Pubdate: Mon, 12 Oct 1998 Source: San Jose Mercury News (CA) Contact: (c) © 1998 Mercury Center Website: http://www.sjmercury.com/ Author: Marlene Cimons NEW APPROACH TO RESEARCH MAY SPEED DRUGS TO MARKET WASHINGTON -- Scientists are drafting an ambitious blueprint for evaluating medical research that could take years off the time it takes to win approval for new drugs. While still in its earliest planning stages, the new and sometimes controversial approach could have profound implications for cardiovascular disease, rheumatoid arthritis, osteoporosis, multiple sclerosis and certain cancers, as well as other illnesses. Dr. Harold Varmus, director of the National Institutes of Health, has convened a working group of scientists to explore the possibilities of this new direction in research, which he says shows ``real potential.'' Huge impact seen Dr. Daniel Hoth, a former AIDS and cancer specialist for the NIH and now a San Francisco-based consultant working on the project, agreed that ``this could transform drug development.'' In recent years, as Americans have been clamoring for faster access to new medicines, Congress and federal regulators have initiated procedural changes and bureaucratic streamlining to accelerate drug approval. But the blueprint goes beyond regulatory reform to the heart of science, putting in place a fresh look at how drugs work. The new effort identifies early signs of a drug's eventual effect -- like blood pressure-lowering medications that ultimately prevent stroke, or drugs that increase a woman's bone density, reducing her risk of later developing fractures. Called ``surrogate markers,'' these are harbingers of a successful treatment or even a cure that scientists and regulatory agencies can use to predict a health benefit rather than waiting for lengthy studies to document it. This surrogate marker approach to drug evaluation differs significantly from traditional, often yearslong clinical trials, which typically involve studying drugs until their usefulness is proved -- or disproved -- definitively. The new concept already is producing results. Increasing bone density is a proven surrogate marker for osteoporosis. Lowering cholesterol is known as a surrogate marker for coronary artery disease. And reducing the level of HIV in the blood is a surrogate marker for AIDS. Only last week, AIDS dropped off the list of the 10 leading killers in the United States, the result of powerful drugs approved using this new approach -- drugs that, under traditional trials, might only just now be coming onto the market. Focusing attention on this method, Varmus said, means that benefits ``will soon be felt for others.'' The Food and Drug Administration, the federal agency that ultimately decides whether to license a drug based on research evidence, itself is exploring the surrogate marker concept. In fact, the FDA reform law passed by Congress last year directs the agency to actively look at surrogate evidence when reviewing new drugs. Scientists involved in the project plan to examine different diseases over the next year, ``selecting the conditions that are ripe -- or nearly ripe -- for surrogate analysis,'' Varmus said. ``We'd like to identify the candidates, confirm the (surrogate) relationship and, later, begin to apply them to drug evaluation,'' Hoth said. ``Right now, we're building momentum -- building steam and interest in this effort.'' Many possibilities The possibilities are endless. ``With the new advances in magnetic resonance imaging, you actually can see areas of disease in the brain of those with multiple sclerosis,'' Hoth said. ``You can see areas of plaque, which is associated with the progression of the disease. Suppose you found a drug that could reduce the plaque, and you could (see) that with an MRI. That may predict a long-term health benefit.'' In rheumatoid arthritis, a crippling joint disease that afflicts an estimated 2.1 million Americans, Hoth said, MRI imaging of the joint also could provide early signs of a drug's effect on joint inflammation, thus predicting an improvement in symptoms. In prostate cancer, certain substances or markers found in the blood that help diagnose cancer -- elevated levels of prostate-specific antigen, or PSA -- also might be worth exploring as possible surrogate markers, Hoth said. But the PSAs would work as surrogate markers only if experimental drugs changed their levels and only if the changes predicted future health improvement, he said. ``The biomarkers have to get worse when the disease gets worse and they have to get better when the drug is given,'' Hoth said. ``And these changes have to precede the actual clinical benefit.'' - --- Checked-by: Patrick Henry