Galileo's Middle Finger (31 page)

This is troubling—OHRP dropping the question of the ethics of the matter. But what is more troubling is that when, in response to OHRP’s inquiries, a Cornell administrator asked New about the pregnant women mentioned in that publication,
New wrote back a curt memo
informing the Cornell IRB rep that, “Prenatal diagnosis and treatment is a standard procedure at the patient’s request and has been performed in France since 1981 and in our lab since 1986.” In other words, she was stating that so far as she was concerned prenatal dex wasn’t experimental—so it didn’t require consent to research. It was “standard” practice given because patients “requested” it.

This, I think, may explain why I can’t find anything, in all the records, indicating actual enrollment numbers for pregnant women in IRB-approved trials of prenatal dex. Although she got IRB approval for fetal research as required to obtain NIH funding,
in practice
, New seems to have treated dex as “a standard procedure [performed] at the patient’s request.” Although
OHRP would later tell us
that “written informed consent (which included disclosure of risks) was obtained from subjects for participations in these studies,” I can’t find any consent forms that appropriately disclosed risks, and I can’t find any direct confirmation of enrollment of pregnant women into consented research for intersex prevention. All we have is
Cornell’s word to OHRP
that they looked into it and nothing had gone wrong. Recall that Cornell’s internal investigation in 2002 also said nothing had gone wrong, and when OHRP came and did a real site investigation, they found much evidence to the contrary.

If Cornell’s IRB administrators had audited their pediatric researchers’ records prior to Sarafoglou’s complaints, they might have picked up that the pregnant women being named in New’s publications might not have given appropriately informed consent to research. But it appears that no such auditing occurred at Cornell’s Children’s Clinical Research Center (CCRC), a unit for which New herself served as director. Via FOIA, I have obtained extensive records and correspondence on IRB review of pediatric research at Cornell during this period, and I can find no reference to any audits—the kinds of inquiries that would have checked to see if people were actually signing consent forms—
until Sarafoglou’s complaints
. The extensive OHRP correspondence resulting from the 2003-2005 investigation also makes no mention of regular internal audits, as one would expect if such audits had occurred. And the previously mentioned
angry whistleblowing memo
specifically decried the complete absence of regular audits, seeming to confirm that no pediatric research at Cornell was being audited during this period to ensure appropriate consent practices:

[New’s IRB protocol] like all the protocols performed in the CCRC has never been through a SAC [scientific advisory committee] review or an IRB audit . . . The Dean’s Office and IRB may indicate to regulatory agencies that Cornell has made “numerous corrective actions” or are “developing new procedures for the IRB” or “initiating an audit program” . . . But these are EMPTY WORDS that do not reflect the reality at Cornell. If Cornell really bothered to perform all the things they say they will when denying charges to regulatory agencies, don’t you think they would have at least properly audited a few protocols in the CHILDREN’S clinical research center, especially protocols begun before 1998.

Whatever she told the mothers, New
consistently led the NIH to believe
prenatal dex was experimental. Odds are NIH wouldn’t have funded it if she’d told them it was standard of care. The portrayal of dex as experimental for grant-getting purposes didn’t change when, shortly after leaving Cornell, Maria New landed herself a position as a pediatric endocrinologist at Mount Sinai School of Medicine, across New York City.
In 2006, in a research progress report
to the NIH from her position at Mount Sinai, New assured the NIH that, even though she had left Cornell, her research on fetuses continued unabated: “The prenatal diagnosis and treatment program has galloped ahead so that we have now diagnosed and[/]or treated 768 fetuses.” She specifically referred to fetuses being “treated” with prenatal dex at Mount Sinai as part of her
research
progress. Because NIH funding requires proof of IRB approval for grant-funded experiments, New got a
letter from the head of Mount Sinai’s IRB
to give to the NIH, indicating Mount Sinai’s IRB had approved the study of “prenatal diagnosis and treatment.” This letter was signed by the
same administrator who told the OHRP
in response to our complaints that there was no fetal experimentation of this kind occurring at Mount Sinai.

It is possible that what happened at Mount Sinai is what I think happened at Cornell: New obtained IRB approval for a study of prenatal dex to show to the NIH, as the NIH would have required to fund her prenatal dex studies, but pregnant women given dex for CAH virilization prevention were, at Mount Sinai, probably treated like patients, not asked to sign consent to fetal research. This seems to be confirmed by what that
Mount Sinai administrator told OHRP
in response to our complaints: “the decision as to whether to treat prenatally with dexamethasone or not was made by the patient and her physician,” not under the auspices of an IRB-approved trial. So even though New very specifically represented to the NIH that these pregnant women and fetuses were human subjects of her research at Mount Sinai, they were probably afforded no protection by an IRB, because they were “just” patients when they were offered dex.

Some might wonder, how did New even manage to get hired at Mount Sinai after the NIH and OHRP investigations of her work at Cornell? Just after she had to relinquish her leadership positions and income at Cornell,
New had written to the NIH
asking for money to support herself under the NIH Merit Award System. New pleaded to her friends at the NIH that, “As I am no longer Chairman of Pediatrics, Chief of Pediatric Endocrinology, and Program Director of the CCRC, I have much more time to devote to the research,” and added, “This is a hard time for me and I am deeply appreciative of your consideration.” Noting that “her circumstances changed abruptly this year when she had to relinquish” her leadership positions “and the salaries entailed in these positions,” her colleagues on the NIH staff “enthusiastically support[ed]” giving her the award and
writing her a big check
. The NIH kept funding her. With a big active NIH grant, and with a brand new Merit Award to her name, Mount Sinai probably saw Maria New as the goose that would keep laying golden eggs. The NIH-Cornell fraud settlement was only announced after New was safely ensconced at Mount Sinai, and by then, OHRP had dropped its questions about her research ethics. So, without any official blemish on her name, she just moved over to Mount Sinai and “galloped ahead” on prenatal dex. Continuing to advertise the intervention as “having been found safe for mother and child,” she drew in more and more families to her relocated clinic. Because she had so many more CAH-affected research subjects than anyone else, the NIH kept funding her. According to one medical school administrator who looked at what I found (one to whom I happen to be married), Maria New seems to have invented a
perpetual motion machine
of NIH funding.

I think it is fair to summarize what happened this way:
The pregnant women given dexamethasone under Maria New’s guidance may never have understood they were in a high-risk experiment, and the NIH may never have understood they weren’t.
Most of the pregnant women, like those who told their stories to the
Time
reporter, probably thought they were taking a drug that was safe and effective, not experimental. And the NIH, being shown by New the official IRB approval for her studies and being told about the “progress” of fetal treatment research, probably assumed that all the women were being actively enrolled in careful experiments that would be meticulously overseen by the medical schools’ IRBs. Because the medical schools’ IRBs appear never to have audited New’s practices—at least until the investigations at Cornell—they do not seem to have been keeping careful track of what was going on.

It is quite possible that the problem of blurring the line between clinical care and human experimentation in Cornell’s pediatric unit went beyond Maria New. Internal minutes from Cornell’s IRB show that, after Sarafoglou raised the alarm, a member of the IRB who had simply been signing off on New’s annual renewals said this: “one of the issues the Program Review Committee is reviewing is the blurring of patient care vs. research and whether patients are being told which procedures are part of their care and
which are part of the research
.”

 • • • 

T
HAT’S WHAT
I
NOW
BELIEVE
happened with New’s work on prenatal dex. Given that I was able to figure all this out—given that I learned all this chiefly through obtaining government records through the Freedom of Information Act (FOIA)—why didn’t the government do something when we made our complaint in 2010? That is a tale in and of itself.

Recall that it was late 2009 when my allies called me to help. In February 2010—not realizing there had ever been an OHRP investigation into New’s work on prenatal dex—Ellen Feder, I, and thirty of our colleagues appealed to the FDA and OHRP.

About three months later,
AJOB
released the target-article manuscript by Larry McCullough and Frank Chervenak attacking us as “unethical” and “transgressive” for our calls for a federal investigation. FOIA confirmed that, as I had suspected, Larry McCullough had sent the
AJOB
manuscript to OHRP while that agency was deciding what to do with our complaints. In his cover letter,
McCullough told OHRP
, “We hope that your [
sic
] will take our critique into account in your deliberations.” None of the authors’ conflicts of interest were disclosed to OHRP. For the target article, McCullough listed Baylor College of Medicine as his only affiliation. As it turns out, he also had two other active, paid faculty positions:
at the medical schools of Cornell and Mount Sinai
. The Cornell chair of Obstetrics, Frank Chervenak, coauthor of the target article, did not mention to OHRP that he had
served as “key personnel
” on Maria New’s NIH grant.

After receiving our letters of concern, the FDA gave the job of the prenatal dex investigation to a physician-ethicist named
Robert “Skip” Nelson
. As I figured out much too late to do anything about it, not only was Nelson serving on the
AJOB
editorial board (with Larry McCullough), but he was also actively
negotiating a new
AJOB
journal editorship in chief
for himself, for a new offshoot journal called
AJOB-Primary Research
. Just to be clear, he was in negotiations with
AJOB
while
he was running the federal investigation that
AJOB
was being used to undermine. Nelson’s new editorship came with a fancy title and ten thousand dollars a year,
to hire an editorial assistant
. In the e-mail exchange in which he informed his ethics supervisors that he was planning to accept this position with
AJOB
, Nelson said he hoped it would allow him to get an adjunct faculty appointment at Georgetown University’s ethics unit, but never mentioned what role the journal was playing in the FDA investigation he had been given to run. Remember the “coincidence” of
AJOB
officially publishing the McCullough et al. target article just as the federal findings were made public? E-mails discovered via FOIA suggest that Nelson, by then working for both FDA and
AJOB,
was keeping track
of when the federal findings would be released.

Nelson’s behaviors would be less concerning if what he had represented in his official findings had been factually accurate. In one of the most important revelations of the whole federal investigation, in the name of the FDA,
Nelson had told everybody
that Maria New sought and obtained an IND (investigational new drug) exemption from the FDA in 1996 for a study using prenatal dexamethasone to prevent virilization in female fetuses. This would have meant that way back in 1996, a high-ranking physician at the FDA had reviewed the intervention and had formally decided that it was not risky enough to require significant FDA review before proceeding.

This seemed almost impossible—the FDA giving a pass on an experiment
meant
to try to change fetal development, with seven of eight fetuses deriving no possible benefit? When Nelson made the claim in 2010, we all believed it. When I obtained a copy of
the 1996 exemption letter
, however, I found that it actually refers to a very different thing. It refers to a proposal from Maria New “to utilize dexamethasone to treat pregnant women with a [
sic
] congenital adrenal hyperplasia.” Based on this wording, it looks quite possible that what New was proposing to the FDA in 1996 was to use dexamethasone on pregnant women who
themselves
had CAH; women with CAH often need to have their disease treated during pregnancy, to maintain their own health, and dexamethasone can be used to treat the disease. In other words, the exemption was probably not, as Nelson claimed, for a study of “the administration of dexamethasone during pregnancy
for the purpose of preventing virilization
in females with congenital adrenal hyperplasia.” It appears to have been meant for a study of using dexamethasone during pregnancy
for the purposes of maintaining the health of pregnant women who themselves had CAH.
That’s presumably why the physician at the FDA didn’t flip out at what New had proposed to do
without full FDA review
. What was most likely being proposed wasn’t a fetal engineering experiment!

When I contacted the physician who had signed the letter back in 1996, he had
no recollection of the matter
. But for his part, in 2010, Nelson knew full well there was no documentation to support his public misrepresentation of the letter. In internal communications, Nelson told OHRP staff that the single vague FDA letter was the only record of all this, so they could know no more than what the letter said. He explained to OHRP that any related documentation (which would have explained exactly what New had proposed) had been
shredded during an FDA move
. But in his 2010 memo to OHRP and the public, rather than providing what the IND exemption letter actually said—that New had been given an exemption to study “dexamethasone to treat pregnant women with a [
sic
] congenital adrenal hyperplasia”—he made it look as though the FDA had already reviewed prenatal dexamethasone for virilization prevention in 1996 and had found it to be nothing especially concerning.