I will tell a story and then ask a question.
The story: “Thousands of Americans are alive today because they were luckily selected to be in the placebo arm of the study”
Paul Alper writes:
As far as I can tell, you have never written about Tambocor (Flecainide) and the so-called CAST study. A locally prominent statistician loaned me the 1995 book by Thomas J. Moore, Deadly Medicine; Why tens of thousands of heart patients died in America’s worst drug disaster. Quite an eyeopener on many fronts but I found some tangential goodies. From page 61:
Scientific articles routinely list so many coauthors that an unwritten code usually determines the order in which the names appear. The doctor who did the most work and probably wrote the article appears as the first-named author.
The unwritten code also provides that the last-named author is the “senior author.”
From page 62:
The authors of the Tambocor study apparently evaded this problem [refusal of journals to accept duplication] by submitting their manuscript simultaneously to three different journals [JAMA, Circulation, and American Heart Journal ].
From page 63;
In all, 3M succeeded in publishing the same study six times. [Seems like a violation of Arrow’s theorem. — ed.]
As a medical doctor once pointed out, thousands of Americans are alive today because they were luckily selected to be in the placebo arm of the study.
I was curious so I looked up Flecainide on Wikipedia and found that it’s an antiarrhythmic agent. Hey, I’ve had arrhythmia! Also the drug remains in use. The Wikipedia entry didn’t mention any scandal; it just said that the results of the Cardiac Arrhythmia Suppression Trial (CAST) “were so significant that the trial was stopped early and preliminary results were published.” I followed the link which reports that “the study found that the tested drugs increased mortality instead of lowering it as was expected”:
Total mortality was significantly higher with both encainide and flecainide at a mean follow-up period of ten months. Within about two years after enrollment, encainide and flecainide were discontinued because of increased mortality and sudden cardiac death. CAST II compared moracizine to placebo but was also stopped because of early (within two weeks) cardiac death in the moracizine group, and long-term survival seemed highly unlikely. The excess mortality was attributed to proarrhythmic effects of the agents.
Alper adds more info from here:
From page 200, “Status on Sept. 1, 1998” with X and Y not being named (as it turned out, placebo and treatment, respectively)
Sudden death 3 19
Total Patients 576 571
But the drug is still in use, I guess it’s believed to help for some people. An interesting example of a varying treatment effect, indicating problems with the traditional statistical paradigm of estimating a constant or average effect.
The question: How to think about this?
The above story looks pretty bad. On the other hand, thousands of new drugs get tried out, some of them help, it stands to reason that some of them will hurt and even kill people too. So maybe this sort of negative study is an inevitable consequence of a useful process?
If anyone tried to bury the negative data, sure, that’s just evilicious. But if they legitimately thought the drug might work, and then it turned to kill people, them’s the breaks, right? Nothing unethical at all, prospectively speaking.
And if you publish your negative results 6 times, that shows a real commitment to correcting the record!