The Billion-Dollar Placebo

The pharmaceutical industry probably isn’t feeling so well after publication of the latest study of the effectiveness of over-the-counter cold medicines.

The results, which appeared in the Journal of Allergy and Clinical Immunology, indicate that at least some of the claims for fast relief from congestion may be on shaky scientific ground.

The focus of the study was phenylephrine, a decongestant found in various cold remedies, including Tylenol Sinus, Sudafed PE and Advil Sinus Congestion & Pain. The results were stark enough to make a lot of people sit straight up in bed: Phenylephrine, the scientists reported, worked no better than a placebo at reducing nasal congestion in people suffering from colds. Even when doses were elevated to four times the normally recommended dosage, symptoms persisted as before.

Scientific studies are often inconclusive or ambiguous, and the authors typically publish their findings with the requisite warnings, calling for further study and on a larger scale. They are well aware of the temptation to overstate the evidence in order to make a big splash in the professional journals and the media. It also provides a fallback if it turns out that nobody can replicate their results in other labs, or a flaw was found in methodology or analysis.

Not in this case.

In an editorial accompanying the report on the research, Leslie Hendeles, a professor of pharmacy and pediatrics at the University of Florida, gave his unqualified opinion:

“It’s a rip-off,” he wrote. “Right now, people with a stuffy nose deserve to get relief from an effective medicine.”

Of course, this isn’t the first time Big Pharma has had to contend with research that contradicts their claims. Happens all the time. So they were ready with a response:

“Phenylephrine 10 mg is safe when used according to the label and has been proven effective for nasal decongestion in multiple clinical trials,” said Barbara Kochanowski, vice president of regulatory and scientific affairs at the Consumer Healthcare Products Association, which represents over-the-counter drug makers.

Nobody has contested the safety of these cold remedies; placebos are safe too. But “proven effective” belongs more to advertising sloganeering than to a serious discussion of the merits of phenylephrine. (The FDA warns against use of over-the-counter cold medicines in children younger than age six, which in some cases could be life-threatening.)

In fact, the evidence for its effectiveness is surprisingly scant.

Hendeles and colleague Randy Hatton, also at the University of Florida, say that FDA approval for phenylephrine has long been in need of review. In 2006, Hatton and Hendeles did their own review and discovered conflicting and questionable data. Overall, four studies supported claims of efficacy (“proved,” in Kochanowski’s parlance), whereas seven studies rated it no better than a placebo.

In 2007, a Food and Drug Administration advisory committee determined that evidence was “suggestive” that it worked. Hardly a rousing recommendation.

Professor Hendeles is drafting his second petition to the FDA to order an official re-evaluation of phenylephrine. He charges that the drug companies are resisting his call for a systematic review for commercial reasons — if they have to relinquish their claims for phenylephrine, they will have to resort to something closer to a real remedy, like pseudoephedrine, which has a better clinical track record.

But the drawback to using pseudoephedrine is that sales of medicines containing it would be restricted to behind-the-counter status, because it can be used to make illegal substances.

That would drive prices up and profits down. Cold medicines accounted for $1.1 billion in annual drug sales in 2014, according to data from the Nielsen Company. Not something to sneeze at, even for Big Pharma.

So, if these dubious elixirs really aren’t worth the money, what are cold-sufferers to do? Demand stronger stuff, like pseudoephedrine or codeine? Or just go on suffering from their cold until it disappears?

Not at all. There is a third way. The Mayo Clinic has taken a hard look at the problem and notes caustically that “the list of ineffective cold remedies is long.”

But the doctors at Mayo make a remarkable recommendation: Besides bed rest, it’s important to avoid dehydration. “Water, juice, clear broth or warm lemon water with honey helps loosen congestion and prevents dehydration,” they say. (Avoid alcohol, coffee and caffeinated sodas, which do the opposite.)

Clear broth, or in laymen’s terms — chicken soup!

The experts at the Consumer Healthcare Products Association might object that no clinical trials have been conducted to prove the effectiveness of such home remedies. But if it’s good enough for the Mayo Clinic…