Science - USA (2020-10-02)

SCIENCE sciencemag.org 2 OCTOBER 2020 • VOL 370 ISSUE 6512 29

clinical trials—or on any specific cases de-

scribed in the Science investigation.

“FDA is just dropping the ball here,” says

Carome, a former research regulation execu-

tive at the Department of Health and Hu-

man Services. “I think the institution should

have gotten a very strong warning letter for

the [latter] ketamine trials, and that letter

perhaps should have noted the prior history

with Dr. Driver, to signal a systemic problem.”

By not coming down hard on IRBs and

the scientists running clinical trials, FDA

lets those parties avoid possible negligence

lawsuits or other legal liability if patients are

harmed, Prasad says. He adds that the lack

of enforcement also lets the drug companies

sponsoring the trials off the hook. “FDA is

a regulatory agency charged with protecting

the public’s best interests. But at times

it behaves like an attorney working on

behalf of the companies.”

SLOW-MOTION DISQUALIFICATIONS

For the most extreme violations of rules

governing human subjects research,

FDA can brandish the threat of a pub-

licly announced disqualification—effec-

tively the death penalty for a clinical

research career. But how the agency

has used that sanction captures many

flaws of FDA’s clinical trial oversight.

Since the beginning of Obama’s pres-

idency, the agency has disqualified just

24 clinical trial investigators, mostly for

deliberate and repeated falsification of

data or other information such as pa-

tient referrals for a trial. And although

disqualification bars a scientist from re-

ceiving any experimental drug or device

or conducting any trial involving FDA-

regulated drugs or other substances,

it can sting less than it sounds. Drug

companies often continue to lavish money

and prestige on disgraced investigators (see

sidebar, p. 27).

Investigators under a cloud also can con-

tinue to run lucrative trials while FDA con-

siders whether to disqualify them, a process

that takes, on average, more than 3 years.

Scientists or IRBs facing FDA accusations,

including those that ultimately lead to dis-

qualification, have collectively conducted or

overseen thousands of trials during the past

decade, Science found in a review of public

records. Take Oregon allergist-immunologist

James Baker, one of only two disqualifica-

tions by Trump’s FDA.

Between 2009 and 2017, FDA inspected

Baker-led trials on four occasions and each

time found violations. Time after time,

Baker promised to do better, according to

agency documents. Again and again, he

broke his promises, FDA documents con-

clude. The agency, however, waited until

2018 to disqualify him.

Baker’s abuses were not mere technicali-

ties. FDA said they “placed unnecessary risks

to human subjects and jeopardized the in-

tegrity of data.” Inspectors found informed

consent breakdowns involving children and

adults—some of whom were injected with

experimental allergy or immunology drugs

or biologics despite taking other drugs, such

as cough medicine and antibiotics, that

could interact with them. He failed to prop-

erly document or follow up on a child’s emer-

gency department visit for severe abdominal

pain. People were enrolled against eligibility

rules—with some participating in more than

one trial, for example, or having conditions

that should have disqualified them. FDA said

Baker kept substandard case histories, over-

dosed patients on experimental medicines,

and repeatedly conducted trials without IRB

approval. Baker conceded to agency inspec-

tors that one of his employees, who had no

relevant medical credentials, prescribed

drugs to trial volunteers. She worked on

30 of his trials.

FDA finally disqualified Baker after he

was caught backdating many clinical trial

reports beginning in 2013. The records indi-

cated he performed patient exams in Oregon

when he was actually in Las Vegas, Hawaii,

and elsewhere attending medical meetings

and, in one instance, a wedding. (FDA in-

spectors had earlier caught him similarly

falsifying records in 2015, when he admitted

he had “gone fishing” on days he purportedly

saw trial patients.)

FDA documents show Baker conducted

at least 115 clinical trials from 2005 until

2017, often testing drugs for which compa-

nies later sought agency approval. Yet his

disqualification stemmed from FDA’s review

of just a few of those trials. Not long before

his disqualification, the agency asked Baker

whether any data or patient records had also

been doctored in his other completed trials.

Baker said he lacked the capacity to review

those studies. As far as Science could ascer-

tain, FDA did not investigate the other trials.

Baker declined to say whether he had in-

formed participants in his many trials that he

had been disqualified. Science also contacted

multiple companies that sponsored Baker’s

trials during the period for which FDA found

falsified information. Asked whether they

told trial volunteers about the government’s

findings, none responded.

Baker, who declined to answer most ques-

tions submitted by Science, contended in an

email that his patients suffered no ad-

verse events. But he also added: “I agree

with [the] way the FDA controls the re-

search world and regret running afoul

with those studies.”

Had FDA acted earlier, Baker’s clini-

cal trial venture—the Baker Allergy,

Asthma and Dermatology Research

Center—might have lost a lot of busi-

ness. The French drug giant Sanofi

and other companies paid him at least

$1.2 million for trials conducted be-

tween the time FDA detected his fal-

sified exams in 2016 through 2019,

according to the federal Open Pay-

ments system, which tracks pharma-

ceutical industry payments to doctors.

Yet the work kept flowing from

Sanofi to his research business even

after he was disqualified. Sanofi as-

signed responsibility for Baker’s trials

to another doctor at his center, which

Baker operated with his dermato-

logist wife in the same building as

their medical practice.

Likewise, the disqualification leaves Baker

free to operate his other company, Xtract

Solutions, a suburban Portland, Oregon, pur-

veyor of allergy and immunology technology

to hospitals and physicians. In 2014, FDA is-

sued a warning letter to Baker and Xtract for

allegedly selling “adulterated devices” and

failing to establish and maintain quality-

control procedures for its syringe-filling

systems—meant to speed up vaccinations

during pandemics.

Xtract eventually dropped its injection

device. But the company still sells software

to guide doctors and hospitals on a subject

Baker has ample experience, if not always

success, with: FDA regulatory compliance. j

With reporting by Meagan Weiland. This story was

supported by the Science Fund for Investigative

Journalism. For more on how the story was reported,

see http://scim.ag/FDA_Methods.

James Baker is one of just two scientists disqualified from U.S.

clinical research by FDA during President Donald Trump’s first 3 years.

PHOTO: CLOUDSHINE MEDIA, “BAKER ALLERGY, ASTHMA & DERMATOLOGY (COVID-19 SAFETY),” 2 APRIL 2020/YOUTUBE.COM