Costs, returns challenge evidence-based molecular imaging
Although evidence-based medicine has been the focus of work by many healthcare researchers, molecular imaging and nuclear medicine has received scant attention in this arena. Clinical colleagues in fields such as cardiology and oncology are able to routinely participate in multinational trials of the latest interventional devices and pharmaceutical agents. Until recently, molecular and nuclear medicine clinicians had to be content with developing and conducting their own evidence-based studies.

U.S.-based practitioners have just begun to enjoy the fruits of the National Oncologic PET Registry (NOPR) data collection efforts. The prospective trial, which began in 2005, has delivered hard evidence as to PET’s capabilities in altering treatment management--earning the modality expanded reimbursement and patients greater access to the technology. Outside the U.S., much of the battle to develop a strong evidence basis for molecular imaging and nuclear medicine protocols and procedures is being carried out seemingly one facility at a time.

Diagnostic imaging is one of the fastest rising physician service expenditures according to the American College of Radiology, the Medicare Payment Advisory Commission, the Radiological Society of North America and the U.S. Government Accounting Office. Due to its rapid rise in expense, policy makers and payors are increasingly demanding that evidence-based data justify the utilization of imaging agents and procedures.

Robert W. Atcher, PhD, SNM President.

“Ironically, there’s some people who believe that we still haven’t had the definitive trial to validate FDG,” said Robert W. Atcher, PhD. “The challenge for us is to sit down with our greatest critics and ask them what it is they believe we have not been doing and what it is we need to do so that it is definitive for any of the probes we’re investigating.”

Atcher, SNM president and team leader for emerging medical technology with Los Alamos National Laboratory in New Mexico, noted that one of the challenges in financing large-scale clinical trials for many novel PET imaging agents is that there is no intellectual property involved.

“Because there’s no intellectual property for a radiopharmaceutical manufacturer to get some sort of patent protection, there’s not much incentive for them to help fund clinical trails,” he noted.

Although multi-national, multi-center molecular imaging trials face a variety of challenges—ranging from economics to turf issues—the persistence and perseverance of dedicated clinical researchers can sometimes beat the odds.

“There are, of course, several difficulties in designing and conducting these trials,” says Johannes Czernin, MD, director of the nuclear medicine clinic and a professor of molecular and medical pharmacology at UCLA’s David Geffen School of Medicine and editor of Molecular Imaging Insight. “First, they are expensive; second, investigators don’t have a great personal benefit from participating; third, there are many regulatory issues that render these studies difficult, which then leads to high costs and complicated approval processes.”

Czernin recently scored a win with the launch of a randomized, multi-national multi-center trial comparing conventional planar 99mTc-MDP bone imaging with 18F-sodium fluoride (18F-NaF) PET/CT in patients with breast, prostate and non-small cell lung cancers.

“This exciting development is the culmination of many months work and an extraordinary level of collaboration,” said Czernin, principal investigator for the study. “Although AMI (the Academy of Molecular Imaging) is the IND (Investigational New Drug application] holder, this important research is a result of cooperative efforts between 13 clinical sites, AMI and the molecular imaging industry.”

Osman Ratib MD, PhD, professor and chair of radiology and head of the nuclear medicine division at Switzerland’s University Hospital of Geneva, observed that evidence-based molecular imaging trials, such as the 18F-NaF study, are crucially important to advancing the possibilities for nuclear medicine.

“There is no question that 18F-NaF PET is superior to traditional bone scans, at a much higher cost,” he noted. “However if the technique is widely adopted, the price of NaF could drop significantly (it is cheap to produce) and with the current growth in number of PET-CT scanners, this could become a very cost effective and improved technique for detection and staging of bone metastases. All the other biomarkers should follow, and yes, there should be large multisite trials to establish the real cost-effective value and evidence-based arguments for establishing these techniques.”

Czernin agrees that much work remains to be done to bring new molecular probes into clinical practice.

“We will only succeed in bringing novel imaging probes to the clinic if we design appropriate trials,” he said. “These need to be multicenter trials, they can be randomized; they need solid outcome data/endpoints. Designing and conducting these trials should be among the foremost goals among the imaging community.”