A new report titled “Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease” issued by the Institute of Medicine (I.O.M.) asserted standards of evidence used by the Food and Drug Administration when evaluating the health benefit claims of food ingredients and dietary supplements should be as scientifically rigorous as those it employs when evaluating drugs.
“Few who are allergic to peanuts, eggs or shellfish would argue that foods are less risky than drugs,” the report’s authors said. “The committee concludes that there is neither rationale nor scientific grounds for basing regulatory decisions on different levels of scientific evidence for different substances — science is science.”
The I.O.M. report recommended a new framework the F.D.A. may use to judge the appropriateness and validity of the scientific biomarkers used in studies that companies provide to support health and safety claims for their products.
A biomarker is defined as a characteristic that is a measure of a biological process, such as L.D.L. cholesterol level in blood, which is known to be related to heart disease. Most health claims on food packages are based on the effect a food ingredient has on biomarkers, not on clinical outcomes. For instance, an ingredient in a breakfast cereal may help lower L.D.L. cholesterol level, but the whole food’s effect on heart disease itself is untested.
Some biomarkers rise to the level of being considered surrogate endpoints, which are used as substitutes for actual clinical endpoints such as incidence of disease or death. Surrogate endpoints are intended to predict benefit or harm based on scientific evidence, and they are used in practice when it is difficult to collect data based on clinical endpoints.
Again using the cholesterol example, L.D.L. cholesterol in blood is an excellent biomarker in many situations, but it does not always fully predict cardiovascular disease outcomes, so it cannot be assumed to be a surrogate endpoint, the I.O.M. report said.
The I.O.M. said the F.D.A. has been slowed in its ability to assess the proliferation of health claims being made by food and nutritional supplement manufacturers because it lacks a process accepted across the regulatory, food, and medical communities to evaluate biomarkers as valid measurements to substitute for clinical outcomes.
“Many people naturally assume that the claims made for foods and nutritional supplements have the same degree of scientific grounding as those for medications, and this committee thinks that should in fact be the case,” said John Ball, chair of the committee that wrote the I.O.M. report and executive vice-president of the American Society for Clinical Pathology, Chicago. “Without changes in the way biomarkers are used and assessed, however, health care providers, regulators, and consumers will not be able to reliably collect or judge information to support claims.”
The committee is proposing a framework it said will give the F.D.A. a way to assess the selection and use of biomarkers across the food, device and drug areas. The proposed framework includes validating that a biomarker may be accurately measured, ensuring that it is associated with the clinical outcome of concern, and confirming that it is appropriate for the proposed use.
For biomarkers with regulatory impact, the committee recommended the F.D.A. convene expert panels to evaluate biomarkers and biomarker tests.
“Initial evaluation of analytical validation and qualification should be conducted separately from a particular context of use,” the committee said. “In addition, the expert panels should reevaluate analytical validation, qualification and utilization on a continual and a case-by-case basis.”
The committee said Congress should enhance the F.D.A.’s ability to study how health-related information may be communicated more effectively to consumers to help them better understand the science behind claims they see on packaging. The typical consumer is not aware that claims for food ingredients and supplements are often made based on studies using biomarkers instead of actual health outcomes, and this may introduce a measure of uncertainty, according to the I.O.M.
The Grocery Manufacturers Association said in response to the report, “The food and beverage industry is committed to providing consumers with the products and information they need to achieve and maintain a healthy lifestyle. G.M.A. agrees with and supports federal laws that require food labels to be a truthful, non-misleading characterization of the science, and should not overstate the findings. We welcome new science that aims to strengthen the evidence base. As the president has indicated, all regulatory action should be based in the very best science available.”
The reaction of the dietary supplement industry was tepid.
The industry generally approved the I.O.M.’s recommendations with regard to developing a framework for the systematic and scientific selection of valid biomarkers but decried the report’s recommendations that seemed to conflate food and dietary supplements with drugs with regard to how they should be regulated.
The Natural Products Association commented, “The I.O.M. committee seems to have veered off course of their target. While the work on the biomarkers is of value, it seems unwise for the committee to present such broad statements regarding the authority of the F.D.A. on food claims, which is neither their expertise nor within the committee’s scope to review the regulatory authority of the agency beyond the viability of using biomarkers.”
The N.P.A. also took umbrage with the report’s assertion that the Dietary Supplement and Health Education Act of 1994, known as D.S.H.E.A., has “hobbled” the F.D.A. regulation of health claims made on behalf of individual supplements. The committee complained that under D.S.H.E.A., “dietary supplements are broadly presumed to be safe, and the F.D.A. does not have the authority to require dietary supplements to be approved for safety and efficacy before they enter the market.”
The N.P.A. responded saying D.S.H.E.A. “has not ‘hobbled’ the F.D.A. but instead has actually provided the F.D.A. with new enforcement authority over dietary supplements not previously available to the agency.”