Editorial: Defending Good Science

By Dr. Vikas Saini and Shannon Brownlee

Cholesterol-lowering statins are the best selling drugs in the history of the world, despite recent controversy about whether or not they should be used in healthy people at low risk for heart attacks and strokes. Now there’s a new wrinkle in this argument that looks like nothing less than an effort to muzzle a medical journal for its willingness to question orthodoxy.

Recent changes in guidelines for doctors have recommended that even low-risk patients be given statins to lower their cholesterol. This recommendation is based in large measure on the reports of the Cholesterol Treatment Trialists (CTT). Based on their analysis of clinical trials funded by the pharmaceutical industry, the CTT says statins offer benefit in low- as well as high-risk populations.

Not so fast, says Dr. John Abramson, a lecturer on healthcare policy at Harvard. In the October issue of The BMJ, Abramson and co-authors in the US and Canada offered an independent analysis of the CTT’s 2012 report published in The Lancet. Their conclusion: statins reduce the risk of death only for patients at the highest risk. For everybody else, statins did not extend life, and provided only modest protection from heart attacks and strokes in lower risk people.

Sir Rory Collins, a professor of medicine and epidemiology at Oxford and a leader of the CTT, has argued in the medical literature and the lay press that statins are good for practically anybody who has elevated cholesterol, even those with a low risk of a heart attack, stroke, or death. He is demanding that The BMJ retract the Abramson paper, but he is basing that demand on what many see as a side issue, and sidestepping the core of the argument.

The central difference between the conclusions of the two sides is important to understand. While the main analysis of the CTT did not separate patients into high and low risk groups, in a side analysis they did look at lower risk groups separately, and their results were contradictory: “low risk” patients without vascular disease showed some benefit from statins, but low risk patients with vascular disease did not. However you might choose to define “low risk,” if you have two such groups, the one with vascular disease is clearly at higher risk than the one without: they actually have developed the symptoms or physical markers of cardiovascular disease that put them at higher risk. Yet in the CTT’s own analysis, those low risk patients did not seem to benefit. This discrepancy begs for attention and explanation since it could be due to some quirk in their data. Meanwhile the rest of us should be cautious in any conclusions we draw, particularly since taking them at face value might put a billion people on statins.

The CTT should be well aware that only some of their low risk patients were helped by statins while some were not. (It is reported in the back of their supplement to the Lancet article.)

Sir Rory Collins is demanding that The BMJ retract the Abramson paper. Such a move in the world of science is usually an indication of fraud, plagiarism, or serious errors that call into question the main results of a work of original research.  Abramson’s article instead represents an alternative analysis and point of view based on data that has been generated by the CTT. Calling for a retraction is remarkably over the top.

Sir Rory Collins is justifying his request for a retraction based on what many would deem a side issue. In the BMJ paper, Abramson and colleagues cited a different Harvard study that found 18 percent of patients on statins had enough symptoms to cause them to stop the drug for at least a year. This is completely accurate and correct, but they did not add the important caveat that when half of those were later re-challenged with a statin they were able then to tolerate it. The BMJ has since made this “correction,” even though it should properly be characterized as a clarification.

While statins are very well tolerated in most patients, claims that they cause virtually no side effects are laughable, as are the headlines appearing in the press to this effect. Anyone taking care of large volumes of patients on statins knows better. The claims are based on the highly controlled clinical trials which routinely underestimate side effects because they eliminate at the outset patients at high risk for side effects, and define eligible patients far more narrowly than eventual usage once the drug is approved for marketing.

If demands that Abramson’s paper be retracted (along with an accompanying viewpoint in The BMJ) are met, the CTT’s attempt to dismiss the uncertainty about this issue and discredit the editorial leadership of the BMJ will be a hollow victory with sad consequences.  And you, dear reader, will be left at risk of being prescribed a drug you may not need, and suffering a side effect you do not want.

The greater long-term danger here is a medical press bullied into avoiding controversy. The BMJ has been a leader among medical journals in its willingness to publish unorthodox views of common medical practices and has broken numerous important stories about corruption of medical science. If the journal had been around in the 17th century, we wager it would have questioned the practice of bleeding. We need more of this kind of risk-taking, not less from our medical journals.

The public needs to encourage journals’ willingness to challenge orthodoxy. Why? Because journals face a perennial contradiction: their reputation rests with their clinician readers as sources of valid science and sound information, but their revenue depends on advertisements bought by drug and device companies. Displease the industry, and revenue can go down in a heartbeat. Only an aware and active citizenry can provide a counterweight to efforts to suppress uncomfortable debates such as this one.

The concerted attack on the statins papers and The BMJ looks like nothing less than an attack on open scientific debate. In bullying The BMJ, opponents seem to be trying to weaken the power of the medical press to question medical orthodoxy and protect patients from the massive medicalization underway in societies worldwide. We must applaud, not suppress, people who are willing to challenge the medical industrial complex if we are ever to succeed in defining the right care for all of us.