Research or innovation? Document differences

Surgery lends itself to new therapies

The IRB process has become more prominent and formal in recent years, and as a result of that change there have been conflicts about the IRB's reach: Is everything that involves a new treatment and outcomes measurements considered research and subject to IRB review?

Also, how should a medical and research institution handle surgical and other innovations?

"It's a progressive thing — there's a major difference between progressive innovation and actual experimentation," says Anthony Atala, MD, W.H. Boyce professor and chairman of the department of urology at Wake Forest University in Winston-Salem, NC. Atala also is the director of the Wake Forest Institute of Regenerative Medicine.

Institutions often have problems drawing a line between what's research and what's under the jurisdiction of the IRB, and what may be innovative therapy and what may be experimental, says Susan Kornetsky, MPH, CIP, director of clinical research compliance at Children's Hospital of Boston.

"Certainly, people who participate in research may receive a therapeutic type of benefit, but that's not the reason overall why an investigator's doing research," Kornetsky says. "Innovative therapy is a non-standard treatment approach where the sole purpose is to enhance the well-being of the individual patient."

For instance, suppose a surgeon is operating on a patient when a problem occurs and the best possible solution might be to try a new surgical technique, Atala says.

So the surgeon takes a chance and tries the technique, discovering later that it worked very well, and the patient had better than typical results, he adds.

"That's an innovative procedure, and then you can actually test that procedure, and you do it by informing patients of the procedure and you do this in a systematic manner," Atala says. "That's very different than sitting around the table and saying, 'I wonder if we did this procedure if it would work better.'"

The planned approach is research, improvisation is innovative, Atala notes.

With the innovative approach, the surgeon will want to make sure it's validated by his peers and that a consensus is reached that the new procedure is beneficial, but at this point it's still not research, Atala says.

"You want to know it's not just a fluke, so you make sure there's consensus among peers," Atala says. "When this process is far enough along that you really do want to make it into a research protocol you can go through a formal process."

However, there is a middle ground between innovation without oversight and research that is reviewed by an IRB. Some institutions, including the Children's Hospital of Boston, recognize and are addressing the issue of providing limited oversight to innovative therapies.

"The way we look at it here at Children's Hospital is that there is something we need to do to protect the patients who are undergoing innovation," Kornetsky says.

Several years ago, a fetal surgeon arrived at the hospital and wanted to start a fetal therapy program. A debate ensued over whether fetal therapy was research or innovation, or a combination of each, she says.

"We took over a year to work with the surgical department and surgeons to try to come to an understanding of whether there was anything we needed to do," Kornetsky says.

"What we decided was that for innovative procedures where we're out at the forefront and don't know the risks or if the risks potentially are significant, we want an oversight mechanism," Kornetsky says. "It's a voluntary oversight and is not under the jurisdiction of the IRB."

This middle ground involves asking any physicians who are planning an innovative procedure to follow this simple process:

1. Write a summary: They are asked to write a summary of the clinical situation, what they propose to do, and why they propose to do it, which will shed some light on potential risks and benefits, Kornetsky says.

2. Have peer review: "We ask them to have it reviewed by two peers, who are uninvolved in this particular case," she says. "The purpose is for someone not involved to look it over and say, 'Yes, this does make sense given the circumstances.'"

The peers could be from outside the institution, and they're asked to write a brief summary, noting that they have reviewed the proposal and determined it to be reasonable, Kornetsky adds.

"Sometimes we see correspondence with some suggestions, and sometimes they get feedback they can incorporate," Kornetsky says.

3. Enhance informed consent process: "In thinking about the protection of patients, we ask that there be an enhanced informed consent process," she notes. "What we suggest they do is write out a consent document, as opposed to taking the hospital consent form and using that."

It's helpful to have this in writing so the patient/family can take it home and reflect on what it says, Kornetsky says.

4. Provide oversight: Department and division chairs are responsible for approving the therapy/procedure and for monitoring the outcome, she says. Documentation of these actions is submitted to Kornetsky's office.

"If they have used a written informed consent document, we file a copy of what they used in the office," Kornetsky notes. "We are the institutional record keeper that this process occurred."

5. Discuss potential research protocols: Occasionally, the IRB chair or Kornetsky will look through these documents and see if the same innovative procedure has been conducted two times or more, she says.

"Then we'll go back to the physician and say, 'You've done this a couple of times, do you want to think about submitting a research protocol now?'" Kornetsky says. "This is a process that might eventually encourage research."

Not all innovative therapies lend themselves to becoming research protocols, but if the therapy is going to be done by more than one physician, then it might be a good idea to set up a registry where everyone involved can document information about patients and their outcomes, Kornetsky suggests.

"We've had procedures here that were a phenomenal success, and all over the country, other physicians were doing it," she says.

For instance, one physician whose innovative procedure quickly spread nationwide established a registry and asked people who were doing the procedure to collect information for the purpose of publishing the results, Kornetsky recalls.

Since forming the voluntary oversight of innovative therapies, the hospital's experience has been mixed: some physicians submit reports and others don't, Kornetsky says.

The hospital took about two years to introduce the innovative process oversight and to achieve buy-in with staff, and Kornetsky says she recommends that other institutions considering making this change also take their time with it.

"We were very sensitive culturally to get the buy-in from the staff that would have to do this, and we were very careful in writing the guidelines," Kornetsky explains. "We want the innovations, and we don't want to interfere with the art of surgery."

The written guidelines are copyrighted, and they begin with definitions of research and surgery, as given by the President's Commission on the Protection of Human Subjects.

More detailed definitions follow in the guidelines, include this sentence about innovative therapy, "Innovative therapy occurs when a practitioner proposes to use a treatment, procedure or intervention in a way that deviates from commonly accepted practice in a clinical encounter."

"The peer review part has gone over very well, and no one has argued against it, especially when they're doing something so novel," she adds.

With the enhanced informed consent, some physicians have included written language that is similar to what's used in a research informed consent document, and others are comfortable using the language they already have in their documents, Kornetsky says.

"This process makes people think about what the next step should be and that serves a purpose in itself," Kornetsky says.

"This is a small step to try as a kind of oversight in the area of innovation," Kornetsky adds.

Small steps may be the best policy, especially when it comes to surgical procedures.

"Traditionally, the surgical suite is one area where for obvious reasons you have to improvise," Atala says. "Many times when you're doing constructive surgery, you really don't know what you're going to be doing until you're in there."

While a surgeon has a general idea of what to expect, there are many surprises, Atala notes.

"As you progress through this process, all of a sudden you have a new procedure," Atala adds. "So the question is, 'How do you monitor those small steps as they finally leap to new procedures and new ways of doing things?'"