The authors of a scientific article describing the results of a randomized clinical trial of two cancer drugs conducted in China have retracted it just months after publication in January of this year, citing Chinese regulators as a factor in the retraction.
The trial included 250 patients with giant cell tumor of bone, a tumor that destroys bone but is usually benign. The patients, who could not be treated with surgery, received either denosumab (multiple brands), which has been approved for this condition in the United States since 2013 and in Europe since 2014, or zoledronic acid (multiple brands). The authors concluded that "denosumab is a safe but costly alternative to zoledronic acid for treatment of surgically unsalvageable giant cell tumor of bone." Giant cell tumors account for about 5% of primary bone tumors in Europe and the United States, but it accounts for 20% of all primary bone tumors in China.
The retraction notice in the Journal of Bone Oncology suggests government regulators had a role, which one expert says could be part of a larger effort to improve the quality of clinical research in China.
According to the retraction notice, the authors of the article requested its retraction. "The authority of Chinese drug administration have advised against dissemination of this research because as per the current guideline, Denosumab is not recommended for the treatment of giant cell tumor of bone," the notice reads. "Furthermore, ethics approval was later withdrawn by the Cancer Hospital of China Medical University review board."
Corresponding author Shenglong Li, of the Cancer Hospital of China Medical University and the Liaoning Cancer Hospital and Institute, did not respond to Medscape Medical News' request for comment.
Although China's National Medical Products Administration (NMPA) did approve denosumab for the treatment of giant cell tumor of bone around the same time that the retraction was published, the drug was not approved for that purpose while the clinical trial was going on, said Eunjoo Pacifici, PharmD, PhDi, director of the International Center for Regulatory Science at the University of Southern California's School of Pharmacy.
The investigators should have submitted a clinical trial application to the NMPA for their oversight, she said. If they didn't, and if the NMPA noticed the publication, that could explain the retraction notice's reference to the Chinese drug administration. If the investigators did not in fact submit a clinical trial application to the NMPA, that could also affect the cancer hospital review board's ethics approval.
It's unclear if this explanation of the retraction is correct, but Pacifici said the Chinese regulators have recently been sending a message to researchers conducting clinical trials "to be more mindful of following regulations and following clinical practice."
In 2015, regulators asked 1622 applicants for drug approvals to audit their own applications, and 1193 then withdrew their applications voluntarily.
Subsequent inspections of drug clinical trial data "found some chaos in the past clinical trials, [and] some of the falsifications were horrifying," according to the regulators' inspection report.
Pacifici said she had not seen a similar retraction before. "Perhaps [the NMPA is] being more vigilant to make sure other investigators are taking note," she said.
Elsevier, which publishes the Journal of Bone Oncology, did not provide Medscape Medical News with more context about the role of the Chinese drug administration in the retraction when asked.
"The retraction notice contains all the information that the journal was able to obtain from the authors, after several requests for clarification and the suggestion by the journal to alternatively update the record via a corrigendum," said a spokesperson for Elsevier. "In case there was any risk to patient safety, the journal eventually decided to fulfill the authors' request to retract."
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Cite this: Chinese Cancer Article Retraction Could Point to Regulators' Drive for Higher Clinical Research Standards - Medscape - Jun 21, 2019.