Complete Health Reporting: Four Tips for Judging a Treatment’s Novelty

When the FDA says that a drug is approved to treat nearly 20 different diseases, you have a choice.

Assume the agency is right and that a true wonder drug is working miracles in the marketplace. Or do what Andrew Pollack at the New York Times did and examine the evidence used to justify those approvals. Here are four tips from Pollack’s recent investigation of Questcor’s drug Acthar that will help you make better judgments about the novelty of a drug or device.

Draw a family tree. Drugs and devices often have complicated histories, and that history can help you understand the drug’s efficacy and the company’s marketing strategy, knowing that the two things might be disconnected. In helping readers understand why Acthar is being sold for $28,000 per vial, Pollack explained: “Companies often charge stratospheric prices for drugs for rare diseases — known as orphan drugs — and Acthar’s price is not as high as some. Society generally tolerates those costs to encourage drug companies to develop crucial, possibly lifesaving drugs for these often neglected diseases.”

Then Pollack took a little trip through history to show why society might think differently in this case.

But Questcor did almost no research or development to bring Acthar to market, merely buying the rights to the drug from its previous owner for $100,000 in 2001. And while the manufacturing of Acthar is complex, it accounts for only about 1 cent of every dollar that Questcor charges for the drug. Moreover, the tiny “orphan” market soon became much bigger. Before long, Questcor began marketing the drug for multiple sclerosis, nephrotic syndrome and rheumatologic conditions, even though there is little evidence that Acthar is more effective for those other conditions than alternatives that are far cheaper. And the company did so without being required to prove that the drug actually works. That is because Acthar was approved for use in 1952, before the Food and Drug Administration required clinical trials to show a drug is effective for a particular disease. Acthar is essentially grandfathered in.

Get to know PubMed. The National Library of Medicine’s scientific study database should be your first stop for any story about a treatment, but I talk to health writers regularly who admit that they never use it. Often a key word search or two will help you find similar research and also find experts who could comment. Pollack noted that Acthar was initially approved for treatment of 50 different diseases. Remember that clinical trials weren’t required. But “by the 1980s, drug companies had learned to synthesize steroids like prednisone, and those became the treatment of choice.” A search of PubMed for “Acthar,” also known as ACTH, turns up an interesting 2009 review, among many others, in Pharmacy and Therapeutics. The review compares Acthar to other drugs for treating three different disorders and concludes, in the case of multiple sclerosis for example, “ACTH has been replaced by high-potency corticosteroids because of their comparable, if not greater, effectiveness.”

Measure size and scope. When browsing PubMed, pay attention to how many people were enrolled in the studies, the types of people enrolled and how the study was conducted. Leslie Batten recently wrote to me that people should pay attention to a full range of questions surrounding studies: “Look, too, at who funds the studies; doses used; type of study; form of substance used.” Pollack noted that there may be problems with the studies that have shown strong benefits from Acthar.

The study that justified calling on rheumatologists involved five patients with rare conditions, all of them treated by a single doctor. All the patients had much improvement on Acthar after failing to benefit from more standard therapies, the doctor, Todd Levine, said in a Questcor conference call.

I will expand on this in later posts.

Look for stop signs. Pollack found that some Acthar studies were halted.

[I]t appears that at least a couple of small studies that may have raised questions about the drug have been suspended.

“From my standpoint it just didn’t work,” said Dr. Sungchun Lee, a Phoenix nephrologist who stopped a small study testing Acthar as a treatment for nephrotic syndrome. “I think they were O.K. with me stopping because we weren’t getting the results,” he said.

Another study that was terminated sought to determine whether multiple sclerosis patients who did not have a good response to steroids should be treated with either another round of steroids or with Acthar. The study was halted midway through “to analyze data,” according to the summary of the trial on the federal clinical trial database.

That link in the last sentence is one of the most useful pieces of information in the story. If you have never browsed the National Institutes of Health’s ClinicalTrials.gov, do yourself a favor. Anyone writing about Acthar could have gone to the site, typed in that one key word and found dozens of potentially relevant studies that are ongoing or were completed or stopped early. About half way down the first page, your eyes may have been caught by the word “terminated,” and you would have then been prompted to ask why.

Have your own ideas about how to judge novelty? Write to me at askantidote@gmail.com or via Twitter @wheisel.

Image by epSos.de via Flickr