Department Weekly Seminar

An intervention to decrease catheter-related bloodstream infections in the ICU.
Pronovost P, Needham D, Berenholtz S, et al. N Engl J Med 2006;355:2725-2732.

Quality-Improvement Research and Informed Consent
Franklin G. Miller, Ph.D., and Ezekiel J. Emanuel, M.D., Ph.D. N Engl J Med 2008; 358:765-767.

Harming through Protection?M.A. Baily N Engl J Med 2008;358:768-769

Pronovost et al. studied effect of implementing evidence-based catheterization at 103 hospitals ICU on the risk of developing catheter-related bloodstream infection by multilevel Poisson regression model. The median rate of catheter-related bloodstream infection per 1000 catheter-days decreased from 2.7 infections at baseline to 0 at 3 months after implementation of the study intervention, and the mean rate per 1000 catheter-days decreased from 7.7 at baseline to 1.4 at 16 to 18 months of follow-up. The regression model showed a significant decrease in infection rates from baseline, with incidence-rate ratios continuously decreasing from 0.62 (95% CI, 0.47 to 0.81) at 0 to 3 months after implementation of the intervention to 0.34 (95% CI, 0.23 to 0.50) at 16 to 18 months. An evidence-based intervention resulted in a large and sustained reduction (up to 66%) in rates of catheter-related bloodstream infection that was maintained throughout the 18-month study period.

The commentary is not on the finding of the study but the surrounding situation on this study. The institutional review board (IRB) at Johns Hopkins had judged that this quality-improvement program was exempt from federal regulations governing human-subjects research. The Office for Human Research Protections (OHRP) claimed that the Pronovost Study has violated the state regulation regarding the study protocol has not fully reviewed by an IRB at John’s Hopkins University and not obtained informed consent from the patients and participating physicians.

Miller and Emanuel argues that the Pronovost Study does not require Informed consent but should be waived by the IRB decision from following reasons:
1 As the program was not a merely analysis of collected data obtained without risk, this quality-improvement initiative involve human-subjects research that should have been reviewed by an IRB. The purpose of the program was to implement evidence-based practice of catheterization that lowers the risk of catheter-related infection. The study is subjected to expedited review.
2 Then in an expedited review, the IRB would need to determine whether informed consent was required or could be waived.
3 Informed consent should be waived.

Bailey argues that the project was a combination of quality improvement and research on organizations, not human-subjects research, and the regulations did not apply. The project was not designed to use ICU patients as human subjects to test a new, possibly risky method of preventing infections; rather, it was designed to promote clinicians' use of procedures already shown to be safe and effective for the purpose.

Most importantly, the OHRP which is supposed to be protecting subjects from harmful intervention is going to become an obstacle for the evidence-beased safety skill implementation, as one of the author of the two commentary has pointed out.


One of my staff, Dr Ryoji Hirota had been working at an Atom Force Microscope measurement and sales venture company a few years ago. His experience on measuring nano-sized materials such as DNA, proteins, liposome, bacterial toxin etc. was shown. One issue of the Cell is covered by his shot of looped DNA.