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

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.”

Koren and his lawyers did not immediately respond to requests to comment for this story and have not responded to questions over the past month related to the Star’s broader investigation. Koren retired from Sick Kids in June 2015 and is working in Israel.

Read more:

Parents lose second bid to launch class-action suit against Motherisk over flawed hair tests

She was convicted of feeding her son cocaine. No one told her the hair tests were flawed

Former head of Motherisk program under investigation by medical regulator

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.