Case Report on Death of University of Rochester Student Issued

Albany, September 26, 1996 --- Research involving human subjects at the University of Rochester was being carried out with insufficient safeguards to adequately minimize risks and protect individuals, State Health Commissioner Barbara A. DeBuono, M.D. said today in releasing the Department's Case Report of the death of a University student after undergoing a bronchoscopy as part of a research project.

"Research protocols for this project were not clearly stated and, in some instances, researchers did not follow approved protocols," said Dr. DeBuono. "As a result, a number of opportunities were missed to minimize the risks to volunteers. When healthy volunteers undergo a research procedure that provides no clinical benefits to them, researchers must pay strict attention to minimizing their potential risk of harm."

According to the report, the most notable deficiency in this case was the failure to establish, as part of the research protocol, a maximum dose of lidocaine, the topical anesthesia used in the research, for healthy subjects undergoing bronchoscopy. Lidocaine is generally a safe topical anesthestic but can have toxic effects when too high a dose is administered. The Health Department's investigation found that, while some institutions have protective measures in place, the lack of adequate safeguards, specifically the absence of a maximum dosage of lidocaine for healthy subjects, exists at many institutions carrying out similar research.

"This case clearly points out the need for institutional review boards to take an active role in ensuring researcher compliance with the protection of human subject provisions in federal and state law and regulations," Dr. DeBuono stated. "For that reason, I will be appointing a workgroup of state and national experts on research and human subject protection to develop guidelines to ensure the protection of human subjects."

The Department's investigation was conducted after the death of a University of Rochester student, Nicole Wan, who was participating in a research project that involved performing bronchoscopy on healthy volunteers. The student collapsed at home shortly after undergoing a bronchoscopy and died two days later. The facility reported and the medical examiner confirmed that the cause of death was lidocaine toxicity.

Based upon the blood level of lidocaine at the time the student was brought into the emergency room, she likely received more than four times the amount of lidocaine during her bronchoscopy than the maximum dosages established in previous research protocols. While a 1981 approved protocol established a maximum dose of lidocaine of 300 mg, subsequent protocols were silent on the maximum amount of lidocaine that should be used.

The University feels that researchers were not subject to any specific limitation because subsequent changes to the research protocol did not establish maximum lidocaine dosages. However, the State Health Department's interpretation was that -- since all changes in protocol are to be approved by the University's review board -- the limit of 300 mg remained in effect. This interpretation was supported by the investigators findings that other less significant changes were brought to the University's review board for approval.

Among other findings:

  • There was no statement in the research protocol that the procedure would be terminated if the need for lidocaine exceeded a specific amount;
  • There was no formal mechanism in place to limit the amount of lidocaine available during the procedure; and,
  • The record of bronchoscopy procedure contained no documentation of the amount of lidocaine administered.

Dr. DeBuono also made the following recommendations to the University to further minimize the risks to human subjects during research:

  • The University should review all ongoing research projects involving human subjects to determine if risks have been adequately assessed and minimized and to confirm that research entailing more than minimal risk is being carried out in accordance with federal and state laws and regulations for the protection of human subjects.
  • The University review board should develop and disseminate guidelines to ensure better researcher compliance with protection of human subject provisions in federal and state law and regulations.
  • The University review board should enhance procedures related to continuing review of ongoing research and should adopt guidelines for when to conduct more extensive and frequent monitoring of research studies.
  • Further revisions in the Strong Memorial Hospital bronchoscopy protocol should be made to enhance safety, including expressing a maximum dose of Lidocaine in mg/kg.
  • Research protocols involving health volunteers who are to receive no clinical benefits from undergoing a procedure must at a minimum offer all of the safety precautions that are provided to clinical patients undergoing the same procedures.

In addition to establishing a workgroup to develop institutional review board guidelines, Dr. DeBuono stated that the Health Department will consult with a workgroup of the American Thoracic Society and American College of Chest Physicians to determine whether there is a need for additional statewide guidelines for bronchoscopy involving healthy subjects. The Commissioner also stated that the case report will be shared with the federal Office for Protection from Research Risks.

The University is required to submit to the State Health Department a plan of action, with an implementation timetable, on how it will address the recommendations contained in the case report. That plan of action is due by October 8, 1996.

9/26/96-115 OPA

Contact: Robert Hinckley, Director, Public Affairs (518) 474-7354
New York State Department of Health Posted 9/30/96