NIH: Report all adverse events in gene studies

New guidelines follow death of study participant

Under new proposed guidelines from the federal government, research investigators would have to report all adverse events that occur during studies involving gene therapy. Currently, scientists are required to report only those adverse events that are unexpected or related to the experimental strategy.

Federal authorities announced the proposed guidelines in a November 1999 statement by the National Institutes of Health’s Office of Recom binant DNA Activities (ORDA).

The new reporting guidelines were proposed in the wake of the death of a gene therapy study participant at the University of Pennsylvania in September 1999 — the first death directly linked to an experimental gene therapy procedure.

The proposed changes were published in a notice in the Nov. 22, 1999, issue of the Federal Register, and ORDA’s 15-member Recombinant DNA Advisory Committee (RAC) began considering the proposed changes at its mid-December meeting last year.

The new regulations also require that adverse events be reported within 15 calendar days of the occurrence.

A significant change to existing NIH policy is the stipulation that the adverse event reports will be considered public information unless NIH/ ORDA permits an exception.

According to the notice in the Federal Register, "some investigators and sponsors have begun to designate human gene transfer protocols or serious adverse events confidential, thereby precluding RAC review."

The proposed guidelines clarify that all adverse events should be immediately reported to ORDA, which is to immediately notify the RAC. The RAC, by definition, conducts its business in the public domain.

Investigator compliance in question

The Associated Press reported in December that the U.S. Food and Drug Administration investigation into the death of a participant in a gene therapy study at the University of Pennsyl vania revealed the investigators may not have complied with all NIH safety rules and did not promptly report problems with the study protocol as current guidelines require.

Jesse Gelsinger, an 18-year-old Arizona man, died days after being injected with a drug containing genetically altered adenovirus during a research study. Gelsinger had suffered since birth from a genetic disorder known as ornithine transcarbanylase deficiency, which weakened his body’s ability to excrete ammonia.

The injection of the study drug was supposed to deliver genes to the malfunctioning liver cells that would repair the disorder. Instead, a severe immune reaction rapidly destroyed Gelsinger’s lungs. Media reports following Gelsinger’s death listed other deaths that had occurred during gene therapy experiments but had not been made public for confidentiality reasons.

The proposed guidelines are under consideration by the RAC and another advisory panel, both of which will make recommendations to NIH. The NIH director will decide whether the recommended changes will be made to the NIH guidelines.