More Biomarkers, More Health Claims?

Originally Published NO June 2010

FDA has been faced with evaluating and regulating an increasing range of health-related product claims from food and supplement companies. Does the agency have the tools to judge whether proposed claims are valid?

Part of this process requires reliance on and understanding of biomarkers. In clinical studies, biomarkers serve as surrogates for clinical or disease endpoints to determine if ingredients or products have an effect on human health. In evaluating claims, FDA must determine whether a study's biomarker is a valid surrogate for whether or not a product may produce a claimed health benefit, such as preventing or treating a condition. For instance, the ability to lower cholesterol is relied on as a biomarker of whether something helps prevent or treat cardiovascular disease.

Recognizing that it had no scientific framework in place for evaluating biomarkers, FDA had asked the Institute of Medicine (IOM) to recommend how to establish such a process. In May, the IOM committee released its report, which advised three steps: 1) validate that a biomarker can be accurately measured, 2) ensure that the biomarker is associated with the clinical outcome of concern, and 3) confirm that the biomarker is appropriate for the proposed use. The committee also stated that FDA should convene a panel of experts to evaluate biomarkers and biomarker tests.

Industry members I have spoken to support all parts of IOM's report that address how FDA can better evaluate biomarkers. And why wouldn't they? By standardizing its method of evaluating biomarkers and employing experts to do the evaluating, FDA will be able to establish additional biomarkers that are employed equally across the board.

"FDA has been hampered in its ability to assess the proliferation of health claims being made by food and supplement manufacturers in part because it lacks a process broadly accepted across the regulatory, food, and medical communities to evaluate biomarkers as valid and appropriate measurements to substitute for clinical outcomes," stated the IOM report. By building a good foundation for biomarkers, FDA will be able to better evaluate the increasing range of health claims coming its way.

It's also good news for industry if, thanks to the process, FDA is able to validate more biomarkers. Currently, the list of biomarkers considered validated by FDA for the dietary supplement and food industries is short. On this basis, the agency has denied a number of health claims in the past.

"There are really only a handful of validated surrogate endpoints. What this has resulted in is FDA rejecting qualified health-claim petitions because petitioners relied on data that use non-validated biomarkers," says Andrew Shao, PhD, senior vice president of scientific and regulatory affairs for the Council for Responsible Nutrition (Washington, DC). "One example would be the petition for lutein and reduction of macular degeneration risk. FDA rejected the qualified health-claim petition, in part because there were data submitted on macular pigment optical density and risk for age-related macular degeneration (AMD). Of course, supplementation with lutein increases macular pigment, and the logic is therefore that lutein decreases the risk for AMD. But macular pigment is not a validated surrogate endpoint for AMD. So FDA threw out that data."

If FDA were to validate more biomarkers, a greater number of health claims are likely to be approved. "The absence of more biomarkers being validated as surrogate endpoints is the number-one obstacle to getting more health claims," Shao adds. "The cost of conducting clinical trials can be dramatically reduced by relying on surrogate endpoints. More surrogate endpoints mean more clinical trials can be conducted on our products. And if we don't get more of these validated surrogate endpoints, we'll see the demise of health claims in the future."

He continues, "We commend FDA for stepping up and taking the initiative to fund this process. Now, that doesn't mean the floodgates are going to open for validated surrogate endpoints. It'll be many years before we get a significant number more, but at least it's a starting point. Biomarkers are not going to start growing on trees now, but it's a great first step because there was no foundation before, and now we have something to go on."