INFLUENCING THE OUTCOME OF CLINICAL RESEARCH

In the past twenty years medical research in this country has increasingly come to rely on the financial support of the pharmaceutical industry - to such an extent, in fact, that industry financial backing is now considerably larger than that provided by the National Institutes of Health.

A group of researchers at the University of North Carolina set out to determine whether, and to what extent, the financial involvement of the pharmaceutical industry influenced the outcome of clinical research. Published in the journal Cancer earlier this year, their report, which focused specifically on the outcome of breast cancer trials, found that clinical studies backed by the drug industry were much more likely to report a favorable result (Peppercorn 2007).

A full 84 percent of industry-backed studies reported positive results, as compared to only 54 percent of those which received no drug company support. And as previous research has repeatedly shown, clinical studies with a positive outcome are far more likely to be published in the medical literature than those with negative findings.

The result of the study comes as no surprise to the many commentators, including myself, who have repeatedly warned that the pharmaceutical industry exerts an unhealthy influence on the way clinical trials are designed, reported and published.

The worth of evidence-based medicine is severely undermined when the evidence on which it is based can be bought in this way. If the medical literature cannot be counted upon for objectivity, how can patients and their caregivers determine which treatments are likely to be of the most benefit? For the newly diagnosed cancer patient, who must quickly make vital decisions based on what is often only a very tenuous understanding of the disease and its treatment, having access to reliable and trustworthy information is of the utmost importance.

DO STATINS INCREASE CANCER RISK? - PART TWO

(Previously we began a discussion of whether or not the cholesterol-lowering drugs statins are associated with an increased risk of cancer. We presented some research suggesting that statins do not cause cancer, and may even exert a mild protective effect against the occurrence of certain cancers. However, this week we present some important new data concerning possible risks associated with aggressive reduction in low-density lipoprotein (LDL) levels.)

A July 2007 paper in the American Journal of Cardiology has introduced an important new perspective on the issue of statins and cancer (Alsheikh-Ali 2007).

The study, carried out by Dr. Richard Karas and colleagues at Tufts University School of Medicine, Boston, was designed to examine whether there was any relationship between a patient’s blood level of LDL and that patient’s risk of cancer. The study also looked at two other statin-related adverse effects: elevated liver enzymes and a rare - but potentially serious - muscular side effect known as rhabdomyolysis.

Perhaps not surprisingly, the Tufts researchers found that the dosage of statins had a direct influence on the likelihood and severity of adverse effects, with higher dosages being associated with an increased incidence of such effects.

However, Karas and his team also discovered that the lower the blood level of LDL achieved through the use of statins, the greater the risk of cancer. The researchers observed "a significant and linear relationship" between LDL levels and the risk of developing a new cancer, an effect that was especially marked at LDL levels below 100 milligrams per deciliter (mg/dL).

The study concludes: "...the risk of cancer is significantly associated with lower achieved LDL levels. These findings suggest that ...the cardiovascular benefits of low achieved levels of LDL-C may in part be offset by an increased risk of cancer."

These are frightening words, and about the last thing that cardiologists and their patients want to hear, since current recommendations specify that the optimal target level of LDL for cardiovascular benefit should be less than 100mg/dL.

Reducing LDL or "bad" cholesterol is a cornerstone of cardiologists’ efforts to control the epidemic of heart disease, America’s (and the world’s) number one killer disease. Moreover, there has been a recent push to drive optimum LDL levels even lower than are currently recommended. In April 2004, some leading cardiologists called for a target reduction of LDL to 65 mg/dL, to be achieved by taking up to 80 mg per day of Lipitor. Although this recommendation grew out of a study that tested this thesis only in patients with severe cardiovascular disease who were already hospitalized because of a ruptured plaque in their coronary arteries, many doctors were quick to extrapolate these findings to patients in general. "This is really a big deal," Dr. David Waters, a professor of medicine at the University of California in San Francisco, said of these findings. "We have in our hands the power to reduce the risk of heart disease by a lot. It’s very exciting." (New York Times, March 8, 2004).