An overwhelming number of phase I cancer clinical trials are designed without advanced statistical methodology, which slows down the delivery of new drugs to cancer patients and adversely impacts trial participants' quality of life, according to a national research study published in the Nov. 1 issue of the Journal of Clinical Oncology.
"Our data suggest a startling paucity of translation of modern statistical methodology into the design of phase I cancer clinical trials," says Andre Rogatko, PhD, professor of biostatistics at the Emory Winship Cancer Institute. "As biostatisticians, it is our responsibility not only to develop new and better clinical trial designs, but also to shepherd new approaches into clinical practice."
A consequence of using less effective clinical trial designs is that more patients are treated with medication doses that may not be effective. In the article, Dr. Rogatko urges regulatory agencies such as the U.S. Food and Drug Administration to more aggressively encourage the use of advanced statistical methodology in clinical trial design to facilitate the translation of research into benefit for the patient.
"Cancer research, biostatistics and treatment communities are working hard to translate basic science and laboratory findings faster into clinical trials," writes Dr. Rogatko. "This reflects our commitment to accelerate improvement in cancer patients' survival and quality of life."
According to American Cancer Society, an estimated 1.4 million Americans will be diagnosed with cancer this year, and approximately 560,000 cancer patients will die. Efforts to develop new and more effective cancer therapies are constantly evolving, and clinical trials play a critical role. The National Cancer Institute defines a clinical trial as "a research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease." Clinical trials typically involve large groups of patients and are broken up into distinct phases. Phase I clinical trials are used to identify a safe dose of a new drug. Phase II and Phase III clinical trials are used to determine how effective the drug is against a certain cancer. There are currently 1,384 phase I cancer clinical trials open to cancer patients in the U.S.
"Phase I trials represent the first testing of an investigational agent in humans," says Dr. Rogatko. "These clinical trials serve as a point of translation of years of laboratory research into the clinic."
Dr. Rogatko writes in the journal article that "dose-finding" is the critical first step in the process to scrutinize whether a new drug will help cancer patients. In designing a phase I clinical trial, researchers rely on biostatistics to compile data on an ongoing basis that will help determine how to slowly increase the dose of the new drug to avoid toxic effects in a large group of patients. Research biostatisticians play a fundamental role in the process of drug discovery and treatment; however, biostatistics and clinical medicine - as professions - don't always speak the same language.
Dr. Rogatko and his colleagues examined records of 1,235 phase I clinical trials from the Science Citation index database between 1991 and 2006. They found that only 20 trials, or 1.6 percent, adopted new statistical designs.
"As in any science, biostatisticians generate results that are published in specialized journals using language specific to the discipline," says Dr. Rogatko. "Knowledge transfer between the professions is difficult, and we must do a better job at effective, two-way communication between biostatisticians and physicians."
Co-authors on the paper, entitled, "Translation of Innovative Designs Into Phase I Trials" were David Schoeneck, William Jonas, MD, Mourad Tighiouart, PhD, Fadlo Khuri, MD, and Alan Porter, PhD.