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.

 

 

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?

Vaccines & Autism: News?

Fascinating.  You can’t look at a newspaper or news feed without seeing today’s AP story on the finding of fraud in Andrew Wakefield’s vaccine-autism study.  CNN is into this story in a big wayHuffington Post ran the AP report.  Amanda Gardner at HealthDay picked it up, which means it will go into further syndication.  I can’t help wondering why it’s so important to put another nail in Wakefield’s professional coffin.

Or is it the vaccine-autism connection that’s supposedly being interred?

Probably both.

The BMJ opened the proceedings this week by publishing journalist Brian Deer’s investigative piece on the original Wakefield study of MMR vaccine and autism (Wakefield’s study was published in Lancet in February 1998).   That report had already been repudiated by Wakefield’s coauthors, and retracted in 2010 by the Lancet‘s editors after investigation of Wakefield’s procedures.  Wakefield is no longer allowed to practice medicine in the UK.   The Deer article was a parting shot.

An accompanying editorial by Fiona Godlee, Jane Smith, and Harvey Marcovitch, BMJ editors, was a well-taken and circumspect attempt at restoring confidence in measles immunization — on which, in their view, the work of Wakefield and colleagues had cast a shadow.  The editors might not be right in blaming the 1998 Wakefield study for contemporary parents’ reluctance to get their kids immunized, but their aim is to make a reasonable, if arguable, public health point.   To my reading, they haven’t got much of an axe to grind.

But then the whetstones began to turn.  Jonathan Adler at Volokh cheers, wondering if now the “vaccine-autism charade” will end.  Nick Gillespie is also celebratory, albeit more sedately, at Reason‘s blog.   

At Age of Autism, John Stone tries to undermine the journalist (Deer) who wrote the fraud story.  Stone is so rabid, and so ad hominem, in his attempts to destroy Deer that he manages to touch on not a single one of the reasons why it remains impossible to rule out a link between vaccines and autism.   Elsewhere at AofA, the UK group CryShame’s response is published; it too focuses on Deer’s methods, not the substance.

Evidently, substance is nobody’s concern here.  It’s about how news gets made.  Gary Schwitzer, a really sharp observer of the journalism scene, notes that journalists made Wakefield’s reports newsworthy back in their day, and are now “playing a key role in uncovering and dismantling” the story.

The vaccine-autism connection is news because it continues to get everyone riled up.

The defenders of vaccination (to judge by their vigorous celebration every time some further insult is visited on Andrew Wakefield) keep hoping that the suspicions of such a connection will go away.

The skeptics about governments’ medical policing of private lives invoke the possibility that vaccines are associated with a really high profile Bad Thing — like autism — to further their case.

The people who are crying out for an explanation for why so many kids function autistically remain unsatisfied.  (It’s not hard to see why they can’t get satisfaction:  policy makers, invested in mass immunization, don’t want to do the studies that would really find out whether or not the multiple vaccinations that kids are supposed to undergo today might be related to neurological changes.)

Of course, all of that has to do with the substance of the problem.  And what we’re seeing here, with Wakefield, with the revocation of his medical license last year, with this week’s fraud charge, and so on, isn’t substance at all.  It’s gloating or it’s grumbling.  Really, it’s not new.  But it’s news.

Mitochondrial Dysfunction: Biologizing Autistic Behavior

Marx famously opined that social phenomena — world-historic events, he called them — occur first as tragedy, then as farce.  That was in 1852.

Today, it would be closer to the truth to say that tragedy only counts if it can be diagnosed.   And diagnosis only counts if it’s biological.

That’s been the story of  the conversation about autistic children, and the implication of so-called mitochondrial dysfunction.

Deficiencies of energy metabolism have been rumored in association with the autistic picture for a while now, and emerged in the Hannah Poling case a few years ago.  They were given a boost by a small European case series (abstract here, PDF here) published in 2005 in Developmental Medicine and Child Neurology.  (The authors of the article gave their paper the deceptive title “Mitochondrial dysfunction in autism spectrum disorders:  a population-based study,” even though the research involved no population at all, just 11 kids.  But business is business.)

Another boost came this week with the publication in JAMA of a methodologically careful study of  energy metabolism in 10 California children diagnosed with autism, contrasted with 10 children drawn from a well-matched sample of comparable control children.   The new study found reduced oxidative activity in mitochondria — the tiny energy-chain entities inside cells that produce chemically based, biologically derived power for the cells’ functions.  The reduced oxidative activity was present in most of the 10 autistic children, and they showed a much-altered mean energy metabolism on several different measures.

Thus, altered energy metabolism at the cellular level has been documented in a small handful of children diagnosed with autism.  It seems not to be present in all children with autistic diagnoses.  It might be a result of autistic behavior rather than a cause, or a bystander phenomenon of some kind.  Or it might be a feature that hastens diagnosis (in the ones who have the unusual metabolic pattern, it has not been shown to precede the diagnosis) without actually playing any predisposing role.  Indeed, the authors of the JAMA paper remark that the

mitochondrial dysfunction observed in this preliminary study performed with children presenting with full syndrome autism may or may not indicate an etiological role.

But this minor and still untested finding on mitochondrial energetics, still not of any self-evident significance regarding the cause of autistic behavior, has created a major stir.  Medscape weighed in.  Business Week ran a story written by HealthDay reporter Jenifer Goodwin.  And it’s no surprise that the story has been front page news at the autism blogs, like Age of Autism and Autism Speaks.

So it seems safe to say that we’re looking at the third coming of a fact.

That some children engage with the world differently than do most kids was the first discovery, an old discovery (some think the 18th-century Wild Child of Aveyron was autistic).  It was codified in 1910 when  the psychiatrist Eugen Bleuler labeled one of the varieties of childhood schizophrenia “autistic.”  Identification.

Next came diagnosis — beginning with Hans Asperger in 1938 and Leo Kanner in 1943.   In the grip of modernity, slow acquisition of words, quirky communication, fixity of focus, failure to multitask, preoccupation with parts rather than wholes, and so on, are no longer signs of diabolical possession, thankfully.  But neither do they signal a broadened sense of what human experience is like.  They’re just signs of disease.

Diagnosis has allowed all sorts of theories to summon support:  about parenting, about the toxic environment, about thimerosal in vaccines, or about immunization itself.  Autism is the diagnosis that lets people express their misgivings about modernity.

Now we’re seeing the beginning of step 3:  biologization.

If autism is to stand up to 21st-century modernity, it has to have a biological basis.  Otherwise it will go the way of the obsolete disorders of old, like neurasthenia, hysteria, or frigidity.  The research on mitochondrial dysfunction in California won’t be the last or the only big-dollar expenditure aimed at finding a biochemical basis for the diagnosis of autism.   And there’ll be DNA studies, too.

The sad thing is that the only good way for troubled parents to get services for their children is to have the kids diagnosed, and to help to get them labeled as biologically off-kilter (Autism Speaks was one of the sponsors of the study just published in JAMA).  Get them labeled as dysfunctional, to use the term of art.

There’s no percentage in betting on need, or social disadvantage, or just plain poverty as an impetus to free up funds and services.  The need doesn’t count if there’s no dysfunction.   Your event doesn’t count as world-historic without a biological basis now.  First as tragedy, then as diagnosis, then as biology…

Autism, ADHD, obesity, addiction — each time our society is confronted with a problem it can’t solve or an irritation it can’t salve, we feed the problem into the medical establishment’s diagnosis mill.  Then we turn it over to the biologists to put some science on it.

Once the problem has a name and a diagnosis and a biological mishap to it — then we can see it.

Why Vaccinate Children Against Flu?

Scientists shill for vaccine manufacturers in doing routine research.  This week, HealthDay reports that University of Rochester researchers found lower flu-immunization coverage in states with less Medicaid coverage for vaccination.   Instead of asking whether pediatric flu immunization has any public health value, research like this assumes that flu immunization is useful.  It helps make sure the vaccine manufacturers sell more flu vaccine.

What is the value of mass immunization of children against flu?

CDC claims that flu is dangerous for children and recommends immunization.  This claim seems to be based on the 50 to 150 pediatric deaths attributed to flu each year.  Preventing children’s deaths is a good reason to immunize those who might get very sick were they to be exposed to influenza.

But to translate a small number of possibly preventable deaths into a national policy of mass immunization?  That takes a special relationship with the vaccine manufacturers (see here and here and here and here for my comments on the collusion of officials with pharmaceutical interests).

The evidence that flu vaccine is effective in children is shaky, as Dr. Tom Jefferson’s exhaustive scrutiny of study data reveals.  Immunization of children seems to be weakly effective at reducing influenza-like illnesses in a general population, as Ritzwoller et al. showed in a study published in Pediatrics in 2005.  Partial immunization was ineffective — an issue worth considering if more than a single dose is required.

A few studies suggest that mass immunization of children is a way to prevent flu among young adults.

A community trial of immunization of children against flu, published in Vaccine in 2005, showed the ineffectiveness of immunizing children:  there was no reduction in acute respiratory illnesses among children in the concurrent or subsequent flu seasons, compared to communities where kids were not immunized.  There were slight reductions in ARI incidences among adults in the community where children were immunized — but this study wasn’t designed to show whether it was the immunizing of kids that protected the adults, or something else.

Similarly, a 2000 study published in JAMA by Hurwitz et al. showed that flu immunization of children in day care had the effect of reducing acute febrile illnesses among household contacts, compared to household contacts of daycare attenders who were not immunized (abstract here, full article requires subscription).  So immunizing children in daycare might help their parents to avoid getting sick.

In general, there’s suggestive evidence that mass immunization of small children against flu lessens the impact of flu outbreaks among young adults.

But few young adults die of flu.  It’s an annoying and sometimes serious illness.  The reason the public health authorities are interested in preventing flu among young adults isn’t to reduce suffering; it’s to keep them from staying out of work.  Should we immunize children so that the nation’s economic machine doesn’t slow down?

To put it a little differently:  should we shift large amounts of taxpayer money into the hands of pharmaceutical and vaccine manufacturers for the purchase of flu vaccine for children, basically in order to spare employers the loss in profits that would arise when workers stay home?

The news from ProPublica this week, that they and associated journalists found many cases of physicians taking money from big pharmaceutical companies, is alarming but comes as no surprise.  ProPublica’s new searchable database shows that the seven pharmaceutical companies (collectively accounting for 36% of market share) that provided data together made $257.8 million in payments to physicians.

What’s more alarming is that pharmaceutical companies often don’t even have to bother paying to push their products.  That’s especially true when the product is a vaccine.  Even flu vaccine, despite its limited and highly variable effectiveness.  Policy decisions made by the Advisory Committee on Immunization Practices and CDC, practice decisions by medical organizations, research-grant funding, and so on are thoroughly organized around immunization.  Despite the evidence.