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Conflicts of interest cloud stroke intervention guidelines

About a year ago, we called attention to the debate around the effectiveness of tissue plasminogen activator (tPA), a medication that breaks up blood clots in the brain, in treating certain types of strokes. While many neurologists see tPA as a “slam dunk,” emergency doctors tend to be more skeptical on the topic.

The latest guidelines from the American Heart Association/American Stroke Association recommend the use of tPA for acute ischemic stroke with Level A evidence (the highest level of evidence). The guideline authors write, “The safety and efficacy of this treatment when administered within the first 3 hours after stroke onset are solidly supported by combined data from multiple RCTs and confirmed by extensive community experience in many countries.” However, emergency medicine guidelines recommend tPA for stroke on Level B evidence, meaning they have only “moderate clinical certainty” of its effectiveness.

Many emergency medicine physicians have pointed out methological issues with the evidence on tPA for stroke. There have been at least 12 studies of tPA for stroke, only two of which showed any benefit for patients given tPA compared to a placebo. No study has shown that tPA saves lives; in fact, four of the studies were stopped early due to harm. The NINDS trial, commonly cited as the “proof” that tPA is beneficial, found that significantly more patients in the tPA group had a better outcome after 90 days. However, in this trial, patients in the treatment group had milder strokes than those in the placebo group, which may explain the improved outcomes in this group.

What could explain the differences in guideline recommendations between the AHA/ASA and emergency medicine societies? Are emergency doctors more cautious about interventions in general? Or are there financial conflicts potentially at play?

In a recent study in The American Journal of Emergency Medicine, Cleveland Clinic medical student Joshua Niforatos and emergency physician at Crozer-Keystone health network Dr. Richard Pescatore compared industry payments received by guideline authors of three sets of guidelines that included tPA recommendations. They defined conflict of interest as receiving at least $5,000 in industry payments in a year directly related to tPA or another endovascular intervention.

“If you look at the people who are going to be on a committee and they have pertinent conflicts of interest they shouldn’t be on the committee” — Joshua Niforatos 

They found that none of the writers for the AAEM and ACEP (emergency medicine societies) had financial conflicts of interest, but 35% of AHA/ASA guideline writers had a conflict. Even more interesting, there was a 300% increase in the proportion of financial conflicts for authors of the 2013 AHA/ASA guidelines after the guidelines were published. The study authors also noted that three of the AHA/ASA guideline writers were part of the speakers bureau of Genentech, the makers of tPA. 

Niforatos pointed out in an interview on the Plenary Session podcast that there is a relatively simple solution to this problem. “If you look at the people who are going to be on a committee and they have pertinent conflicts of interest, they shouldn’t be on the committee,” he said. “I don’t really buy the argument that people who have conflicts of interests are necessarily more knowledgeable about a topic.” 

This may sound like common sense, but it has been extremely difficult to get doctors and researchers to even disclose conflicts of interest, let alone to exclude them from positions of power. We need more health professionals like Niforatos and Pescatore to speak up about the need for policies to keep industry influence out of clinical practice guidelines.