OHRP action shuts down quality improvement research in Michigan

Conflict raises confusion about the need for informed consent

Recent actions taken by the U.S. Department of Health and Humans Services' Office for Human Research Protections (OHRP) have resulted in the temporary suspension of collaborative research of Johns Hopkins University and Michigan hospitals involving a checklist for reducing the incidence of infection in intensive care units. Far beyond the ongoing back and forth between OHRP and Hopkins as they seek resolution, the OHRP action has unleashed a storm of protest in the quality community and has, at the least, raised questions about whether the vast majority of QI projects might be in danger of similar actions.

Here are the basic issues, as outlined by OHRP, in a statement issued Jan. 15:

"The purpose of the study was to find out whether that intervention [i.e., the checklist] decreased the rate of certain infections, which had not previously been proven. In research studies where the regulations apply, an institutional review board [IRB] must review the study before it begins to ensure that the appropriate protections for the prospective subjects are in place. For example, the IRB looks to see whether the risks to the subjects participating in the research study have been minimized, and whether the informed consent of the subjects must be obtained before participation or whether the proposed research satisfies the regulatory criteria for waiver of informed consent (see 45 CFR 46.116[d]). OHRP received a complaint about the research study and determined that no such IRB review had taken place before the research study began."

Part of the issue was that the checklist had been the subject of earlier research, published in the New England Journal of Medicine,1 and that it already was a proven intervention. The checklist address key behaviors such as hand-washing, cleaning the skin with chlorhexidine, avoiding the femoral site, removing unnecessary lines, and using barrier precautions.

In a Jan. 2 letter to Michael Leavitt, secretary of the U.S. Department of Health and Human Services (HHS), Karen Linscott, PT, MA, who at the time was acting CEO of The Leapfrog Group, wrote:

"The checklist program consists of five steps that are proven to reduce the incidence of infection in intensive care units. While it can be argued that the program does not adhere to the specific language in the informed consent regulations, it cannot be argued that the checklist poses a danger to 'subjects.' On the contrary, the checklist has been proven to save scores of lives quickly and efficiently. The checklist is a far cry from an experimental drug for which informed consent is crucial. It is in fact consistent with your efforts related to the Four Cornerstones, with [the Centers for Medicaid & Medicare Services'] progress toward true value-based purchasing, and with the significant progress led by [the Centers for Disease Control and Prevention] to reduce hospital-acquired infections."

And, in a widely read Op-Ed piece in the New York Times,2 Atul Gawande, a surgeon at Brigham and Women's Hospital in Boston, argued:

"The agency issued notice to the researchers and the Michigan Health and Hospital Association that, by introducing a checklist and tracking the results [our emphasis] without written, informed consent from each patient and health care provider, they had violated scientific ethics regulations. Johns Hopkins had to halt not only the program in Michigan but also its plans to extend it to hospitals in New Jersey and Rhode Island."

To which OHRP responded:

"While some expressed concern that OHRP has prohibited hospitals in Michigan and elsewhere from implementing a program intervention consisting of a checklist and other measures to prevent certain hospital-acquired infections, OHRP has taken no such action. On the contrary, if any hospital or intensive care unit decides to implement the use of checklists or other measures only for the reason that they believe those measures will improve the quality of care provided, they may do so without consideration of the requirements of the Department of Health and Human Services regulations . . ."

In response to inquiries from Healthcare Benchmarks and Quality Improvement, Joann Rodgers, a spokeswoman for Johns Hopkins, adds: "OHRP has stated that its regulations do not apply when institutions are only implementing practices to improve the quality of care, but do apply [our emphasis] if institutions are planning research activities that look at the effectiveness of interventions to improve quality."

The issue that remains unclear (and hopefully will be further explained) is this: Do all QI projects that involve the tracking of results potentially put them in the crosshairs of OHRP? If so, how many QI projects would not be subject to their oversight?

"The regulations do not apply when institutions are only implementing practices to improve the quality of care, even when this includes collecting information to track/monitor/confirm the results of that implementation," says Patricia C. El-Hinnawy, public affairs coordinator for OHRP. "But, if institutions are planning research activities examining the effectiveness of interventions to improve the quality of care, then the regulatory protections apply and they are important to protect the rights and welfare of human research subjects."

Peter Pronovost, MD, PhD, medical director of the Center for Innovation in Quality Patient Care, an assistant professor in the department of anesthesiology/critical care medicine at Johns Hopkins School of Medicine, and lead author of the NEJM paper, says, "I was shocked to see [OHRP's] statement. My reading is exactly what you said: If you at all try to collect data, it will fall under the regulations, and that's just wrong.

"I believe very strongly that the science of quality improvement and health care has been very sloppy — more marketing rather than true evidence — and we have shown it is valid to collect evidence on a large scale, which is the whole idea of benchmarking. [The OHRP statement] shows an almost complete lack of understanding of what quality management is, or quality in general," Pronovost adds.

Is this a first?

In any event, this may in fact be the first time OHRP has intervened in a QI project. "They've shut down Hopkins before, among others; they have the power, and they exercised it," notes Ezekiel J. Emanuel, MD, PhD, chair, department of bioethics, NIH Clinical Center, National Institutes of Health. "In this area of quality improvement, I do believe, yes, this may in fact be unusual, although I don't know for sure if it is the first."

Emanuel adds that the study was being done with "five proven interventions in more than 100 hospitals." The Agency for Healthcare Research and Quality, he notes, supported the study.

How does he see the informed consent issue? "Part of what we have argued, and what is important to recognize, is that there is not an ethical requirement or a regulatory requirement for every research project to get informed consent," says Emanuel. "If you look at the regulation, there is permission for emergency research and large epidemiology studies, and this fits it like a glove."

There was no risk involved in the study, he continues. As for why OHRP took the action it did, Emanuel confesses, "I'm not sure what the motivation was. The regulations provide for this kind of exception; there is a specific list of rules you need to fulfill and this fits them perfectly."

"We don't mean to argue that informed consent is not critically important — it is — but this just does not seem like the same type of research," adds Linscott.

"I still don't think they've answered why this is different than any other population-based research, which does not require informed consent."

Linscott goes on to say the move was short-sighted. "The larger problem in our health care system is that we are not aligning our regulatory and research activities and prioritizing to reach the greater good," she says.

In seeking an explanation for the OHRP action, Linscott posits, "I have to say my guess is that this was a mistake. I can only surmise this and that they are now standing behind it."

What are the implications?

For Linscott, one of the most important ramifications of the OHRP action is that work she considers vitally important has been delayed. The work that resulted in the checklist, designed by Pronovost, "has been some of the most important lifesaving work being done in health care; it is tremendously powerful and important and will save thousands and thousands of lives; but like any advance, we have to have extremely strong evidence — and he has," Linscott asserts. "It's not just the checklist. This was just one piece; my understanding is he was seeking to build an incredibly broad base around this subset. The fact that he was unable to make this case slows down the progress we are all trying to make."

Pronovost notes that "the implications for QI are profound, because for far too long health care has not focused on QI. Now we seem to have momentum, where people seek data-driven efforts from which they can make valid inferences. Most importantly, the risks are much more on the side of not doing it than doing it. If we ask docs to wash their hands, what is the risk-benefit ratio? If we put up barriers, the net result will almost certainly be worse patient harm."

As for where things go from here, OHRP's Rodgers notes: "Moving forward, we're continuing to discuss and work with OHRP to determine whether or not organizational QA/QI studies and projects similar to Dr. Pronovost's do in fact constitute human subject research subject to IRB approval; and if it is determined by OHRP that these studies do constitute such research, whether or not review and consent waiver is an acceptable IRB procedure."

"A lot of this will be slugged out in the court of public opinion," predicts Emanuel. "My real hope is that someone, hopefully within the Health and Human Services agency, says we really need to examine what we are doing in terms of oversight of human research, so we don't again have what was clearly a mistake. We can do better than this."

Pronovost is even blunter. If OHRP holds fast to its position, he asserts, "Any kind of QI effort in a hospital would essentially be void of data."

References

  1. Pronovost P, Needham D, Berenholtz S, Sinopoli et al. An Intervention to Decrease Catheter-Related Bloodstream Infections in the ICU. N Engl J Med 2006;355:2,725-2,732. (Correction published: N Engl J Med 2007;356(25):2,660.)
  2. Gawande A. A Lifesaving Checklist. New York Times, Dec. 30, 2007.

[For more information, contact:

Ezekiel J. Emanuel, MD, PhD, Chair, Department of Bioethics, NIH Clinical Center, National Institutes of Health, Bethesda, MD. Phone: (301) 435-8706.

Karen Linscott, PT, MA, The Leapfrog Group. Phone: (202) 292-6709, Fax: (202) 292-6809.

Peter Pronovost, MD, PhD, Medical Director, Center for Innovation in Quality Patient Care, Assistant Professor, Department of Anesthesiology/ Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Phone: (410) 502-3231. E-mail: ppronovo@jhmi.edu.]