up and running
by Tiffany Heady

Clinical trials test-drive new drugs and procedures.

eering down the damaged front end of a Ford, Andre Ritter, assistant professor of operative dentistry, can't help but think how the process of repairing this damage is similar to a process he plans to use to restore gum-line defects in teeth. Like repairing a dented fender, this new procedure begins by cleaning the surface. After rinsing the tooth surface with water, a coat of adhesive is applied to the tooth, much like the primer for a car. Upon "curing" the primer and applying the filling material, the tooth is shaped. The process finishes with a polish, making the tooth as shiny as a fresh paint job. The whole job takes 10 to 15 minutes per tooth and is an improvement over older techniques because it rarely requires anesthetic or drilling.

.: Andre Ritter says the dental procedure he's testing in a clinical trial is something like doing body work on a car. Photo by Steve Exum; click to enlarge. :.

These gum-line defects are notch shaped and caused primarily by toothbrush abrasion and erosion from acidic foods and drinks. Unlike cavities, these are clean defects that require no invasive cleaning. As a result, the American Dental Association recommends them as models for the clinical evaluation of adhesive restorative material, such as the one Ritter uses. "With traditional restorative techniques, we have to cut teeth so that the filling will stay in the teeth mechanically," Ritter says. This new procedure fixes defects with a dental adhesive, often making it unnecessary to cut into an otherwise sound tooth. If clinical evaluation at 6 and 18 months reveals at least 90 percent retention of the filling, the procedure is considered effective.

The tests that Ritter is conducting are called clinical trials — patient studies that determine the safety and efficacy of new drugs, treatments, or procedures. Ritter's clinical trial tests a new procedure, but most clinical trials involve new drugs or treatments.

uccessful drug clinical trials progress through four phases. The first two phases primarily establish safety of the drug. Phase III enrolls the largest number of patients, lasts longer, and generally costs more than the preceding phases because it's designed to prove efficacy. All participants in Phase III are assigned, at random, to either the drug in question or a placebo — a process called randomization. Because a placebo is the inactive form of the drug and has no treatment value, comparing it to the drug allows assessment of the drug's effectiveness. Those who receive the placebo are referred to as the control group or standard. After FDA review and approval, the drug enters Phase IV and becomes commercially available although its long-term effects are continuously monitored. The entire process from Phase I to Phase IV takes from 5 to 10 years.

Clinical trials provide national exposure for Carolina and are a growing enterprise. Industry-sponsored clinical trials numbered well over 300 and topped $34 million in fiscal year 2001, compared to about $11 million brought in by clinical trials in fiscal year 1998. But that growth has made these studies more difficult to get under way. So much so that in 2001, the university established a new office to help organize and shorten the process of initiating and conducting clinical trials. The Office of Clinical Trials, which opens this Fall, will consolidate where and by whom all the necessary paperwork gets processed. John Case, associate vice chancellor for research and interim head of the new office, calls it a "one-stop shop for principal investigators and their sponsors." He says, "As a major health research institution, the more trials you get, the more exposure you get and the better for UNC-Chapel Hill to be nationally recognized."