Friday, November 5, 2010

The Tuskegee Mentality: Condemning Antiretroviral Treatment for ME/CFS

Guest post by Larry Gilman.

In the latest issue of The Journal of Infectious Diseases, Drs. M. Kearney and F. Maldarelli (K&M) have “strong words,” as Paul Sax puts it, for doctors prescribing antiretrovirals for XMRV/MLV-positive ME/CFS patients.  K&M write:
At this time, such an approach is premature and medically indefensible outside the secure oversight of a well‐controlled clinical trial. “Real world” coping with severe diseases like chronic fatigue syndrome and prostate cancer creates understandable desperation on the part of patients, caregivers, and health care professionals. Such pressures are not justification for testing of therapies in an uncontrolled manner. Indeed, because they are of no help whatsoever to other patients, physicians, pharmaceutical companies, or regulatory agencies, such uncontrolled therapy works directly against the goal of providing effective therapy to the million or more individuals experiencing these serious conditions.
Unfortunately, this righteous reprimand is riddled with fallacies.

(1) Off-label prescription of drugs (prescription for conditions not named in FDA approvals) is legal and common. One can slight such usage as “uncontrolled” — and it is, in the rarified sense that it is not overseen by an Institutional Review Board (as it would be in a research trial) — but it is not necessarily unreasonable, unethical, or ineffective.

(2) It is also normal to prescribe therapies despite uncertainty about whether they will work for a given patient.  Even approved treatments always carry some burden of uncertainty.  It is clearly defensible to attempt any therapy for any patient if an informed judgment has been made jointly by patient and doctor that the likely benefits outweigh the risks.  K&M, in condemning ad hoc treatment of retrovirus-positive ME/CFS with antiretrovirals found effective in vitro, imply that flawed risk-benefit judgments are being made.  But in which cases?  Flawed how?  They haven’t said.  Nor, so far as I know, has any other critic of these efforts.

(3) Observations of statistically insignificant numbers of patients (e.g., clinical experience, pilot studies) often inform the design of large, rigorous studies.  Far from preventing or impeding scientific studies, small-scale experience commonly stimulates them.  Every rigorous study begins with an educated guess; clinical experience with small numbers is often part of the education.  Researchers should try to learn from the nonsystematic but clinically reasonable use of antiretrovirals with ME/CFS, not shame it out of existence.

(4)  It is not true that ad hoc treatment of a few patients with particularly dire ME/CFS outside of randomized, controlled clinical trials “works directly against the goal of providing effectual therapy” to other patients.  The number of patients receiving ad hoc treatment — even if it grew to the tens of thousands, which it seems unlikely to do — is far too small to impede the conduct, now or later, of large, strictly designed trials, which have an ME/CFS population of at least a million (judging by CDC studies) to draw from in the US alone.  K&M do not say how, they think, scattered ad hoc efforts will impede research — and I don’t think they can. The vanishingly tiny fraction of ME/CFS patients that receives antiretroviral treatment will simply be excluded from studies using such drugs, with no harm done.

(5)  Most seriously, K&M—like other critics of ad hoc treatment — seem to me to confound research ethics with clinical ethics.  Researchers are obliged to gather the most objective, accurate scientific knowledge they can while doing, so far as is humanly possible, no harm: clinicians are obliged to do all the good they can for the people in their care, period.  In the clinic, only the individual patient’s well-being, not the advancement of science, may be consulted.  The patient has a right to demand, and the doctor a duty to provide, any treatment that in their joint judgement may improve the patient’s overall condition.  Far from being obligatory, it is forbidden for a doctor to consider the advancement of science in deciding whether to withhold any reasonable therapy from a patient who wants it.  The idea that patients must—or even may—be denied treatment in order to advance science is nothing short of a Tuskegee mentality.  Thus, even if it were true that ad hoc antiretroviral treatments are somehow impeding rigorous research (which they aren’t), it would still be unethical to urge the blanket denial of such treatments for the sake of the research.

Strong words, yes—for radically wrongheaded condemnation of the treatments now being attempted. 

The ethical shoe is really on the other foot.  Doctors prescribing antiretrovirals for retrovirus-positive ME/CFS are making a reasonable attempt to help very sick patients.  Those who argue that doctors should never do any such thing because it might somehow (how?) slow the gathering of scientific knowledge show a disturbing tendency to view patients as a source of scientific information, rather than as people deserving the best care possible—even in the midst of uncertainty.


My essay comparing the recent controversy over XMRV/MLV to an earlier controversy in bioscience, the maize transgene flap, is here.  I blog sporadically on science-related issues here.  Professional website here, religion-and-science blog here


  1. If I had been under the so-called "care" of Drs. K&M, for example...I wouldnt be READING this excellent post..let alone COMMENTING on what I'd read! Prior to my "experimental" 5 yr. treatment with high dose/long term Acyclovir (under the supervision of the compassionate Dr. John Chia) my ME/cfs cognitive and memory deficits were so pronounced that I couldnt read the label on a box of oatmeal! I wasnt part of any clinical controlled study (and, in fact, the drug I used received dismal results in a few "controlled" studies!)...yet I doggedly continued to take it, reporting any "anecdotal" improvements versus side effects...hoping that any gains I experienced might somehow benefit others struggling with ME/cfs. And look at me now! I intend to do the same with Antiretrovirals. One person at a time, attempting these treatments/therapies (however agonizingly slow and sometimes futile it seems)...WILL amount to a step forward for the rest. I have to believe that. But we MUST be given the chance. AND...the support!

  2. Thank you Larry Gilman, and this blog, for a brilliant exposee of Dr Sax - and his colleagues'- flawed logic. Bravo!

  3. Thank you for this post, Larry. I am so glad you are responding to the unsubstantiated assertions of these critics of antiretroviral therapy. The sooner ARV's become available for people with XMRV, the happier I'll be.

    Patricia Carter
    XMRV+, 24 years ME

  4. I wonder why they bothered...vested interests? Patent protection?

    I believe all "holds" on treatment are connected to other scientists trying to find a way to get a patent on a new process rather than using the WPI's.

    Follow the money.

  5. Couldn't agree more. Drs K & Ms’ comments reveal their lack of appreciation of the issues for doctors and their patients and are also breathtakingly hypocritical. Exercise therapy and drug experimentation has been the norm for decades with this illness! Exercise is still being prescribed in spite of the huge body of evidence that it is harmful, and every drug prescribed in an attempt to control the symptoms is in effect an experiment as no clinical trials have been carried out in connection with any of these drugs on ME patients.

    So why all the boo hooing about using ARVs to treat a retrovirus? ARVs are possibly the most well studied class of drugs in existence. All drugs have side effects. That's a given. It's for treating clinicians to decide if the possible benefits to the patient outweigh the side effects.

    Their comments merely reveal the low status and contempt that people with this illness are held in. If they think that seriously ill people and the doctors who witness their suffering firsthand are going to put the welfare of the world at large before a chance at recovery from the first real treatment on offer, I’m afraid they must have lead very sheltered lives. They have many more disappointments ahead of them in life if this is really their thinking. The doctors, scientists and government agencies who hold this view of ARV use in ME need to look at the reality of the situation they are faced with, not what is ideal. Best case scenarios are unrealistic and indeed inappropriate here. Every day, month and year they delay clinical trials the possibility of the situation that they fear occurring – uncontrolled ARV use – increases exponentially. I say to them what I would say to anyone faced with such a solvable situation: do something about it.

  6. BRAVO Larry and EXACTAMUNDO Lisa ~

    That's WHY I am SO worried about the supposed
    co-incidence of what I saw happening with the Tran-Atlantic attack on drugs that we are allowed to take. If you don't know what I am referring to please read my latest post #93 about the USA: FDA and "the Park Doctrine" and their attempt NOW to bring "criminal charges" against the CEO's of Big Pharma whose drugs are used "off label."
    Thx from another 23 yr ME/CFS with OI/POTS

  7. Thanks to everyone for their testimony and excellent points. Yes to the 10th to Lisa's point that _everything_ being done for ME/CFS patients is "experimental" in exactly the same sense that antiretrovirals are -- only without, in many cases, the clear chain of logic supporting antiretroviral therapy (virus association with disease + positive test for virus + in-vitro efficacy of drug against virus).

    Thank you for reading!

  8. Thank YOU for your excellent post Larry. This is the kind of public comment we need to see more of.

    This blatant hypocrisy over the use of ARVs needs exposing for what it is - under-researched, unsupported, unwarranted scaremongering, and further evidence (if it's needed) of the denial of appropriate medical care and respect afforded ME patients. A year on and with not a clinical trial in sight it should be viewed for what it is - criminal neglect.

  9. Before they pin the XMRV tail on this theory of viral causation, they need to explain the proposed means of transmission.

    The first recorded outbreaks of what became known as "CFS" occurred in Incline Village, NV, upstate NY, and Miami, FL in the middle 1980's -- unless these cohorts had some previously undisclosed contact with each other, then what is being proposed is an airborne retrovirus, an entity that is unknown to date. I smell a rat.

  10. I do not agree that transmission must be explained in order to establish causation. I am not a virologist -- or even a biologist -- but, logically, one could establish that a virus causes disease without knowing how the virus gets into people. If you go to the emergency room with stomach pains and X-rays reveal a tenpenny nail in your gut, and the pain resolves with removal of the nail, cause of the pain has been pretty well established -- never mind why you ate the nail.

    Besides which, I do not think that any researcher on XMRV and related viruses has suggested airborne transmission as the sole or foremost possibility (if they have mentioned it at all). Consider Epstein Barr virus: ~95% of adults have it, but it is transmitted through contact with saliva, not through the air ( ). Endemicity and rapid spread do not require airborne transmission.

    As for when XMLV and related viruses entered humans, it's anyone's guess -- but probably long before the 1970s. HIV probably entered humans before World War II, decades before it went epidemic ( ).

    We shouldn't jump to conclusions. Whenever a point seems commonsense or obvious, all the more reason to double-check our reasoning and facts.


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