Medical journal corrects two flawed articles by Dr. Gideon Koren

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A medical journal that for more than 20 years published advice about drug safety for pregnant women has issued a rare correction related to two questionable articles by the column’s lead author.

Canadian Family Physician (CFP), the official journal of the College of Family Physicians of Canada, published the correction in its January 2019 edition outlining concerns with the articles co-authored by Dr. Gideon Koren, former head of the SickKids’ Motherisk program and director of its discredited lab.

Former head of Motherisk program under investigation by medical regulator

The 177-word correction comes after a Star investigation that exposed flaws in medical publishing, including the inability and unwillingness of journals and research institutions to correct and preserve the integrity of the scientific record.

Corrections, the Star found, routinely take years to be published, if they happen at all.

The Star investigation prompted the Hospital for Sick Children to announce in December it will conduct a wholesale review of Koren’s vast body of work. In its review of 1,400 articles co-authored by Koren over 30 years, the Star identified what appear to be problems in more than 400 of his papers, including nearly 200 published in Canadian Family Physician.

The problems include inadequate peer review, failures to declare, perhaps even obscure, conflicts of interest and, in a handful of cases, 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.

The two articles being corrected by CFP, Nausea and vomiting of pregnancy. Evidence-based treatment algorithm and Treatment of nausea and vomiting in pregnancy. An updated algorithm, were not properly peer-reviewed, according to the correction, and failed to disclose a conflict of interest.

The correction also said the articles “did not provide satisfactory evidence that would have justified the recommendation” to prescribe Diclectin, a combination of antihistamine and vitamin B6, as a first-line of defence.

That recommendation was among the guidelines to treat morning sickness that were developed by Motherisk and endorsed and published by The Society of Obstetricians and Gynaecologists of Canada.

The journal withdrew its endorsement of the guideline in 2017, acknowledging in an editorial that it hadn’t subjected these regular articles to double-blind, peer reviews because of its “long-standing relationship with Motherisk.” The journal published regular articles under the title “Motherisk Update” from 1995 to 2016.

Until now, the two articles stood uncorrected in the literature.

Dr. Nav Persaud, a researcher and family physician at St. Michael’s Hospital, who co-authored a paper five years ago that questioned the recommendations in these two articles, said the medical profession in Canada has failed pregnant women with nausea and vomiting during pregnancy by issuing and recommending the faulty guideline. He said the two papers are not reliable and should be removed from the literature.

“I hope that this is a temporary measure on the road to doing what needs to be done,” Persaud said. “The fact that this is the second time that Canadian Family Physician has addressed this issue indicates that they should deal with it definitively.”

Visitors to each of the articles, which are still published on CFP’s website, are met with a note directing them to the correction. The correction guides them to a 2017 commentary written by Dr. Nick Pimlott, CFP’s scientific editor, that describes several concerns the journal had found with Koren’s work.

Neither Koren nor his lawyers responded to the Star’s request for comment.

Pimlott told the Star that the journal’s Editorial Advisory Board decided several months ago that these two articles did not meet criteria for retraction which he said is “commonly defined as conclusive evidence of scientific fraud or misconduct.”

“The Board felt that it would be important to provide clarification of the issue for CFP readers,” he said. “For this reason, a decision was made by the (board) to publish a correction.”

CFP’s correction says that for the two articles there was an undisclosed conflict of interest with Duchesnay, the manufacturer of Diclectin.

The articles, published in 2002 and 2007, were among 270 articles that the Star found referenced, in some way, “The Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation.” This was not an actual fund, SickKids has said, but a name Koren created to describe “unrestricted funding he had available at different points in time.”

In 2015, SickKids said that the primary donor in the years leading up to the Motherisk scandal was Duchesnay. The hospital has said that in some cases where Koren used the “Research Leadership” name, he did not acknowledge funding from that drug company.

Persaud and co-authors had re-analyzed a 1997 Koren paper that underpinned his views of Diclectin and led to the guideline to prescribe the drug.

SickKids has confirmed some of Persaud’s findings, including that Koren’s 1997 paper overstated the number of subjects involved in that study. SickKids also said that an independent reviewer, hired by the hospital to assess the paper, concluded that its claim that the antihistamines in Diclectin have a protective effect against major malformations was not supported by the data. Antihistamines, the reviewer concluded, are neither protective nor harmful.

Pimlott said CFP is reviewing all Motherisk articles it has published.

Michele Henry is a Toronto-based investigative reporter. Follow her on Twitter: @michelehenry

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Inside the flawed world of medical publishing that allowed a lie in a paper coauthored by Dr. Gideon Koren to pollute the scientific record

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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.

Dr. Gideon Koren is one of Canada’s most prolific scientific authors. The Star’s review of more than 1,400 papers co-written by Koren over 30 years reveals the inability — and unwillingness — of journals and research institutions to preserve the integrity of the scientific record.
Dr. Gideon Koren is one of Canada’s most prolific scientific authors. The Star’s review of more than 1,400 papers co-written by Koren over 30 years reveals the inability — and unwillingness — of journals and research institutions to preserve the integrity of the scientific record.  (Toronto Star)

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.

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 — is 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, SickKids, 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.

The Hospital for Sick Children announced last week it will undertake a wholesale review of Gideon Koren's vast body of published work.
The Hospital for Sick Children announced last week it will undertake a wholesale review of Gideon Koren’s vast body of published work.  (Richard Lautens / Toronto Star File)

Sick Kids’ announcement follows a 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 SickKids 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 SickKids 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 SickKids 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.

SickKids 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.

***

The Star’s findings were in many ways foretold 15 years ago, when the University of Toronto’s dean of medicine tried — and failed — to get a journal to retract one of Koren’s papers.

In April 2002, at a faculty council meeting, Dr. David Naylor, who is now interim CEO at SickKids, recorded a finding of research misconduct against Koren related to a 1999 study published in the journal Therapeutic Drug Monitoring.

The public chastisement was intended as a coda to Koren’s dispute with Dr. Nancy Olivieri, a blood diseases specialist at Sick Kids who, like Koren, held cross-appointments at U of T. Tensions boiled over while the pair was running a clinical trial with partial funding from the Canadian generic drug-maker Apotex. Olivieri voiced concerns about the efficacy of the drug, which Koren did not share.

Dr. Nancy Olivieri, a blood diseases specialist at SickKids who also held cross-appointments at U of T, was the subject of disparaging "poison pen letters" that DNA testing eventually proved were written by Koren.
Dr. Nancy Olivieri, a blood diseases specialist at SickKids who also held cross-appointments at U of T, was the subject of disparaging « poison pen letters » that DNA testing eventually proved were written by Koren.  (Carlos Osorio / Toronto Star File)

In 2000, the heads of SickKids and U of T suspended and fined Koren, who was also stripped of an endowed chair for “repeatedly lying” and sending anonymous “poison pen letters” to doctors and the media disparaging Olivieri and her supporters. He denied writing the letters until DNA evidence provided irrefutable proof.

A committee formed by the U of T Faculty of Medicine found that Koren had published the 1999 paper without consulting the other researchers, failed to disclose Apotex’s support for the trial, and had not discussed the safety concerns about the drug.

“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 correspondance, 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 SickKids 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 SickKids 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.” SickKids, 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 SickKids 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” SickKids 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.

***

SickKids 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.

Justice Susan Lang, the retired Ontario judge who conducted the independent review of the Motherisk lab, identified five hair-testing papers in her 2015 report as containing lies about using the gold-standard testing to confirm results.
Justice Susan Lang, the retired Ontario judge who conducted the independent review of the Motherisk lab, identified five hair-testing papers in her 2015 report as containing lies about using the gold-standard testing to confirm results.  (Bernard Weil / Toronto Star File)

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.

SickKids 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, SickKids 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 SickKids 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. SickKids 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.

***

Naylor said Koren’s case is an “ugly and outsized” example of the systemic problems with conflicts of interest and protecting the scientific record.

The “only way to move forward,” he said, is for institutions to keep better tabs on researchers’ financial relationships, ensure the penalties for not disclosing are clear and collaborate with journal editors to “work out a more explicit system” to share information and “oversight of the processes for correcting the scientific record.”

Naylor said it would be “a huge help if all industry payments made directly to physicians were simply disclosed publicly by the payers.”

Koren continues to submit manuscripts to journals to be considered for publication.

He published a study in August about a severe form of morning sickness. The paper acknowledges he is “a consultant for Duchesnay.”

In September, Koren was singled out among the world’s “hyperprofilic” authors in an article in Nature. These were researchers who wrote more than 72 papers in any year from 2000 to 2016 — roughly one paper every five days — which, the study authors noted, “many would consider implausibly prolific.”

Lead author, Stanford University professor John Ioannidis, said the study is an attempt to understand hyper-prolific authorship, for better or worse.

Koren responded to a request from the study authors to comment on his output. He credited teamwork, 16-hour work days, and two “very supportive work environments.”

“I perceive myself as an individual who is highly committed to scientific discovery,” he said. “I do not feel I have to apologize for my high productivity.”

With files from Tania Pereira, May Warren, Stefanie Marotta, Jason Miller and Brendan Kennedy.Ryerson note: The Star’s investigation into Koren’s publications was conducted in partnership with Ryerson University School of Journalism students Stefanie Phillips, Emerald Bensadoun, Kate Skelly and Alanna Rizza.

Rachel Mendleson is a Toronto-based investigative reporter. Follow her on Twitter: @rachelmendleson

Michele Henry is a Toronto-based investigative reporter. Follow her on Twitter: @michelehenry

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Sick Kids orders ‘systematic’ review of Dr. Gideon Koren’s published works

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Toronto’s Hospital for Sick Children has announced a wholesale review of the vast body of published work by Dr. Gideon Koren, the former director of the discredited Motherisk lab, amid a Star investigation that identified what appear to be problems in more than 400 of Koren’s papers.

Sick Kids reacted after the Star presented the hospital with the results of the newspaper’s review that found these papers had been inadequately peer-reviewed, fail to declare, perhaps even obscure, conflicts of interest and, in a handful of cases, contain lies about the methodology used to test hair for drugs.

Many of these articles stand in the scientific literature, despite two government commissioned inquiries and an internal investigation by the hospital into Motherisk, following concerns that were first raised about the program by the Star four years ago.

“Despite the actions taken to date, fresh concerns have surfaced in the area of scientific reliability and academic publication conflict of interest disclosures,” Sick Kids said in a news release on Friday. “Here SickKids wishes to acknowledge the investigative work of reporters Rachel Mendleson and Michele Henry of The Star who brought relevant findings to the organization’s attention. They have unearthed publications where, on initial review, it appears that Dr. Koren did not disclose industry support that appears relevant to the primary focus of the publication or otherwise related to the published work.”

Sick Kids acknowledged that while institutions rely on the good faith of scientists to disclose conflicts that could bias their work, “it is regrettable that the Hospital did not conduct any audits of Dr. Koren’s publications which may have identified disclosure issues sooner.”

A prolific author, Koren has published more than 1,500 research papers over the last 40 years, Sick Kids has said. The Motherisk Program he founded at the hospital in 1985 became a trusted source of drug-safety advice for pregnant women and their doctors. Motherisk’s affiliated hair-testing lab made more than $11 million from 2007 to 2015 alone, selling its drug and alcohol tests, primarily to child welfare agencies, as evidence of parental substance abuse in child protection cases.

Sick Kids closed the Motherisk lab in 2015. The counselling function of the Motherisk Program continues at the hospital under new leadership.

The hospital said it will conduct a “systematic examination” of Koren’s published work in an effort to “protect the integrity of the existing medical literature.” It will also undertake a “focused scientific review” of Koren’s hair-testing papers and his “primary research” related to the popular morning-sickness drug Diclectin — two of the problems areas the Star flagged — and will add “new measures to strengthen institutional oversight of publication disclosure practices.”

Koren held cross appointments in the faculties of medicine and pharmacy at the University of Toronto. In an email, Vivek Goel, Vice-President, Research and Innovation, at the university, said the Sick Kids reviews “relate to the clinical testing done by the Motherisk laboratory which is in its jurisdiction.”

“If in the course of the SickKids reviews, issues are identified that involve research conducted under the auspices of the University, then we will be engaged, as appropriate,” he said, adding that the university will “take appropriate actions” if the hospital’s findings involve individuals at U of T.

The more than 400 papers co-authored by Koren that the Star flagged as possibly containing problems include research articles, conference papers, literature reviews, editorials, book chapters, and magazine articles.

We found more than 60 papers that relate to drug and alcohol hair-testing that we deemed problematic because retired judge Susan Lang’s 2015 review of Motherisk exposed failings in the lab, including that hair test results were “inadequate and unreliable” but were used in thousands of child protection cases and a handful of criminal cases.

Sick Kids said it is “in the process of identifying” publications related to the Motherisk drug-testing lab “that could potentially have therapeutic or diagnostic implications to conduct a review.”

“The journals that have published these studies share responsibility for addressing this issue and to the extent our work results in any findings, our plan is to disclose same to the journals,” the hospital said.

Lang, in her 2015 report, pinpointed five papers that falsely claimed that lab’s results had been verified with gold-standard testing, when in fact Motherisk rarely confirmed its screening test results before 2010, contrary to international standards for evidence presented in court. Following Lang’s report, Sick Kids said the hospital’s research integrity adviser reviewed these papers and found that Koren violated some of the guidelines that govern the use of federal research funds, which it reported to the Secretariat for Responsible Conduct of Research, which oversees the Canadian Institute for Health Research.

Koren sent letters identifying “corrigendum” — or correction — to the editors of the journals in which these articles appeared, and corrigenda were published in relation to three of the papers.

However, Sick Kids said that pediatrician-in-chief Ronald Cohn took issue with Koren’s claim in the corrections that “the fact that not all positive results had been (confirmed with gold-standard testing) had no impact on the results,” and wrote to the journals. One of the journals, Therapeutic Drug Monitoring, revised its position and this past summer issued a more severe “expression of concern” in relation to a 2007 article on cocaine detection in maternal and neonatal hair.

The Star, in its ongoing investigation, found that Therapeutic Drug Monitoring, which Koren edited from 2003 to 2015, has recently flagged six more of his papers as requiring further scrutiny. Sick Kids said it is “looking into these articles,” following questions from the Star.

The hospital’s promise to investigate Koren’s work on Diclectin comes five years after Dr. Nav Persaud, a researcher and family physician at St. Michael’s Hospital, co-authored a paper exposing inaccuracies in a 1997 article Koren co-authored on the safety and effectiveness of the drug.

Persaud praised Sick Kids for undertaking a thorough review of Koren’s work, but said, “It’s sad that it took questions from journalists for this to happen.”

“Many red flags have been raised over the years, and hopefully this announcement from Sick Kids means that the red flags will be heeded,” he said.

The Star’s review identified roughly 30 articles that reference morning sickness or Diclectin but do not disclose his financial ties to the manufacturer of the drug, Duchesnay. Koren has served as a paid consultant to the Quebec-based pharmaceutical company, which was also a long-time sponsor of the Motherisk Program, until the relationship ended in 2015.

The hospital reassigned oversight of Motherisk in the spring of 2015 after the Star asked about a morning sickness booklet — co-authored by Koren — posted on the Motherisk website that recommended the drug Diclectin but failed to disclose financial support from Duchesnay.

The Star found about 270 papers that reference, in some way, “The Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation.” Sick Kids disclosed in 2015 that Koren created this name to refer to donated funds, and that the primary donor in the years leading up to the Motherisk scandal was Duchesnay.

Sick Kids said Friday that the hospital “was unaware that Dr. Koren had published on morning sickness and/or Diclectin without disclosing his relationship with Duchesnay.”

“The responsibility for disclosing relationships (conflicts of interest) in a publication rests with the author,” Sick Kids said.

In addition to reviewing the financial disclosures on nearly 20 years of Koren’s published work, the hospital told the Star it is “undertaking an analysis of Dr. Koren’s industry funding over time with a view to aligning funds on hand with dates of disclosures, for purposes of notification.”

Sick Kids will also review the science behind seven of his studies on the effectiveness of Diclectin.

Following questions from the Star last month, Sick Kids interim CEO, Dr. David Naylor, sent a letter to Koren asking him to contact journals to inform them of papers about morning sickness or Diclectin in which he did not disclose support from Duchesnay as well as all papers referencing The Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation in which he did not disclose funding sources. Naylor, in the letter which has been posted on the Sick Kids website, also warned Koren to “cease and desist” from identifying himself in publications as being affiliated with Sick Kids.

“Falsely claiming an ongoing affiliation with an institution where you no longer work is a form of academic misconduct,” Naylor said.

The Star also identified nearly 200 articles that appeared in Canadian Family Physician, the official journal of the College of Family Physicians of Canada. The journal acknowledged in an editorial last year that it did not subject these articles — published regularly beginning in at least 1995 as “Motherisk Updates” — to a double-blind, peer-review process because of its “longstanding relationship with Motherisk.” The journal withdrew its recommendation of Diclectin as a first-line treatment for morning sickness, citing Persaud’s findings.

Sick Kids said on Friday that it “would be pleased to assist Canadian Family Physician in reviewing a sample of these studies to determine whether they accurately reflected the literature available at the time of publication, and is prepared to do so independently as needed.”

Dr. Nick Pimlott, Scientific Editor of Canadian Family Physician, said that it will work with its editorial advisory board to “systematically and thoroughly review articles authored by Dr. Koren.” Articles with evidence of fraud or scientific misconduct would be retracted, he wrote to the Star in an email. Pimlott said it is “highly likely” the advisory board would implement “a process of peer review for all such articles” going forward.

In regards to the 1997 study that Persaud raised concerns about, Sick Kids said on Friday that, after confirming that the study overstated the number of subjects, the hospital retained an independent reviewer to assess the paper’s claim that antihistamines — one of the main ingredients of Diclectin — have a protective effect against major malformations. The review found this claim was not supported by the data, concluding that antihistamines are neither protective nor harmful.

Koren then sent these findings to the journal where the study appeared but the journal declined to print a correction “given the length of time that had passed,” Sick Kids said.

The Star’s investigation into Koren’s publications is being conducted in partnership with Ryerson University School of Journalism students Stefanie Phillips, Emerald Bensadoun, Kate Skelly and Alanna Rizza.

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