Ellen Roche died in a study of the effect of hexamethonium on lung function at Johns Hopkins in 2001. In the Guide, I wrote that a careful review of the literature by either the investigator or the IRB might have uncovered evidence of prior problems with hexamethonium and saved Roche’s life.
This is not correct, and I am grateful to Ed Fuchs, who is a research associate in the Department of Medicine at Johns Hopkins, for correcting my error. Ed wrote to give me the real story:
I was at Hopkins at the time and have studied the internal committee report, the external committee report, reviewed the consent form from the project. I’ve also read the prior papers on inhaled hexamethonium, as well as the case reports going back to the 1950’s of respiratory problems with hexamethonium. I’ve also presented these findings at a national meeting of the Association of Clinical Research Professionals.
To correct the record, hexamethonium was not withdrawn from the market due to prior serious reactions. It came off the market because better antihypertensive agents became available and it was falling out of use. Second, the prior respiratory case reports were noted in patients that had been on hexamethonium by the intravenous route, and for some length of time, often up to months before any respiratory problems developed. There were four prior inhaled hexamethonium challenge studies in the literature, none of which reported any adverse events in the subjects that participated. Retrospectively, one of the teams went back after Ellen Roche’s death, and looked at their adverse event profile. A couple of subjects were noted to have mild respiratory syx’s after inhalation, but the investigators did not attribute these symptoms to the drug at the time.
You mention that a thorough literature search might have uncovered the evidence and saved Ellen Roche’s life. At the time, typical on-line PubMed databases only went back to 1964, so it would have had to have been something more thorough than what investigators or any IRB would have usually done. Clearly process errors were made by the investigator and IRB as the application was being reviewed at Hopkins. It is a little less clear to me if the processes had been better, whether this would have prevented a tragic and what I have come to view as a somewhat idiosyncratic event.
The most important thing we can do, out of respect for Ellen and for her family, is to use this as an opportunity for self-examination and look for lessons to minimize risk and protect subjects in future studies, while as you point out, balancing that risk with the opportunity to help others.
Edward Fuchs, PA-C, MBA
Drug Development Unit
Johns Hopkins School of Medicine
600 N. Wolfe St.
Balto., MD 21287-5554
Phone: (410) 614-8762
Fax: (410) 955-9708