If things go well with future experiments and clinical use, we may someday look back on this trial as a turning point for this new class of drugs that affect how our bodies manage cholesterol, but this story takes the corner too fast. The results of the trial of anacetrapib give researchers confidence that they can safely proceed to the next round of testing without exposing patients to the life-threatening side effects caused by a similar drug, torcetrapib. However, this story (which misspells the drug’s name throughout the online version) emphasizes potential, but uNPRoven, health effects. There is good material in the story, including several cautionary statements (deep in the story) about how anacetrapib has yet to demonstrate it can save lives or reduce disease. It also reports that the trial was sponsored by the company developing the drug, though it fails to point out the financial ties of the researcher that is quoted.
Trials can demonstrate only what they are designed to investigate. This trial was designed to rule out major safety problems and document changes in cholesterol levels in people. It was not designed to produce evidence that this method of altering cholesterol levels translates into health benefits. The next round of trials should provide answers to important questions about health outcomes, but readers of this story may not understand that this trial did not.
Over 20 million Americans currently take statin drugs. Anacetrapib works on cholesterol in a different way, by inhibiting a protein called CETP (cholesterol ester transfer protein). These drugs also offer hope to drug companies that are losing patent protection on the leading brands of statins. That marketing angle means journalists need to be vigilant about claims of benefits. The early tests of an earlier CETP inhibitor, torcetrapib, also indicated powerful effects on cholesterol, especially in raising levels of the “good” HDL form. However, as this story notes, larger trials then discovered dangerous side effects. It turned out that drug actually caused more heart problems than it prevented.
In reality it takes a lot of subjects to even begin to get a picture of the risks and benefits of a new drug. While encouraging, the results of this study are far from conclusive.
This and other CETP inhibitor drugs are being tested in combination with statins. More than 20 million Americans currently take statins, so an approved drug would be expected to be widely prescribed. Stock market jumps that quickly followed the announcement of these trial results show that market watchers expect a lot of money would be spent. So even though this cholesterol drug is still being tested, if the lead sentence of the story promises people that it may be available “soon” then it is reasonable to expect the story to tell them how much they may soon be paying. Readers would be curious to know if the “jaw-dropping” effects (to quote from an American Heart Association news release) will be accompanied by a jaw-dropping price… for individuals and for the nation.
The story does include several comments that further testing is needed before researchers will be able to say whether or not anacetrapib can save lives or reduce the risk of heart disease. However, it appears to ignore all the cautionary statements when talking about the “benefits” shown in this specific trial. It reports the changes in cholesterol levels seen in this trial and then continues with a comment about the potential life-saving effect “if the same benefit” were seen in all patients at risk of heart disease.
The problem is that this new class of drugs alters cholesterol levels using a different biological mechanism than statins. While it is understandable to hope that the changes in cholesterol will predict changes in disease risk, the way they sometimes can for certain patients taking statins, that fundamental question has yet to be tested… and it certainly was not asked in this trial.
As mentioned above, despite the cautionary statements from independent experts, the thrust of this story assumes that changing cholesterol numbers means changing lives. Not only is that link yet to be proven for this class of drugs, but journalists have an obligation to remind people that the simple marketing messages used to promote cholesterol-lowering statins obscure a far more complex reality.
Readers of this story are likely to conclude that anacetrapib is safe. They aren’t told that what the researchers actually reported is that based on their statistical analysis, they are at least 94 percent sure that the drug doesn’t cause the 25 percent increase in cardiovascular events that was seen in experiments with a similar drug, torcetrapib. That “promising” drug was yanked from testing.
The story did report the dangerous turn taken in trials of torcetrapib, but it could have done a better job of explaining to readers that while researchers breathed a sigh of relief that the same sort of hazards weren’t seen in this trial of anacetrapib, the safety picture is still only short-term and sketchy.
The story does tell readers that another drug in this class showed initial promise, but was then dropped because it caused more health problems and deaths than it prevented. And while the story describes key details of the trial, t it fails to make clear that the whole point of this trial was to look for major safety problems, not primarily to test effectiveness. Indeed, the title of the journal article in the New England Journal of Medicine is “Safety of Anacetrapib in Patients with or at High Risk for Coronary Heart Disease.” Nowhere in the article is there a claim that this trial could demonstrate the drug actually improves the health outcomes of patients.
The fundamental problem with this story is that it promotes the common misconception that equates elevated cholesterol numbers with heart disease and death. The relationship between cholesterol and health problems is far more complex and murky than most people realize, but this story takes the same short cuts used by advertisements promoting statins to millions of people who don’t actually fit the definition of those shown to benefit from drug treatment.
The story points out that the current trial involved people with existing heart disease or at very high risk and that they were all already taking a statin, and the lead sentence also refers to new options for people who are already taking a statin, so it meets this criterion.
Nevertheless, readers are likely to miss the point that the drug has yet to be tested in people who are generally healthy except for having somewhat high cholesterol numbers. This is an important point, because statins are already being prescribed for many people who are at relatively low risk of heart disease and may derive little if any actual health benefit from the drug. The story would have been better if it included stronger caution against a similar premature leap from people with existing disease or very high risk to the far larger number of people with milder cholesterol concerns.
This is a strong point of the story. It offers readers comments from several independent experts who highlight some of the key questions that still need to be investigated. (However, the story leaves all the caveats out of the lead paragraphs, so readers have to dig down to find the vital context.) It also points out that the trial was sponsored by the company developing this drug.
The story should have pointed out that the lead researcher has financial ties to this drug company and others, including board membership and grants.
The lead sentence of this story portrays the experimental drug as a potential complement to lifestyle changes and statin treatment.
We’ll let this story pass on this criterion because it mentions that the next phase of clinical trials will take at least four years to complete and because it notes that success is not a sure thing.
However, the lead sentence about people having a new cholesterol treatment option “soon” gives us pause. Also, the prediction in the story attributed to a drug company spokesman that application for approval could come in 2015 seems questionable, since the next study is not scheduled to begin recruiting participants until April 2011, and then there will be four years of observation, followed by data analysis. The trial just presented began in April 2008 and the participants were followed for an average of 14 to 16 months, yet it took more than a year after that for these results to be announced. The next trial may include 20 times as many patients.
The story points out that this drug is one of a new class of drugs intended to alter cholesterol levels using a different biological mechanism than statins.
The story does not appear to rely on a news release.