San Francisco, CA—Personalized medicine is evolving to become an integral part of modern medicine, but regulators are grappling with the assignment of value to new medical technologies, said Andrew Stainthorpe, PhD, Associate Director of the UK National Institute for Health and Care Excellence (NICE), who discussed regulatory aspects of personalized medicine in oncology at the Third Annual PMO Live Conference, a Global Biomarkers Consortium Initiative.
NICE provides guidance on coverage decisions in the United Kingdom for new therapies, technologies, and diagnostics entering the market. Unlike the FDA, NICE makes its recommendations based not only on safety and efficacy but also on cost-effectiveness and questions of cost versus quality.
Value Considerations
“Does the current regulatory landscape work well for manufacturers and researchers?” Dr Stainthorpe asked. “And does it work well for patients, clinicians, payers, and health technology assessment committees? In some respects it doesn’t, and that’s why, perhaps, you’re seeing from NICE…a number of negative decisions about the cost-effectiveness of diagnostic tests, and for new technologies and the cost-effectiveness of those.”
Healthcare expenditures are outpacing growth domestic product in most countries at a rate that is not sustainable. Key parts of regulatory agencies and health technology assessment committees are the process by which decisions are made with budget constraints in mind.
Payers have a difficult role, because they work with tightly controlled budgets, said Dr Stainthorpe. They must be convinced of the value of medicines and new technology, especially in the context of current treatment options.
Cancer is not a uniform disease, because there are different molecular subsets of most cancers. In addition, increasingly, new drugs are effective for the treatment of several rare cancers and are receiving approval for a variety of cancers, such as imatinib for chronic myelogenous leukemia with the oncogene BCR-ABL translocation and gastrointestinal stromal tumors with KIT mutations, or trastuzumab for HER2-overexpressing breast cancer and gastric cancer.
Current research is leading to a plethora of different cancers, and questions arise regarding the best way to treat them, “and which technologies work best to treat patients who may have more than one tumor type expressing a range of different mutations,” Dr Stainthorpe said.
Cost-Effectiveness
NICE typically considers a range of factors in making its guidance. It assesses the evidence provided by manufacturers of technology. A threshold of £20,000 per quality-adjusted life-year has been accepted as cost-effective, but NICE may allow higher prices for innovative technologies, Dr Stainthorpe said.
The difficulty lies in establishing a transparent process that outlines NICE’s appraisal parameters that enter into its decisions, “so the manufacturers bringing such technology to market will know what evidence to collect, and what actually makes a difference in the technology appraisal,” he said.
“There are technology appraisals for which a manufacturer might bring a companion diagnostic into the process,” Dr Stainthorpe said. “And there’s a diagnostic appraisal program with appraisal of a new diagnostic without it being linked to a drug. Those are the 2 programs where NICE operates where a biomarker is featured.”
NICE may give a qualified “yes” to a new technology, usually if in a post-hoc review of the data it determines that a subset of the population benefits more than the overall population from the technology. “It may be that there’s a genetic aspect to it,” Dr Stainthorpe said.
“There are still situations in which there’s a good match between a companion diagnostic and its indication, but it’s not cost-effective, and NICE has said that it can’t recommend that treatment,” he pointed out.
Patient Perspective
NICE also considers the patient perspective in its decisions. Evidence must now show benefit of a treatment on quality of life, not only on the disease.
With personalized medicine, regulators face not only the challenge of small sample size (in some instances, an “n” of 1), but also patients with a number of “n’s” in the form of different genotypes. How that fits into decisions about which therapies to make available, and their costs, is uncertain.
“It’s an exciting time, but I think we need more research and more input in a way that’s digestible for the regulators and the health technology assessment community,” Dr Stainthorpe said.