Philip Alcabes discusses myths of health, disease and risk.

HIV, Contraception, and (More) Unethical Conduct by U.S. Researchers

Brava! to Caitlin Gerdts and Divya Vohra at Daily Beast for a superb, and much-needed, dissection of the flaws in this week’s heavily hyped Lancet study by Heffron et al.  The study purported to show elevated HIV risk associated with hormonal contraceptive use among women in parts of Africa (abstract here, subscription needed for full text).  The NY Times ran a front-page story, claiming that

[t]he most popular contraceptive for women in eastern and southern Africa, a hormone shot given every three months, appears to double the risk the women will become infected with H.I.V.

and almost everybody else (as diversely situated in newsworld as the Atlantic, CNN health blog, Catholic News Agency, and Voice of America) joined the NYT in failing to examine it critically.

Gerdts and Vohra add the essential context that was missed by the newsmedia:  about a half-million women die during or because of childbirth each year, almost all of them in poor countries.

At RH Reality Check, Jodi Jacobson summarizes the main cautions about the Heffron study, and points to a Guttmacher Institute white paper.  She takes into account concerns about high maternal and infant mortality in parts of Africa, the harms associated with complications of pregnancy and unsafe abortions, and, of course, the substantial possibility of vertical transmission of HIV in places where antiretroviral therapy isn’t universally available.

To claim that poor women should give more weight to the rather remote risk of acquiring a virus that might cause serious illness years down the road than to the dangers of pregnancy itself in the near term is to reduce real women to automata.  Facing dire straits they might be, but they’re supposed to be reasoning machines, programmed to engage in the AIDS industry’s preferred calculus, risk.

A quick summary of the shortcomings of the Heffron et al. research:  comparing users of hormonal contraception to nonusers, the difference in actual risk of acquiring or transmitting HIV was very small, amounting to 1 to 3 new infections per one hundred contraceptive users over and above the infection rate for nonusers.  And it’s impossible to say that these excess infections were actually attributable to the contraceptive — because the study wasn’t a clinical trial.  A great many aspects of social setting, relationships, health, and welfare of the study subjects would have been different between contraception users and nonusers, some of which would undoubtedly account for differences in rate of HIV transmission.

And since all of the subjects were in so-called discordant couples — one partner infected with HIV, the other not — it would be unusual to expect no HIV transmission at all.

Unless, of course, the subjects had been offered antiretroviral therapy, ART.  But this the researchers did not do.  They referred eligible subjects to HIV clinics.  They seem not to have checked whether people who needed ART were getting it.  They seem not to have offered ART to women who got pregnant, either.  Certainly, their Lancet article makes no report of doing so.

I wondered if this was too much to expect of researchers — so I asked the students taking my course on global AIDS and human rights.  Undergraduates, I find, generally have a clearer sense of ethics than most medical researchers.

Even the students who felt that the Heffron study was worth doing and basically sound were troubled by the researchers’ lack of curiosity as to whether HIV-infected subjects were getting the ART drugs they needed.  And most of the students thought this was a disabling ethical fault, which should have caused human subjects committees to make the researchers redesign the study.  One student pointed out that the Bill and Melinda Gates Foundation, one of the study’s funding sources, could easily afford to pay for antiretroviral therapy for all of the roughly 2,000 HIV-infected people in the study.

In the end, my students had the questions that Marcia Angell raised in her editorial in the New England Journal of Medicine in 2011 (PDF at this link angell editorial nejm 2000 ):  Don’t physician researchers have the same responsibility to study subjects that they do to their own patients?  And therefore, when their subjects lack resources to obtain effective therapy for treatable conditions, don’t the researchers have a moral obligation to make the therapies available?

Heffron et al. didn’t do this.  They watched HIV-infected people transmit HIV to their partners (the researchers provided HIV testing and counseling about avoiding transmission — but they don’t make clear whether they notified uninfected partners that they might be in harm’s way).  They did little to prevent transmission.  Notably, they didn’t offer ART to people with low CD4 counts.  Nor did they offer post-exposure prophylaxis to uninfected people who had had intercourse with an infected partner.  They just watched.

On this account, the Heffron study wasn’t only flawed — it was so questionable on ethical grounds that the Lancet should be ashamed to have published it.  And the funders — the NIH as well as the Bill & Melinda Gates foundation — censured.

 

 

Bean Counting HIV Infections

Larry Kramer told the NY Times today that there is no  AIDS policy in the U.S.  To which  Kevin Fenton, the aimless director of CDC’s AIDS efforts, replied, non-sequitur-ly, “CDC is not resting.”

The occasion was CDC’s publication in PLOS One of new figures claiming that the annual number of new HIV infections in the U.S. is only around 50,000.

And if you read the CDC’s new Fact Sheet on HIV infection, just posted, you find out that

The current level of HIV incidence in the United States is likely not sustainable. Prevention efforts in recent years have successfully averted significant increases in new HIV infections, despite the growing number of people living with HIV and AIDS who are able to transmit the virus.

CDC English is a little difficult for native speakers to interpret, but I think that the translation of “likely not sustainable” is:  “we need more money or else the incidence is going to go up.”

Now, 50,000 new HIV infections each year is bad news for 50,000 Americans.  But on a population basis, it’s not a very high number.  The HIV prevention industry will wring its hands, and perhaps Mr. Kramer will, too.  They can all grumble that after 30 years of AIDS there should be no new infections at all.   But that’s ridiculous.  A pipe dream.  HIV is a sexually transmissible infection.  And STIs can’t be eradicated — because, well, people have sex.  No matter what.  And sometimes the kind of sex that isn’t recommended by the experts. With the wrong people.  And so forth.

Really, that there are only 50,000 new infections each year is a sign of (a) the low inherent infectiousness of HIV and (b) Americans’ sharp awareness of how to protect themselves from HIV infection.   It’s not really clear that any new prevention is needed.

What is needed:  get effective treatment into more HIV-infected people.   Obviously, to slow the progression of HIV-based impairment in the individual — but also as a public health measure, to reduce the HIV carrier’s infectivity and thereby reduce the probability of transmission.  It would have medical value and public health value.  But there’s not much policy on that.

CDC officials are bean counters, not policy makers.  That’s why, Mr. Kramer, your expectations are too high.  The CDC’s job is not to do anything about AIDS.  CDC’s job was never to do anything about AIDS.  CDC’s job was, and is, and presumably will always be:  to keep CDC in business.

They’re terrific bean counters, obsessive, scrupulous, punctilious, completely absorbed in their own assumption that their data are a source of truth, committed to deciphering the supposedly unequivocal message the data send.

The message, always, is “CDC needs to do more of what it’s been doing.”

I gave the CDC a hard time in August 2008, when the agency published its estimate that there are 56,000 new HIV infections in the U.S. each year.  That seemed too high, I told the NY Times at the time.  Of course, it was useful for the CDC’s rudderless AIDS division to claim that HIV incidence was higher than everyone thought:  suddenly, lots of people were urging that HIV  prevention programs be beefed up.

Now, the agency has backpedaled. The 2006 incidence wasn’t 56,000 after all, the CDC now figures, it was only 48,000.  And anyway 56,000 is the same as 48,000, the agency now says.

Let me summarize:  Back in 2008, the CDC’s estimate supposedly showed that prevention wasn’t working, so the agency needed to do more of it.  The new estimate, which is almost the same as the old estimate, shows that prevention does work, so the agency needs to do more of it.  All CDC calculations point to the same conclusion:  keep CDC in business.

If CDC were interested in the nation’s health, more so than maintaining its meager status quo, it would be advocating for more treatment (to Donald McNeil’s credit, he makes that point in today’s NYT article).

And if CDC were interested in HIV as a public health problem, and not just in bean counting for the purposes of keeping itself in business, it would stop putting its beans into 30-year-old jars.  What’s the point of the tired “race/ethnicity” breakdown?  Does anybody know anymore how to categorize people into the ancient non-Hispanic-black/Hispanic-including-black/non-Hispanic-white codification?  Does anybody know what it means?

And the famous transmission categories, the MSM-IDU-heterosexual-other breakdown:  that was useful early on, when we weren’t sure that the modes of communication of HIV were fully known.  But that era ended in 1985.

Dear CDC:  Could you please put your beans into some useful jars?

No, it’s asking too much.  Because CDC’s aim isn’t to be useful.  It’s to keep counting beans exactly the way it knows how to count them, and put them into the same jars as always, and keep on concluding that the data — the beans — show that CDC must keep on doing exactly what it has been doing.

 

 

 

 

Cholera: Problem Solved?

Once again I’m grateful to H5N1 for bringing cholera news to my attention.   This week, epidemiologists from France have presented evidence suggesting that the Haitian cholera outbreak began when the causative bacteria were brought in by Nepalese UN troops.

In an article in the July issue of Emerging Infectious Diseases, just out, Piarroux and colleagues assert that (quoting from their abstract) “Our findings strongly suggest that contamination of the Artibonite [River] and 1 of its tributaries downstream from a military camp triggered the epidemic.”

So the mystery is solved, more or less.  The news media have taken note:  articles on the EID report have already been written by the AP, Guardian, and other sources, and are being picked up fairly widely today.

The news, based on a report ordered by UN Secretary-General Ban Ki-moon,  is being treated as an about-face on the UN’s part — because the organization, along with WHO and CDC, refused last fall to do an in-depth investigation of the origin of the outbreak.  So, according to the media’s coverage, this week’s report exposes some hypocrisy on the part of the health organizations.

That’s silly, and wrong.   I’m usually critical of WHO and CDC, but in the case of the Haitian outbreak they were completely correct to refuse to “investigate.”  As I wrote last fall, cholera isn’t a detective story, it’s a disaster.  To investigate the so-called origin of an outbreak that is as self-evidently the result of  calamitous conditions, state poverty, and helpless officialdom is to shift the blame.  Dodge the truth.

The work by Piarroux and colleagues in establishing a clear description of the origin and progress of the Haitian outbreak is impressive, often elegant, quite convincing.  But to believe, as some do, that it somehow proves that the UN and WHO are responsible for a catastrophe, or that sending foreigners into Haiti is always bad, or even that (as the authors of the EID paper say)

Putting an end to the controversy over the cholera origin could ease prevention and treatment by decreasing the distrust associated with the widespread suspicions of a cover-up of a deliberate importation of cholera

is to misunderstand public health.

The problem in Haiti is, and has been, a problem of predisposition — nature out of balance, people on the move, dire straits of all kinds (food, medicine, clean water, toilets, housing, etc.)  too tolerable to weak leaders.  Colonization by one aid group after another (UN included).  It was inevitable that cholera was going to break out.

To take the Piarroux report as definitive is to mistake the germ for the disease, mistake the outbreak for the problem, mistake the detective story for the real disaster — the real disaster being self-explanatory and not in need of “investigation”:  not enough money and not enough political will to keep the public from getting sick.

Profiting from Preparedness

Don’t miss Helen Epstein’s brilliant exposé in the latest issue of The New York Review of Books. She shows how the profit motive shapes the “preparedness” industry — worth $10 billion worldwide in 2009 (the year of the Flu Pandemic That Wasn’t).

I’ve covered the profit-motivated thinking behind vaccine recommendations generally and specifically with regard to flu immunization.  Epstein’s main interest is in the role of pharmaceutical companies in promoting oseltamivir (Tamiflu®) and other neuraminidase inhibitors as public health responses to flu fears.  Her story features the brilliant work of Tom Jefferson and colleagues, and the shady behavior of the global biotech firm Roche in trying to block Jefferson et al.’s efforts to investigate the safety of neuraminidase-blocking agents.

Jefferson was lead author on the Cochrane Collaborations’ main paper on neuraminidase inhibitors for flu prevention and treatment.   But when reports of adverse effects of these drugs emerged and he and colleagues tried to re-assess the underlying reports on which the effectiveness of oseltamivir and similar drugs was based, Jefferson was stymied.  His colleague, Peter Doshi, related the story in BMJ.   The journal’s editor-in-chief, Fiona Godlee, along with Cochrane director Mike Clarke, wrote in an accompanying editorial:

The review and a linked investigation undertaken jointly by the BMJ and Channel 4 News cast doubt not only on the effectiveness and safety of oseltamivir (Tamiflu) but on the system by which drugs are evaluated, regulated, and promoted.

The take-home message is that while there is evidence that Tamiflu can be effective in treating flu, the evidence is shakier than it seems, and troubling reports point to potentially serious adverse effects.

How does a questionable medication get to be the basis (or part of the basis) for public health policy?  The answer is that the policy makers and the money makers work hand in hand.

Maryann Napoli at Center for Medical Consumers tried to point out the troubling links between WHO and big pharma last year, and Steven Novella at Science-Based Medicine brought it up around the same time.

But most of the coverage focuses on the involvement of individual scientists and/or physicians who are receiving payments or other forms of remuneration directly from drug companies.  It’s not hard to police such straightforward conflicts — and so it was easy for Margaret Chan, WHO Director-General, to say last year that “at no time, not for one second, did commercial interests enter my decision-making.”

Epstein’s great contribution is in showing that obvious conflicts of interest aren’t the main way that for-profit companies influence policy.  It’s done through stonewalling, as Jefferson encountered when he tried to examine Roche’s data.  It’s done through widely accepted collusions.

For instance, the CDC Foundation — “Helping CDC Do More, Faster” is its motto — is a nonprofit organization, created by the U.S. Congress, whose job is to

connect the Centers for Disease Control and Prevention (CDC) with private-sector organizations and individuals to build public health programs that make our world healthier and safer.

Of course, calling them “private-sector organizations” suggests that these are not-for-profits — and some, like the District of Columbia Department of Health, the Medical College of South Carolina, and UNICEF, really are.  But most of the private-sector collaborators who are linked with CDC’s policy makers by the CDC Foundation are big corporations.  They include all the giants of Pharma world:  Merck, Pfizer, Roche, Sanofi-Pasteur, etc.  (They also include some who are just giants:  Google, Dell, YUM! Brands, and IBM, to name a few.)

So when CDC’s updated flu response plan now recommends antiviral (i.e., neuraminidase-inhibitor) treatment “as soon as possible,” it’s worth asking whether this is because it has any public health value (answer:  no) or just because CDC is cozy with companies that make money when people get sick.

Vaccine Crusaders Arm for Battle

I’m not sure I want to feel sorry for Andrew Wakefield — a nudnik, possibly even a charlatan.   And although I worry that MMR vaccine, especially as part of the intense dosing schedule for childhood vaccination overall, might have bad effects on some kids’ immune systems,  I’m not categorically opposed to immunization.

Still, it’s hard to avoid wondering:  is Wakefield right when he alleges that he’s being persecuted by the vaccine industry?

Last week, I discussed the BMJ article by Brian Deer asserting that Wakefield’s research was fraudulent, and the accompanying editorial supporting immunization.  At that point, I thought that the BMJ pieces were, together,  a one-off.

I was wrong.  In fact, it looks this week like the vaccine industry has armed some of its main warriors and sent them out to do battle.

The Battle Against Anti-Vaccinationism

In the Jan. 13th issue of the New England Journal of Medicine, two powerful chiefs, Gregory Poland and Robert M. Jacobson, claim that there’s an “age-old struggle” to make vaccines available.  Their aim is to vilify the “antivaccinationists” who “have done significant harm to the public health.” [Note the use of the holy article in this phrase, to signal just how sacred these warrior-priests hold “the” public health to be.]

The Poland-Jacobson piece is pure propaganda.  Theirs is a tale of heroic struggle on the part of ever-embattled Believers against the satanic forces of Antivaccationism — who have been trying “since the 18th century” to shake people’s faith in the vaccine gospel.  And nowadays the nasty antivaccinationists are using scarily modern forms of communications, such as TV and the Internet, in order “to sway public opinion and distract attention from scientific evidence.”

Wow:  TV and the web.  Sounds satanic alright.

I guess I shouldn’t be surprised that a couple of crusaders make their own work sound salvationist.  What troubles me is that they make it sound like they’re disinterested do-good-ers.

In fact, Poland and Jacobson are in bed with Big Pharma.  Poland runs the Mayo Clinic’s Vaccine Research Group.  Although as far as I can tell, Poland and Jacobson are not currently in the direct pay of the vaccine manufacturers, they and the VRG have benefited handsomely from vaccine makers’ largesse.

For instance, Poland’s and Jacobson’s work on human papillomavirus vaccine, as they acknowledge in a 2005 Mayo Clinic Proceedings paper, was funded by Merck, and their co-workers were Merck employees.  Later, in conjunction with a continuing medical education module on meningococcal vaccine in 2009, Poland disclosed the following ties:

Sources of Funding for Research: Merck & Co, Inc, Novavax, Inc, Protein Sciences Corp; Consulting Agreements: Avianax, LLC, CSL Biotherapies, CSL Limited, Emergent Biosolutions Inc, GlaxoSmithKline, Merck & Co, Inc, Novartis Vaccines, Novavax, Inc, PowderMed Ltd

And on his disclosure form for this week’s NEJM article Poland acknowledges funding from Pfizer and Novartis for vaccine studies.

So when Poland and Jacobson write that our society “must continue to fund and publish high-quality studies to investigate concerns about vaccine safety,” they’re really talking about preserving their livelihood.  It’s very much in their interest to ensure a steady flow of such funding.

And when they say that “society must recognize that science is not a democracy in which the side with the most votes or the loudest voices gets to decide what is right,” they’re being completely disingenuous.  Because Poland and Jacobson know quite well why science is not a democracy:  in the type of research they do, it’s the big money that decides what is right.

A High Priest of Vaccine “Science”

Then there’s Paul Offit making the rounds.  Offit has been the subject of lots of attention by Age of Autism, most recently as a “denialist.” Offit probably profited somewhat from the licensing of Rota Teq vaccine, which he helped invent — although AofA’s allegation that he is therefore beholden to Merck seems unsubstantiated.

What’s obvious about Offit is that he is contemptuous of people who don’t agree with his version of truth.

Offit appeared on Lenny Lopate’s radio show in New York yesterday, and presumably will be appearing elsewhere.  His aim is to explain the “grave public health problem of vaccine avoidance.”  The “anti-vaccine movement threatens us all,” he says.  In fact, that’s the subtitle of his new book, Deadly Choices.

Where Poland and Jacobson are militant and sanctimonious, Offit sounds a note at once sentimental and officious.  It’s “tragic” that there have been measles outbreaks because of parents refusing to have their kids vaccinated, he says.  And the problem is that people just don’t understand science.  In fact, Dan Olmsted at AofA gets it quite right when he critique’s Offit’s blinkered version of science:

Anyone concerned about [possible harms of vaccination] fits Offit’s definition of anti-vaccine, because vaccines don’t cause any of them, because Paul Offit says so, a solipsism that is really quite breathtaking: “[B]ecause anti-vaccine activists today define safe as free from side effects such as autism, learning disabilities, attention deficit disorder, multiple sclerosis, diabetes, strokes, heart attacks, and blood clots — conditions that aren’t caused by vaccines — safer vaccines, using their definition, can never be made.”

I had the same reaction to Offit’s self-important — and, to my mind, unscientific — claims.  Offit shows no interest in the open inquiry that marks science.  People who don’t agree with him are uneducated, poorly informed, maybe just stupid.  And, of course, dangerous.

“Tragic” Consequences of Unbelief

On the Lopate show, Offit resorted to the now-common formula of the “tragic” consequences of parents’ belief in Andrew Wakefield.

What’s the tragedy, exactly?   It’s true that there have been outbreaks of measles in the British Isles that have been traced to parents’ refusal to have their children immunized.  An excellent review in BMJ in 2006 provided some of the data for the U.K. — including that one child died in a 2006 measles outbreak that was related to poor immunization coverage.  A few children died in Ireland in 2000.  A CDC account of a measles outbreak in California in 2008 reports that it hospitalized a few children, although none died.

It would be great if nobody ever died from an infection that could be prevented in any way.  It’s surely tragic to the parents of a child who dies from a preventable infection.   The sympathies of each of us should go out to such parents, as to those whose kids are killed by bad drivers, sports injuries, or infections for which there’s no vaccine.

But in what sense is one child’s death more of a collective “tragedy” for all of us than the other deaths that go unremarked every day?   Why is it tragic when one child dies of a vaccine-preventable infection and not when a lot of them die of poorly regulated handguns or as troops fighting wars that never endanger our leaders, only our young?

The Ramp-up of Aggression by the Vaccine Crusaders

Why are the vaccine warriors rampant now?  Perhaps the vaccine makers are terrified that the low uptake of H1N1 flu vaccine despite all the hype in 2009, along with low MMR compliance in some places (the U.K. especially), means that their profits are going to slide.  Maybe their friends, like Offit and Poland, are worried that reduced uptake of vaccines will translate into diminished research funding or fewer conferences in delicious places.

Or maybe the vaccine industry finds Wakefield so obstreperous that they can’t rest until he is destroyed. Wakefield’s no choir boy, but he might not have realized just how much control the pharmaceutical industry can exert in the U.K.

In a review essay in last week’s New York Review of Books, Simon Head points out that Big Pharma is “the only major segment of the British economy that is both world-class and an intensive user of university research,” and implies that it exerts control over both the substance and volume of U.K. research productivity, especially in medicine.  Head sees reason to believe that Pharma will “tighten its hold over scientific research in the UK” in the future.

It’s Not a War

There need be no either-or about vaccines.  If our society can live with guns and automobiles (together accounting for roughly 50,000 American deaths a year), if we tolerate alcohol, processed foods, acetaminophen, high-rise construction, and all the other things that occasionally cause harm but mostly contribute to the way of life we prefer — then we can stop calling it “tragic” when a few parents don’t have their kids immunized.

Because to call one measles death “tragic” is to further the vaccine warriors’ campaign — the campaign that pretends to be on behalf of science or healthy kids, but is really fought to protect the fortunes of vaccine makers.

The campaign protects the power of shiftless public officials who claim to be protecting the public from harm when they serve up millions of taxpayer dollars to vaccine manufacturers for barely useful vaccines (H1N1 2009), or for vaccines that are undoubtedly helpful but might be harmful in some cases and haven’t been thoroughly examined (HPV vaccine).  And who, to this day, won’t even consider the very good question that Andrew Wakefield posed in the 1990s:  is it a good idea to give kids three immunizations in a single preparation?

I had my child immunized when she was the right age for that.    But I’m not certain that absolutely everyone has to do the same.  Neither are the courts, which is why they allow exemptions from immunization for personal belief.

I don’t think measles is a menace to civilization.  I know that only a very tiny percentage of children who contract measles get dangerously sick from it, that flu vaccine doesn’t work for everyone (and isn’t an effective public health measure to stop flu outbreaks even though it can protect individuals from illness), and that varicella vaccine can make the problem of shingles worse even though it reduces the problem of chicken pox.  And so forth.

I mean that immunization is complex and fraught.  Not everyone can be expected to agree with every vaccine recommendation.   Even while some people are opposed to vaccination and refuse to immunize their kids, life will go on, and society will continue to thrive, and Paul Offit can continue to say arrogant things about “science.”

So, could someone please call off the crusade?