Since I recently wrote about statins, I thought I would follow up with today’s story about cholesterol drugs. It is actually a story of most everything proceeding in a way that makes perfect sense, though it seems to have created a lot of consternation.
Having lower “bad cholesterol” reduces cardiovascular disease (CVD) risk; statins lower bad cholesterol; and trials have shown that taking statins provides the health benefits. Also, statins do not cost much (apart from the pharma industry profits that can be made via patents) and do not seem to have much downside. All in all, a straightforward story of preventive medicine. The story I wrote about was that they seemed not to be doing so well in practice in Sweden, but that was a “hmm, we should try to explain that” moment, not a case of “whoa, it looks like we were wrong.”
In a story that turns out to be dissimilar, having higher “good cholesterol” and lower triglycerides reduces CVD risk;vniacin, a B vitamin, raises good cholesterol and lowers triglycerides; but the studies do not seem to show that taking niacin improves CVD risk. This is disappointing, since niacin is also cheap, though for some people it causes an annoying skin flush and sometimes other superficial side effects. It is fairly odd to find a case where having a particular physiologic status is good for you, but causing that status is not good for you. It becomes more likely, though, when the method of causing it departs substantially from what causes it in nature, as it were. However, this was not the first time a drug to raise good cholesterol failed to have the expected health effect, so it was not totally shocking.
The way this transpired should not be seen as troubling, however, despite the way some new reports have portrayed it. Consider the sequence of events: Observational research supported the conclusion that the cholesterol levels in question (when not drug-induced) result in lower CVD risk. Simple short-term studies supported the conclusion that niacin causes those levels. Niacin is cheap and low-risk (and those who hate the side effects can rationally choose to not take it). Therefore it was the obvious rational choice for people to have been taking niacin while awaiting further information. Further research that connected up the whole proposed causal pathway (niacin causes reduced CVD risk) rather than breaking it into pieces, however, finally suggested there was no benefit. Oh, well. Note much harm done, and that is why we do this research: to find out if what we believed before seems to be wrong.
So, what is disturbing about this story? One issue is that the the study, and apparently the popular medical regimen, consisted of taking Abbott’s drug, Niaspan, which is basically niacin with a slow release. Presumably someone somewhere concocted a reason why this drug should be used rather than cheap generic niacin, but it certainly was not because it was shown to be more effective (obviously: we only just learned how effective it is, which is to say, not at all). I guess the only good news in this turning of a common nutrient into private profits was that, sadly, if people had just been taking niacin from competitive market sources, the study might have not been done.
Also mildly disturbing was the cessation of the study early because the group taking niacin had a somewhat higher rate of stroke (and no reduction in heart attacks, as was hoped). In this particular case, the good effects were not happening, so quitting the study was a good idea. But the rules for stopping studies early because they have become “unethical” are quite misguided – but that is a story for another day.
But since there was no apparent benefit, rather than a complicated uncertain tradeoff between costs and benefits, stopping in this case seemed entirely sensible. Not so sensible is:
Wells Fargo Securities analyst Larry Biegelsen said the surprise findings could cut Niaspan sales by 20 to 30 percent.
So the message will be “this does not seem to work, so we advise only three-quarters of you to keep buying and taking it”? You really have to love our medical industry. Notice also that it is the Wall Street guys who are assessing the effects of this. I did not notice any broad comments about how this should affect behavior from the medical or public health people. Health research, in the mind of those in the halls of power, is not primarily a story about health.
Of course, it is possible that some consumers will get a benefit, people different from those who were studied (who had a history of heart disease, and like most trial subjects, were rather different from most of the target population). I think this is what the study leader was trying to say when interviewed, though it came out as unintentional comedy:
But it’s not clear if niacin would have any effect on people at higher risk or those who don’t have a diagnosis of heart disease yet but take niacin as a preventive, said study co-leader Dr. William Boden of the University at Buffalo.
“We can’t generalize these findings …to patients that we didn’t study,” he said.
I would have to say that any study whose results cannot be generalized beyond the few thousand people in the study is really not worth doing.
Yes, it is always possible that some unstudied types of people will benefit, but there are three strikes here: No studies show this drug helps, one study shows this drug does no good, and other good-cholesterol-raising drugs have not shown health benefits either. I think this falls into the category of “stop recommending this unless some new evidence emerges to change our minds.”
So if you piece together all the claims, we have a study that showed there is no benefit from causing what is known to be a beneficial difference under other circumstances, which focused on one patented version of common nutrient, which was stopped for no good reason, but could not be generalized beyond a few thousand people, though it is relevant to maybe a million people taking the nutrient for the non-existent benefit, the implications of which are being studied by finance guys rather than health policy makers, and that will end some but not all use of the apparently useless treatment. And yet, all in all, compared to much of what we see, this story arc is a case of health science working mostly like it should.
“stopping studies early because they have become “unethical” are quite misguided – but that is a story for another day.”
Carl, I am intrigued! If you could explain it in one sentence , what would that sentence be?
I am not sure I can do one sentence. I will try three, which make it only slightly less vague, and then will write a whole UN about it sometime soon when there is nothing too exciting in the day's news.
Almost all trials force some people to endure a believed-inferior regimen (despite the fact that the trials people like to pretend otherwise). We impose this cost on some people in order to contribute to the greater good — gaining additional knowledge that will allow for better decisions by/for many people in the future. The stopping rules are designed based on the fiction that no harm is being done to people, and because of that almost always stop way too early from the perspective of the greater good that we are asking people to make sacrifices for.
I know that is still dense and vague. I will get back to it.