A Robust Future for Phase IV Trials May 2005 VIEW on Biotechnology Clinical Trials Dimensional HealthCare Inc., Cedar Knolls, N.J., designs, implements, and provides community-based research to the pharmaceutical and medical-device industries, focusing on the design and implementation of large, simple trials in the periapproval stages (Phases IIIb and IV) of drug development. For more information, visit dhcare.com. Responsible for approving new therapies while ensuring public safety, the FDA in recent years has frequently mandated that companies conduct late-phase community-based research to evaluate specific safety concerns, sometimes requiring Phase IV studies of newly approved drugs as a condition of approval. This trend, coupled with an increased interest from the pharmaceutical industry to test their products in real-world environments, has spurred rapid growth in Phase IV research activities. Phase IV trials are designed to address commercialization issues just prior to, during, and after core registration studies have been conducted. Conducting late-stage trials is one of the most effective ways to assess public safety and efficacy of a product, evaluate outcomes and pharmacoeconomics, and bolster commercial drug performance. Pharmaceutical companies have identified specific clinical and commercial objectives for Phase IV studies. Clinically, the primary objectives are to compare a drug with other drugs already in use, monitor a drug’s long-term effectiveness and impact on a patient’s quality of life, and determine the cost effectiveness of a drug therapy. Commercially, the aims are to increase product awareness and market penetration, expand product demand, and establish positive relationships with practicing physicians, with the goal of increasing market penetration. Postapproval research spending by pharmaceutical companies has dramatically outpaced spending for preapproval clinical-research projects over the past couple of decades. According to CenterWatch, in 2002 sponsors spent $1.6 billion on Phase IV projects — an annual growth rate of 21% during the most recent three-year time period. In contrast, growth rates for Phase I and Phase II studies were 14.4% and 8.5%, respectively. The Real World Historically, most clinical trials have been conducted at academic medical centers, but the trend in clinical research is toward involving community physicians as investigators. For example, in 1991 academic medical centers accounted for 70% of the revenue of all industry-sponsored trials; by 1998, that percentage had dropped to 43%. The number of private practitioners conducting clinical trials almost tripled from 1989 to 1999 — and that trend is growing. Everybody Can Win The Sponsor. Well-conducted Phase IV clinical trials can benefit everyone involved — the sponsor, the physician-investigator, and the patient. The sponsor acquires a sizeable database of information about a drug’s performance — safety, efficacy, and quality of life — in a large and diverse patient population. Additionally, widespread product exposure enhances market penetration and can lead to increased sales. The Physician. Community-based clinicians who participate in Phase IV trials gain valuable experience in patient care. They offer new treatments under well-defined protocols, and receive expert training in patient selection and drug-usage regimens. Some investigators feel that there is a degree of prestige associated with clinical-trial participation that enhances the image of their practices with patients and the community. The clinical-trial experience can offer the busy practicing physician an opportunity to collaborate with other trial investigators and share evidence-based methods that can enhance his or her practice. The Patient. Patients in community-based, Phase IV trials have the advantage of being treated by their own physicians, who know their medical, drug, and often social history, so are well qualified to determine whether they are suitable candidates for a trial. Patients can be treated in their own community and can try a new treatment at no cost. Many patients feel privileged to be selected for a study and appreciate the attention they receive as participants. It is likely that keeping research in the community setting contributes to patient participation and possibly to compliance. A Robust Phase IV Future Postmarketing studies are likely to increase in the future because of competitive marketing pressures on products that face patent expiration in the next few years. To maintain as much market share as possible, pharmaceutical companies will need to take steps to differentiate their products from the competition and to expand the use of their products in the clinical setting. Additionally, the FDA may require more Phase IV data in support of expedited approvals. Given these trends and the increase in spending on late-phase research, the future of Phase IV clinical trials appears robust. To maintain as much market share as possible, companies will need to take steps to differentiate their products from the competition and to expand the use of their products in the clinical setting. Michael Morales President and CEO
