By Sarah C P Williams

The approval this year of the first direct-acting antiviral drugs for the hepatitis C virus has ushered in a new era of treatment. Since the mid-May launch of Incivek (telaprevir) and Victrelis (boceprevir) — both of which disrupt viral replication by inhibiting HCV’s protease protein — physicians have rapidly been prescribing the pills to many of the estimated 180 million people worldwide who are infected with HCV. This is reflected in October earnings reports showing that sales of Incivek reached nearly $420 million in the third quarter of this year alone, which puts it on pace to become the fastest blockbuster in the history of the pharmaceutical industry.

But Incivek, from Vertex Pharmaceuticals of Cambridge, Massachusetts, and Victrelis, from Merck of Whitehouse Station, New Jersey, currently have a catch. Each medicine must be taken with a broad-acting antiviral pill called ribavirin as well as with regular injections of pegylated interferon. Historically, viral clearance occurs in around half of all people who take interferon together with ribavirin, but another 20% can be cured of their HCV when doctors throw one of the new polymerase inhibitors into the mix. Interferon stimulates the immune system but comes with side effects ranging from flu-like fatigue to severe depression to cardiac arrhythmias. Up to a third of people on the protein ultimately stop the therapy early because of adverse reactions.

Against this backdrop, there was much fanfare over the 1 November announcement by the Princeton, New Jersey–based company Pharmasset that it would initiate the world’s first phase 3 clinical study involving an all-oral, interferon-free protocol before the end of the year. The 500-person trial will compare a three-month regimen of the company’s experimental polymerase inhibitor, PSI-7977, together with ribavirin against a six-month course of interferon plus ribavirin. PSI-7977 works by becoming incorporated into RNA chains being made by HCV, stopping the virus from replicating.

“There’s been real concern that we might never be able to get away from interferon entirely, but now we’re starting to get an inkling that that might not be the case,” says Gary Davis, director of the general and transplant hepatology unit at the Baylor University Medical Center in Dallas.

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John Darsee was a young clinical investigator with a long list of publications in top-tier journals and a promising career ahead of him in cardiology research. Described by a former supervisor as “one of the most remarkable young men in American medicine,” Darsee was offered a faculty position at the Harvard Medical School in Boston at the age of 33. But then his career quickly started to unravel. One day, colleagues caught Darsee fraudulently labeling data for a study into heart attacks; further investigations revealed scientific misconduct on a massive scale, and, eventually, Darsee was fired and barred from receiving federal grant money for ten years. More than 80 of his papers were withdrawn from the literature. He ultimately apologized for publishing “inaccuracies and falsehoods.”

That was twenty years ago. But the problem of retractions has not gone away — in fact, it may be getting worse, with the number of such notices on the rise. And whereas the Darsee case took more than decade to come to light (and only then because of an accidental discovery), these days image detection software and the vigilance of media outlets such as Retraction Watch (see ‘The Yearbook’) can catch irregularities — be they due to innocent error or misconduct — much sooner. The ability to track these changes provides benefits to biomedicine, as experiments in the scientific literature lay the foundation for future experiments. Here we look back at instances from the past year where multiple papers from certain investigators came under scrutiny.

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Retracting a paper is perhaps the most unpleasant task a journal has to face, particularly if the retraction involves scientific misconduct. With the number of retractions on the rise, an improved mechanism to deal with misconduct is necessary.

Click here to read the editorial from the December 2011 issue of Nature Medicine.