In the News

Institute of Medicine Report on Biomarkers: What You Need to Know

US Food and Drug Administration Proposes Transparency

Cranberry Anthocyanins May Influence Cellular Metabolism

Magnetic Stimulation Could Be the New Antidepressant

Institute of Medicine Report on Biomarkers: What You Need to Know

In May, at the behest of the US Food and Drug Administration (FDA), the Institute of Medicine (IOM) released its report on the evaluation process for biomarkers—those characteristics that indicate biological processes like cholesterol levels for cardiovascular health or immunoglobulin levels in allergy response. Doctors, scientists, and other health professionals use biomarkers to obtain information about a person’s health status or response to interventions.

IOM’s report recommends that FDA impose a consistent scientific framework for biomarker evaluation in order to achieve a rigorous and transparent process. It states that the biomarker evaluation framework should consist of an analytical validation to ensure biomarker tests are reliable, reproducible, and adequately sensitive and specific; that qualifications should be set to ensure the biomarker is associated with the clinical outcome of concern; and that analysis should be made to determine the biomarker is appropriate for the proposed use.

Of greatest import to the natural products industry, however, is the IOM recommendation that FDA use the same measure of scientific rigor for evaluating biomarker use across regulatory areas, including drugs, medical devices, biologics, foods, and dietary supplements.

Therein lies the rub. The natural products industry, while applauding the call for expert panels to evaluate biomarkers and biomarker tests, objects to the plan’s implicit idea that it will judge foods as pharmaceuticals. Industry insiders worry that the report privileges the pharmaceutical evaluation system and thereby assumes that foods and dietary supplements are subject to a less rigorous system. What the IOM report forgets, they assert, is that foods and drugs are different entities.

Those concerned about the possibility of FDA evaluating functional food ingredients and dietary supplements using pharma standards see drugs as quick fixes and dietary supplements and functional foods as lifestyle investments. Furthermore, they argue, the FDA already has safety frameworks in place for supplements and foods, some of which are more rigorous than those for the pharmaceutical industry. After all, adverse events are tolerated, even expected, with pharmaceuticals, but once a natural product demonstrates an unwanted side effect, it is pulled off the market.

The report and objections to it promise to heat up the IOM Biomarkers Discussion Forum in Washington, DC, on June 21-22. To download the report, go to http://www.iom.edu/Reports/2010/Evaluation-of-Biomarkers-and-Surrogate-Endpoints-in-Chronic-Disease.aspx

US Food and Drug Administration Proposes Transparency

To help consumers and stakeholders understand how the FDA makes its decisions, the FDA Transparency Task Force recently released 21 draft proposals and invited the public to comment.

Available in the Federal Register, the draft proposals are part of the second phase of FDA’s Transparency Initiative launched last summer by FDA Commissioner Margaret Hamburg. Her goal is to create transparency that promotes public health and innovation while protecting trade secrets and confidentiality. The full report is available from the agency website, fda.gov.

During the past year, the Task Force has held two public meetings, launched an online blog (http://fdatransparencyblog.fda.gov), and opened a docket. The first phase of the transparency initiative was completed in January 2010 with the launch of a web-based resource called FDA Basics (http://www.fda.gov/fdabasics).

For more information and to offer comment on these proposals, go to http://edocket.access.gpo.gov/2010/2010-12314.htm. FDA will welcome public comments on the proposals in the draft report until late July and consider the feasibility, resource requirements, and priority of each proposal when compiling recommendations for Commissioner Hamburg.

Cranberry Anthocyanins May Influence Cellular Metabolism

The humble cranberry has been linked to protection against heart disease, cancer, and age-related motor deficits in recent studies, but the latest research demonstrates that cranberries’ health benefits may extend to the cellular level.

A study published in the June issue of The Journal of Nutrition measured the absorption of cranberry juice anthocyanins, a subgroup of flavonoids that are powerful antioxidants and protect the body from oxidative stress, in 15 volunteers (average age, 62). These subjects, who had established coronary artery disease, fasted overnight and then drank 480 mL of a double-strength cranberry juice containing 94 mg anthocyanins. Plasma samples were collected immediately prior to juice consumption and then at measured intervals. Urine samples were analyzed for anthocyanin concentrations.

The researchers found that the anthocyanin concentrations detected in plasma indicated a low level of intestinal absorption of the flavonoids, which means that circulating anthocyanin levels after cranberry juice consumption are too low to control free radicals. However, the team also concluded that the levels may be sufficient to influence cell signal transduction, gene expression, and cellular metabolism and could therefore have a more sustained health beneficial effect.

Magnetic Stimulation Could Be the New Antidepressant

Depressed patients who don’t respond to or tolerate antidepressant medications may benefit from a noninvasive treatment that stimulates the brain with a pulsing electromagnet, a study in the May issue of the Archives of General Psychiatry suggests. The industry-independent, multisite, randomized, controlled trial of repetitive transcranial magnetic stimulation (rTMS) found that it produced significant antidepressant effects in a subgroup of patients.

The treatment works by stimulating underactive mood-regulating circuitry to target the top left front part of the brain with an electromagnetic coil that emits 3000 pulses over a session lasting less than 1 hour. It can be safely administered in an outpatient setting with few side effects, unlike more invasive brain stimulation treatments like electroconvulsive therapy.

The study, funded by National Institute of Mental Health (part of the National Institutes of Health), involved 190 patients who had previously failed to respond to antidepressant medications. The 92 patients in the active group received at least 3 weeks of randomized, controlled magnetic stimulations with an rTMS magnet aimed at the brain's left prefrontal cortex. Those who showed improvement received up to an additional 3 weeks of such blinded treatment. The 98 patients in the simulation group received sham treatment that blocked the magnetic field but otherwise imitated the active treatment.

Thirteen patients (14%) who received the active treatment achieved remission compared to 5 (about 5%) of patients who received the sham treatment. Patients who received active rTMS were significantly more likely to reach remission, particularly if they had been moderately resistant to treatment. The remission rate climbed to nearly 30% in an open-label phase of this study during which there was no simulation control.

Since the rTMS treatment did not trigger any seizures or other notable side effects, the researchers propose that higher levels of magnetic stimulation may be used in future studies, as evidence suggests antidepressant effects of such stimulation are dose-dependent. They cautioned that although rTMS treatment may be effective in at least some treatment-resistant patients, it is not yet a replacement for more invasive therapies.