Statistical Significance is Nothing to be Sneezed at Says US Supreme Court

If you have ever had a stuffy nose or invested your hard-earned cash in the stock market, the facts of a recent Supreme Court case will probably disturb you.

The case, Matrixx Initiatives Inc. v. Siracusano involved the popular homeopathic nose spray – Zicam.

This product was responsible for the vast majority of Matrixx’s revenues, and investors loved the company because the nasal remedy sold well.  The stock price soared, but then the company learned that Zicam had caused some users to lose their sense of smell.  As it turned out,  approximately 130 users had reported the adverse side effect, the medical term for which is anosmia.

Although the common view of anosmia is that it is a trivial inconvenience, it can have a number of harmful effects.  Not only do patients find food less appetizing, their loss of smell can also be dangerous because it hinders the detection of gas leaks, fire, and spoiled food. Loss of smell may also lead to the loss of libido.

Matrixx, however, concerned that the news would lead to a loss in sales, decided not to report the rare side effect to investors.    The company’s reasoning?  The side effect was not the kind of “material information” that securities laws would require it to disclose because it was not statistically significant when considered in the context of the patients who had used the drug.

The problem for Matrixx arose when national news got wind of the anosmia side effect.  This lead to the issue of FDA warnings and ultimately Matrixx’s decision to take the drug off the market, causing stock prices to fall.

So, investors sued the company saying that the undisclosed information was indeed “material” and might have caused them to make a different decision about whether to buy Matrixx stock.

During the trial, in a brief to the court, PhRMA said, “A collection of adverse event reports that is not statistically significant does not permit a reasonable inference that a particular medicine actually caused the reported adverse event.”

The Supreme Court disagreed.  In a unanimous opinion by Justice Sotomayor, it made clear that the word “material” does not equate with “statistically significant”.  Instead, the Court said, the important consideration is what information a reasonable investor would regard as relevant to the decision to buy stock; such an inquiry would include questions about the source and reliability of the information.  While not all reports to authorities about side effects would be material under this test, the Court held, those about the Zicam side effect would have been because they came from medical experts.

While almost everyone involved in pharmaceutical marketing is aware of the FDA’s “Fair Balance” requirements it seems that full disclosure must now include all corporate, as well as product, information.  In fact, the Supreme Court ruling may have greater repercussions for adverse event reporting by the drug industry than any guidelines the FDA has ever issued!

He who felt it, probably smelt it

On the other hand, people who can’t feel pain, due to a rare genetic defect, also lack the sense of smell.  At least this seems to be the case according to a new small scale study just published in Nature. The unexpected discovery shows that nerves that detect pain and odors rely on the same protein to transmit information to the brain.

Researchers examined three people with mutations in the SCN9A gene which means they can’t feel pain.  All those studied had suffered multiple broken bones without feeling any pain, and two had gone through childbirth birth painlessly. However they weren’t aware that they also couldn’t smell a thing.

None of the study participants could distinguish balsamic vinegar, orange, mint, coffee or perfume from plain water, even when researchers poured on so much perfume and vinegar that the scents were unbearable to people with a normal sense of smell.

It may not be so strange that none of the people realized that they lacked a sense of smell. “If this was a genetic defect from birth they wouldn’t even know what they were missing,” says Graeme Lowe, a neurophysiologist at the Monell Chemical Senses Center in Philadelphia who was not involved in the study.

As oblivious as the patients were to their smell deficit, the scientists had been equally clueless that smell and pain shared a common communication gateway.

Researchers had previously shown that SCN9A controls pain sensitivity in people. The gene makes a sodium channel that lets sodium pass in through a nerve cell’s membrane when the nerve detects something painful. That flood of sodium sends an electrical signal racing toward the brain.

In the new study, the team discovered that odor-detecting nerve cells have the same sodium channel.

Because the sodium channel is missing in people with SCN9A mutations, the messages sent by pain and odor-sensing nerves never actually make it to the brain.

It was completely surprising that these two sensory systems would use the same sodium channel,” says Frank Zufall, a neurophysiologist at the University of Saarland School of Medicine in Homburg, Germany. “But it’s clearly not needed for all senses.” None of the people with the faulty gene had hearing or vision problems. The researchers next plan to test whether those people have a sense of taste, and whether taste cells also use the sodium channel to communicate.

These findings are particularly interesting given that some drug companies are working on painkilling drugs that block the sodium channel’s activity.  The results of this study suggest that such drugs could have the side effect of eliminating smell, and could also compromise people’s ability to taste.

Imagine going though life never knowing the smell of newly baked bread, or the delights of freshly ground coffee?  Now that would be painful!