How Common is Dishonesty in Medical Research?

Seth Roberts10 Comments

Richard Smith, former editor of the BMJ, writes about Peter Wilmshurst, a British cardiologist, an unusually brave and honest man:

He was the coprincipal investigator on a trial funded by NMT, an American company, to see whether closing a hole in the heart of patients with migraine would cure their migraine. It didn’t. He refused to agree to be an author on a paper published in the journal Circulation because the paper was misleading, and he gave an interview to a journalist in the US pointing out the problems in the study. NMT sued him for libel, not in the US, where proving libel is difficult, but in England, where the onus is on the defendant to prove his innocence. NMT probably assumed (rightly in the case of most people) that the financial risk would cause Wilmshurst to cave in. They were wrong, and the case collapsed when NMT went bust.

The interesting thing about the stories Smith tells about Wilmshurst is the high rate of misconduct they imply:

[In 1996] we invited him to come to the BMJ and give a talk—behind closed doors—to our staff and advisers and colleagues from the Lancet. He reeled off case after case of misconduct, many of them involving prominent people. The audience listed intently, but I was unsure of the reaction. Might somebody leap up and say “How dare you accuse x of misconduct. He is one of the great men of British medicine”? In fact in my memory the reaction was the opposite. People said things like “Actually, it’s worse than you know…” . . .

Many of [Wilmshurst’s stories] involve doctors who are guilty of misdemeanours but who sit in judgement on others. He told the story of Peter Richards who decided to bury the fact that Clive Handler, a doctor, at Northwick Park Hospital, was found guilty of using NHS research funds to subsidise his private practice at a time when Richards was medical director of the hospital and chair of the professional conduct committee of the GMC. Previously he had been dean of St Mary’s Medical School, prorector for medical education at Imperial College, and chair of the Council of Deans of UK Medical School and Faculties. When Handler eventually appeared before the GMC, the GMC’s lawyers ask that Richards stand down from chairing the committee. As Wilmshurst said, it’s as if a judge at the Old Bailey were to say “I’ll have to excuse myself from hearing this case as I helped the accused bury the body.” After having to stand down from this committee Richards continued to chair other conduct committees. Wilmshurst told several stories of doctors who had been found guilty of research misconduct but [had] gone on to be deans and others in charge of researchers.

Smith does not point out what this means. Doctor X is found guilty of research misconduct. Everyone knows this. Doctor X is still appointed dean or whatever. Maybe the people who make these appointments don’t care. Or maybe research misconduct is so common it cannot be a disqualification.

At the end of the article Smith points out his long friendship with Wilmshurst:

RS has known Wilmshurst for 16 years . . . the BMJ was sued for libel over an article by Wilmshurst that was published when RS was editor of the journal. The article has not been retracted but is not available on the BMJ website.

Presumably Smith was forced by BMJ lawyers to be this vague. I have not been able to locate the article. From a talk by Wilmshurst. “Eventually Rubin got his report published in [The New England Journal of Medicine, under the editorship of Dr. Arnold Relman], because he threatened that unless his report was published he would go to the press and point out the collusion between the journal and Sterling-Winthrop.”

Wilmshurst’s conclusion: “Dishonesty is common in medical research.”

Thanks to dearime.

Assorted Links

Seth Roberts7 Comments

Thanks to Paul Nash.

The 2012 Nobel Prize in Physiology or Medicine

Seth Roberts4 Comments

As usual, there is plenty of disease and disability in the world: depression, diabetes, heart disease, cancer, stroke, obesity, autoimmune disease, and so on. As usual, the Nobel Prize in Physiology or Medicine — supposed to be given for the most useful research — is given for research with no proven benefit to anyone (except career-wise). Once again implying that the world’s best biomedical researchers — judging by who wins Nobel Prizes — either don’t want to or don’t know how to do useful research.

Once again the press release tries to hide this. “From surprising discovery to medical use” reads one heading. If you read the text, however, you learn there is no actual “medical use”. Here’s what it says:

These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells. For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.

Apparently you can make “remarkable progress” in medicine without helping a single person, which says a lot about what passes for medical progress. Although iPS cells are supposedly “invaluable tools” for understanding disease mechanisms, we are not told a single disease that has thereby been understood or a single therapy that has been developed.

The Guardian printed a roundup of responses to the award. I read it eagerly. Maybe one of the comments will explain how the prize-winning work actually helped someone (besides career-wise). After all, Yamanaka, one of the winners, had previously won the Finland Prize, given to research that “significantly improves the quality of human life today and for future generations”. Paul Nurse says the prize-winning work did such-and-such, “paving the way for important developments in the diagnosis and treatment of disease” unfortunately not saying what those “important developments” are. Martin Evans says:

The practical outcome is that now we not only know that it might be theoretically possible to convert one cell type into another but it is also practically possible. These are very important foundation studies for future cellular therapies in medicine.

Emphasis added. Another comment: “These breakthroughs will ultimately lead to new and better treatments for conditions like Parkinson’s and improve the lives of millions of people around the world.” A bold prediction, given that they have not yet improved the life of even one person. Julian Savescu, an ethicist at Oxford, says “This is as significant as the discovery of antibiotics. Given the millions, or more lives, which could be saved, this is a truly momentous award.”

Year after year, the Nobel Prize in Physiology or Medicine is given for research that, we are told by biologists with huge conflicts of interest, will — no doubt! — be incredibly valuable in the future. Indicating there was no research that might be honored that had already been useful. It is as if you have a baseball award for best hitter but all hitters all over the world strike out all the time so you end up giving the award to people who strike out best. They are the best hitters, you tell credulous sportswriters. They receive the prestigious award for best hitter at an elaborate ceremony, with toasts all around. Nobody says they cannot hit.

 

New Product: Cascal Fermented Soda

Seth Roberts3 Comments

This low-calorie soda (60 to 80 calories in a 12-ounce can) falls somewhere between kombucha and less-sweet sodas such as the aptly named GUS (Grown Up Soda). Its hook is the use of fermented juices as its base, resulting in a more complex flavor than sodas and sparkling waters based on plain juice.

$1.25 at Whole Foods. I’m in.

My interest in fermented foods partly derives from learning about a similar product. At a Fancy Food Show a few years ago, I learned about someone who wanted to develop a high-end non-alcoholic alternative to wine. He found he couldn’t get enough complexity without fermentation. That emphasized to me how our food preferences — in this case, a desire for complexity — push us to eat fermented foods.

JAMA Jumps to Conclusions About Vitamin D

Seth Roberts10 Comments

A recent experiment published in JAMA, one of the most prestigious medical journals in the world, found that giving people a very large dose of Vitamin D (100,000 IU) once/month did not prevent colds, even though it greatly increased blood levels of Vitamin D. This finding supports my view that it is important to take Vitamin D in the morning. (Because a study in which this wasn’t done found no effect.) My view implies that blood levels may not matter — you can get high levels of Vitamin D by taking it at what I consider the wrong times of day. The usual thinking about Vitamin D has been that blood level is all that matters.

The editors of JAMA considered the Vitamin D study so important that they asked someone (Dr. Jeffrey Linder, associated with Harvard Medical School) to write a commentary — an associated editorial that puts the new finding in context.

Linder’s commentary (might be gated) is important because (a) it is a kind of random sample of how top research doctors think (he was selected to write it) and (b) he completely fails to grasp that the time of day Vitamin D is taken might matter. Colds, the immune system, sleep, time of day — it’s not far-fetched. When you do an experiment to see if X causes Y, and find no effect, I believe that there are usually many possible reasons other than X never causes Y. Something was wrong with the equipment, something was wrong with your X (e.g., it was stale), something was wrong with your measurements (e.g., ceiling effect), and on and on. Linder did not see it this way.

The 2011 IOM report called for additional research to determine whether vitamin D therapy reduces the incidence of respiratory tract infections. The VIDARIS trial [= the new study] has rigorously addressed this question. Results suggest that vitamin D should join the therapies listed in the Cochrane reviewsas being ineffective for preventing or treating upper respiratory tract infections in healthy adults.

He seriously thinks one null result proves something. Sure, the new study is “rigorous” in certain ways. But it was far from exhaustive. It did not explore the many ways Vitamin D may be given, for example. It did not consider the possibility that blood levels don’t matter. Linder’s combination of (a) interest in rigor and (b) failure to understand the importance of exhaustive reminds me of a friend. When she was in 1st grade she had a pile of pennies. She knew how many she had — she had counted them. However, she did not know how to subtract. When she spent some of her pennies, to find out how many she had left she had to count them all over again.

My friend had half the skills an accountant needs. Linder’s commentary reflects only half the skills a scientist needs. To the extent that he is representative of top research doctors, this is shocking. It is as if most accountants at Arthur Andersen didn’t know how to subtract.

I have asked Dr. Linder if he has any response. If he does, I will post it.

Vitamin D3 Eliminated Colds and Improved Sleep When Taken in the Morning (Stories 24 and 25)

Seth Roberts12 Comments

A year and a half ago, the father of a friend of mine started taking Vitamin D3, 5000 IU/day at around 7 am — soon after getting up. That his regimen is exactly what I’d recommend (good dose, good time of day) is a coincidence — he doesn’t read this blog. He used to get 3 or 4 terrible colds every year, year after year. Since he started the Vitamin D3, he hasn’t gotten any. “A huge lifestyle improvement,” said my friend. His dad studied engineering at Caltech and is a considerable skeptic about new this and that.

Much more recently his mother changed the time of day she took her usual dose of Vitamin D3. For years she had been taking half in the morning (with a calcium supplement) and half at night. Two weeks ago she started taking the whole dose in the morning. Immediately — the first night — her sleep improved. She used to wake up every 2 hours. Since taking the Vitamin D3 in the morning, she has been waking up only every 3-6 hours. A few days ago, my friend reports she had “her best sleep in years”.

Sleep and immune function are linked in many ways beyond the fact that we sleep more when we’re sick. A molecule that promotes sleep turned out to be very close to a molecule that produces fever, for example. I found that when I did two things to improve my sleep (more standing, more morning light) I stopped getting colds. So it makes sense that a treatment that improves one (sleep or immune function) would also improve the other (immune function or sleep).

A few days ago I posted a link about a recent Vitamin D study that found no effect of Vitamin D on colds. The study completely neglected importance of time of day by giving one large injection of Vitamin D (100,000 IU) per month at unspecified time. I commented: “One more Vitamin D experiment that failed to have subjects take the Vitamin D early in the morning — the time it appears most likely to have a good effect.” These two stories, which I learned about after that post, support my comment. What’s interesting is that the researchers who do Vitamin D studies keep failing to take time of day into account and keep failing to find an effect and keep failing to figure out why. I have gathered 23 anecdotes that suggest that their studies are failing because they are failing to make sure their subjects take their Vitamin D early in the morning. Yet these researchers, if they resemble most medical researchers, disparage anecdotes. (Disparagement of anecdotes reaches its apotheosis in “evidence-based medicine”.) The same anecdotes that, I believe, contain the information they need to do a successful Vitamin D clinical trial. Could there be a serious problem with how Vitamin D researchers are trained to do research? A better approach would be to study anecdotes to get ideas about causation and then test those ideas. This isn’t complicated or hard to understand, but I haven’t heard of it being taught. If you understand this method, you treasure anecdotes rather than dismiss them (“anecdotal evidence”).

 

Hidden Side Effects of Statins and How Easily You Can Uncover Them

Seth Roberts6 Comments

In 2009, a British rheumatologist named Andrew Banji wrote about the hidden side effects of statins in the Daily Mail:

I discovered the link between statins and rheumatic side-effects quite by chance. My attack of tendon inflammation occurred at the front of my shin – a highly unusual place for tenosynovitis – so I decided to do some research into what could have triggered this. I was amazed to discover the only other related case was linked to a patient on statins.

Following a high cholesterol-reading of 9.2 a couple of months before, I’d been put on the drug. Intrigued by the connection, I decided to stop taking my statin to see what happened. Within a couple of weeks, the pain had gone.

I went back to my GP and, over successive months, tried various statins, including rosuvastatin which is one that is often prescribed.

Each form of the drug caused terrible problems, including night cramp, muscle pain, severe muscle disorders known as myopathy and general fatigue. In fact, I became so tired I couldn’t lift anything when I was gardening or even walk the half-mile from my home to the center of town.

Yet whenever I halted the medication, my symptoms disappeared within a few weeks. . . .

I began to realize many of my patients with musculoskeletal conditions such as polymyalgia – pain, stiffness, and tenderness in the muscles – were on statins. When I advised them to stop taking their medication, their problems went away.\

By 2009, statins were perhaps the most heavily prescribed drugs ever, making tens of billions of dollars for drug companies. Yet this story shows that at that point a doctor who was taking statins was not yet aware of major common side effects. How convenient for drug companies. The story also shows that patients with a variety of muscular problems had to be told by a doctor to stop taking their statins to find out if the statins were causing the problem. That should have been common sense. On a more positive note, this story shows how easily some health problems can be fixed (“when I advised them to stop taking their medicaiton, their problems went away”).

Kahneman Criticizes Social Psychologists For Replication Difficulties

Seth Roberts7 Comments

In a letter linked to by Nature, Daniel Kahneman told social psychologists that they should worry about the repeatability of what are called “social priming effects”. For example, after you see words associated with old age you walk more slowly. John Bargh of New York University is the most prominent researcher in the study of these effects. Many people first heard about them in Malcolm Gladwell’s Blink.

Kahneman wrote:

Questions have been raised about the robustness of priming results. The storm of doubts is fed by several sources, including the recent exposure of fraudulent researchers [who studied priming], general concerns with replicability that affect many disciplines, multiple reported failures to replicate salient results in the priming literature, and the growing belief in the existence of a pervasive file drawer problem [= studies with inconvenient results are not published] that undermines two methodological pillars of your field: the preference for conceptual over literal replication and the use of meta-analysis.

He went on to propose a complicated scheme by which Lab B will see if a result from Lab A can be repeated, then Lab C will see if the result from Lab B can be repeated. And so on. A non-starter, too complex and too costly. What Kahneman proposes requires substantial graduate student labor and will not help the grad students involved get a job — in fact, “wasting” their time (how they will see it) makes it harder for them to get a job. I don’t think anyone believes grad students should pay for the sins of established researchers.

I completely agree there is a problem. It isn’t just social priming research. You’ve heard the saying: “1. Fast. 2. Cheap. 3. Good. Choose 2.” When it comes to psychology research, “1.True. 2. Career. 3. Simple. Choose 2.” Overwhelmingly researchers choose 2 and 3. There isn’t anything wrong with choosing to have a career (= publish papers) so I put a lot of blame for the current state of affairs on journal policies, which put enormous pressure on researchers to choose “3. Simple”. Hardly any journals in psychology publish (a) negative results, (b) exact replications, and (c) complex sets of results (e.g., where Study 1 finds X and apparently identical Study 2 does not find X). The percentage of psychology papers with even one of these characteristics is about 0.0%. You could look at several thousand and not find a single instance. My proposed solution to the problem pointed out by Kahneman is new journal policies: 1. Publish negative results. 2. Publish (and encourage) exact replications. 3. Publish (and encourage) complexity.

Such papers exist. I previously blogged about a paper that emphasized the complexity of findings in “choice overload” research — the finding that too many choices can have bad effects. Basically it concluded the original result was wrong (“mean effect size of virtually zero”), except perhaps in special circumstances. Unless you read this blog — and have a good memory — you are unlikely to have heard of the revisionist paper. Yet I suspect almost everyone reading this has heard of the original result. A friend of mine, who has a Ph.D. in psychology from Stanford, told me he considered Sheena Iyengar, the researcher most associated with the original result, the greatest psychologist of his generation. Iyengar wrote a book (“The Art of Choosing”) about the result. I found nothing in it about the complexities and lack of repeatability.

Why is personal science important? Because personal scientists — people doing science to help themselves, e.g., sleep better — ignore 2. Career and 3. Simple.

Assorted Links

Seth Roberts4 Comments

Thanks to Bryan Castañeda.

When You’re a Lawyer, Everything Looks Like an Opportunity to Argue

Seth Roberts5 Comments

I recently posted about Unaccountable by Mart Makary, a book about the bad behavior of doctors. One of his points is “The when-you’re-a-hammer problem plagues modern medicine at every level.” He illustrated this with a case where transplant surgeons said an otherwise-healthy person with a small liver tumor should get a liver transplant. Which struck Makary as ridiculous.

A lawyer who reads this blog sees the same thing in lawyers. He told me the following story:

One of the sixteen defendants we sued moved to transfer the venue of our case from [Southern California city] to [Northern California city]. Both plaintiffs, all of his doctors (over a dozen), all of the witnesses (again, about a dozen), and all of locations where the incident took place are in or near [N. California city]. When we got the motion I took it to my boss who said, “Huh. We should’ve filed it in [N. California city] to begin with. I don’t know why we didn’t.” It would’ve been inconvenient for us, b/c we’re in [S. California city], but we’ve filed cases up there before, so we could handle it.
So, did we stipulate with the defendant and just transfer the case up north? No. We filed a pathetic, perfunctory opposition. We had an argument, but it was very weak: one of the defendants was located in [S. California city]. That’s basically all we had to hang our hat on.
We filed our opposition, defendant filed their reply. We all trekked down to court to argue our positions in front of the judge. The hearing should’ve taken 30 seconds – “Defendant’s motion granted.” — but the judge actually entertained oral argument. Finally, he granted the motion.
When I got back to the office, I noted to my secretary what a huge waste of time all of this was. The law was clear, virtually all of the facts were on opposing counsel’s side, we should’ve filed up north to begin with, so why fight it? Why not save everyone — us, opposing counsel, the judge and his staff — time and just agree? “Well, you gotta take a shot,” was her reply. Which is what I hear from attorneys all the time. “You gotta try, you gotta make the argument.” In other words, we have hammers so the hammers must be used no matter what.

No, it isn’t quite like a transplant surgeon who says a new liver is needed b/c of a small tumor – no one’s life or health is at risk — but how much time and resources are wasted in the legal system on bullshit like this?