Development of New Therapies

Medicines play an important role in the health of many Americans. Yet, it can take 30 years or more until a potential beneficial compound is identified, tested and approved for marketing. According to Pharmaceutical Research and Manufacturer's Association, only one of every 5,000 to 10,000 potential compounds tested ever becomes a marketed therapy. Last year, the biopharmaceutical industry spent about $51.3 billion on drug research and development. The average cost of developing just one drug is about $800 million.

Drug development is a long and costly process because scientists must engage in an enormous amount of research to ensure a drug will work and is safe for patients to take, with a minimal number of side effects. Scientists may search for years for potential compounds that may have medical value. In preclinical studies, laboratory models help to pinpoint key ingredients and potential usability and actions of the ingredients. Once a potential compound is identified, it's tested in animals.

When preclinical testing has been completed and research still suggests the compound may be of benefit, application is made to the FDA for approval of human trials. There are three main phases of human clinical trials. Phase I studies test a drug in a small number of participants (usually fewer than 100 volunteers). The goal of phase I testing is to look at the safety of the drug and determine safe dosage ranges. This phase generally lasts from about six months to a year.

In Phase II studies, the drug is tested in a larger number of participants (usually about 100 to 500). The goal of this stage is to determine if the drug is working. Researchers also continue to monitor the safety of the medication and watch for side effects. Phase II studies may take six months to one year.

Phase III studies involve the largest number of patients, usually 1,000 or more, and often take place at several different sites. Researchers continue to study the drug's effectiveness and safety, and identify side effects. This phase can take one to four years.

Once a Phase III study is complete and data has been reviewed, a New Drug Application is filed with the Food and Drug Administration (FDA). The FDA reviews the results. If approval is not accepted, scientists may need to clarify research data or complete further studies. It takes nearly 17 months for the FDA to approve a new drug for marketing.

Devotion to Research

Sometimes researchers spend an entire lifetime looking for and developing a viable therapy that may cure, treat or prevent disease or illness. They often face funding problems, long hours and many setbacks. Yet, their dedication and determination may eventually bring fruitful rewards.

David Matson, M.D., Ph.D., is a researcher studying Pediatric Infectious Diseases. He has devoted much of his lifelong research to finding a vaccine for rotavirus, a disease that can cause severe, life-threatening diarrhea in children. According to the CDC, about 55,000 children are hospitalized in the U.S. for rotavirus. Worldwide, more than 600,000 children die from the disease.

Matson spent two decades studying the disease and helped to develop a vaccine that was finally approved and released in 1998 (RotaShield®, Wyeth). However, after a year on the market, the vaccine was withdrawn because of concerns about a possible risk for bowel obstruction. The development was a disappointing blow to the many dedicated years of research. But Matson didn't give up hope. In 2001, Merck asked him to become the lead U.S. investigator for their version of a rotavirus vaccine. The new vaccine, called RotaTeq® (Merck and Co., Inc.), was approved for marketing in February 2006. Matson's next goal is to find a vaccine for Norovirus, the highly contagious virus that has been associated with outbreaks of gastrointestinal illness on cruise ships.

Carmen Guerra, M.D., a specialist in Internal Medicine at the University of Pennsylvania Hospital, is passionately researching how to prevent polyps in people with an inherited condition, called familial adenomatous polyposis (FAP). Patients with FAP tend to develop large numbers of abnormal growths, or polyps, in the colon and rectum. In the classic form of the disease, patients may develop hundreds to thousands of polyps. Although initially benign, the polyps often turn into colon cancer.

Studies have shown that some of the lowest rates of colorectal cancer are among those from India. When comparing diets, one particular compound sparked Guerra's interest - curcumin, an ingredient found in the spice Tumeric, that's used to make curry and other Indian dishes. She examined 20-years of research looking at the effects of curcumin in animals. While the precise benefits are still not known, she says the results appear to be promising. Now, Guerra hopes to enroll 68 human participants in phase II studies of curcumin. Guerra cautions against the use of Tumeric as an agent to prevent colorectal cancer. The spice contains only about five percent curcumin, so people would have to eat very large amounts to gain the same benefits as their concentrated version of the study compound.

For general information on careers in medical research:

American Association of Medical Colleges

National Center for Research Resources

For information related to drug development:

Pharmaceutical Research and Manufacturer's Association

For information on rotavirus:

Centers for Disease Control and Prevention

Information about the new vaccine is available at:

http://www.rotateq.com

For information about familial adenomatous polyposis:

American Society of Colon and Rectal Surgeons