An FDA expert study has found that cough and cold medicines should not be used in children younger than six years old. Rob Steinreports
For years, Joshua Sharfstein shuddered whenever he walked down a supermarket aisle lined with cough and cold products for babies and toddlers.
"It never ceased to aggravate me," says Sharfstein, a paediatrician and father of two young boys. "Kids with colds were getting these medicines that had never been shown to be either effective or safe."
So when Sharfstein became Baltimore's health commissioner, he launched a campaign that led an expert panel of the Food and Drug Administration (FDA) to conclude earlier this month that the products should not be used in children younger than six, shocking many parents and setting up a possible clash between the FDA and the pharmaceutical industry, which is vowing to continue selling the products.
The case has also raised many questions: How could the products remain on the market for so long without proof they work? Why didn't the FDA act sooner? Why didn't the medical establishment warn parents? Are there other medicines in a similar situation?
Although there are other over-the-counter medicines of questionable effectiveness, no one could point to a specific product or class of products used as widely as the cough and cold medication that were a cause for obvious concern. But several experts noted that about two-thirds of prescription drugs had never been studied in children.
"There are a huge number of drugs that are regularly given to children that have never been tested in children," says Michael Shannon, a professor of paediatrics at Harvard Medical School. "I'm very concerned many of these agents may also be inappropriate for children."
According to Peter Lurie of Public Citizen's Health Research Group, a consumer group: "It really is unbelievable. You're just left scratching your head about how this could go on for so long."
The answers lie in the history of drug regulation and the evolution in scientific thinking about how drugs work in adults and children: Many over-the-counter medicines arrived on the market before government requirements for stringent testing, and it was long considered unethical and unnecessary to test drugs in children.
Over-the-counter cough and cold medications are among many products that have been sold for decades, well before the FDA had authority to regulate them closely. Once the FDA got that power in 1962, the agency began systematically reviewing broad classes of products.
"They had a massive job involving hundreds of products and hundreds of ingredients," says William Schultz, a former FDA deputy commissioner. "They gave priority to prescription drugs, for understandable reasons. The over-the-counter drug review was never made a priority in the agency, and so it dragged on for years and years."
The agency did, however, organise a review of nonprescription cough and cold medicines, which concluded there was enough evidence to endorse 35 of the 92 ingredients in products. But the recommendation was based on studies in adults. So the panel made a crucial decision: recommending in 1976 that doses for children be extrapolated from data from adults.
"At that point in time, it was felt that was the best level of evidence we could have," says Marsha Rappley, a professor of paediatrics at Michigan State University who co-chaired last week's panel. "We now understand that we can organise studies in children and don't have to extrapolate from adults. But that wasn't the case back then."
Although the agency revisited adult dosing guidelines periodically in the ensuing decades as it finalised a series of monographs regulating the products, no significant changes were made for children and the products never again received any kind of detailed scrutiny.
But as researchers began testing some of the products directly in children, they slowly started to raise disturbing questions. The Journal of the American Medical Association published an analysis in 1993 that concluded there was no good evidence the medications worked.
The Cochrane Collaboration, an independent international project that regularly evaluates medical therapies, reached a similar conclusion in 2004.
Although many paediatricians were aware of the mounting doubts and began urging their patients not to use the products, some doctors continued to counsel the patients they could, and the products remained a mainstay.
The American Academy of Pediatrics adopted a policy in 1997 stating cough products were ineffective, and the American College of Chest Physicians produced a similar statement in 2006. But other groups, such as the American College of Family Physicians, never issued any formal guidance to doctors, and no major medical groups ever officially questioned the class of products or campaigned against their use.
Some experts defend the medical groups, saying policy statements from doctor groups can only do so much, especially against the aggressive marketing by large pharmaceutical companies, which spend more than $50 million a year to sell the products.
"For the past 25 or 30 years we've been warning about violence on TV," says Wayne Snodgrass, a professor of paediatrics at the University of Texas Medical Branch, who also chairs the American Academy of Pediatrics committee on drugs. "What has that done? In this case we're up against a multibillion-dollar industry. The American Academy of Pediatrics is not a multibillion-dollar industry. We try to do what we can, but there's only so much we can do. Where are the companies in this? Where was the FDA in this?"
But Sharfstein and others wonder whether the medical profession could have been more aggressive.
"When I was trained as a paediatrician it was just accepted that these products had no role. This was known in the profession," Sharfstein says. "It's a fair question why there wasn't a strong regulatory challenge by the profession. They could have justified one. But what really stunned us was that this was never really looked at from the legal-regulatory side."
Using powers it received from two new laws, the FDA has begun demanding some prescription drugs be tested in children before being approved, and it has enticed drug companies to conduct paediatric studies of those already on the market.
Officials at the agency said they acted quickly on Sharfstein's petition because they had become alarmed by the studies questioning the cold products' effectiveness and mounting reports of possible dangers. The Federal Centers for Disease Control and Prevention had reported in January, for example, that more than 1,500 children, including three who died, had suffered adverse reactions to the medications in 2004 and 2005.
The FDA is now reviewing this month's recommendations, but because of the history of the products it says any formal action could take years.
The industry has voluntarily withdrawn products designed for children younger than two, but it maintains that the remedies are both safe and effective for older children when used properly, blaming the problems primarily on overdoses.