GIST: "In
January 2000, a paper was published in a respected academic journal
that trumpeted the successes of a Canadian lab in a burgeoning area of
drug testing.
The researchers who wrote the paper claimed they had
analyzed strands of hair to trace long-term exposure to illicit drugs,
such as cocaine, and used gold-standard testing to verify its results. What
everyone failed to notice — from the medical institution where the lab
was housed to the federal agency that funded the study to the journal
that published the article — was that the gold-standard claim was a lie. In fact,
Dr. Gideon Koren’s Motherisk lab at The Hospital for Sick Children rarely confirmed its results with gold-standard testing before 2010. That
lie was exposed in 2015, amid a scandal that tore apart vulnerable
families and prompted two government-commissioned inquiries, which found
Motherisk made millions selling its hair tests for use in criminal and
child-protection cases despite the fact that it often failed to verify
its preliminary results. This was contrary to international forensic
standards for evidence presented in court. Three
years later, the article that was published in Forensic Science
International still stands, uncorrected, polluting the scientific
literature.
The
paper has been cited 54 times, as recently as May 2017. The journal
told the Star this week that it will be “looking into these issues.” Citations — when other researchers cite the study as a reference in their published work — are an indication of its influence. A
researcher’s publication record is the currency of modern-day science.
It is the pre-requisite to securing competitive tenure-track positions
at prestigious universities, the key to unlocking funding and the
measure by which research institutions are assessed. But it is a moment of reckoning for medical publishing. Last week, Sick Kids, which housed the Motherisk lab,
announced it will undertake a wholesale review
of Koren’s vast body of published work, after the Star presented the
hospital with findings from this investigation that identified what
appear to be problems in more than 400 of Koren’s papers, including the
Jan. 2000 hair-testing article, collectively cited more than 6,000
times. These papers appeared problematic because they have been
inadequately peer-reviewed, failed to declare, and perhaps even obscure,
conflicts of interest, and, in a handful of cases, contain lies about
the methodology used to test hair for drugs. We identified just 18
instances in the 400 studies flagged by the Star where it appears
journals have taken action, in the form of a correction or
clarification. Sick
Kids’ announcement follows similar cases in the U.S. There, a research
misconduct scandal recently prompted the resignation of Dr. Jose
Baselga, the former chief medical officer of Memorial Sloan Kettering
Cancer Centre in New York City, after a New York Times-ProPublica
investigation found he failed to disclose payments from healthcare
companies. Elsewhere, Ohio State University cancer scientist Ching-Shih
Chen resigned after he was found to have falsified data. The
Star’s review of more than 1,400 papers co-written over 30 years by
Koren, one of Canada’s most prolific scientific authors, reveals the
inability — and unwillingness — of journals and research institutions to
preserve the
integrity of the scientific record. Several
concerns about Koren’s research were identified in 2015 by a Sick Kids
internal review. The hospital posted a summary of its findings on its
website, and told the Star it sent a copy to the province’s medical
watchdog, which is investigating Koren. The Star’s investigation
has found the system of medical publishing is one with little
accountability, where the onus is on authors to voluntarily disclose
conflicts of interest. Journals don’t vet these claims (or the authors
who make them). Institutions have discretion to investigate allegations
of misconduct as they see fit. Corrections, if they happen at all, routinely take years to be published. The
Star’s findings are consistent with the systemic problems that have
been identified by Retraction Watch, a pioneering organization with an
online database of retractions and corrections. Founded in 2010,
the organization began collecting retractions, by searching journals
online and in print, and, by the time the database went live in October
2018, it had amassed more than 18,000 retractions. This made it the most
extensive catalogue of such notices available, says the site’s
co-founder, Ivan Oransky, a doctor, journalist and professor at New York
University. Despite the commonly held belief in the power of
peer-review and the ability of academic publishing to root out cases of
misconduct and fraud, Oransky describes “the vaunted self-correction
mechanism of science” as one that is “held together by spit and bubble
gum.” From the institutions who rely on researchers to bring in
grant money to the journals and authors whose reputations and careers
are at stake, “at every stage the incentives are against doing the right
thing,” he said. “I don’t know if the barrel is totally rotten,
but there are a lot more rotten apples in the barrel than people would
like us to admit.” Koren, who retired from Sick Kids in June 2015,
has continued to publish since his departure. Neither he nor his
lawyers responded to emails and phone calls seeking comment for this
story. Koren, who now lives in Israel, had been working as a
senior researcher for Maccabi Health, a healthcare provider. In late
October, Physicians for Human Rights Israel, a medical ethics’ watchdog,
wrote to Maccabi Health with concerns that Maccabi may not know about
Koren’s role in two Sick Kids controversies, including the Motherisk
scandal. On Dec. 5, Maccabi, in a letter obtained by the Star, wrote
back saying it had appointed a committee to “examine the role of
Professor Koren in these incidents.” Israel Hayom, a national
newspaper, reported on Dec. 18, that Maccabi Health said Koren will be
on leave until the end of the investigation. Haaretz, another Israeli
newspaper reported that day that Koren defended the Motherisk lab by
saying it was clinical, not forensic, and “won praise.” He said,
according to the newspaper, that claims of biased or misleading research
were outright libel. Sick Kids said last week that it is
“regrettable” that an audit of Koren’s work had not been conducted
sooner and that there should have been “closer oversight of his
disclosure and publication practices.” In the 30 years he spent at
the helm of Motherisk, Koren’s staggering publication record helped
make the program the foremost source of advice for generations of
pregnant women and their doctors. He held editorial positions at more
than 15 academic journals, attracted more than $29 million in grants
from public and private sources, won prestigious awards and supervised
up to a dozen graduate students per year, the Star found. The
institutions and journals that benefited now face possible problems in
hundreds of papers in a case that reveals problems ailing the system of
academic publishing, and provides a prescription for much-needed
improvement.
“I sincerely hope that resolution of this … brings the
entire episode to an end,” Naylor told the faculty council in 2002,
according to the meeting minutes. Naylor said that he insisted
Koren write to the journal to acknowledge his error and request the
article be deleted from the scientific record. “He has done so, and also
sent appropriate personal letters of apology,” Naylor said, according
to the minutes of the faculty council meeting. “I consider the matter
closed.” The article was never withdrawn. An erratum was
published in April 2004, stating that “the specific industry sponsor,
Apotex Inc., of Weston, Ontario, was not mentioned.” Koren’s failure to consult with his co-researchers and discuss the safety concerns, were not addressed in this correction. In
response to questions from the Star for this story, Naylor said Koren
contacted the editor, Dr. Steven Soldin, within weeks of being notified
of Naylor’s decision. Naylor said Soldin was made aware of the
“inappropriate use of shared data” and the “non-disclosure issue,” but
that Soldin declined to retract the article. Soldin, who is now a
senior scientist at the National Institutes of Health Research in
Maryland, told the Star he doesn’t recall a conversation with Koren
about the paper after it was published and said he was never contacted
by any official from U of T. “If the Toronto academic faculty
felt strongly about something, they should definitely have spoken with
me,” he said. “It’s got to be a serious conversation, or it’s not going
to be taken seriously.” The matter was still outstanding when, in
early 2004, Koren became North American editor of Therapeutic Drug
Monitoring, based in part on the recommendation of his predecessor,
Soldin. In February 2004, Naylor wrote to Olivieri with an update.
In that correspondence, obtained by the Star, Naylor said he wrote a
letter urging retraction of the 1999 article, and, “as agreed,” Koren
passed it to the publisher.
In a recent email to the Star, Naylor said that he reached out to the publisher who rejected his request. The
current journal editor, Dr. Uwe Christians, said he “cannot comment
further on the matter,” but, in general, “the journal editor and
editorial board have full editorial independence; the publisher is not
involved in editorial decisions.” Arthur Schafer, founding
director of the University of Manitoba’s Centre for Professional and
Applied Ethics, said Koren should have been fired for his conduct in the
Olivieri affair. That U of T and Sick Kids allowed him to continue
publishing after his proven research misconduct, apparently without
adequate oversight and supervision, is “astonishing,” he said.
Naylor,
speaking in his capacity as U of T’s former dean of medicine, said he
rejects the suggestion that the university’s “handling of this case
somehow accounted for Koren’s ongoing failures to disclose industry
funding sources and personal payments.” “(Third) parties gave
critical and wide public airing of Dr. Koren’s disclosure misconduct
during and after these proceedings,” he said, referring to U of T’s
investigation into the research misconduct allegations. “(His) aberrant
conduct apparently continued regardless …. He was evidently impervious
to discipline or criticism.” A spokesperson for Sick Kids said
that the issue surrounding the 1999 paper, “was addressed many years ago
by the University of Toronto and the Hospital has no further comment.”
***
In his recent book,
Doctors in Denial: Why Big Pharma and the Canadian Medical Profession are Too Close for Comfort,
Dr. Joel Lexchin, a health policy expert at York University, writes
that since the ’90s, pharma money has increasingly flowed to scientists
who are regarded as having a favourable view of a company’s products and
could be a willing, positive ambassador at conferences and dinners with
colleagues. Doctors who receive money from pharmaceutical
companies “are almost uniformly resolute that they are promoting the
product because they believe in its effectiveness and that they are
independent and able to say what they believe,” Lexchin writes. He adds
that “they sometimes indulge in self-censorship to avoid the risk of
losing funding for research and attendance at conferences.” In the U.S., federal law requires drug companies to disclose payments to doctors.
No such law exists in Canada. Legislation,
passed by Ontario’s former Liberal government last year to make these
disclosures mandatory, has yet to be proclaimed by the new Tory
government. Dr. Andrew Boozary, an assistant professor at U of T and the co-founder of Open Pharma, a leading
advocate for pharmaceutical payment transparency,
said that there is no universal standard for disclosing conflicts of
interest, ties to industry or anything else that could be seen to bias
academic publishing. When submitting a manuscript, authors are
often asked to complete an online form that asks a simple “yes” or “no”
question: “Are there any relevant conflicts of interest?”
Journal editors told the Star they rely on authors to be honest. Koren
has acknowledged in published papers and on one version of his C.V.
that about 10 drug companies, including Pfizer, Duchesnay and Apotex,
have provided him with money. The Star found nearly 300 papers
that contain concerns related to undisclosed, or possibly obscured,
conflicts of interest. That includes roughly 30 papers that discuss
morning sickness or Diclectin, the only medication approved by Health
Canada to treat this condition, and do not acknowledge Koren’s long-term
support from Duchesnay, the Quebec-based maker of the drug. Duchesnay
provided funding to Koren beginning in 1994, according to his C.V.
Of
the nearly 300 papers, about 270 cite “The Research Leadership for
Better Pharmacotherapy During Pregnancy and Lactation.” Sick Kids,
following its internal probe of Motherisk in 2015, said Koren created
this name to refer to funds donated “by a variety of individuals and
organizations.” In the years leading up to the Motherisk scandal, the
primary donor was Duchesnay, the hospital said, and, in some cases where
Koren used the “Research Leadership” name, he did not acknowledge
funding from that drug company. The Star requested a complete list
of donors and the amount of money provided, but Sick Kids said this is
“not possible,” because this was “not an actual fund set up at the
hospital.” In a statement, a spokesperson for Duchesnay confirmed
the company “terminated its partnership with/and funding of” Sick Kids
and Motherisk in 2015, but said “it is not our policy to announce the
specific amounts it pays or has paid to Canadian health professionals
for various consultations, speaker and research services.” None of the other drug companies provided to the Star the amount or details of the funding to Koren or Motherisk. Thomas
Knudsen is editor-in-chief of the journal Reproductive Toxicology,
which has published 13 papers co-written by Koren that the Star deemed
problematic, because they relate to hair-testing, cite the Research
Leadership name or discuss morning sickness or Diclectin without
acknowledging support from Duchesnay. Knudsen said that his
editorial staff does not generally investigate conflict-of-interest
disclosures. Peer reviewers are “not going to do a Google search” of the
author, Knudsen said; their job is to review the science. Without a
whistleblower or a note from a researcher’s institution, he asked, how
was he supposed to know who or what to look into? We are not police officers,” he said. “That’s up to the university.” The
journal published two more of Koren’s articles this year. A third was
stopped by reviewers with concerns about the study design and
conclusions. Knudsen recently rejected this study. He said that
information provided by the Star about the findings of the news
organization’s investigation into Koren’s papers, and the problems at
Motherisk “made it easier” to render the “unfavourable” decision.
***
Sick
Kids vowed to communicate the results of its recently announced review
to “all involved journals.” This could prove a monumental task. The more
than 400 papers identified by the Star as containing possible problems
were published in roughly 75 journals and co-authored by more than 450
doctors, nurses and academics. In these cases, publications can be slow to act, if they do at all, said Oransky of Retraction Watch. Retractions, the most severe form of punishment a journal takes, are rare. Corrections, known as “errata” or “corrigenda,” are more common. But they can take years to materialize, are difficult to find and tend to be opaque. In
a search of three online scientific article databases, the Star found
corrections related to 18 of the more than 400 articles we flagged.
Most are not appended to the online versions of the original articles. The
problems in the system were evident in our search for corrections
related to five hair-testing papers that retired judge Susan Lang
identified in her 2015 report on Motherisk as containing lies about
using the gold-standard testing to confirm results. In
her report, Lang said that Koren told her that he had sent erratum
letters to the affected journals explaining the inaccuracies in these
articles. Sick Kids reiterated Koren’s claim in the press release last week. Three
years later, the Star’s online search found corrections related to two
of those articles: an erratum related to a 2007 article published in
Therapeutic Drug Monitoring, and a corrigendum related to a 2009 article
published in Forensic Science International. When asked why
Forensic Science International did not publish a correction related to
the 2000 paper discussed at the beginning of this story, the editor, Dr.
Christian Jackowski said “no further corrigendum/erratum was published
or provided by the author.” The editor of a third journal, on request, sent the Star the corrigendum that was published in relation to a 2007
article. None of these notices mentioned that the Motherisk lab has been discredited. They claim that, despite the fact that results were not confirmed with gold-standard testing, this did not affect results. Dr.
Ronald Cohn, Sick Kids pediatrician-in-chief, took issue with Koren’s
assertion that the gold-standard lie “had no impact on the results” of
the study. That prompted Therapeutic Drug Monitoring, one of the
journals, to also issue an “expression of concern,” a stronger
statement, about one of the articles. Jackowski, the editor of
Forensic Science International, said he told a Sick Kids official that
he would additionally publish a letter to the editor stating the
hospital’s position. But it was never submitted, he told the Star. Sick
Kids told the Star it did send the letter, but would reach out to the
journal again to clear up any misunderstanding. Meanwhile, Dr.
Togas Tulandi, the editor of Elsevier’s Journal of Obstetrics and
Gynaecology Canada, which published an opinion piece by Koren in 2017,
said that he was unaware of Koren’s research misconduct until he was
contacted by the Star. He said his associate is “looking into it” and
the journal may “withdraw (Koren’s) article.” Therapeutic Drug
Monitoring, which Koren edited until 2015, has recently taken the most
aggressive approach of any journal towards Koren’s articles; Christians
said the current president of the society that runs the journal asked
Koren to step down as editor after he learned of the Motherisk scandal.
Koren “accepted the termination without question,” he said. In
2017, the journal reviewed all of the roughly 90 articles Koren
co-authored, and sent 19 to independent reviewers for additional
scrutiny. In seven, the reviewers recommended action, such as requesting
proof of confirmation testing and ethics-board approval from the
authors. Christians said that the follow-up on these actions was
delayed by the transition to a new editor, but that it “is now being
prioritized.” Following the Star’s inquiries, Christians said he
is now considering retracting the 1999 paper that resulted in the
research misconduct finding against Koren.
