While appealing his conviction, W. Scott Harkonen is serving six months… (/Kirsten Harkonen )
Is it a crime for a medical researcher to hype his results? To put a heavy spin on the findings when there are millions of dollars, and possibly lives, at stake?
Just ask W. Scott Harkonen.
“I get four hours for errands, once a week. With good behavior, that could go up to six hours,” the 61-year-old physician said recently. “I feel part of an interned population.”
Once the well-paid head of a publicly traded biotech company called InterMune, Harkonen began six months of home confinement July 1. Several times a day he gets a robo-call that checks to make sure he’s inside. His status is an embarrassment, and few people come to visit.
Of course, things could be worse. A federal prosecutor wanted him to get 10 years in prison. Instead, he got a half-year of home detention in his three-story Tudor in San Francisco. But unless his appeals are successful, he won’t ever be able to work as a pharmaceutical researcher and maybe not as a physician, either.
Harkonen’s crime, according to the U.S. government, a federal jury and the 9th Circuit Court of Appeals, was willfully overstating in a press release the evidence for benefit of a drug his company made.
The press release described a clinical trial of interferon gamma-1b (sold as Actimmune) in 330 patients with a rapidly fatal lung disease. What’s unusual is that everyone agrees there weren’t any factual errors in the four-page document. The numbers were right; it’s the interpretation of them that was deemed criminal. Harkonen was found guilty of wire fraud in 2009 for disseminating the press release electronically.
The conviction has wended through motions and appeals since then, and last month Harkonen’s lawyers petitioned the Supreme Court to hear it. The case has gotten little attention outside the world of pharmaceutical law. Some people, however, view it as a sleeping monster, a threat to free speech in science.
“If you applied this rule to scientists, a sizable proportion of them might be in jail today,” said Steven N. Goodman, a pediatrician and biostatistician at Stanford University who submitted a statement supporting Harkonen’s appeal. “The courts don’t quite realize the significance of what is in front of them or the furor that might erupt if this kooky precedent is allowed to stand.”
A drug for the desperately ill
The drug that Harkonen’s company made is a “biologic response modifier” and had FDA approval for use in two rare inherited diseases. InterMune sought approval to market it for a more common ailment, idiopathic pulmonary fibrosis (IPF). In that disease, the lungs slowly fill with scar tissue, killing a person within two or three years. There’s no good treatment, and about 50,000 new cases are diagnosed each year in the United States.
A study of 18 patients in 1999 found that shots of interferon gamma-1b improved their lung function and lessened their breathlessness. Because nobody died in that one-year study, it was impossible to tell whether the drug increased life span. In September 2000, InterMune launched a study at 58 hospitals around the world to see whether the drug staved off worsening of the disease or death.
Some lung specialists were already prescribing interferon gamma-1b “off-label” for the disease. That’s legal. The company, however, wanted to get Actimmune FDA-approved for IPF, as that would lead to greater use of the drug, which cost up to $50,000 a year. A month before the study began, Harkonen called IPF “a $2 billion market opportunity for InterMune.”
In all, 330 patients were randomly assigned to get either interferon gamma-1b or placebo injections. Disease progression or death occurred in 46 percent of those on the drug and 52 percent of those on placebo. That was not a significant difference, statistically speaking. When only survival was considered, however, the drug looked better: 10 percent of people getting the drug died, compared with 17 percent of those on placebo. However, that difference wasn’t “statistically significant,” either.
Specifically, the so-called P value — a mathematical measure of the strength of the evidence that there’s a true difference between a treatment and placebo — was 0.08. It needs to be 0.05 or smaller to be considered “statistically significant” under the conventions of medical research.
Technically, the study was a bust, although the results leaned toward a benefit from interferon gamma-1b. Was there a group of patients in which the results tipped? Harkonen asked the statisticians to look.
It turns out that people with mild to moderate cases of the disease (as measured by lung function) had a dramatic difference in survival. Only 5 percent of those taking the drug died, compared with 16 percent of those on placebo. The P value was 0.004 — highly significant.