress to Phase III based on efficacy in specific subgroups of patients, or are dropped.
Two successful drug candidate transitions were recently reported from the I-SPY 2 trial. Veliparib (an AbbVie compound) proved
promising against so-called triple-negative breast cancer, an aggressive form of the disease for which there are few effective
treatments; and neratinib (from Puma Biotechnology) was reported to be similarly effective against a different form of breast
The success of I-SPY 2 has triggered similar designs in other disease areas such as the Alzheimer's disease collaborative
trial recently announced by the European Union's Innovative Medicines Initiative (IMI). This €53-million project will allow
evaluation of several drugs at once using an innovative adaptive design in a similar way to I-SPY 2, and involve a number
of biotechnology and pharmaceutical companies working together with academic centers, patient groups, and regulators.