Deborah Borfitz
Investigator-initiated (mostly post-marketing) studies are "a black hole" for major pharmaceutical companies, according to Jeff Williams, CEO of Clinipace, in Research Triangle Park, N.C. "The investigator is funded and then they wait and hope the study gets completed on time. They get insights from the trial...and they get data that is publishable. Often, they get none of that back."
Part of the problem, Williams says, is that companies are compelled to have a "hands off" relationship with investigators so as not to influence study results. Left to fend for themselves, investigators submit data "on an Excel spreadsheet or 4-by-5 cards."
Based on data from the FDA, investigator-initiated trials (IITs) accounted for about 62 percent of the 12,778 total active investigational new drug applications (INDs) at year-end 2004, reports Kenneth Getz, senior research fellow with the Tufts Center for the Study of Drug Development: "Each year, 1,395 new investigator-initiated INDs enter clinical testing." Oncology, central nervous system, and immunologics are the top three therapeutic areas. Grant sizes range from $50,000 to millions.
Medical science liaisons (MSLs), being pharmaceutical companies' main point of contact with investigators in the field, facilitate IITs by keeping investigators on task with agreed study milestones, says Jane Chin, Ph.D., founder and president of the Medical Science Liaison Institute in Los Angeles. If requested, the liaisons help investigators build an awareness program with their colleagues. Technology can also help investigators streamline study reports and pharmaceutical companies track IITs "in a compliant manner."
One solution being tried by top-five firms is to provide investigators with Tempo, Clinipace's Web-based platform, Williams says. "Our product is extremely flexible, configurable, and there's a huge simplicity factor. It has a clinical workflow engine that can map to any clinical protocol. We're involved with our first few investigator-initiated trials now," including a $30 million project. Williams says he won't be ready to offer up particulars for a few months, but that Clinipace will "support the overall management of the [IIT] process."
IITs present unique and costly challenges, says Chin. Universities believe they should own the rights and risks to the information collected, since the study idea originates with one of their investigators. But the drug under study is owned by the supporting pharmaceutical company. Further, it is sometimes difficult to tell if the pharmaceutical company in fact approached the investigator with the idea - violating the very definition of "investigator-initiated." There are also different levels of risks and responsibilities, depending on whether the investigator or company is the designated sponsor.
"Companies are concerned about compliance," says Chin. "If federal regulators look at a trial, the company has the burden of proof that the [study] idea really came from the investigator, bears scientific merit, and wasn't used as an incentive to reward or induce a physician to use the company's products."
Of course, pharmaceutical companies are also busy with registrational trials for new indications. Because efficacy and safety data coming from a small number of patients "can be exaggerated," an IIT can potentially detract from a larger, ongoing trial involving the same drug - in some cases, creating the need to build in an additional variable, says Chin. "That, in itself, is not good." The outcome of an IIT can also create "unwelcome media attention" for a company.
The IIT itself may languish if the investigator is involved in 10 other trials, adds Chin, since the burden of data management falls on the study coordinator or research nurse. Famous doctors may be distracted by too many other demands to meet recruitment promises. "the time a clinical study finally completes, the data may no longer be clinically relevant," says Chin.
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Deborah Borfitz, is a Vero Beach, Fla.-based freelance writer who previously contributed to the clinical trials publication CenterWatch. She is co-author of Informed Consent, covering the risks and benefits of volunteering for trials. She also writes extensively about healthcare trends, marketing, business development, and Internet intelligence.