Clinical Trials for Women
(continued)

Heart disease provides a good example of the importance of gender-based differences and the need for continued gender-based research.  While it is the leading killer of both men and women, we know that heart disease develops approximately 10 years later in women. When women are diagnosed with heart disease, however, their condition is typically far more advanced than in men; they often have different symptoms and ironically, they may be treated less aggressively.  Nearly 44 percent of women who have heart attacks die within a year-compared to 27 percent of men.

In this century we will see a great increase in new medicines developed from the revolutionary research techniques developed in the 1990's using genetic engineering and biotechnology to discover and develop more effective and targeted medicines. Many of the medicines currently in the pipeline for women attack diseases in novel ways. These include:

• Two genetically engineered medicines that inhibit a protein believed to trigger rheumatoid arthritis and that might be able to slow joint destruction.
• A vaccine to provoke the body's immune system to attack breast tumors.
• A gene therapy for ovarian and other cancers that delivers a tumor-suppressor gene right to the cancer site.

Critics of pharmaceutical clinical trials like to point out that many new medicines are actually simply "me too" versions of existing drugs rather than novel compounds, breakthrough new drugs, or new chemical entities.  While this is true, the criticism is misplaced and the need for second generation versions of original compounds is misunderstood.  First of all, it is unrealistic to think that every new drug developed will be a breakthrough new chemical entity.  Furthermore, to suggest that just because a new medicine is not a novel compound it does not have value is simply incorrect.  For every minor modification of an existing compound, the side effect profile can vary.  For some patients, an apparently inconsequential change in one molecule of a drug can make the difference between being nauseated every day or having a headache.  For some patients, it may make the difference between being able to take a medication and experience the desired effect, and not being able to take the medicine at all.  For some patients, these little changes can ultimately mean the difference between life and death.  For example, the minor differences between Tylenol (acetaminophen) and aspirin make a world of difference to people who are allergic to aspirin.  From a medical perspective, every new medicine developed adds one more choice to our overall armament; it gives us one more way to customize care.  From an economic perspective, every new medicine developed adds competitive pricing competition.

Medicines continue to be studied for new uses even after they are on the market for other conditions.  Once the FDA approves a New Drug Application (NDA) and the medicine is available for physicians to prescribe, companies must still continue to submit periodic reports to the FDA, including any reports of adverse reactions and other quality control records.  In addition, for some products, the FDA requires additional "post marketing surveillance trials" (Phase IV) to evaluate long-term effects.  In many cases, companies continue research on approved products to determine further uses, to expand the approved indication, or to develop new dosage forms.

By the time a medicine is studied in humans, it has already been extensively studied in animals (pre-clinical testing) and its manufacturer has received FDA consent to proceed with human trials.  The first phase of clinical testing (Phase I) involves normal, healthy volunteers to test safety, dosage, absorption, metabolism, excretion, and length of action.  The next stage of clinical testing (Phase II) usually involves 100 to 500 closely monitored patients with the relevant condition to evaluate effectiveness.  Phase III clinical trials usually involve 1,000 to 5,0000 closely monitored patients to confirm efficacy and to identify potential adverse effects. After completion of these studies, a company compiles and analyzes all of the data and composes an NDA.  This document contains all of the relevant scientific information available to date about the product and is typically over 100,000 pages!

The drug development process is costly and time-consuming.  It takes from 12 to 15 years for an experimental drug to go from discovery in the lab to usage in American patients.  Of 5,000 compounds that enter pre-clinical testing, only 5 will even make it into human testing.  Only one of these 5 will be approved for distribution.  This process costs approximately $500 million to get one new medicine from the lab to the drugstore.