On June 22, Johns Hopkins Medicine released the following statement.

Earlier this month, Johns Hopkins announced to the public, the medical community and federal agencies the tragic death of a research volunteer at Johns Hopkins Bayview Medical Center, and pledged to work with all government agencies to determine the cause, as well as to conduct a thorough review of its processes and procedures for studies involving volunteers.

At the same time, Hopkins recognized the need to respect the wishes of the family of the volunteer, who also was an employee, with regard to release of personally identifiable, or even potentially identifiable, information to the public. (See earlier statements and documents on http://www.hopkinsmedicine.org.) This commitment remains in place.

It may be helpful to know that the ongoing inquiries are following two basic paths, one examining biological and medical outcomes and one seeking procedural and administrative information. The formal inquiries, both internal and external, are continuing, and final results await further finding of facts and decisions by relevant agencies. However, as Hopkins pledged to do, we are releasing further information in order to keep the public informed about questions and issues that are being thoroughly investigated.

Background

The research in question was part of an ongoing series of studies funded by the National Institutes of Health and conducted by senior scientists at the Johns Hopkins Asthma & Allergy Center at the Johns Hopkins Bayview campus. These scientists are exploring fundamental mechanisms at work in the onset and course of severe, life-threatening asthma. The rising incidence of, and death toll from, asthma has led to intensive scientific efforts to explore its causes and treatment. This was not a clinical study of a new drug or treatment, and no pharmaceutical company was involved.

The study was, in fact, a baseline physiological study using inhaled hexamethonium to examine how an important function of the lung protects the airways from narrowing. This function plays a critical role in the development of asthma. Hexamethonium, the substance used in the study, was long used to treat hypertension and decrease bleeding during surgery using the intravenous route of administration. It also has been used as an inhaled substance without reported serious adverse effects in numerous physiological studies by investigators in and outside of Hopkins.

In the case at hand, the volunteer became ill three days after inhaling hexamethonium. The individual was admitted to Bayview Medical Center and subsequently to its intensive care unit, where continuous efforts were made over many weeks to determine the cause of the volunteer's condition and to restore health.

While not in any way diminishing the grievous impact of the volunteer's death on the family, it is important to note that serious, unexpected adverse events in research studies involving normal healthy individuals are extraordinarily rare, and deaths even rarer. Across Hopkins each year, faculty conduct many studies with the help of informed volunteers, without whom scientific understanding and new treatments for many diseases could not advance. For example, studies using volunteers have been used to develop the new, life- extending drugs for treating AIDS. At Hopkins, the last death of a research volunteer occurred in a diabetic patient more than 15 years ago. There is no previous record at Hopkins of a death in a healthy volunteer.

Areas of concern

Although Hopkins' investigation is not complete, we already have learned that there are some problems regarding adherence to the established processes of the Institutional Review Board. For example, we have found that the principal investigator dissolved hexamethonium in buffered distilled water instead of saline, as originally proposed in the study protocol. While he believed this modification is consistent with past practices as reflected in the scientific literature and was intended to enhance the comfort of the volunteers, such modification should have been presented to the IRB for approval.

To address this issue and others raised by our preliminary inquiries, we have convened a special review committee made up of Hopkins physicians and outside experts. We have charged this committee with determining the answers to many questions, and a report containing its findings will be sent to the Office of Human Research Protection by July 13. We also will take the additional step of convening an independent outside group of experts to review their findings, and will send that report to government agencies, the president of the university and the university board of trustees.

The review groups are to consider questions regarding the consent form, substances used in the study, information provided to our IRB, subsequent IRB procedures, timeliness of notification concerning the illness, and whether there is a way to establish the most likely cause of the volunteer's death in light of the best available clinical and laboratory evidence.

While these investigations continue, we are taking steps to reinforce or add measures designed to ensure the safe conduct of research studies. For example, we have reminded all investigators regarding their ongoing responsibility to seek approval from the IRB for any change to an approved protocol. It is also important to emphasize that as we continue our own investigations of all circumstances involved in this subject's death, we are cooperating fully in the investigations by the U.S. Food and Drug Administration and the Office of Human Research Protection.

Finally, it must be said again that the volunteer's loss is deeply felt and mourned by Hopkins faculty and staff. We are seeking the family's suggestions and approval for appropriate ways to commemorate her life and her contributions to the institution. After more than a century of extraordinary progress, the quest for new knowledge leading to better health remains the defining mission of Johns Hopkins Medicine. In attaining this knowledge, we are dependent on the goodwill and cooperation of thousands of volunteers who share this goal and want to be a part of such progress. The protection of these individuals is paramount. We will do all in our power to ensure that the recent tragedy is never repeated.