Antivaccination warriors vs. research ethics

It's been a very interesting week for those of us who try to keep an eye on antivaccination warriors who scare mothers with claims based on either no science or bad science of dire consequences that will come from vaccinating their children.

A very interesting week indeed, kind of like that old curse, "May you live in interesting times."

Last week, eight years after his study that set off scare whose repercussions continue even now, Andrew Wakefield was finally called to account for professional misconduct for unreported conflicts of interest and highly unethical and unprofessional behavior. As you may recall, his now discredited study (from which 10 of the original 13 authors have sought to disassociate themselves) claimed to find a link between the MMR vaccine and autism, as well as inflammatory bowel disease. At least that's how it was represented by the antivaccination crowd. In fact, it showed nothing of the sort, so shoddily was it performed. Britain's General Medical Council has drawn up preliminary charges that he published "inadequately founded" research; failed to obtain ethical committee approval; obtained funding "improperly" (specifically, from lawyers representing "vaccine-injured" litigants); and subjected children to "unnecessary and invasive investigations." Basically he did colonoscopies on children who probably didn't need them in order to get tissue specimens to test for the measles virus, without obtaining proper ethical approval, nor did he disclose when he published his results that he had applied for a patent for a single jab vaccine for measles that would have been highly profitable if MMR was abandoned.

Wakefield's "results" and his charismatic selling of his results to the British public resulted in a dramatic drop in vaccination against measles, mumps, and rubella, resulting in a serious measles outbreak in the U.K., with the number of measles cases having risen to levels not seen in 20 years. Overall vaccination rates have fallen to just under 90%, and in some parts of the U.K., as low as 77%, far below the rate needed to maintain herd immunity, and the U.K. has seen its first death from measles in 14 years. And it's all because of Wakefield. As Christina Odone put it in a recent editorial White Middle Class Mums. And Their Stupidity Could Kill Your Child::

Measles can kill, mumps can lead to infertility and deafness, and a pregnant woman infected with rubella has an 83 per cent chance of giving birth to a child with some deformity. Yet parents such as her get away with it. They are middle-class and clean-cut, well meaning and well spoken. We indulge them because they assure us, ever so eloquently, that they are motivated by parental love. We cut them slack because we are convinced that even irrational fear, when in such cosy packaging, cannot have dangerous consequences.

We are wrong. Last week the Health Protection Agency reported the worst incidence of measles in 20 years. Three months ago the first child in 14 years was killed by the virus. Pockets of infection have surfaced in Surrey and in Yorkshire. We face a real health scare, because rogue parents fell for a bogus health scare -- the one linking the MMR vaccine to autism.

It is eight years since Andrew Wakefield began agitating against the MMR jab. In that time he managed to persuade hundreds of thousands to keep their children from taking part in the immunisation programme. Dr Wakefield, a former gut surgeon, was an extraordinarily convincing spokesman: when he made public his claims at a press conference at the Royal Free he throbbed with messianic ardour and heartfelt concern for those poor innocents whom the State wished to inject with poison.

When he faced critics who pointed out that he built his thesis on a skewed sample of only 12 children, he played the medical martyr who risked his career for the good of others.

Ms. Odone gets Orac's very first Respectful Insolence Award for outdoing even Orac himself and making him wish he'd said that.

Sadly, now on our side of the pond, it's looking more and more as though we have our own version of Andrew Wakefield. Except, lucky us, it's not just one person, but rather a father-son team of mercury maniacs who blame vaccines other than the MMR for autism. (Note that MMR doesn't and has never contained mercury.) Instead of waving their hands and invoking vague immune reactions from MMR as a cause for autism, as Wakefield does, they wave their hands and blame the mercury in the tiny amount of thimerosal used to preserve vaccines (using horrifically bad statistics to make their case), then, when the evidence seems to be indicating that mercury is not the cause of autism, start waving their hands even more and claiming that testosterone somehow "potentiates" the toxicity of that mercury and that shutting down all sex hormones with with a powerful drug called Lupron is the way to treat autistic children. Then they try to patent their dubious therapy.

Yes, it's Mark and David Geier.

Again.

Recently, Kathleen Seidel reported how David Geier misrepresented himself as being affiliated with George Washington University on several papers. I found such a misrepresentation distasteful and dubious, but what Kathleen's discovered now makes that little impropriety pale in comparison. In essence, the Geiers formed their own Institutional Review Board (IRB) to review their own studies. The IRB reported as having approved their most recent study, the one I deconstructed last week was from an entity listed as The Institute for Chronic Illnesses. As Kathleen reports, it's an elusive institute whose address is the same as that of Dr. Mark Geier's residence. (I wonder what the neighbors think of his doing biomedical "research" in a residential neighborhood.) It also has a lovely tennis court. But, elusive or not, it does have its own IRB, and that IRB is actually registered with the federal government. Leave it to Kathleen's tenacity to track down through a Freedom of Information Act request some information on this particular IRB. What she found is very disturbing indeed.

In order for you to understand why what Kathleen discovered is so disturbing, a word is in order about just what an IRB is and does (or should be and is supposed to do). After the horrors of Nazi medical experimentation and the abuses during the Tuskegee syphilis study right here in the good ol' USA, it was clear that rules were needed to protect human research subjects from such abuses. A historic document in the development of such rules in the U.S. was the Belmont Report on Ethical Principles and Guidelines for the Protection of Human Subjects of Research finalized on April 18, 1979. This report identifies three essential and fundamental ethical principles for human subject research (respect for persons, beneficence, and justice) that form the basis of all Department of Health and Human Services human subject protection regulations to this day. It is essential reading for anyone doing human subject research in this country. In 1991, these regulations were codified into what is now known as The Common Rule. All institutions doing federally funded research are required to adhere to The Common Rule. Moreover, some states, such as Maryland (where the Geiers have their businesses) require that all human research, regardless of funding source, must conform to the Common Rule.

A key aspect of The Common Rule is the IRB. The IRB is in essence a committee that oversees all human subject research for an institution and makes sure that the studies are ethical in design and that they conform to all federal regulations. Basically, IRBs are charged with weighing the risks and benefits of proposed human subject research and making sure that (1) the risks are minimized and that the risk:benefit ratio is very favorable; (2) to minimize any pain or suffering that might come about because of the experimental therapy; and (3) to make sure that researchers obtain truly informed consent. Once a study is in progress, regular reports must be made to the IRB, which can shut down any study in its institution if it has concerns about patient welfare. Indeed, the IRB at my particular institution is like a bulldog; it's utterly ruthless in how it deals with researchers. The same is the case at most institutions that receive significant federal funding, and these are the criteria for approving a study:

(a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied:

(1) Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

(3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.

(4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by �46.116.

(5) Informed consent will be appropriately documented, in accordance with, and to the extent required by �46.117.

(6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

(7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

(b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

It sounds pretty clear-cut. And, from discussing studies with members of different IRBs, I know that good IRBs take the above guidelines very seriously, almost always erring on the side of being more protective of human subjects. (If you're interested in learning more about federal human subject research guidelines, check out this course.) Now here's where it gets even more interesting. The membership of an IRB must be at least five persons according to these guidelines:

a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects.

(b) Every nondiscriminatory effort will be made to ensure that no IRB consists entirely of men or entirely of women, including the institution's consideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender. No IRB may consist entirely of members of one profession.

(c) Each IRB shall include at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific areas.

Well, guess who's on the IRB of the Institute for Chronic Illnesses? If you've clicked on the link to Kathleen's article you already know, but for those who haven't done so yet, now's a good time to do so:

Mark Geier, Chair
Affiliated Scientist; MD, PhD; Genetics

David Geier
Affiliated Scientist; BA; Biochemistry

Lisa Sykes
Unaffiliated Non-Scientist; MA; Clergy (Rev. Sykes is a Richmond, Virginia Methodist minister, anti-thimerosal activist, and mother of a participant in Dr. Geier's study. The clinical data for Patient #1 in the Hormone Research article is identical to data from her son's medical records, which were displayed at the 2005 and 2006 Autism One conferences.)

Kelly Kerns
Unaffiliated Scientist; RDH; Dentistry (Mrs. Kerns is a Lenexa, Kansas dental hygienist, anti-thimerosal activist, and petitioner in vaccine injury complaints for each of her three autistic children.)

John Young
Unaffiliated Scientist; MD; OB-GYN, Genetics (Dr. Young is Dr. Geier's business partner in Genetic Consultants of Maryland and Genetic Consultants of Virginia; he, Dr. Geier and various business entities were codefendants in a 1994 medical malpractice lawsuit.)

Anne Geier
Affiliated Scientist; BS; Educator (Mrs. Geier is wife of Dr. Mark Geier and mother of David Geier. She is a ranking member of the U.S. Tennis Association.)

Clifford Shoemaker
Affiliated Non-Scientist; JD; Legal (Mr. Shoemaker is a vaccine injury lawyer, a member of the Vaccine Injury Alliance, and a member of the Omnibus Autism Proceeding Petitioners' Steering Committee. Dr. Geier has testified on behalf of his clients in Price v. Wyeth et al, Platt v. HHS, Jenkins v. HHS, Lewis v. HHS, Raj vs. HHS, Jefferies v. HHS, and other cases.)

Holy conflict of interest, Batman!

Notice how conveniently every single member of this IRB is either one of the Geiers, an anti-thimerosal activist, a Geier associate, or a lawyer suing on behalf of "vaccine-injured" clients. Anyone want to make a bet about how closely they adhere to the guidelines for human research listed above? It almost doesn't matter anyway because, as Kathleen points out, besides the fact that none of the members of this IRB has any expertise in endocrinology, Mark and David Geier would not be eligible to debate or vote on their own protocols anyway; Anne Geier wouldn't be eligible to vote because of her relationship to Mark and David; and Lisa Sykes wouldn't be eligible to vote if her child is to be a subject in the research protocol being reviewed. And does anyone really think that any of the other members of this particular IRB has research subject protection as his or her overriding concern?

But it doesn't end there. If the FOIA information that Kathleen has obtained is complete, then it looks as though the research reported under the auspices of this IRB was done before the IRB of The Institute for Chronic Illnesses was even registered with the federal government. It is hard not to strongly suspect that the Geiers were told by someone while submitting their paper that human subjects research had to be approved by an IRB and that no reputable journal would publish such research without a statement to the effect that the research encompassed in the manuscript had been approved by an IRB.

So there we have it. In the U.K., there's Andrew Wakefield likely being brought up on charges of scientific misconduct, and here in the U.S. we have the Geiers playing fast and loose with human research subjects protections, all in the name of implicating vaccines as a cause of autism on the basis of very poor science. The ironic thing to me is that the alties and mercury moms who castigate big pharma for supposedly not protecting patient welfare and of having engineered a massive conspiracy to keep the "truth" from being found out will likely give both Wakefield and the Geiers a pass. Indeed, certain alties are vociferously defending Andrew Wakefield and painting him the "victim" of an "evil empire" (presumably us members of eeevilll conventional medicine) conducting a witch hunt.

I'm sure it won't be long before we see such articles defending the Geiers. After all, they're on the side of good and right and don't need such pesky rules to make sure that they act in the best interests of autistic children, right?

Please, read all of Kathleen's report An Elusive Institute and judge for yourself.

More commentary:

Mark and David Geier Carry On Misrepresenting
Fun and Pretense chez Geier
Mark Geier, David Geier, and an IRB