Prominent Chinese scientist failed to disclose company ties in COVID-19 clinical trial paper

One of China’s leading scientists in the fight against COVID-19 failed to disclose ties to a pharmaceutical company in a paper stemming from a clinical trial, Retraction Watch has learned. A co-author on the paper is married to the daughter of that pharmaceutical company’s founder, who herself sits on the firm’s board of directors. 

Nanshan Zhong first rose to prominence during the 2003 SARS outbreak for developing “a controversial steroid treatment that cured many SARS patients but left some with debilitating bone issues,” according to NPR. In 2020, TIME named him to the magazine’s list of the world’s 100 most influential people. He was appointed to lead China’s National Health Commission investigation into COVID-19 early last year, and in February 2020 Harvard announced that Zhong would share in a $115 million effort with university scientists to develop therapies for COVID-19.

Last May, Zhong published results from a clinical trial that tested whether a traditional Chinese medicine could be used to treat COVID-19 patients. That paper, titled “Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: A multicenter, prospective, randomized controlled trial,” was published in Phytomedicine. It has been cited 67 times, according to Clarivate Analytics’ Web of Science, and has two corresponding authors: Zhong, of the Guangzhou Institute of Respiratory Health, and Zhen-hua Jia of Hebei Yiling Hospital, in China. 

None of the authors on the paper disclosed a conflict of interest. However, last year an anonymous whistleblower found documents financially tying Zhong and Jia to Shijiazhuang Yiling Pharmaceutical, which supplied the Lianhuaqingwen capsules for the study and  applied for and sponsored the trial, according to China’s clinical trial database. That detail was not disclosed in the paper.

Shijiazhuang Yiling Pharmaceutical  was founded in 1992 by Yi-ling Wu, a billionaire with whom Zhong has collaborated since 2015, according to the South China Morning Post. The newspaper reported last October that “Wu invited Zhong to join a 460 million yuan [$71 million] research lab set up for academicians by his company,” and that, “in 2016, they co-founded a research centre to tackle lung diseases using [traditional Chinese medicines] in the southern city of Guangzhou.” 

Zhong also signed a “cooperation project” agreement with Shijiazhuang Yiling Pharmaceutical in 2015 to test Linhuaqingwen’s antiviral properties, according to a report in Ta Kung Pao, a Chinese newspaper.

The other corresponding author, Zhenhua Jia, is married to the pharmaceutical company’s director and secretary of the board of directors, Rui Wu, according to a public stock incentive plan that the company issued in March 2013. Rui Wu is the daughter of Yi-ling Wu.

Jia and Rui Wu also own a consulting company called Yiling Luobing Health Management Co., Ltd., which operates under the same parent group as the pharmaceutical company.

In August 2020, the whistleblower — who did not wish to be identified because “research projects of my current lab rely on the funding support from the Chinese Academy of Sciences in which some authors on that paper have tremendous influence” — emailed Princy Alexander, a journal manager at Phytomedicine, about the possible undeclared conflicts of interest. 

Their email was passed to the journal’s editor-in-chief, Thomas Efferth, who asked Jia to provide a point-by-point reply and write a draft erratum that could be published in Phytomedicine, according to emails seen by Retraction Watch.

Jia replied on September 22 and attached four documents confirming that Jia and Rui Wu are spouses and that they own a “brother company” to the pharmaceutical firm. But they deny that their consulting firm had ever been involved in the clinical trial, and said that the two companies are “completely independent legal entities,” and “will not have any substantial impact on the implementation and results of the clinical research.”

The documents also state that Jia did not contribute to the actual research or statistical analysis of the paper, and thus his involvement wouldn’t diminish the objectivity of the results:

As an independent medical scientist, Prof. Zhen-hua Jia has participated in the study design, drafting and revision of the manuscript. In light of the enormous contribution, Prof. Jia has been unanimously elected to be the co-corresponding author of the article. Professor Zhen-hua Jia did not participate in the specific research process and the statistical analysis of the results, so it does not affect the scientificity, objectivity and authority of the research results.

The documents do not offer a rebuttal to the whistleblower’s concerns about Zhong’s academic collaborations with Yi-ling Wu. Zhong, Jia, and multiple spokespeople for Shijiazhuang Yiling Pharmaceutical did not reply to requests for comment.

An erratum prepared by the authors also suggests the following edits to the conflict of interest disclosures:

Shijiazhuang Yiling Pharmaceutical Co., Ltd. provided part of the funding and the study drug (Lianhuaqingwen capsules) for this research and had no role in the data acquisition, analysis and writing of this article. 

When asked if an erratum would be published, Efferth told us to contact a legal representative at Elsevier. That legal representative has not responded to requests for comment. Meanwhile, Michelle Harding, a journal manager for the publisher, referred our questions back to Efferth, who has not replied.

Lianhuaqingwen was originally listed as a treatment for flu and respiratory illnesses in 2004, by China’s National Health Commission. Traditional Chinese medicines, like Lianhuaqingwen, were recommended for treating COVID-19 patients in China in January 2020. 

After the pharmaceutical company sent boxes of Lianhuaqingwen capsules to Chinese students in Canada last year, a spokesperson for Health Canada told CBC News that they would “take action to stop this activity,” while doctors (and the company’s own website) said that the tablets might treat symptoms of COVID-19, but not the disease itself.

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