Foundation Tackles CNS Trials

Success rates within drug development vary by indication, with CNS drugs averaging lower than many other categories. There are many contributors to drug trial failure, but in CNS, in the clinical trial phase, methodology using subjective assessments could be a major cause. The Foundation for Improving Data Quality (FIDQ) was recently formed to advance the evaluation of clinical trial methodologies that aim to improve the clinical integrity and reliability of clinical data. The Foundation is particularly focused in those disease areas where subjective measures—clinician rated and patient reported outcomes—represent pivotal study endpoints.

FIDQ Scientific Council Members

The FIDQ is governed by CNS research experts chosen for their specific expertise in psychiatry and neurology (see sidebar). Amir Kalali, MD, vice president, medical and scientific services, global therapeutic group leader for CRO Quintiles, told Applied Clinical Trials, "Pharmaceutical companies spend billions of dollars developing CNS drugs, but very little money on understanding how to develop them and how trial methodology affects study outcome."

According to Kalali, questions related to CNS trial methodology have been discussed for many years both informally as well as formally, in well respected industry associations including the International Society for CNS Drug Development and The International Society for CNS Clinical Trials and Methodology; as well as within sponsor companies, academia, and investigator sites. While some sponsors and research centers have adopted scales and/or new clinical trial methodologies to minimize the variance inherently seen with subjective measures and improve study outcome, these scales and methods have not gained wide acceptance because they were typically not developed in the context of a collaborative effort. "The goal of the Foundation is to encourage methodological research," said Kalali.

David Daniel, MD, senior vice president at United BioSource Corporation (UBC), said "A major tenet of the Foundation's philosophy is that methodological research initiatives should be approached collaboratively with all of the relevant stakeholders—industry, academia, sites, and service providers. This approach is designed to ensure that the methodological research initiatives supported by the Foundation will not be theoretical, but instead have practical applications in day-to-day clinical development. Additionally, the Foundation is targeting research initiatives that seek to fill 'methodological gaps' where there is limited or no evidence to either support or refute a specific methodology."

When evaluating the relatively high failure rate seen in CNS clinical trials, it is important to understand how clinical trials methodology affects study outcome. "There are many variables to consider," said Kalali. Patient selection, which encompasses accurate diagnosis and illness severity; site experience and training; and trial design are just a few," says Kalali.

Methodological research has been very poorly funded in the past, according to Kalali. Historically, clinical trial methodology as it relates to CNS studies has not changed for decades. Additionally, many of the methods used today were not designed for the scientific, data-driven, large-scale operational process needed for clinical trials. Regardless, many sponsors developing CNS drugs are hesitant to use new methods and change the way things are done so as not to interfere with their ability to compare their data to industry standards, nor jeopardize regulatory approval of their compound.

"While there is consensus that currently accepted clinical trials methodologies are not optimal, no one is leading the charge to systematically develop alternative options," said Daniel. "All stakeholders are asking for better approaches that are supported by evidence—the Foundation is committed to responding to this challenge."—Applied Clinical Trials Staff