Applied Clinical Trials
New approaches for conducting clinical trials and developing therapies that actually prevent and cure disease are key to the future of effective drug therapy, according to Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research (CDER). Personalized medicine has achieved mainstream status, accounting for more new drug approvals and promising pipeline candidates, she noted in the “State of Personalized Medicine” address sponsored by the Personalized Medicine Coalition May 21, 2013 in Washington, D.C. This is particularly visible in developing new treatments for cancer, genetic disorders and infectious diseases, as new therapies emerge that are particularly effective for limited groups of patients, Woodcock observed. But the need to study ever smaller subsets of individuals requires new clinical research approaches.
“We have to change the way we develop drugs,” Woodcock stated. The current method is very expensive and doesn’t provide important information on why people respond differently to drug interventions. Sponsors are moving to personalize dose by patient genotype and examine why different drugs are effective for different genotypes of a virus, such as Hepatitis C. But it is “not feasible,” she said, to do a separate trial to determine who should receive a drug, at what dose and with what likely adverse effects for every patient group.
Instead, this FDA official proposed to “turn the clinical trial paradigm on its head” and for research organizations or coalitions to set up ongoing, standing trials to examine patient responses to multiple issues raised by test therapies and biomarkers for certain diseases or conditions. Woodcock cited the I-Spy study launched by the National Institutes of Health to screen new compounds for breast cancer, and similar efforts by disease groups and professional societies to establish networks able to make rapid evaluations of genetic subsets and biomarkers.
Such approaches will support rapid approval of highly effective “breakthrough” therapies, as authorized by the FDA Safety and Innovation Act (FDASIA) to streamline approval of serious and life-threatening treatments. FDA continues to receive and grant requests for breakthrough designations and expects to see more highly targeted and effective drugs come to market, Woodcock noted. These approaches, moreover, are likely to modify FDA’s usual requirement for two randomized, controlled clinical trials to support the approval of new treatments.
Reliable diagnostics are the foundation of these approaches and are desperately needed to make sense of the large volume of information emerging from genomic testing, Woodcock added. FDA has published guidance on how to develop and gain approval of companion diagnostics to ensure the validity of tests used to make critical treatment decisions. Still in development, though, is long-awaited guidance on drug-diagnostic co-development, a rapidly evolving field that remains hard to define for industry and FDA alike.
Focus on value
Woodcock also raised concerns that the high cost of many new, targeted therapies and related diagnostics may contribute to rising health care expenditures and draw opposition from payers. Unusual for an FDA official, she noted increased resistance to reimbursement for “high tech” therapies and diagnostics that offer only limited gains in efficacy. The new field of targeted therapy needs to focus on “adding value,” she commented; manufacturers should strive to develop combinations of treatments that actually control or cure disease, as opposed to short-term improvements in efficacy.
The emergence of more breakthrough drugs has produced a number of “game changers” that are more effective in treating serious diseases, she pointed out, but noted the need to do more. The future of personalized medicine is to deliver “new treatments at reasonable cost that have significant impact in treating or preventing disease,” she stated. For cancer, the goal is to find out how to alter the course of disease, and not stop at incremental improvements, she observed, adding that a cure for Hepatitis C won’t raise any complaints about cost.
Personalized therapies have to be more effective, less toxic – and more cost-effective – than today’s interventions, Woodcock concluded, for this field to really become a major factor in healthcare.