A therapy for headache once given up for dead has achieved a surprising reincarnation—and a growing niche in the medical marketplace. But does it deserve its newfound reputation as an effective treatment? The answer is “probably not.” But a Wall Sreet. Journal article never makes that clear. It oversold the efficacy of the treatment, soft-pedaled potential side-effects, and didn’t adequately emphasize that the results of this treatment are somewhat marginal.
Clinical trials in the past showed that injections of Botulinum toxin A—i.e., Botox—were ineffective in the management of tension headaches, daily headaches and episodic migraines. An editorial in a prominent headache journal in 2006 suggested these studies marked the “end of the road” for Botox in the management of headache. (See Evers and Olesen, 2006)
But two recent clinical trials indicate that Botox injections may be somewhat effective in the prevention of chronic migraines, defined as headaches lasting at least four hours per day for at least 15 days per month.
Based on these clinical trials, the FDA recently decided to approve the marketing of Botox for this indication. (See Aurora et al., 2010; Diener et al., 2010). However, the jury is still out on the long-term viability of this prevention strategy. Some prominent headache researchers opposed the regulatory approval of Botox for chronic migraines, pointing out that the modest advantage of Botox over dummy injections might be explained by study issues and placebo effects. (See Olesen and Tfelt-Hansen, 2010)
Newly approved therapies for difficult pain conditions often reach clinical practice without adequate evidence regarding their risks and benefits. Such is the case with Botox. This poses a challenge for patients and journalists alike.
How much weight should they give to company-sponsored studies? How seriously should they take the views of experts who have a financial relationship with the company? How should they interpret therapies that have never been compared to other standard treatments? And how much credence should they give to a treatment that only has about a 10% advantage over placebo injections? (See Olesen and Tfelt-Hansen, 2010)
On the surface, an article in the Wall Street Journal navigated this tricky area competently. It provided a skeletal description of the two trials. The journalist clearly identified the evidence from the two studies as conflicting. The article presented both enthusiastic and skeptical views of the effectiveness of Botox.
But the article veered too close to the viewpoint of Botox proponents. It quoted a researcher who is also a senior vice-president of the company that developed this injection therapy—as well as experts who have financial relationships with this company. It didn’t adequately describe some of the potential flaws in the two clinical trials.
And it didn’t specify the need for further independent research to document that this treatment actually provides a clinically significant treatment advantage—and not just a statistically significant advantage over injections of a salt solution.
Migraine headaches affect some 13% of the U.S. population, with a disproportionate impact on women. Roughly two percent of U.S. residents experience chronic migraines.
These severe headaches have huge medical, social and economic implications. They are the most common headache treated in specialty clinics. They impose a steep toll in terms of pain, disability, and quality of life.
People with chronic migraines have lower incomes, are less likely to be employed full-time, and have greater occupational disability than those who do not experience headaches with such regularity.
Chronic migraines frequently defy effective treatment. And even when treatments are effective they usually have side-effects.
In terms of prevention, there is no proven gold standard that can predictably eliminate chronic migraines in the majority of people affected by them. So anything that might be an effective prevention strategy will draw great interest among migraine sufferers—as well as abundant marketing hype from those who sell these therapies.
The article gave a bare-bones estimate about the costs of Botox. However, it didn’t provide any real-world estimates of the total long-term costs of the injections and any ancillary services from specialists.
Since chronic migraines can be a life-long complaint, the total costs may be jaw-dropping. The article also did not address the cost-effectiveness of Botox for chronic migraines. Will patients and insurers be interested in paying steep prices for meager clinical results?
The story was careful to explicitly describe the modest advantage of Botox over placebo injections—in terms of the absolute number of headache days associated with each intervention.
The article did not adequately address potential adverse events and harms related to the Botox injections. The journalist offered a fairly standard list of Botox side-effects but then soft-pedaled by offering the reassuring viewpoint of a consultant for the manufacturer.
There is no mention that twice as many adverse events occurred in the Botox group than the placebo group in both clinical trials.
And the story did not address the fact that long-term side-effects and adverse events may differ from those it describes. These clinical trials described adverse events that occurred over a matter of months. Yet those with chronic migraines might have Botox injections every 12 weeks for years and decades. It is possible that the number of adverse events might grow with increasing usage.
The story offered a bare-bones description of the two clinical trials and their conflicting results. It could have provided more detail about the scope, size, and quality of the studies. But because it conveyed the minor effect accurately, we’ll give it a satisfactory grade.
The article did not adequately address study issues and potential placebo effects that might have accounted for some or all of the positive results. For example, the clinical trials did not present evidence on blinding of the study subjects. If the subjects who received Botox injections were aware they got the active treatment, expectation-related responses could have come into play.
And the tone of the article suggests that Botox has persuasive efficacy—which is as yet uNPRoven.
The article did not engage in explicit disease-mongering. Chronic migraines are painful, disabling and potentially debilitating.
However, the article over-emphasizes the views of authors who have relationships with the developer of Botox. Careful reading of the study suggests that the study subjects had a special and severe type of migraine—and may not be representative of the larger population with chronic migraines. The results of the study may not apply to many individuals with chronic migraines.
On the plus side, the story was careful to emphasize that the treatment may not be beneficial for those with less frequent and less severe migraines.
It is not clear that any of the experts who commented in this study were independent, disinterested sources. All appeared to have some kind of relationship with the developer of Botox. How hard can it be to find a headache specialist who is not on the company payroll?
The article did not adequately describe the relationships of the quoted experts with the company that manufacturers and markets Botox. For instance, the article noted that one of the quoted experts is the principal investigator of one of the Botox trials. However, the journalist didn’t reveal that this expert has also been a consultant to the drug company.
The article mentioned that other drugs are employed to treat migraines, but it didn’t mention any by name.
The Wall Street Journal story never discussed non-pharmacologic therapies. Yet addressing triggers related to diet, stress, sleep deprivation, and medication side-effects are front-line preventive treatments for migraines. And they are certainly viable alternatives to Botox injections.
And since Botox injections have never been compared to other standard treatments for chronic migraines in clinical trials, it is quite possible that those interventions could be superior to Botox injections.
Botox injections are so widely available in the U.S. that this doesn’t merit much discussion. The article accurately identified the regulatory status of Botox injections for chronic migraines.
The article makes it clear that Botox is in use for other clinical conditions and has been studied extensively in the headache arena.
The article did not appear to rely on a news release.