This release from Cedars-Sinai Medical Center describes a phase 2 clinical trial that looked at whether an existing surgical procedure could be used to reduce the rate of recurrent strokes or death among patients with severe brain artery blockages.
It gives a numerical comparison between those benefiting from the surgery and those who only received “intensive medical management.” And the researchers state that those results show that the procedure — encephaloduroarteriosynangiosis (EDAS) — “significantly decreases the rate of stroke recurrence and death.” However, the difference between these groups for the main outcome of the study was not statistically significant — which should have been clearly disclosed and which contradicts the stated claim that the surgery is more effective. We call on Cedars-Sinai Medical Center and EurekAlert! to retract or correct the release before it leads to misleading news coverage about this procedure.
It’s clear that patients with intracranial atherosclerotic disease (a condition involving severe brain artery blockages) are at considerable risk of both strokes and death, so any new alternative approach to treating this condition would be a welcome addition to the options these patients and their families can consider. But like any brain surgery, this procedure would be complicated and information about its risks and benefits and the evidence behind it needs to be clearly communicated to patients.
The release doesn’t mention cost although the surgical procedure used in the research is both already established practice and a complicated and extensive operation. Given that the surgery is being compared to simple medical management, the cost of the new approach will be substantially higher, and therefore deserves mention in this release.
The release provides readers with a numerical comparison of the study’s results, in this case, the prevention of subsequent strokes or death among these patients. According to the release, in those receiving the EDAS procedure, after one year, 9.6% of patients had a later stroke or died, compared to more than twice that number (21.2%) from a matched control group who didn’t receive this surgery.
(We discuss the limitations of these results under the Evidence criteria, below.)
The release addresses harms criteria with the following statement: “Two of the EDAS patients had small wound openings that required additional surgical interventions, but there were no intracranial hemorrhages or other serious adverse events, the researchers reported.”
While we’ll award a borderline satisfactory, we wish that the release had cautioned that a study of 52 people is incapable of identifying harms that might occur with a larger and broader sample of patients.
The release adequately explains that this was a phase 2 trial enrolling 52 patients with severe brain atherosclerosis, also known as intracranial atherosclerotic disease, or ICAD, who showed symptoms of either a recent stroke or a mini-stroke, called a transient ischemic attack. These patients received the EDAS procedure and intensive medical management. The comparison control group used patients who “received only intensive medical management,” which included “diet and lifestyle changes, blood thinners and other medications to control blood pressure, cholesterol and blood sugar levels.”
However, the study results were not statistically significant. (Reviewer Dan Mayer, MD, who is a retired professor of emergency medicine at Albany Medical College and taught statistics for 22 years, calculated the absolute difference as 11.5% with a 95% confidence interval of -2.6% to +25.5%, therefore not statistically significant.) Accordingly, the claim that the surgery “significantly decreases the rate of stroke recurrence and death” is inaccurate and misleading. The 11.5% difference between the groups met the researchers’ “criteria for non-futility and advancement to phase 3,” meaning that they believe the results warrant additional study in a larger trial. But the results do not establish that the surgery was more effective than medical management as claimed in the news release. The release should be corrected by both the issuing institution, Cedars-Sinai Medical Center, and the EurekAlert! public relations newswire which carried it.
No disease-mongering here. The release includes context on the annual rates of recurrent stroke or death for ICAD patients.
The release explains that the study was funded by grants from the National Institutes of Neurological Disorders and Stroke of the National Institutes of Health.
The release covers alternatives to the EDAS surgery with the following: “Current ICAD therapies — in addition to intensive medical management — include bypass surgery to connect a blood vessel from outside the brain to a vessel inside the brain, as well as angioplasty with stenting, which involves inflating a tiny balloon inside a cerebral artery to open it up and placing a stent device inside the artery. Despite advances in medical care, annual rates of recurrent stroke and death remain high, at 15 percent or more for ICAD patients, according to published research.”
Since the therapy was compared to intensive medical therapy only, it is not clear how this procedure compares to other vascular surgical therapies (such as bypass surgery or angioplasty with stenting, both named in the release). If 52 patients with 9.6% recurrent stroke (5 patients) were compared to 52 hypothetical patients with a 15% recurrent stroke rate (8 patients), the results would not be statistically significant and would have a significantly high likelihood that they occurred by chance alone. This kind of statistics manipulation can mislead readers into believing there is a big difference between this new therapy and older vascular surgical therapies.
This procedure is currently available, as explained here: “EDAS has been used for moyamoya disease, a rare cerebrovascular disorder that affects younger patients.” However, there are relatively few facilities that treat moyamoya disease. Saying how many sites have the ability and expertise to do the EDAS procedure would have been more helpful.
The release quotes an expert stating that “This clinical trial moves us significantly closer to preventing strokes and death in high-risk populations.” But is that really the case when the results show lack of statistical significance?
This release and potential news coverage of it could lead to false hopes by patients who have had a TIA or stroke and are looking for any available therapy to reduce their risk of recurrence.
The release claims that the described procedure “significantly decreases the rate of stroke recurrence and death for patients with severe atherosclerosis of the brain arteries” but as noted under the Evidence criteria, the results did not demonstrate statistical significance.