Mario Ehlers, MD, PhD At a Glance Title: Chief medical officer and chief operating officer Company: Pacific Biometrics, Inc. Education: MD and PhD, biochemistry, University of Cape Town, Cape Town, South Africa. Research interests: Ehlers is a physician-scientist with 11 years of experience in academic research and seven years in the biopharmaceutical industry. He has extensive experience in business development and product design in therapeutic areas such as diabetes, cardiovascular, and osteoporosis, including research and testing, and facilitating progress through regulatory pathways. Web site: www.pacbio.com

The problem of serious physical risks associated with pharmaceutical drugs is not going away. While the arthritis drug Vioxx, pulled from the market by its manufacturer last year after it was shown to double the risk of heart attack and stroke, remains the most high-profile example, a significant number of pharmaceutical medications have been linked with health risks in recent years.

Rezulin, for type 2 diabetes, was taken off the market in 2000 because of its association with severe liver toxicity. This past year, Celebrex and Bextra, in the same class as Vioxx, made headlines for their adverse effects. In February, sales of the multiple sclerosis drug Tysabri were suspended after it was suspected of triggering a rare brain disease in three patients, two of whom died from the disease. Most recently, safety concerns have emerged about the heart failure drug Natrecor, and doctors at the Cleveland Clinic are considering curtailing its use, after two medical journal studies reported that it increased kidney problems and death rates among patients.

Some people fault the FDA, claiming that the agency does not sufficiently monitor pharmaceutical drugs for safety during clinical trials. But no matter how carefully the FDA and drug companies monitor for safety, the potential for a low incidence of serious side effects will always exist: There is simply no way to guarantee that pharmaceutical drugs will ever be entirely risk-free.

That said, there are actions that legislators and drug-development scientists can take to minimize serious health risks associated with pharmaceutical agents. (On the science front, progress is already underway.) What’s more, this can be accomplished without unduly delaying the development of new medical treatments. These measures fall into two categories:

Greater FDA Control Following Drug Approval: Although a pharmaceutical drug cannot be marketed without FDA approval, the agency has insufficient control over what happens to a drug after it reaches the market. Federal laws governing drug safety withdrawals are limited and therefore in the event of reported health risks the FDA generally asks manufacturers to withdraw the drug voluntarily. While drug makers almost always comply, there is a question about the completeness and promptness of product withdrawals.

To prevent the availability of potentially unsafe medications, legislation is needed that will give the FDA greater resources for post-marketing surveillance and unilateral power to withdraw drugs that the agency regards as posing insufficient benefit or serious risk.

Identifying At-Risk Consumers: As the Human Genome Project and other scientific advances brought about a greater understanding of human genetics and biology, one very promising result has been the increased use of biomarkers in drug discovery and development. A biological indicator that can be used to measure the progress of disease or the effects of treatment (the biomarker hemoglobin A1C, for instance, shows how well a diabetes drug is controlling blood glucose), biomarkers are used today during drug discovery in every therapeutic area.

The newest generation of biomarkers, still in its incubation phase, will enable a new treatment paradigm known as theranostics (for "therapeutic" and "diagnostic"). Theranostics involves a tight coupling between diagnostics and therapies, such that a biological indicator determines in advance which patients will respond to a particular treatment. By targeting these patients, the biomarkers favorably alter the risk-benefit profile of pharmaceutical drugs, allowing nonresponders to avoid potential side effects unbalanced by therapeutic gain. These biomarkers promise to eliminate much of the uncertainty involved in prescribing medications, which can result in significant health-care savings.

The best-known theranostic currently on the market is the biomarker for Herceptin, a drug for suppressing tumor growth in patients with metastatic breast cancer.

Once there is a way to target the tiny minority of individuals who cannot safely take a particular drug, the medication can then remain available to the overwhelming majority of patients able to use it without adverse effect. Theranostics is taking us closer to what, arguably, is our ultimate goal: true personalized medicine.