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.



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.

NYC: Unethical Research by Bloomberg Administration

I had missed this story when the NY Daily News broke it in September, but  the front page of today’s NY Times made it impossible to ignore:  Mayor Mike Bloomberg’s administration is conducting unethical experimentation on human beings.

The News describes the experiment very simply:

[New York City’s] Department of Homeless Services split 400 struggling families into haves and have-nots.

The “haves” get rental assistance, job training and other services through a program called Homebase.

The other half … were dubbed the “control group” and shut out of Homebase for two years. Instead, they were handed a list of 11 agencies and told to hunt for help on their own.

The aim of the experiment, allegedly, is to find out whether Homebase, a $23 million program, is effective.  The city’s Commissioner of Homeless Services told the Times that

When you’re making decisions about millions of dollars and thousands of people’s lives, you have to do this on data, and that is what this is about.

(If you thought that what it’s about, for a commissioner meant to deal with homelessness, is making sure that people have homes — you were so wrong.  Silly you.)

To make matters worse: what’s being tested is a program whose effectiveness the city has already asserted. As Mike, who blogs brilliantly on this and many related topics at SLO Homeless, notes:  the 2010 Mayor’s Management Report, issued in September, claimed that Homebase helped “ninety percent of clients in all populations receiving prevention services to stay in their communities and avoid shelter entry.”

So, to make sure this is clear:  New York City is deliberately denying a couple of hundred families access to an existing homelessness-prevention program that it has already declared to be highly effective.

The scenario is identical to one that kicked up storms of controversy in the medical-research world in the 1990s (neatly contextualized and summarized here):   experiments were conducted in Africa and southeast Asia supposedly to test the effectiveness  of an already-proven preventive regimen, AZT.  Administered during pregnancy, it reduced the likelihood of mother-to-fetus or mother-to-infant transmission of HIV.  In the poor-country experiments, half of the women enrolled got the effective regimen; the other half got placebo.

In other words, if you were pregnant and infected with HIV and you had had the wisdom to live in the U.S., you got a treatment that protected your infant from infection.  If you lived in a poor country you got:  studied.

There’s something about poor people, and especially about poor women with kids, that seems to make them smell like catnip to the always evidence-hungry technocrat cats.

Want to run a placebo-controlled trial?  Find something that already works (antiretrovirals, homelessness prevention, or, in other circumstances, syphilis treatment, TB prevention, etc.), then find a few women with kids who need it — then tell them you’ll flip a coin.  Heads, they get what they need; tails… well, too bad.

I’m a scientist.  I believe that evidence can be helpful.  Sometimes, it’s crucial.  When you’re truly unsure whether to pick prevention A or prevention B, data can help you to choose right and avoid harm.  That’s the great promise of science.

But sometimes the appeal to evidence is baleful — like here in Bloomberg’s New York, where evidence on homelessness is just a way of furthering the aims of the technocracy.  Which always means that some people will avoid harm.  Others will pay the price.

And the others are, so often, poor women with children.

A Must-Read Book

I urge you to stop what you’re doing and read Rebecca Skloot‘s The Immortal Life of Henrietta Lacks (Crown, 2010).   It’s a rare combination: clear reporting on how medical science works, insightful consideration of deep moral issues about the uses of human tissue for the advancement of knowledge, and a moving, often troubling, family narrative.

Henrietta Lacks died of cervical cancer in the “colored” ward at Johns Hopkins Hospital, in 1951.  From samples of her cervical tissue, the immortal cell line called HeLa was developed (by Dr. George Gey, at Hopkins).  Skloot’s story covers the family’s travails before and since, but also digs deep into the problem of race in the business of American medicine.  Her account challenges, or should move us to challenge, the smug certainties about our supposedly post-racial society, and the convenient formulae about “informed consent” and “access to care.” I guess I should say, The Immortal Life should make us ask just what “care” means in today’s system.

Henrietta Lacks and her family members were almost never taken seriously as humans with real problems.  First, they were poor and uneducated black people from tobacco country relocated to Baltimore; then, they were the bearers of the same genes as a woman (Henrietta) who had died of a remarkably aggressive, and therefore medically interesting, cancer; later, they were background and local color to the story of the origin of the thriving, and therefore scientifically interesting, HeLa cell line.

To Skloot’s credit, she’s taken to heart, and acted on, the problem:  she founded the Henrietta Lacks Foundation to help raise funds for education and medical expenses for Henrietta Lacks’s family.  Skloot’s blog, Culture Dish, carries updates about some of the achievements of the foundation and sometimes takes up issues germane to the book, especially regarding personal rights to genetic information (here, for instance).

It’s also impressive that Skloot interweaves in her narrative (and takes up more fully and explicitly in an Afterword) the vexing question of ownership of tissue samples.  She highlights how the expanding capacity to extract information from genetic sequencing ups the ante on the questions of privacy of tissue samples — since it’s now possible to ascertain potentially identifying information from genetic sequences even in a sample from which the usual verbal identifiers (name, address, and so forth) have been removed.  And she asks how the profits potentially available from exploitation of new discoveries should be shared.

The intersection of these problems with the matter of race makes The Immortal Life of Henrietta Lacks, like James Jones’s Bad Blood and Harriet Washington’s Medical Apartheid, a book that should be required reading for everyone involved in the health sector today.

Bodies Using Bodies

Larissa MacFarquhar’s article on kidney donation in the July 27th New Yorker reminds us that our society remains uncomfortable about the satisfying of bodily needs by making use of other people’s bodies.

This is a good discomfort, no?  Nobody should blithely take advantage of another person, coercing him into donating his organs or making use of her for sexual pleasure without consent.  Watching Stephen Frears’s 2002 film Dirty Pretty Things leaves you appalled and angry at the kidneys-for-passports trade, as it must.  Slavery is an outrage and an offense, a rejection of the values that make ours a civilized society.   Every thinking person decries the trafficking of women for sex.   In modern society, it feels wrong when one person’s body is used to  advantage another’s body.

The exchange of money in the process seems to change the moral valences without exactly alleviating the discomfort.  That children’s families are paid for their manual labor in processing cocoa for the chocolate we eat doesn’t make the practice of child forced labor seem less heinous.  Maybe we even boycott chocolate manufacturers who use chocolate from Ivory Coast, where child labor is involved.  Taking advantage of children’s bodies disturbs us (even to the point of limiting our chocolate purchases).

Money registers differently when it comes to adult sexual exchange.  In the usual American view, there is a bright line between sexual enjoyment obtained through the use or threat of force, and the same enjoyment procured by payment but without force.   Both forcible rape and prostitution are illegal, but most people would recognize a distinct difference between the moral repugnance elicited by rape and the tinge of moral corruption carried by sexual advantage obtained by payment.

Payment introduces a legal twist to sex, too:  the law holds the man who procured sexual advantage through force to be culpable in the act of rape.  Yet, when it comes to paid sex, the legal code holds the woman who provided the sexual service accountable.  The bluenose might scorn both the sex worker and her client equally, but the law makes a distinction.

By contrast, payment makes all the difference when it comes to the use of someone else’s body for productive manual labor.  Your neighbors would be repelled if you were to use force to make a passer-by reshingle the roof of your house, and might have you arrested.  But they aren’t bothered when you hire a roofer.  Most aren’t very bothered when the roofer has some immigrant laborers do the scut work for below-minimum wage — which seems someplace in between a true fee-for-service contract (you in need of a new roof, a roofer able to build one) and slavery.  When money changes hands, it softens the moral impact of making use of someone else’s body.

But the moral flavor doesn’t disappear.  If your roofer refused to let his immigrant workers come down off the roof during a lightning storm, his meager payments to his workers would feel less important than his endangering their welfare.   In other words, onlookers would still be moved by the moral flavor involved in making use of someone else’s body.

Now for the tricky part. What about the use of others’ bodies for medical research? An article in today’s Times laments the shortage of willing bodies for testing cancer treatments.  Contemporary medical ethics presupposes a human trait called “autonomy” and requires that researchers respect this characteristic – for instance by refusing to experiment on a person unless she has signed a consent form acknowledging that she agrees to be experimented on and asserting that she understands the risks and rewards involved.

Of course, the reward system is often obscure, no matter how verbose the researchers are in the process of obtaining consent – in part because it’s often hard to predict who will benefit if new treatments are deemed to be effective, in part because it’s often hard to know how effective a treatment is likely to be, and in part because a big chunk of the benefit accrues to the researchers (articles published, grants funded, awards won) and the research industry (grant funding justified, administrative costs rationalized).

Nobody would accept a system in which people are forced to become medical research subjects.  In fact, the discoveries at Nuremberg about forced participation in medical experiments during the Second World War gave the impetus to the modern field of medical ethics.

But how much does it change the moral outlook if you are rewarded for allowing your body to be used by medical researchers with a cash payment?  The researcher has to be able to claim that her  subjects are not forced to participate – and the medical ethicists who are attached to the autonomy concept will still worry that the subject’s decision to lend his body for research will be coerced, not free and autonomous, if the payment is too grand.

For some classes of people, including children and addicts, payment is deemed to be especially coercive.  The thinking being that if the researcher were to offer $100  to an addict, the addict would use it to buy dope, and that would be harmful, and therefore the researcher would be doing a bad thing even though her research was really meant to do good.   Physician researchers always need to feel that they’re doing a favor to society (not to themselves).

Meanwhile, others decry payments that are too small, arguing that time, angst, and (sometimes) physical or mental suffering involved in being a research subject ought to be reimbursed at respectable rates.   Although the idea of a professional workforce of permanent research subjects, who might receive a retainer in return for surrendering their bodies and tissues for research, rubs physician researchers the wrong way.

Our society really likes medical research. We don’t want our doctors to stop looking for ways to help us to live longer and more comfortably.   Bodies must be used, but they shouldn’t be used without consent, they shouldn’t be purchased outright (that would be slavery), they can’t be paid too much, they shouldn’t be paid nothing, they shouldn’t be recruited for research use in perpetuity or receive the sort of ancillary benefits of employment that professionals get, and they should preferably not be “vulnerable” (young, developmentally disabled, imprisoned, or pregnant).

Which brings us back to kidney donation.  Should kidneys only be allocated anonymously and through a universal system that provides kidneys in accord with a complex algorithm that takes account of the likely benefit of the transplant?  Should there be a federally controlled market in kidneys, or at least some system that encourages donors through market-value incentives (like tax breaks), as Sally Satel has advocated?  Should there be a fully open market through which you could purchase the organ you need from a suitable and willing donor?

The conjunction of bodies-in-service-to-other-bodies and dollars makes the kidney question — like sex work, child labor, and medical research — fraught with moral meanings.  Simple solutions won’t serve.