Making sense of the data in a controversial trial of a 'clot-busting drug' for treating stroke

This week, PLoS Medicine launches a new section, called Guidelines and Guidance. The articles in this section contain advice on the conduct and reporting of health research.

Making sense of the data in a controversial trial of a “clot-busting drug” for treating stroke

In December 1995, a highly controversial trial was published, which tested a clot-busting drug called rt-PA (recombinant tissue plasminogen activator) in patients who had suffered an acute stroke. The trial, known as the National Institute for Neurological Disorders (NINDS) rt-PA Stroke Trial, had a profound effect on how patients with stroke were managed, and yet many stroke experts had concerns about the study. For almost eight years these experts asked for access to the trial data, which were finally made public on a CD-ROM for purchase in October 2003. In this week’s PLoS Medicine, Dr Robert Dachs (Department of Emergency Medicine, Saint Clare’s and Ellis Hospitals, Schenectady, New York, USA) and colleagues document their efforts to access and decipher the NINDS rt-PA Stroke Trial dataset.

Based on the trial findings, the FDA approved the use of rt-PA for the treatment of acute ischemic stroke and subsequently both the American Heart Association and the American Academy of Neurology endorsed the use of rt-PA for selected patients with stroke. But several stroke experts have been concerned about the study’s design, results, and ramifications; about whether the trial results could ever be replicated in a community hospital setting; and about an unacceptably high risk of harm from giving rt-PA with limited benefit to patients.

"The NINDS authors have attempted to address many of these concerns, and supporters have defended and encouraged the increased use of rt-PA in patients with acute stroke," say Dr. Dachs and colleagues. In hopes of clarifying many of the issues raised, researchers who were not involved in the NINDS study made repeated requests for access to the NINDS rt-PA trial data. But access to these data was initially denied, even after petition to the Food and Drug Administration under the Freedom of Information Act.

For their PLoS Medicine article, Dr. Dachs and colleagues purchased the trial dataset. They found the process of gaining access to the information on the CD-ROM convoluted and difficult and, unfortunately, some of the crucial trial data are missing. In their article, they summarize the steps they took to access the information and provide access to the entire database for researchers who wish to analyze the data from this landmark trial for independent research queries.

Source: Public Library of Science