April 17th, 2018
At a time when major news outlets are having to defend themselves from accusations of “fake news,” it’s a little disheartening to see the New York Times publish a story that gets a debate in medical science so wrong.
The misleading story in this case is Gina Kolata’s recent article on tissue plasminogen activator (tPA), a clot-busting medication often used to treat strokes. Kolata tries to claim that tPA has been shown definitively to be an effective treatment, and any doctor who fails to deliver the drug is acting out of some misguided rejection of the evidence — and is likely harming patients in the process. In framing the debate in this way, Kolata ignores one of the central tenets of good medical science: when multiple studies say something doesn’t work, it’s dangerous to believe the single study that says it does.
A bit of history: tPA works by breaking up blood clots in the brain, which are the cause of most strokes. Unfortunately, tPA can also cause bleeding in the brain, a serious and sometimes fatal side effect. So the question is, do the potential benefits of tPA outweigh the potential risk of brain hemorrhage?
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, there are several methodological issues with this trial, including the fact that the patients in the treatment group had milder strokes than those in the placebo group. In addition to this rather glaring problem, the researchers changed their primary endpoint mid-study from 24 hours to 90 days. Changing endpoints is generally a no-no in these kinds of studies.
Kolata skates right past these concerns to quote Dr. Christopher Lewandowski, the lead researcher on NINDS, along with three other neurologists, all of whom who think the evidence in favor of tPA is a slam dunk. These doctors are the heroes of her story; the villains are emergency doctors who, in Kolata’s telling, “do not believe in TPA.”
As Mary Chris Jaklevic points out in Health News Review, by calling emergency doctors who are unpersuaded by a single clinical trial “disbelievers,” “doubters,” and “naysayers,” Kolata makes them sound like members of the anti-vaccination movement, who ignore the overwhelming evidence against their point of view in favor of a cult-like evidence-free movement. Other write-ups on tPA in the media have taken a similar tack, blaming ER docs for “deficient training” in neurology for the low rate of tPA use for stroke patients.
This is a gross misrepresentation. As emergency medicine doctors have pointed out, there are numerous considerations to take into account when deciding whether or not to administer tPA – how much time before the patient presents at the ER, the possibility the patient is not actually having a stroke, more than a dozen exclusion criteria, and of course, the risk of fatal side effects. Even for outspoken critics of tPA, it’s a very difficult decision. For example, Dr. Jerome Hoffman, cited as a leader of the anti-TPA wing, is openly ambivalent about TPA:
There is too little evidence for us to know whether, on balance, [TPA] does more good than harm, more harm than good, or has no appreciable effect…I am often asked what I would do if I, or a member of my family, had a stroke and ‘qualified’ for thrombolysis…I typically answer along the lines of ‘I wish I knew.’
Emergency doctors aren’t skeptical of tPA’s benefits because they’re ignoring the evidence, or paying more attention to social media and blogs than the medical literature, as Kolata’s sources claim, but rather because they’re analyzing the studies and find the results are not convincing.
Kolata also failed to report on the financial connections some of her sources have with the manufacturers of tPA. Given this incomplete picture, no wonder many readers who commented on the story sided with the experts who claimed to have the evidence on their side:
If reporters are going to wade into the middle of scientific controversies, they should know the evidence. It makes for a great story to have crusading doctors on one side, who seem to want only to help their patients avoid the devastating consequences of a stroke, versus a group of naysayers on the other.
But the real story here, as Jeanne Lenzer writes in another HealthNewsReview article, is the money. Medical journals now require that authors disclose their conflicts of interest. As Lenzer suggests, maybe it’s time for journalists to do the same, and make a habit of disclosing the conflicts of their sources.