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