Process Devised for Integrating Imaging Biomarkers into Clinical Pharma Trials

A major barrier to the development of new and effective drugs is the time, complexity, and cost of the regulatory process. There is widespread agreement that the use of imaging biomarkers in the drug development process can considerably reduce this burden and speed the timelines to clinical use. To specifically address this opportunity, SNM has designed a first-of-its-kind model for the use of imaging biomarkers in clinical trials that covers drug development, molecular imaging, radiolabeled probe development, and manufacturing and regulatory issues to integrate the use of investigational imaging biomarkers into multicenter clinical trials.

The network is designed to provide centralized investigational new drugs (INDs) for biomarkers of interest to the pharmaceutical and imaging communities and coordinate standardized imaging protocols across qualified multicenter clinical trial sites. According to SNM president Robert W. Atcher, Ph.D., M.B.A., "The plan specifically includes creation of a Biomarker Use Pathway, which will provide SNM-sponsored centralized INDs that pharmaceutical manufacturers can cross-reference for their multicenter trials. Large trials of investigational therapeutics can often demonstrate safety and efficacy more efficiently if imaging biomarkers are included in the protocols. SNM is taking the lead to establish FDA- [U.S. Food and Drug Administration]-friendly imaging biomarker protocols via approved INDs.”

The network will also provide information on qualified radiopharmaceutical manufacturers to help design and develop clinical trials. "We believe the network will stimulate the development of additional novel imaging biomarkers,” said Alexander J. B. McEwan, M.D., immediate past president of SNM. "Therapeutic drug development trials using novel imaging biomarkers can also ultimately serve as surrogate parents for these non-proprietary probes. Simultaneously, the drug development time can be reduced. It is really a win for everyone involved.”

According to Dr. Atcher, SNM plans to work closely with FDA to assure accurate definition of imaging and manufacturing protocols for biomarkers with central INDs approved through the network. "If we work with FDA and the pharmaceutical industry to design the clinical trials, then we know the biomarker data from these studies will be in a format acceptable to FDA,” stated Dr. Atcher.

The network received approval for the first centralized IND in September 2008 for F-18 fluorothymidine (FLT)--an investigational positron emission tomography (PET) imaging biomarker that has apparent promise for demonstration of tumor proliferation as a surrogate marker of effectiveness in the development of novel cancer therapies. Several pharmaceutical developers have already expressed interest in utilizing this approved IND in near-term clinical trial work. Active clinical trials utilizing FLT are expected to begin in 2009.

SNM's extensive membership of molecular imagers and relationships with radiopharmaceutical manufacturers uniquely positions the society to create and maintain this multifunctional network. A major aspect of the network is a registry of clinical imaging centers that will participate in ongoing assessment, monitoring, and certification programs to maintain imaging quality, standardization, and consistency. In the past, FDA has struggled with inconsistent imaging methods at different centers, making it very difficult to evaluate results in multicenter trials. Sites listed in the clinical trials imaging registry will have demonstrated a willingness to adhere to standardized methods. According to Dr. Atcher, "We're actively building the registry now for imaging centers interested in participating in the first round of clinical trials.”

One challenge of imaging-based multicenter trials is ensuring that all entities follow a standardized protocol and that results are evaluated consistently. To help address this challenge, the new network has developed a PET phantom program that will help all registered sites in the network to demonstrate current standard imaging capabilities, including state of technology, staff training, and ability to adhere to standardized methods. Registry participation will require ongoing certification of qualifications.

In order to aid the imaging community in understanding the roles and responsibilities of participation in the registry, the phantom program, and multicenter clinical trials, the Molecular Imaging Clinical Trials Network will sponsor ongoing forums to educate imagers. The first of these workshops is scheduled for February 8-9, 2009, in Clearwater, FL, USA. The workshop will provide detailed information on the clinical trials network, train attendees on the roles and responsibilities of participation in multicenter clinical trials, and discuss the specific imaging and manufacturing protocols contained in the FLT IND.

The network is anticipated to be fully functional in the first quarter of 2009. Enrollment in the imaging registry is active now, and discussions have already begun with pharmaceutical developers interested in near-term clinical trials using F-18 FLT. Dr. Atcher commented, "We couldn't be more excited about removing the bottlenecks that have existed for both drug developers and imagers. The FDA, pharmaceutical companies, and the SNM community have all been extremely cooperative in designing the Molecular Imaging Clinical Trials Network because it is about building bridges and moving the field forward.”

Related Links:
SNM
Molecular Imaging Clinical Trials Network