Executives inside pharmaceutical giant AstraZeneca faced a high-stakes dilemma.
On one hand, Chicago psychiatrist Dr. Michael Reinstein was bringing
the company a small fortune in sales and was conducting research that
made one of its most promising drugs look spectacular.
On the other, some worried that his research findings might be too good to be true.
As Reinstein grew irritated with what he perceived as the company's
slights, a top executive outlined the scenario in an e-mail to
colleagues.
"If he is in fact worth half a billion dollars to (AstraZeneca)," the
company's U.S. sales chief wrote in 2001, "we need to put him in a
different category." To avoid scaring Reinstein away, he said, the firm
should answer "his every query and satisfy any of his quirky behaviors."
Putting aside its concerns, AstraZeneca would continue its relationship
with Reinstein, paying him $490,000 over a decade to travel the nation
promoting its best-selling antipsychotic drug, Seroquel. In return,
Reinstein provided the company a vast customer base: thousands of
mentally ill residents in Chicago-area nursing homes.
During that period, Reinstein also faced accusations that he
overmedicated and neglected patients who took a variety of drugs. But
his research and promotional work went on, including studies and
presentations examining many of the antipsychotics he prescribed on his
daily rounds.
The AstraZeneca payments, filed as exhibits in a federal lawsuit,
highlight the extent to which a leading drug company helped sustain one
of the busiest psychiatrists working in local nursing facilities.
In an interview and in response to written questions, Reinstein said
industry payments he has received for speeches and other engagements
have had no bearing on his research results or patient care. He said he
does not "accept any money from corporations to study their
medications. This eliminates any possible conflicts of interest."
But he does receive money from the Uptown Research Institute, a
for-profit business that conducts industry- and government-funded
studies on psychotropic drugs to help mentally ill patients.
Reinstein's office in Uptown is adjacent to the research institute,
which is owned by John Sonnenberg, a clinical psychologist who
describes Reinstein as "a mentor of mine" and "brilliant."
Sonnenberg said drugmakers and others pay his institute to do research,
and the group, in turn, pays Reinstein a consulting fee of "under
$2,000 a month" and has for many years. A decade ago, Sonnenberg said,
Reinstein was an active researcher for the institute but since then has
served only as an adviser.
"My research organization is separate from him, financially and organizationally," Sonnenberg said.
While payments from drugmakers to researchers are legal, critics have
long argued that they should be publicly disclosed. Legislation to make
Illinois one of a handful of states to require disclosure died in
Springfield this year but is included in the U.S. House and Senate
versions of health care reform proposals.
"We need to know that we can fully trust the relationship we have with
our doctor and that another, more lucrative relationship with industry
does not outweigh it," Sen. Herb Kohl, D-Wis., who is pushing for such
reform, said in an interview.
Health professionals who have encountered Reinstein have had similar
concerns. When he gave promotional presentations about various
medications at Grasmere Place nursing home in Chicago, case manager
Staci Burton recalled that she was pleased to get free lunches. But she
said she wondered why Reinstein put his patients on twice as many drugs
as other psychiatrists who treated residents.
"I was thinking, 'Why are you using so many medications?' " Burton, who
worked at the facility from 2004 to 2006, said in an interview. "(His
patients) would have symptoms, they'd have all these side effects, and
their doctor was not listening."
Psychotropics to lose weight?Chanile Hayes, a South Side
resident, says she came under Reinstein's care at a psychiatric
hospital after she suffered a nervous breakdown nearly 10 years ago.
She found it odd, she said, when Reinstein told her that taking
Seroquel would help her lose weight.
"I couldn't understand why he wasn't taking it because he was a
plus-sized man himself," said Hayes, now 37. She is one of thousands of
people nationwide suing AstraZeneca on allegations it concealed
Seroquel's links to weight gain and diabetes.
While she is a plaintiff in New York state, a federal suit is playing
out in Orlando, Fla. Reinstein is not a defendant in either case, but
Orlando plaintiffs have cast him as a key figure: an influential
promoter of Seroquel who was financially backed by AstraZeneca. They
allege that Reinstein has claimed that the antipsychotic drug helps
patients lose weight.
Hayes said she went from 140 pounds to nearly 300 within two years of taking the drug and later developed diabetes.
Reinstein has done studies, funded by AstraZeneca and two other
drugmakers, that found that various medications, including Seroquel,
carry an unexpected yet welcome side effect: They help some patients
shed pounds.
That claim runs counter to established research that links so-called
atypical antipsychotic drugs, such as Seroquel, to considerable weight
gain. Drugs in this class, approved for schizophrenia and bipolar
disorder, can have other serious side effects that include spastic
movement disorders and seizures and can cause premature death among the
elderly.
A Seroquel flier dated 1999 features a photograph of Reinstein on the
cover. Inside, Reinstein describes one patient losing weight and no
longer needing insulin shots because his diabetes had improved so much.
In a 2001 promotional telecast to 5,000 physicians nationwide,
Reinstein said he had "jokingly kind of suggested to AstraZeneca" that
the drug could be used for "taking away excessive appetite."
"There's actually some nurses in some of our facilities who have
actually requested (Seroquel) because they noticed it really did
suppress the appetite, and they wanted to lose weight themselves,"
Reinstein said, according to a transcript of the speech, sponsored by
AstraZeneca and broadcast from Somerset Place, a Chicago nursing home.
Two years after the speech, the Food and Drug Administration, armed
with mounting research, asked AstraZeneca to warn patients of
Seroquel's diabetes risk. The drug's label now cautions that the
medication is linked to diabetes and weight gain -- with nearly four
times more patients gaining weight on Seroquel than on a placebo.
In his response to reporters, Reinstein characterized Seroquel as
"generally weight neutral, although some patients gain weight and
others lose weight."
"I would never recommend" that patients take antipsychotics "to lose weight," he wrote.
AstraZeneca spokesman Tony Jewell said plaintiffs have not proved that
Seroquel was responsible for their injuries. He said the company, based
in London, provided appropriate safety data about Seroquel to the FDA.
Chanile Hayes, who said she saw Reinstein during visits to his office,
questioned why he prescribed her the drug: "How could you tell me that
it would help me lose weight if it doesn't help (people) lose weight?"
At AstraZeneca, early doubtsIn the corporate halls of AstraZeneca, the company's scientific staff also questioned Reinstein's work.
Copies of e-mails filed as part of the Seroquel litigation in Orlando
reveal executives' misgivings about a Reinstein study involving
patients on high doses of the drug. The results that came back were too
rosy for AstraZeneca's own executives to accept.
One called Reinstein's conclusion that patients experienced no adverse
effects "suspect" and "hard to believe." Executives "decided that we
would ... try to distance ourselves from this study," according to
e-mails from John Tumas, an AstraZeneca publications manager.
Reinstein presented his findings in 2001 at the annual meeting of the
American Psychiatric Association, the profession's most high-profile
gathering. At least three researchers have subsequently cited his study
in medical journals.
During a deposition for the Orlando case, Reinstein said he was unaware of any criticism from AstraZeneca about his research.
But he had some criticisms of his own, according to an internal company
e-mail filed in federal court. Reinstein vented to an AstraZeneca
employee in 2001, saying the firm was giving him the "run around." He
also complained that the company did not help present his research
findings or include him in high-profile studies.
Within days, Reinstein wrote a letter to AstraZeneca's CEO in the U.S.,
identifying him and four doctors he works with as "the largest
prescribers of Seroquel in the world." He said his travel expenses
weren't paid upfront and called for "new leadership" in Seroquel's
marketing.
Reinstein's complaints caused a stir.
In a strongly worded 2001 e-mail, Georgia Tugend, the U.S. brand
manager for Seroquel, told colleagues that research conducted by
Reinstein and his partners "is often criticized by their peers in
psychiatry."
Some scientists have "significant and numerous issues ... with the
quality of research this group has produced in the past," Tugend wrote,
yet Reinstein's group persists in "demanding research grants from us."
At one point, according to an e-mail from an AstraZeneca executive,
Reinstein and his partners had "blatantly threatened" to switch
patients to a Seroquel competitor. Reinstein later denied that
accusation during a deposition, testifying that he "cannot imagine"
making such a threat.
Malcolm May, AstraZeneca's U.S. sales director, reacted to Reinstein's
discontent by saying that the company should be careful not to alienate
a psychiatrist worth up to a half-billion dollars to the firm.
"I am not suggesting we kowtow to his whims, nor to support any
unethical behavior," May wrote in 2001 in an e-mail to fellow
AstraZeneca executives. "I am suggesting ... we need to be more
responsive to his opinion and needs."
May continued: "It seems we are annoying possibly our most important
single customer, and that is not acceptable. ... My concern is that Dr.
Reinstein could be looking for a trigger to leave our fold. That would
be disastrous for our Seroquel business in the short and long term."
May's message did not cite a basis for the half-billion-dollar
estimate. Reached by phone, May said he did not recall sending the
e-mail.
Court documents show that AstraZeneca continued to pay Reinstein to
promote Seroquel until 2007. A Reinstein ledger lists hundreds of
payments beginning in 1997. The payments, in increments from $10 to
$20,000, totaled $490,000.
During that period, Reinstein ordered Seroquel for as many as 1,000
Chicago-area Medicaid patients per year at a total cost of $7.6 million
to taxpayers, records show.
AstraZeneca spokesman Jewell said the company wasn't paying Reinstein
to prescribe its drug but rather to make promotional speeches.
Reinstein and AstraZeneca mutually declined to renew their ties in
2008, but Jewell would not say why.
Reinstein said in an interview that some AstraZeneca officials grew
critical of him only after his complaint to the firm's U.S. chief
executive.
Today, Reinstein said, he gets money from the maker of a dissolvable
form of clozapine, another antipsychotic that he often prescribes. He
said he receives less than $25,000 per year to be in the manufacturer's
speakers bureau, which drug companies commonly set up to promote their
products.
In his deposition last year, Reinstein himself expressed surprise about
some of his research results, saying one study's findings were "hard
for me to believe" -- in line with concerns expressed at AstraZeneca.
When asked about another study in which patients lost weight on
Seroquel, he said the results could have been affected by a change in
the nursing home's cook or possible problems with scales.
In all, Reinstein has published at least eight research articles,
mostly about antipsychotic drugs. He has been cited in at least 20
others. The Uptown Research Institute is now working on eight studies
involving psychotropics, said Sonnenberg, the owner.
Sonnenberg said studies by his institute "are highly scrutinized for
accuracy and credibility" by the drugmakers, third-party ethics review
boards and, potentially, the FDA.
Dr. Jerome Kassirer, a professor at Tufts University School of Medicine
and a former editor of the New England Journal of Medicine, read the
AstraZeneca e-mails at the request of ProPublica and the Tribune. He
concluded that editors of medical journals should investigate
Reinstein's published studies.
"Once you know that he has done a study that has been discredited,"
Kassirer said, "you have to ask yourself about all other studies done."
Sam Roe is a Tribune reporter. Christina Jewett is a reporter for ProPublica, an independent, nonprofit investigative newsroom in New York. Funded primarily by the Sandler Foundation, ProPublica publishes its work at propublica.org and through partnerships with the Tribune and other media.
christina.jewett@propublica.org
sroe@tribune.com