With all the cheery tidings from Wall Street, we resolved to examine where the clinical industry is. Let’s review a few items.
The average timelines for clinical trials have doubled. Protocols are as stuffed as a Coney Island hot-dog-eating champion. Seasoned investigators typically work on one industry project—and bolt for the exit. Prodigious quantities of paper are used, even in so-called “electronic” trials. The FDA is raising the bar.
The U.S. patient, meanwhile, is increasingly difficult to recruit. Patients in developing countries are easier to enroll, but may not offer truly informed consent. Forrest Gump-like legislators who do not comprehend addition and subtraction (if the federal budget is any guide) now routinely attempt to interrogate biostatisticians from Oxford University.
It’s in that context that the Clinical Trial Transformation Initiative (CTTI) is a rare nugget of good news. CTTI is a somewhat unconventional three-way marriage. But it’s one that should be happy. The FDA, academia and industry are all at the same table.
To name just four prominent names on the CTTI executive committee: Robert Temple (FDA); Alberto Grignolo (Parexel); Ken Getz (Tufts University); Jay Siegel (JNJ). The full list is here.
The project is being hosted at Duke University by Robert Califf, who is not exactly new to industry, academic research or large projects. This is the A-team. If it can’t come up with evidence and ideas for reconsidering the rules for clinical trials, it can’t be done. Everything will be transparent and visible for the public to inspect, as this memorandum of understanding between Duke and the agency explains.
Last week, at the 2008 meeting of the Regulatory Affairs Professionals Society (RAPS), the FDA and Duke discussed CTTI. Melissa Robb, from the FDA’s Office of the Commissioner, began the session. “It’s kind of looking at that time between the bench and getting [the drug] to patients and how we can make it more efficient and optimal for everybody,” she said.
Robb reviewed some of the recent challenges facing the industry. It is clear to the FDA that the present method of finding and approving new drugs isn’t working well. It’s also clear that daily pressures at the agency don’t always allow it to take a step back and consider ways to improve the entire process.
That’s always been the objective of the Critical Path Initiative (CPI), of which the CTTI is the most noteworthy element. Robb noted CPI has recently received $33 million from Congress. (That’s not a serious amount of money in a $2 billion regulatory budget or a $700 billion industry. But it is what Congress could afford.) Fortunately, CTTI will have funding from industry and academic participants that will have a vote in selecting its projects. One big-picture theme guiding the CTTI effort is the degree to which some trials might be nudged back to the U.S. from overseas.
Monitoring The Monitors
On a more detailed level, CTTI is already diving into difficult territory. Robb described a few. One item: a re-evaluation of data monitoring. Given that the industry feels it must be undertaken intensively, and the FDA has long said otherwise, could a new consensus be forged?
Some in the industry feel that the monitoring guidelines have been left deliberately ambiguous to ensure the FDA’s control of the situation. The FDA clearly takes issue with that view. “We hear all the time that monitoring is so expensive and that we have too high expectations for monitoring,” Robb said. “Bob Temple is going to meetings and saying, ‘we don’t expect you to go every two weeks.’”
Our normally relaxed posture changed. We’re old enough to remember many clinical technology vendors saying they were going to be able to reduce the frequency or cost of monitoring. It remains a healthy niche in the industry. So far, technology has not impacted monitoring.
But the CTTI’s convergence of FDA, industry and academia may be potent enough to begin an informal process of considering more clearly written, mutually agreeable and potentially more efficient monitoring rules. Since contract research organizations (CROs) are also participating in CTTI, it will be interesting to see how they react to any proposals that would alter the minimally required amount of monitoring on every trial, which is obviously years away at this point.
Next, the executive director of CTTI was at the podium. Judith Kramer is on the medical faculty at Duke, but worked in industry for a decade. At Burroughs Wellcome, she supervised 220 employees and ran the clinical research areas of antiviral, oncology, central nervous system, cardiovascular, and pulmonary/critical care. She also oversaw the preparation of seven full NDAs and fourteen INDs.
Kramer began by noting that there is negative attention directed toward industry at the moment, fairly or not. “We’re dealing with a not very friendly external environment,” Kramer said.
Because of that climate, Kramer continued, even if industry did discover a magic bullet for all its operational problems, it would not be politically tenable to use it. Said Kramer: “Because of the issues of public trust, even if [industry] had the perfect solution, it would not be the best action for them to take unilateral action. There would be mistrust and lack of support.”
She sounds energized about the prospects of CTTI finding new ways to do things. “There hasn’t been a joint effort, truly, to changing this,” she said. “FDA is not only at the table but putting their sweat equity into this. We need industry, academia, NIH. We need consumers.”
Kramer then reviewed what CTTI has already green-lighted. In addition to data monitoring, CTTI will be launching projects to look at how to expedite serious adverse events reporting; at best practices for oncology data management; and at clinical trial quality and results communication. Criteria for CTTI projects can be found here.
We know some readers roll their eyes when the Critical Path is mentioned. It’s not clear when something truly transformative will emerge from it. (This ClinPage story describes clear Critical Path progress on biomarkers.) But the CTTI is a serious and energetic attempt to reconsider pivotal trial processes and assumptions in a panoramic, historic manner. Both the opportunity and the individuals involved are unique.
Editor’s note: CTTI is looking for members; the fee for large companies is $70,000; academic organizations can join for $5,000.d9A2t49mkex