By Keith L. Black, MD

In 1982, Genentech Inc. sparked the biotech revolution when it unveiled its extremely successful human insulin. More than 30 biotech firms were formed the following year, and today there are thousands just within one biotech research area, such as recombinant DNA. As the industry matured, focusing on a single project can spell economic doom for a company if that project fails; so most companies pursue several promising projects with a strong focus on developing projects that clinicians can use. These broader-based research efforts can only advance the frontiers of science faster, leading, much sooner, to the discovery of more effective treatments and cures.

Even with a promising research plan supported by a solid business plan, competition is still intense, especially since a dozen companies may be addressing the same problem using the same techniques. The benchmark for success is a demonstrated ability to bring new discoveries rapidly from the laboratory bench and put it into the hands of clinicians. Those who have a successful track record of translating laboratory discoveries into treatments for humans are in high demand, especially in such fields as clinical research, bioinformatics and bioengineering. The path from lab bench to bedside, however, is a long one and there is no guarantee of success even for discoveries that appear to hold the most promise.

To develop new treatments and technologies, researchers test a theory in the laboratory, and then design a clinical trial. The rules for the clinical trial are called a protocol, which describes who can participate in the trial, the schedule of tests and medications, and the length of the study. Clinical trials have three steps or phases, and the average trial takes 12 years. Only about one in five drugs are ultimately approved for use. Each phase has different requirements for patients to participate, depending on their condition, type and stage of their disease, and what therapy, if any, they have already undergone.

Pre-clinical: The drug is tested in the laboratory to determine that it is safe and that it has some effectiveness in fighting a disease. This pre-clinical process often takes four years. Researchers then file an Investigational New Drug Application (IND) with the Food and Drug Administration (FDA). The IND outlines the results of the pre-clinical testing and sets out plans for future studies.

Phase 1: If the FDA approves the IND, then researchers conduct a Phase 1 clinical trial to assess a drug's safety. The drug will, for the first time, be administered to humans, usually between 20 and 100 healthy volunteers to determine what, if any, side affects occur as dosage levels are increased. This phase usually takes up to a year and about 70 percent of drugs pass this phase.

Phase 2: Most Phase 2 trials are randomized and test a drug's effectiveness. Randomized means that one group of patients receives the experimental drug while a second "control" group receives a standard treatment or a placebo (a substance containing no medication). Often these studies are blinded: neither the researchers nor the patients know which group each patient is in, until after the study. Phase II may take up to two years, involve several hundred patients and only about 30 percent of drugs successfully complete this phase.

Phase 3: This phase tests the drug's effectiveness and side effects on a much larger population, usually several hundred to several thousand patients. Most Phase 3 studies are randomized and blinded, last several years and 70 to 90 percent of drugs successfully complete Phase 3.

Marketing: Once a drug passes Phase 3, researchers can request marketing approval from the FDA by filing a New Drug Application (NDA)/Biologics License Application (BLA). The NDA/BLA must contain all of the data from all of the trials, showing that the drug is safe and effective. After FDA review, that can take two years, if approved, physicians can then prescribe the drug. Even then, oversight is not over. As drugs are sold, all adverse events must be reported, quality standards must be met, and, sometimes, post-marketing studies are required to evaluate the long-term effects of the drug or the effect on patient populations not yet tested, such as pediatric patients.

The biotech industry promises greater successes in the future as the technologies that launched the industry, recombinant DNA, monoclonal antibodies, and cell culture, have been expanded to include gene targeting, transgenic technology, antisense technology, and the polymerase chain reaction. The Human Genome Project also promises to open a new field for biotech innovation. The future is bright in the biotech field, for researchers, for clinicians and, most importantly, for patients who will benefit from research discoveries by living longer, healthier lives.

For more information about MDNSI clinical trials, please contact (310) 423-7900.