With a broad-based and seasoned executive board in place, the recently formed FDA/Duke University partnership aimed at improving clinical trials is gaining momentum and seeking to fill out its ranks.

On May 12, "The Gray Sheet" touched base with Clinical Trials Transformation Initiative (CTTI) executive board member Susan Alpert, chief quality and regulatory officer at Medtronic. Prior to overseeing all of Medtronic's quality, regulatory and clinical compliance efforts, Alpert held several positions at FDA in the centers for drugs and devices, including a six-year stint as the director of the Office of Device Evaluation.

The lone device industry rep on the group's executive board, Alpert said she will make it her priority to bring device-specific issues to the group's attention.

The 12-member executive board, named May 5, is led by Judith Kramer, associate professor of medicine at Duke. Jay Siegel of Johnson & Johnson's biotechnology business, Bram Zuckerman, director of CDRH's cardiovascular devices review division, as well as contract research organization and patient reps will also serve on the board.

Device Trial Woes: Patent Battles, Blinded Studies

While some of the challenges to conducting clinical research are common across drug, device and biologics trials - such as defining monitoring protocols and consistently training the hospitals, centers and investigators involved in trials - device developers face a unique set of headaches, Alpert said.

"One of my goals as a member of this executive committee is to make sure that the issues that face the device industry and device trials are on the table," she said May 12 in an interview.

One basic challenge for device companies is patent protection, Alpert explained.

"Unlike pharmaceutical companies, although we patent our devices, they are not exclusivity patents," she said. "We have patents on our implantable cardioverter defibrillators. Well, so do all our competitors."

For a unique chemical entity, patent infringement is more straightforward to prove than it is for complex new technologies, software or algorithms.

Further, because devices are often used in surgical therapies, researchers have struggled to design appropriate clinical trials that evaluate the contribution of the product to the success of the entire procedure for the patient, Alpert said.

Randomization and blinding are also huge challenges in device trials. Alpert highlighted the difficulty of adequately randomizing patients in trials that compare standard operative procedures to new technologies, and of blinding trials where "we're not talking about two devices that look alike or operate alike."

These trial design issues lead to concerns about bias on the part of investigators, evaluators and even patients, she added.

Bringing Trials Back On U.S. Soil?

Last November, FDA and Duke formed the public/private coalition in response to widespread frustration about the quality and efficiency of clinical trials. The group is being co-chaired by Robert Califf, M.D., vice chancellor for clinical research at Duke University, and Rachel Behrman, director of FDA's office of critical path programs (¹ Also see "FDA News In Brief" - Medtech Insight, 12 May, 2008., In Brief).

"Everyone's realized that clinical trials have become very inefficient and time-consuming and extremely costly," executive board director Kramer told "The Gray Sheet."

However, "although everyone realizes they're doing a lot of things that don't make sense, they just keep doing them, because how can one company decide to change it on their own?"

According to Kramer, the number of clinical trials conducted in the U.S. has declined by 30 percent since 2001.

"The U.S. is perceived by many as a sluggish and inefficient environment for clinical research," she said.

But while Kramer raises concerns about outsourcing clinical research to countries like India and China, where labor costs are lower and timeframes are shorter, Medtronic's Alpert pointed to some potential benefits of global trials.

"The capacity and the skills of the people doing clinical trials outside the U.S. have improved greatly," Alpert said. "I think it would be more beneficial to all of us - patients and companies and regulators alike - to have more global trials, where the same or similar trials are ongoing across a broad variety of countries, including the U.S."

The public worries, however, about products that are not well tested in the target U.S. population, Kramer pointed out, particularly as some treatments have diverse effects in different genetic pools.

"That's something that needs to be considered based on the type of disease and type of intervention," Alpert suggested. "If the disease and the disease state are common, then there are more things that we can do in integrating the data."

Board Will Set Coalition's Research Agenda

The executive board is charged with setting the direction and priorities of the initiative, by approving projects conducted by CTTI, setting short- and long-term goals, and issuing final documents that recommend new practices to increase the efficiency and quality of clinical trials.

The group will be funded by yearly membership fees, ranging from $5,000 for professional societies, academic institutions and non-academic investigators, to $70,000 for companies with annual worldwide sales of more than $20 billion. Each organization that pays the membership fee will gain a seat on the steering committee.

Given the price tag, Alpert questions whether all sectors of the device industry - made up largely of small firms - will be able to afford a seat on the steering committee.

"Because there is a significant cost to being on the steering committee, I'm not sure that we will get ... all of the distribution that we would like," she told "The Gray Sheet."

The steering committee will propose specific projects based on priorities defined by the executive board, assemble project teams, review conflicts of interest for projects and white papers, and also may collaborate with other public/private partnerships and critical path initiative activities.

Non-paying members of the coalition include FDA, the European Medicines Agency, the HHS Office of Human Research Protections, the National Institutes of Health, CMS and two patient representatives.

IRB, Adverse Events Collection "Reforms"

Issues the group may tackle first include clinical trial adverse event reporting procedures and interactions with institutional review boards, Duke University's Califf wrote in a letter to participants. He has indicated that institutional review board and contract manufacturing reforms could be the most achievable in the near term (² Also see "IRB Reform Is Low-Hanging Fruit For FDA-Duke Clinical Trial Initiative" - Medtech Insight, 10 December, 2007., p. 7).

"We should be able to have IRB processes that are robust, but don't take six months in every single facility, where you can move more quickly and be more responsive," Alpert agreed. "We can help IRBs be more efficient, quickly."

The problems surrounding adverse event collection stem from a lack of clarity, she explained. Companies need more guidance on distinguishing between process- or intervention-related events and true adverse device events, and they would benefit from a common adverse event vocabulary, as well.

"We use different terminology across the medical device industry and definitely around the world," she said.

According to participants, the Clinical Trials Transformation Initiative will likely result not only in white papers, but in proposals for FDA guidance, regulation changes and new methodologies for evaluating clinical data.

The agenda-setting executive board is slated to meet face-to-face for the first time in June. It is expected to convene in Washington, D.C., about four times a year.

- Jessica Bylander (j.bylander@elsevier.com)

Medtronic Exec Will Bring Device Perspective To Clinical Trials Coalition

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