Update on Matters Related to Dr. Koren’s Research

In 2014, the Toronto Star began investigating the Motherisk Program at The Hospital for Sick Children (SickKids). The Star raised questions about the accuracy and reliability of hair analyses undertaken by staff working under the direction of Dr. Gideon Koren in the Motherisk Drug Testing Lab (MDTL). An internal Hospital review was launched along with an independent government-commissioned review by Justice Susan Lang. Subsequently, MDTL was closed. In her report, Justice Lang deemed MDTL hair testing to be “inadequate and unreliable” for use in criminal or child protection proceedings. She also identified five questionable studies, which prompted wider concerns about Dr. Koren’s research.

Drawing on Justice Lang’s findings, SickKids implemented various measures to increase oversight of the management of labs, staff interactions with the justice system and internal hospital conflict of interest disclosures. The Hospital reviewed all of Dr. Koren’s active research at the time and investigated research that was identified as concerning.  

For a report on the actions SickKids has already taken to investigate concerns regarding Dr. Koren’s research please refer to this Summary.  

Despite the actions taken to date, fresh concerns have surfaced in the area of scientific reliability and academic publication conflict of interest disclosures. Here SickKids wishes to acknowledge the investigative work of reporters Rachel Mendelson 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.  

The Star has identified 422 research papers, where they point to, among other things: concerns with disclosure; uncertain scientific validity of hair testing research; publications in a particular journal in which the journal did not peer review the articles; and the potential for bias in publications relating to nausea and vomiting during pregnancy. We have addressed these issues in the Appendix (below).

Readers familiar with academic publishing will be aware that, in general, standards for disclosure have shifted higher over time. That is true at SickKids as well. However, our initial examination of these publications shows departures from what SickKids currently considers to be best practice.  

It is also the case that, when it comes to financial disclosures in academic research publications, most institutions rely primarily on the good faith of scientists working in their employ and/or in their facilities. It is regrettable that the Hospital did not conduct any audits of Dr. Koren’s publications which may have identified disclosure issues sooner.  

At this point, SickKids will be pursuing three courses of action.  

• First, to protect the integrity of the existing medical literature, the Hospital will be undertaking a systematic examination of Dr. Koren’s published work to identify/confirm instances of incomplete disclosure in academic publications.  
• Second, for the same reason and in light of Justice Lang’s findings, we will be undertaking a focused scientific review of subsets of Dr. Koren’s papers that we believe merit further attention.    
• Third, to help ensure the integrity of all ongoing published work carrying the SickKids name, we are re-examining our policies, including those updated recently, and adding new measures to strengthen institutional oversight of publication disclosure practices.  

These measures are outlined in more detail below.  

Publication Disclosure Review

The Hospital recently wrote to Dr. Koren to request that he address issues of disclosure with journals where his work has appeared. We have not heard back from Dr Koren. Thus, we are reviewing the disclosures of funding sources on all of Dr. Koren’s publications since 2001. This will be a lengthy task involving hundreds of articles and commentaries and review of all institutional information related to funding he may have received for any reason from industry. We will be communicating with all involved journals to ensure that the journals have accurate information about Dr. Koren’s sources of industry funding for research as applicable, and to request that they register the relevant information in such a fashion that it is accessible through digital searches of the scientific record.

Focused Scientific Review

The Hospital has already communicated concerns about five of Dr. Koren’s hair analysis publications to the relevant journals. Details can be found here (summary). Dr. Koren contacted the journals at our request but we found his correction to be inadequate, and SickKids followed up to attempt to correct the record.   

We will be initiating independent reviews of Dr. Koren’s primary research related to Diclectin and those papers in which hair analysis was the primary focus or analytical method used. We will also be arranging examination of a sample of his highest-cited papers, looking for evidence of inconsistencies and errors. We are aware that our inability to access raw data may limit these reviews, particularly for older papers.  

As necessary, relevant findings will be communicated to the journals where the affected studies are published.  

A Caveat

SickKids acknowledges that, apart from concerns already addressed in past investigations, it has not received other complaints about Dr. Koren’s work containing allegations of fraud, falsification, plagiarism, or duplicate publication – matters of misconduct in publication that commonly lead journals to post notices of concern or retraction. Furthermore, a large amount of Dr. Koren’s work was published with highly reputable and senior co-authors, and we in no way wish to impugn their work. Last, while it is evident that concerns have already been found with respect to his work, we are not pre-judging this matter, or casting any general aspersions on the extent to which his contributions to the field of maternal and child health should continue to be relied upon in clinical care.    

Policy Review and Oversight of Publication Disclosures

Currently, our relationship management process requires scientists, clinicians and clinician-scientists to disclose any relationship that may be a perceived, potential or real conflict of interest. Annually, each faculty member is required to attest to a) the accuracy of information we have on file about ongoing consulting relationships with industry and those in the previous year, b) having made the requisite disclosures for each relationship, and c) their understanding of ongoing disclosure obligations. We are reviewing this system to determine what additional information should be routinely compiled.    

The SickKids Foundation also has taken a number of steps to mitigate conflict of interest. This includes processes to manage how the Foundation works with donors that could have a real or perceived conflict of interest and the inclusion of a disclosure clause in all pharmaceutical gift agreements allowing the Hospital and the Foundation to publicly disclose the gift.  

Moving forward, SickKids will be implementing a process whereby compliance with publication disclosure requirements is monitored by random audits of disclosures in publications. The focus of audits will be individuals who have research support or personal compensation from industry, pharmaceutical companies or private third-party funders. Disclosures in publications will be tested for accuracy against all available information systems. To the extent possible, the auditing process with be automated.

Last, we note that in 2017, the Government of Ontario enacted the Health Sector Payment Transparency Act, 2017 that would provide another publicly available source of information about industry payments in the health sector. The Act has not yet been proclaimed in force. The Hospital would welcome the government moving forward to enact this legislation.

Conclusion

For well over two decades, the health research community has grappled with the issue of disclosures of potential conflicts of interest, and potential biases in project design, execution, analysis, and reporting of studies arising when sponsors of the project or authors have a financial interest in the outcome. These issues are by no means unique to SickKids as a recent New York Times article indicates; and debate continues in major medical journals (see links below) as to how best to manage these challenges.

• Conflicts of Interests, Authors, and Journals: New Challenges for a Persistent Problem
• Should Failure to Disclose Significant Financial Conflicts of Interest Be Considered Research Misconduct?

As indicated above, until recently, the responsibility for dealing with disclosures in the context of publications has fallen primarily with authors and journals.  We are proud of the work done by the scientists at SickKids and we are mindful that this situation is not representative of the practices of our scientists. However, as we examined other jurisdictions, it is clear that more organizational efforts are now being made to regularize and improve financial disclosures. SickKids has concluded that greater institutional facilitation and oversight of financial disclosures will be part of any sustainable solution to these ongoing challenges, and essential to ensure that members of the scientific community have the information necessary to evaluate the work of their colleagues on its merits.   

SickKids believes that the responsibility for the quality and integrity of academic publications is shared by authors, journals and the institutions where the scientists work. The steps outlined above signal the Hospital’s commitment to that shared endeavour.  

We will be continuing to post updates intermittently as work proceeds along the lines set out above.

Appendix: Research Integrity Concerns Raised by The Toronto Star