Note: The study discussed here has also been covered by Mark Crislip. I wrote this before his article was published, so please forgive any repetition. I approached it from a different angle; and anyway, if something is worth saying once it’s probably worth saying twice.

Is Echinacea effective for preventing and treating the common cold or is it just a placebo? My interpretation of the evidence is that Echinacea does little or nothing for the common cold. Initial reports were favorable, but were followed by four highly credible negative trials in major medical journals. A Cochrane systematic review was typically wishy-washy  The Natural Medicines Comprehensive Database rates it as only “possibly effective” commenting that

Clinical studies and meta-analyses show that taking some Echinacea preparations can modestly reduce cold symptom severity and duration, possibly by about 10% to 30%; however, this level of symptom reduction might not be clinically meaningful for some patients. Several other clinical studies found no benefit from Echinacea preparations for reducing cold symptoms in adults or children…

A review on the common cold in American Family Physician stated that Echinacea is not recommended as a treatment.

I have a friend who believes in Echinacea. She says for the last several years she has taken Echinacea at the first hint of a cold, and she hasn’t developed a single cold in all that time. I told her that if that was valid evidence that it worked, I had just as valid evidence that it didn’t. For the last several years I have been careful not to take Echinacea at the first hint of a cold, and I haven’t had a single cold in all that time either. So I could claim that not taking Echinacea is an effective cold preventive! I thought my “evidence” cancelled out hers; she said we would just have to agree to disagree.

A recent study looked at the effect of belief on response to Echinacea and dummy pills. “Placebo Effects and the Common Cold: A Randomized Controlled Trial” was published by Barrett et al. in the Annals of Family Medicine. 

A news report about the study said “the placebo effect reduced the duration of common colds.” And that the study “reflected the power of mind over body.” But that is not what the study showed.

Methods

719 subjects with colds were randomized into 4 groups:

1. No pills
2. Placebo, blinded (didn’t know whether they were getting placebo or Echinacea)
3. Echinacea, blinded (didn’t know whether they were getting placebo or Echinacea)
4. Echinacea open label (knew they were getting Echinacea)

How do we know the subjects had colds? We don’t, really.

• They answered yes to either “Do you think you have a cold?” or “Do you think you are coming down with a cold?”
• They scored at least two points on the Jackson scale (8 self-reported symptoms rated from 0 to 3 for severity).

How was improvement measured? Were they really improved? We don’t know.

• Twice a day they answered “Do you think you still have a cold?”
• They answered a questionnaire rating 19 cold symptoms and functional impairment.
• Biomarkers of immune response and inflammation were measured from nasal wash on day 1 and day 3: interleukin 8 and neutrophil counts. Are these biomarkers a reliable way to measure objective improvement in colds? I don’t know. It doesn’t matter anyway, since they didn’t change significantly.

Belief in Echinacea was assessed by asking if they had ever taken Echinacea before and how effective they thought it was on a 100 point scale.

Blinding was adequate: on an exit interview, patients in groups 2 and 3 couldn’t tell which group they were in.

Results

Compared to those receiving no pill, those receiving any pill reported modest improvement regardless of the content of the pill. They reported that their illness was 0.16 to 0.69 days shorter and 8% to 17% less severe. But these results were not statistically significant! Rather than showing that placebos reduced the duration of common colds, it showed that they didn’t have any statistically significant effect.

Contrary to expectations, open label was not superior to blinded Echinacea. (“I know I’m getting it” was no better than “I might be getting it.”) I found that intriguing.

Changes in biomarkers were not statistically significant.

Interestingly, four of the 6 assessed side effects were reported most frequently in the no-pill group. Headache was reported by 62% of those without pills compared with less than 50% in the other 3 groups. Statistical analysis showed that this was not due to chance. Does this mean that not taking pills causes headaches? Or that Echinacea and dummy pills are effective headache remedies? 62% seems like an unusually high incidence of headaches; does that mean that people who enroll in studies are unusually susceptible to headaches? Even if it was “greater than chance,” I suspect that it just represents noise in the data.

The most interesting finding was that those who believed in Echinacea did better regardless of which pill group they were in.  Among the 120 participants who had rated Echinacea’s effectiveness as greater than 50 on a 100-pointscale, illness duration was 2.58 days shorter in those given Echinacea or placebo than in those who got no pill, and mean global severity score was 26% lower but not significantly different.

A Further Question

In his book Snake Oil Science, R. Barker Bausell analyzed research showing that those who believed they got real acupuncture reported more relief than those who believed they got sham acupuncture, regardless of which they actually got. I wondered if this would be true for the Echinacea study as well, if those who believed they got Echinacea reported more improvement than those who believed they didn’t, regardless of whether they actually did or didn’t. I wrote the lead author to ask that question, and he replied

that data hasn’t [sic] been properly analyzed or presented.  Given small subsample sizes, confidant [sic] conclusions would likely be impossible.

I asked if it would be possible for someone to go back and look at the data and he answered:

It would take many dozens of hours to adequately address the question, and I’m afraid that the sample size is too small.  And resources too limited. I am advising several post-docs and leading several papers and this one just doesn’t merit the attention.  If you want to come to Madison for a month and can write up the background and methods section for the paper beforehand, I could probably get someone to do the data analysis and join you as a co-author.

I’m still curious, but I don’t want to know that badly!

Conclusion

The significant new finding of this study was that belief in Echinacea was more important than the content of the pill, regardless of whether subjects received Echinacea or placebo. To be more precise, it showed that subjects who thought they had a cold and who thought Echinacea was effective and who got either Echinacea or a placebo and who either knew they were getting Echinacea or thought they might be getting Echinacea were more likely to think their cold was gone sooner than if they got no pills.

Otherwise, the study only confirms some things we already knew. Patients report more subjective improvement with any pill than with no pill, and with any intervention compared to no intervention. Administering a placebo elicits self-reports of improvement. Echinacea is no more effective than placebo. The placebo phenomenon in colds is subjective and of such small magnitude that it can be considered not clinically important.

The authors said

Overall, this trial could be interpreted either as an appropriately powered trial that failed to conclusively show placebo effects, or as a trial suggesting small but perhaps meaningful effects related to expectation and pill-allocation.

Then they misrepresented their findings in the abstract when they said

Participants randomized to the no-pill group tended to have longer and more severe illnesses than those who received pills.

Yes, they “tended” to have (more correctly, to “report”) longer and more severe illnesses, but the tendency was not statistically significant. Why didn’t they follow the usual convention for scientific articles and say there was no significant difference between the groups?

No matter how you look at it, the news report was wrong:  the study is interesting, but it didn’t show that the placebo effect reduced the duration of common colds and it didn’t show the power of mind over body. It did show the power of mind to put a spin on study findings.

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