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IND monitoring program wins protection award
IND trials tracked carefully through life of trial
An innovative program at M.D. Anderson Cancer Center in Houston, TX, provides continuous oversight of investigational new drug (IND) trials over the life of a trial, using a monitoring services office created expressly for that purpose.
The IND Regulatory and Monitoring Program, which began at M.D. Anderson in 2002, recently was awarded the 2008 Award for Excellence in Human Research Protection — Best Practice from the Health Improvement Institute in Bethesda, MD.
Paul Papagni, JD, CIP, executive director of the Office of Clinical Research at M.D. Anderson, says his institution's IND program takes responsibility for such trials out of the hands of investigators and puts it more firmly under the oversight of the institution.
"We don't allow investigators to hold an IND," Papagni says. "Investigator-held INDs are the area where there is the biggest problem maintaining oversight, because typically, brilliant investigators have great ideas but either they are not aware of all the responsibilities that go along with holding an IND or don't have within their area the support or funding to fully oversee all the responsibilities.
"M.D. Anderson recognized back in 2002 that this was a risk area and they started this program."
Papagni says the IND monitoring program is part of a unique three-pronged human subjects protection structure at the cancer center:
-The Office of Protocol Research, which includes the institution's IRB and scientific review systems;
-The Office of Research Education and Regulatory Management (ORERM), headed up by Kristin Bialobok, MSN, RN. The office includes IND Services, which assists with IND submissions, as well as the IND Monitoring Services Office. This is the area that received the HII award;
-The Office of Multicenter Clinical Research, which monitors and audits multicenter studies.
All three components fall under Papagni's supervision and that of the Vice President for Clinical Research, Maurie Markman, MD.
The IND monitoring program begins even before an IND application is submitted to the U.S. Food and Drug Administration (FDA), with pre-IND telephone conferences with the FDA. It continues through the FDA submission and the IRB review process.
"Since the institution is agreeing to be the sponsor, the institution is taking on these responsibilities and works with the investigator on the submission, as well as working with the investigator to come up with a monitoring plan," Papagni says.
M.D. Anderson requires that investigators enter data into the institution's own computer system, in order to facilitate monitoring. In addition, there are monitoring visits from ORERM staff to make sure that the protocol is being adhered to, that IND maintenance is occurring and that necessary reports are sent to the FDA in a timely manner.
Papagni says this ongoing monitoring is critical for these types of studies, which may be high risk. Continuous oversight means that potential safety problems are caught as quickly as possible.
"It's not just monitoring what's going on from a safety standpoint; it's monitoring adherence to the protocol," he says. "You sometimes have investigators who take an approach of 'My protocol is the outline of how I'm going to do the study,' when actually, it's exactly the directions that you've put forth as to how you're going to conduct the study and you need to adhere to it.
"If you're not adhering to it, you need to report that and/or you need to amend the protocol to reflect what you're really doing. The last thing you want on an IND study is the FDA coming in and finding out that you're not adhering to the protocol that they have reviewed and approved."
To date, the IND office manages about 120 IND protocols, and the Monitoring Services Office currently is monitoring about 80 studies in the active treatment phase.
Papagni says this has required a substantial commitment of resources. ORERM has about 37 educators, monitors and auditors. While there are only six dedicated staff for the IND program, staff are drawn from elsewhere in ORERM to meet the program's needs, depending upon the caseload, he says.
"It's a pretty ambitious endeavor, and a pretty expensive one," Papagni says. "But from personal experience, the cost of cleaning up when it's not done right is far more than doing it right."
He says that as the program has matured, staff have gained more experience working with FDA, which has improved the IND process.
"That's one of the key features of this – now you have dedicated people who are communicating with the FDA on a regular basis," Papagni says. "You establish relationships, you establish a certain level of quality of work in submission, so they know you, they know your staff, and they know what they can expect when you're submitting."
He says that while some investigators initially were hesitant about the new IND structure, they've come to see the value of it.
"Because investigators can experience a lot of headaches from not being fully aware of what they're responsible for (in an IND trial), they start to appreciate how much is being done for them," he says.
Papagni says he has heard interest from other institutions in M.D. Anderson's IND monitoring program. He says such an effort can start with dedicated resource people who can help walk investigators through the IND process. But at some point, he says, an institution is going to want to have more centralized oversight.
"Anytime you realize that you have a number of INDs being held, if you want to centralize the process, then you need to create a monitoring system to make sure you're aware of what's going on," he says. "Luckily M.D. Anderson has accepted the responsibility and recognized that if you're going to have quality IND studies, this is a way to ensure that they're done properly."