Abuses of statistics in HIV/AIDS research

There are many ways of lying under the cover of statistics. One that I’ve not previously emphasized is to imply a correlation where none exists; for example, “the declining incidence in the control group in Rakai — which, although not statistically significant, reduces the difference between the groups” [emphasis added; Gray et al., “Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial”, Lancet, 369 (2007) 657-66].

The whole point of this type of statistical analysis is to determine whether or not an association plausibly exists. If there is no statistically significant association, then no association has been found.
The proper statement would be significantly different:
“The declining incidence apparently had nothing to do with the difference between groups”.

Here’s another example: “The odds of being HIV-positive were nonsignificantly lower among MSM who were circumcised than uncircumcised (odds ratio, 0.86; 95% confidence interval, 0.65-1.13; number of independent effect sizes [k]=15)” (emphasis added; Millett et al., “Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men”, JAMA, 300 [2008] 1674-84).
The enumeration of odds ratio, confidence interval, and effect sizes conveys a sense of technical correctness which, whether intended or not, lends rhetorical weight to the assertion of “lower” when, in actual technical fact, no significance has been established at the 95% probability level.
It is unwarranted, irresponsible, pseudo-scientific to say “nonsignificantly lower”, because that suggests that it is actually lower, though perhaps for purely technical statistical reasons not statistically significantly so.

Again: If the statistics delivers a verdict of “not significant”, then nothing has been established, not lower and not higher. Once more the proper statement would be significantly different:
“No association was found between circumcision and ‘HIV’ status”.

The silver lining in these instances, such as it is, is that I have stimulated many belly laughs — though also some very puzzled expressions — by inviting statistically literate friends to explain to me what “nonsignificantly lower” means.

The dark clouds, however, are that these people — who work at the Centers for Disease Control and Prevention, no less — are capable of writing such a phrase. They are either statistically illiterate or seeking deliberately to deceive. I don’t know which of those two would be the more depressing.

It is also worth noting and regretting that these statistical illiteracies passed the editorial- and peer-review processes of the Lancet and the Journal of the American Medical Association. “Peer review” is no better than the reviewers and the editors make it.

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Oxymoronic jargon like “nonsignificantly lower” surely comes about because of an unshakeable belief that there is — must be — a lowering, in the face of data that do not support the belief. There exists a persistent unwillingness among HIV/AIDS mainstreamers to accept facts that contradict their belief — they suffer cognitive dissonance, as I’ve had occasion to remark all too often [Cognitive dissonance: a human condition, 26 December 2008; The debilitating distraction of “HIV”, 21 December 2008; State of HIV/AIDS denial: carcinogenic HAART, 21 November 2008; True Believers of HIV/AIDS: Why do they believe despite the evidence?, 30 October 2008; “SMART” Study begets more cognitive dissonance, 11 June 2008; Death, antiretroviral drugs, and cognitive dissonance, 9 May 2008; HIV/AIDS illustrates cognitive dissonance, 29 April 2008].

Of course, one might try to argue that “95%” is just an arbitrary criterion: one could choose 85%, or 70%, or any other value; or one might say that “lower” is simply expressing the raw numbers in words without attempting statistical analysis to attach a particular probability. But that would mean jettisoning any pretence of being scientific by using statistics to guide judgment as to whether an effect is plausibly real or not. If one offers statistical details then one should also abide by what the statistical analysis concludes and not try to fudge it.

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Another abuse of statistical analysis that also may not be obvious until made explicit:

Upon finding  no correlation, divide the data into sub-groups in the hopes that one or other might show an apparently significant effect. This is statistically improper, a prelude to lying with statistics, because if you look at enough sub-groups the probability becomes appreciable that there will be found one or a few that appear to have a statistically significant association. Recall that if one uses a criterion as weak as “95% probability”, one apparently but not actually significant association will show up on average at least once in every twenty times — more often if the looked-for association is inherently unlikely [R. A. J. Matthews, “Significance levels for the assessment of anomalous phenomena”, Journal of Scientific Exploration 13 (1999) 1-7].

In the present instance, there was no association in the sub-group of insertive anal sex, nor between circumcision and sexually transmitted infections, two sub-groups where an association would not be implausible. On the other hand, highly implausible apparent associations were noted in studies conducted before the introduction of HAART, and between “HIV”-preventive circumcision and study quality. It is not easy to conceive why an association between circumcision and “HIV” acquisition would have anything at all to do with what treatment is provided people who have AIDS, long after acquiring “HIV”; and “study quality” is a highly subjective variable.

No. The Millett article leads to only one legitimate conclusion: No association found between circumcision and “HIV” status among MSM.

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The problem for HIV/AIDS dogmatists is that they have failed to find any way of preventing people from becoming “HIV-positive”. The mistaken view that it has to do with infection and with sex keeps them searching for data to support that view, rather as rats or guinea pigs are doomed to try eternally to scale the turning wheels in their cages. Study after study gives the same result, no association. At the 4th International AIDS Society Conference, Sydney 2007:
Guanira et al., “How willing are gay men to ‘cut off’ the epidemic? Circumcision among MSM in the Andean region”)
— “No association between circumcision and HIV infection when all the sample is included. A trend to a significant protective effect is seen when only ‘insertive’ are analyzed.”
Note again the unwarranted, illegitimate attempt to assert something despite the lack of evidence: a “trend” toward a significant effect, when the statistical analysis simply says “nothing”, no correlation.
Then there was Templeton et al., “Circumcision status and risk of HIV seroconversion in the HIM cohort of homosexual men in Sydney”)
— “Circumcision status was not associated with HIV seroconversion . . . . However, further research in populations where there is more separation into exclusively receptive or insertive sexual roles by homosexually active men is warranted” [emphasis added].
More research is always warranted, of course, that’s what pays the researchers’ bills [Inventing more epidemics; the Research Trough; and “peer review”, 2 August 2009; The Research Trough — where lack of progress brings more grants, 10 September 2008].

Circumcision pseudo-science

The possible benefits and drawbacks of male circumcision have been argued over for decades, centuries, probably millennia. The coincidence that a procedure originating as a religious ritual should turn out to have beneficial, health-protective side-effects is by no means impossible, though no one argues that case for the religious ritual of female circumcision. What’s clear is that medical opinion has been and continues to be divided [David L. Gollaher, “From ritual to science: the medical transformation of circumcision in America”, Journal of Social History, 28 #1 (1994) 5-36]:
“Ironically, but predictably in the context of the history of medical arguments for circumcision, some doctors have conjectured that removing the foreskin may protect men from the most dreaded epidemic of the post-modern world: the human immunodeficiency virus (HIV). Using retrospective data (the epidemiological equivalent of empiricism) from a venereal disease clinic in Kenya, for example, researchers observed that there were higher rates of HIV infection in the home communities of uncircumcised than circumcised men. Ignoring racial, ethnic, and sociocultural variables — the chief factors dictating whether or not an African boy is circumcised in the first place — they hypothesized that circumcision might serve to inhibit the transmission of the AIDS virus. One wonders whether this theory will endure. But within a medical community desperate to find some weapon against AIDS, its appeal is understandable. Even a physician who is a sober skeptic of the methodologies behind such studies allows that they ‘do suggest that HIV may be more infective during heterosexual intercourse if the male partner is uncircumcised and has a mucosal or cutaneous ulcer.’ [77] AIDS, the nemesis of modern science and medicine, remains a mystery. By some equally mysterious process, it is surmised, circumcision may help”.
[77: Simonsen et al., “Human Immunodeficiency Virus infection among men with Sexually Transmitted Diseases: Experience from a Center in Africa,” NEJM 319 (1988) 274-8; Cameron et al., “Female to male transmission of Human Immunodeficiency Virus Type I: Risk factors for seroconversion in men,” Lancet 2 (1989) 403-7; Marx, “Circumcision may protect against the AIDS virus,” Science, 245 (1989) 470-1; Poland, “The question of routine neonatal circumcision,” NEJM, 322 (1990) 1312-5”]

It is worth noting that circumcision as a way of avoiding becoming “HIV-positive” was mooted already in the late 1980s, and enthusiasts have continued to pursue definitive evidence for that for some two decades, despite contraindications no less probative than the pro-indications: a number of studies have found circumcision to be NOT associated with a lower rate of “HIV-positive”; see, for example, those cited in “Rwanda: Circumcise all men — even if it means more ‘HIV’ ‘infection’” [3 February 2008].

I’ve commented before on the remarkable similarities between HIV/AIDS and topics often labeled pseudo-science [“Science Studies 102: Burden of proof, HIV/AIDS ‘science’, pseudo-science”, 22 July 2008;  “HIV/AIDS and parapsychology: science or pseudo-science?”, 30 December 2008;  “Mainstream pseudo-science good, alternative pseudo-science bad”, 25 February 2009]. The failure after two decades of effort to find conclusive proof that circumcision prevents “HIV-positive” is somewhat reminiscent of decades of enthusiastic seeking of evidence for the reality of UFOs or the existence of Nessies; though one might have imagined, perhaps naïvely, that it might be easier to observe circumcision and frequency of “HIV-positive” than to investigate objects like UFOs or Nessies that cannot be brought under observation on command. Still, as Scientific Explorers like to say, “absence of evidence is not evidence of absence”.

At any rate, two decades of observational studies have been inconclusive as to whether there is an association between circumcision and “HIV-positive” status. A recognized problem is the number of potentially confounding factors in these observational studies, primarily cultural and religious characteristics that are often correlated with genetic characteristics.

A powerful argument that CIRCUMCISION DOES NOT PROTECT against “HIV-positive” status comes from solid and consistent observational data on cohorts of gay men. Universally, the groups most frequently testing “HIV-positive” are drug abusers and gay men; in the official jargon, injecting drug users (IDU) and men who have sex with men (MSM). Since IDU are supposedly infected via needles that do not normally make contact with the foreskin, MSM are the group most at risk for acquiring “HIV-positive” status via the foreskin; therefore this would be the ideal group for detecting any preventive effect of circumcision. But a review of 18 such studies found no preventive effect of circumcision against “HIV-positive” among MSM: Millett et al., “Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men”, JAMA, 300 [2008] 1674-84.

How then does it come about that the HIV/AIDS Establishment has accepted as an article of faith that circumcision reduces by half the risk of becoming “HIV-positive”? For example,

“CDC mulls routine circumcision of infants to reduce spread of HIV” (Tracy Miller, 25 August 2009)
“In an effort to reduce the spread of the AIDS-causing HIV virus, the Centers for Disease Control are currently mulling routine circumcision for all baby boys born in the United States . . . . The controversial recommendations, scheduled for a formal release by the end of the year, come on the heels of research that shows circumcised men in African countries hit hard by AIDS had half the risk of getting infected as those who were uncircumcised.
Critics say that focusing on newborns in the United States would only have an effect years down the road, and that circumcising infants subjects them to medically unnecessary surgery without their consent.
But CDC experts maintain that any step to reduce the spread of HIV is worthy of serious consideration.
‘We have a significant H.I.V. epidemic in this country, and we really need to look carefully at any potential intervention that could be another tool in the toolbox we use to address the epidemic,’ Dr. Peter Kilmarx, chief of epidemiology for the CDC’s division of HIV/AIDS prevention, told the Times. ‘What we’ve heard from our consultants is that there would be a benefit for infants from infant circumcision, and that the benefits outweigh the risks.’
Experts acknowledge that a new circumcision policy is unlikely to have a dramatic effect in HIV infection rates, as most adult men are already circumcised. Additionally, scant evidence exists to prove circumcision protects homosexual men from getting HIV.
79 percent of adult American men are already circumcised, according to public health statistics, though circumcision of newborns has dropped to about 65 percent in recent decades” [emphases added].

Note the usual bureaucratic prevarications:
— Unnamed “experts” and “consultants” are cited in the attempt to outweigh the actual scientific evidence;
— “a significant H.I.V. epidemic” is asserted to exist in the USA, contrary to fact;
— however, insofar as there may be an appreciable frequency of  “HIV-positive” instances in the USA, a large proportion is among MSM, who have been found NOT to benefit in this respect from circumcision;
— and that fact is euphemized or obfuscated by saying “scant evidence exists” instead of that the evidence speaks clearly against any benefit from circumcision.

Note too, “on the heels of research”: It is elementary that new research is not to be relied on until it has been confirmed over time by independent investigators and in a variety of circumstances. This rush to judgment is junk science. REAL SCIENCE ISN’T NEWS [Scientific illiteracy, the media, science pundits, governments, and HIV/AIDS, 15 January 2009].

Since HIV/AIDS theorists do not hesitate to swallow absurdities wholesale, they do not blink at the suggestion that “While circumcision may help protect heterosexual men in Africa from contracting HIV, . . .  it does not appear effective in doing so for American gay men, according to the largest study yet on the issue. . . . Circumcision ‘is not considered beneficial’ for gay men concerned about lowering their risk of becoming infected with HIV, Dr. Peter Kilmarx of the CDC told the Associated Press. He released the study findings at a conference on Tuesday. . . . But circumcision may not offer the same protection when it comes to anal sex, Kilmarx said.” [“Circumcision won’t shield gay men from HIV: Study” ].
Here once more the HIV/AIDS gurus would like to swing both ways, or perhaps every way. On the one hand, it is an hoary shibboleth that gay men are particularly at risk because anal sex is more conducive to “HIV transmission” than is vaginal sex, because of a greater likelihood of skin breakage and blood contact. But in order to justify a program of universal circumcision, it becomes expedient to take somehow the opposite view.

Why would circumcision be preventive?
“Scientists think circumcision can protect against HIV because the tissue of the foreskin has a high number of target cells for HIV infection and is susceptible to tearing during intercourse, providing an entry point for the virus” [“Circumcision: Change in medical opinion possible”].
But, again, anal sex is supposed to pose a greater risk for tearing skin than does vaginal sex. “I also find it fascinating that the male prepuce has gone straight from being an inconsequential ‘flap of skin’ to being a complex immunological organ, just in time to be infected by a virus that targets immune cells” [Winkel, “Rush to judgment”, PLoS Medicine 3(1) (2006) e71].

So the official conclusion is not only highly implausible, it is contrary to the facts accumulated over some twenty years or so. Yet all that is jettisoned by reliance on 3 brand-new clinical trials in Africa, all of them stopped prematurely after a year, that have supposedly shown definitively that circumcision reduces by about 50% the risk of becoming “HIV-positive” — among African heterosexual men, that is, though not among American gay men [Gray et al., “Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial”, Lancet, 369 (2007) 657-66; Bailey et al., “Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial”, ibid., 643-56; Auvert et al., “Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 trial”, PLoS Medicine 2(11) (2005) e298].
A detailed deconstruction of these reports has to be deferred to a later post, this one is already longer than I prefer, but at least one feature of them is readily cited and adds greatly to the implausibility of the conclusion drawn:
In all three trials — in South Africa, Uganda, and Kenya —, the purported effect of circumcision was essentially the same at 50-60%, and it was independent of all other observed variables, among them number of sexual partners, non-marital relationships, condom use, paying for sex, drinking alcohol before sex, age, marital status, education (so stated specifically in Gray et al.).
Think about that. The probability of acquiring any sexually transmitted infection must depend on the probability of intercourse with an already infected person, which itself depends on the prevalence of the infection in the population; also influential will be the number of acts of intercourse and the number of partners, and whether sex is “social” or paid for, because prostitutes are by shibboleth supposed to be a reservoir of HIV and STDs; important too must be the care taken to protect via condoms, which is supposedly influenced by the state of sobriety or lack of it. Yet in 3 different cultures, in 3 widely separated regions of Africa, with groups of different age ranges, and where the incidence of “HIV-positive” in the control groups differed  significantly, somehow all those variables turn out to balance one other so precisely that the overall effect of the studied treatment is almost exactly the same. This strikes me as about as likely as 2 blue moons in the same year, or as Nessie surfacing just as I’m greeted by an alien emerging from a landed UFO.

There is quite a good reason, actually, why all 3 studies should have delivered the same apparent effect of circumcision, but it has nothing to do with “HIV” or sexual transmission: Surgery is well known to suppress immune function. Now the standard test for “HIV” is actually a test for antibodies, and the evidence is ample that “HIV” tests are highly non-specific, reacting “positive” when large numbers of a variety of antibodies are present. Since post-operative antibody production is lower as a consequence of surgery, post-operative apparent “HIV” incidence will be lower.

These clinical trials have demonstrated only that surgery cuts by about half (50-60%) the production of non-specific antibodies.