A nasty fight that pits big-name scientists at Harvard University and the University of Oxford against each other on the effectiveness of a multibillion-dollar class of drugs may be headed toward a settlement by month’s end. The trans-Atlantic spat centers on statins, the popular drugs such as AstraZeneca’s (AZN:LN) Crestor and Pfizer’s (PFE) Lipitor that lower cholesterol levels, and whether they provide benefits that outweigh side effects for people at low risk of heart disease.
Harvard Medical School lecturer John Abramson and colleagues from California and Canada threw the first punch last October, when they published an analysis in the BMJ—formerly known as the British Medical Journal—concluding that statins convey no overall health benefit in such low-risk cases.
That was a direct shot at the Oxford-based Cholesterol Treatment Trialists’ Collaboration, known as CTT, which in 2012 published its own findings that statins significantly reduced the risk of death among that very same low-risk group. Abramson’s paper was based on the data published by the CTT group.
Then the gloves came off.
Rory Collins, an Oxford professor of medicine who heads the CTT collaboration, found a mistake in Abramson’s analysis that overstated the side-effect risk of statins. He pounced, and a correction was published in May. But Collins wants the entire paper retracted; he has met twice with BMJ’s editor in chief, Fiona Godlee, to make his case. He says other errors and misstatements are in the piece.
“I don’t understand the Abramson paper,” Collins says. “It is full of misrepresentations of the evidence.” Collins also charges that Abramson and his colleagues are “going to do harm by persuading people to stop treatment.”
Abramson acknowledges the error in the side-effect rate but says his paper’s main point—that statins do not reduce the risk of overall mortality for people with less than a 20 percent risk of cardiovascular disease over the next decade—remains accurate.
“Sir Rory doth alter his protests too much and is grossly exaggerating the problems with the article,” Abramson says.
The debate has big financial implications. Sales of lipid regulators, which are primarily statin drugs, were $29 billion last year, according to IMS Health, which tracks sales of pharmaceuticals. That number is down 11 percent from the year prior, largely due to the introduction of cheaper generic alternatives. Expanding the use of the drug to healthier patients is one way to counter declining sales.
Abramson noted in his BMJ analysis that he and a co-author serve as experts for plantiffs’ attorneys in litigation involving the drug industry, including a statin. The CTT says it receives no drug industry funding for its work; much of the data it analyses, however, come from industry-funded research, and some individual researchers in the collaborative have received honoraria or worked as consultants for pharmaceutical makers.
To decide if the BMJ should make additional corrections or retract the Abramson study, Godlee has appointed a panel of experts from the U.K. to investigate the case and advise. The panelists include Harlan Krumholz, a cardiologist at Yale University; and Iona Heath, a former chairman of the Royal College of General Practitioners. The panel is slated to deliver its findings by the end of this month.
Godlee says it is the first time the BMJ has appointed such a panel. She said the controversy has attracted international attention because statins are so commonly used.
Meanwhile, more than 500 physicians and scientists from around the world have signed a letter urging the BMJ to resist calls for retracting the Abramson paper.