“SMART” STUDY BEGETS MORE COGNITIVE DISSONANCE

Someone recently alerted me to a 2006 paper comparing adverse events on “continuous” vs. “interrupted” ARV therapy:

“CD4+ Count-Guided Interruption of Antiretroviral Treatment: The Strategies for Management of Antiretroviral Therapy (SMART) Study Group”, NEJM, Volume 355:2283-2296, November 30, 2006, Number 22

The study was trumpeted in the media as the death knell for so-called “interrupted” or “intermittent” ARV therapy, following the conclusion:

“Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy.”

The original study was intended to last 6-9 years:

“We calculated that 6000 patients would need to be enrolled for the study to have a statistical power of 80% to detect a 17% relative reduction in the rate of opportunistic disease or death from any cause in the drug conservation group as compared with the viral suppression group, with a two-sided alpha level of 0.05. Follow-up was to continue until 910 primary end points had occurred (estimated to be at least 6 years for each participant), assuming an event rate in the viral suppression group of 1.3% in each of the first 2 years and 2.6% per year thereafter.”

but was stopped short after a mean patient follow-up of just 16 months, for “ethical reasons”:

“On January 10, 2006, at its sixth meeting, the board recommended stopping enrollment in the SMART trial because of a safety risk in the drug conservation group and because it appeared to be very unlikely that superiority of the drug conservation treatment would be shown. On January 11, 2006, investigators and participants were notified of these findings, enrollment was stopped, and participants in the drug conservation group were advised to restart antiretroviral therapy.

What I found most revealing about this study was:

“Only 8% of deaths were due to opportunistic disease.”

The cognitive dissonance here is astounding.

Among all patients, grade 4 events occurred about 3.5 times as often as opportunistic disease: a total of 89 patients experienced any type of opportunistic disease; by contrast, a whopping 321 patients experienced grade 4 events.

Even more shocking is the following: out of all 85 patients who died, more than 5 times as many experienced grade 4 events as compared to opportunistic diseases, because 37 of the 85 patients who died experienced grade 4 events, compared to only 7 who experienced opportunistic diseases.

Opportunistic diseases did occur about 3.5 times as often in the DC (drug conservation) group as in the VS (viral suppression) group (69:20), but only 7 of these 89 patients died (8%), 4 from the DC group and 3 from the VS group. By contrast, grade 4 events occurred slightly more often in the DC group as in the VS group (173:148), but 37 of these 321 patients died (12%).

This also means that out of all patients who died, between 41 and 48 patients (48-56%) died due to causes that were either unknown or not related to either opportunistic diseases or grade 4 events. I wonder why the researchers didn’t stop to ponder this incredibly bizarre finding.

Let’s put these numbers into perspective: We have a study on giving ARV to HIV patients, and 5 times as many have drug reactions as AIDS defining illnesses, and this fact doesn’t even register with the authors of the paper? HALF of all deaths have nothing to do with AIDS or ARVs, and this bizarre fact doesn’t register with the researchers either?

The half of all deaths having nothing to do with AIDS or ARVs is several times higher than the average national mortality rate for all Americans among that age group. Why are they dying so much? They can’t blame their low CD4 counts, because their deaths weren’t AIDS related. They can’t even blame the drugs! Obviously, simply being told you’re HIV positive and have a low CD4 count greatly increases your probability of dying from things that have absolutely nothing to do with HIV or CD4 counts… very strange.

Never mind that the whole explanation why this study supports “continuous” therapy is prima facie absurd. The reasoning goes something like this: After controlling for other factors, lower CD4 counts and higher viral load were associated with higher risk of adverse events, and so the reason the patients on “interrupted” therapy had more adverse events was because they weren’t getting enough ARVs to keep HIV viral load in check, to keep their CD4 counts high enough to stave off the adverse events caused by the ARVs in the first place.

Try wrapping your mind around that one!

THE “GALILEO GAMBIT STRAWMAN”

Perhaps the most common reaction to dissident arguments is the argumentum ad populum, more commonly known as the “argument from consensus”. You know, “Fifty Million Frenchmen Can’t Be Wrong”. This is perfectly exemplified by a quote Robert Gallo gave to Anthony Liversidge in 1989:

“There is no organized body of science that thinks it is anything but comedy with Peter right now. That’s the fact. Why does the Institute of Medicine, WHO (World health Organization), CDC (Centers for Disease Control), National Academy of Sciences, NIH, Pasteur Institute and the whole body of science 100 percent agree that HIV is the cause of AIDS? If there was anything to what Peter is saying, wouldn’t it occur to you that there would be some other scientists that would agree with Peter? Can you tell me anyone?”

Twenty years later, little has changed:

“Debating denialists dignifies their position in a way that is unjustified by the facts about HIV/AIDS. The appropriate way for dissenting scientists to try to persuade other scientists of their views on any scientific subject is by publishing research in the peer-reviewed scientific literature. For many years now, AIDS denialists have been unsuccessful in persuading credible peer-reviewed journals to accept their views on HIV/AIDS, because of their scientific implausibility and factual inaccuracies. That failure does not entitle those who disagree with the scientific consensus on a life-and-death public health issue to then attempt to confuse the general public by creating the impression that scientific controversy exists when it does not.” — “Answering AIDS Denialists”, AIDSTruth.org

The argument from consensus is a logical fallacy. The truth of a claim is not dependent on how many people hold the claim to be true. There are many counterexmaples from history, but a favorite is Galileo’s advocacy of Copernicanism. The response runs as follows: “Almost everyone thought Galileo was wrong, but he turned out to be right. Therefore, just because almost everyone thinks something is true, doesn’t make it so.”

The fallaciousness of the argument from consensus is a banal fact which is hardly in dispute. Therefore, people arguing from consensus are forced to either defend their claims with other valid arguments or to defend the argument from consensus with further logical fallacies. The clever try their hand at the former; the dim-witted almost invariably try their hand at the latter by using a logical fallacy I like to call the “Galileo Gambit Strawman”.

The idea behind the fallacy is to replace the above response to the argument from consensus with a strawman called the “Galileo Gambit”. The fallacy runs like this: “Yes, Galileo was right when almost everyone thought he was wrong. However, for every Galilieo, there are a thousand Bozo the Clowns who are wrong. Just because you compare yourself to Galileo, doesn’t mean you are right. You are far more likely to be wrong. Stop using the ‘Galileo Gambit’.”

The “Galileo Gambit” has become a favorite tactic of pseudo-skeptics, as it was recently popularized by one of our favorite surgeons-turned-blogger “Orac” (“Respectful Insolence”), certainly familiar to many readers of this blog. Unfortunately for dear Orac and his readers, it is a strawman argument.

When someone invokes Galileo as a counterexample against the argument from consensus, they are not asserting that because almost everyone disagrees with them, they are necessarily correct in their claims. Such an argument is patently absurd, and I have rarely, if ever, seen it advanced. When someone invokes Galileo, they are not claiming that such a comparison is sufficient to establish their claim, they are simply asserting that the example of Galileo provides evidence that consensus itself is insufficient reason to reject a claim.

The Galileo Gambit Strawman is committed in response to a perceived use of the Galileo Gambit, not the Galileo Gambit itself. It is ironic that such an elementary and obvious logical fallacy as this is perpetrated almost invariably by those who most claim to be “rational”, “skeptical”, and “scientific”.

APPENDIX

=======

For those wishing a more precise mathematical explication of the “Galileo Gambit Strawman” fallacy:

Let

D = “Everyone disagrees with me.”, and

R = “I am right.”

The skeptic is saying

“~(D ==> ~R),”

where “~” indicates logical negation, in words,

“It is not the case that because everyone disagrees with me, I am necessarily wrong.”

The defender counters

“~(D ==> R)”

in words,

“It is not the case that because everyone disagrees with you, you are necessarily right.”

The statement

“(D ==> R)”

in words,

“Everyone disagrees with me, therefore I am right.”

is called the “Galileo Gambit”, and it is correctly described as a fallacy.

But the skeptic did not say “(D ==> R)”, they said “~(D ==> ~R)”. So I call the strawman counter above from the defender the “Galileo Gambit Strawman”.

The Galileo Gambit Strawman then takes the precise form:

“~(D ==> ~R) <==> (D ==> R)”

The first statement is the correct argument against the argument from consensus. The second statement is the fallacious Galileo Gambit. Taking the two statements to be logically equivalent is the fallacious Galileo Gambit Strawman.