‘Too good to be true’: A Chinese study on timing cancer therapy is retracted

BEIJING - Early this year, a medical journal article caught the attention of cancer patients and doctors worldwide because of its extraordinary conclusion. Simply changing the time of day that immunotherapy was administered appeared to produce a stunning benefit for lung cancer patients.

Those who received IV infusions in the morning had their cancer kept at bay for twice as long as those who got it in the afternoon, according to the results from a clinical trial in China and published in the journal Nature Medicine in February.

The study also reported that the patients lived nearly twice as long.

Several oncologists said that in recent months they and their hospitals had received a flurry of calls from patients inquiring about switching to morning infusions.

But on June 25, Nature Medicine retracted the study, citing a list of inconsistencies and irregularities in the trial’s design and results.

“It was too good to be true,” said Toni Choueiri, an oncologist at the Dana-Farber Cancer Institute in Boston, who helped conduct the post-publication review that led to the retraction.

Among the issues that the journal cited in its retraction notice: Records that were supposed to be locked before the study started were changed midway through.

There were discrepancies between the Chinese version of the study’s plan and the translated version.

Every patient remained treated and tracked in the study’s first year, and no one dropped out because of side effects – highly unusual in an oncology study. And unusual patterns were found in the timing of follow-up scans.

“Due to the amount and nature of the problems identified, the editors no longer have confidence in the integrity of the results,” the journal said.

Most of the study’s 28 authors were in China, with several collaborators in Europe. The study was funded by the Chinese government.

China has been pumping money into its hospitals and drug companies, fueling a surge of patents, publications and new clinical trials.

In just a few years, the country has rapidly transformed into a powerhouse in drug development, a shift that some US officials, doctors and executives see as a threat to long-standing American dominance in the field.

China’s critics often question the reliability of its biomedical research. Experts said that, similar to studies in the United States, China’s research output spans a wide range in quality: Some Chinese scientists run their studies at the most meticulous standards. Others were said to cut corners.

Yongchang Zhang, the study’s senior author, said in a statement that an internal review had “confirmed that part of the study execution and manuscript preparation might not reach the standards for publication in a high-impact journal”.

Zhang, a researcher at the Chinese hospital where the study was conducted, added: “We acknowledge these shortcomings and sincerely apologise for any inconvenience caused to the journal and its readers.”

He did not provide an explanation for the problems cited by the journal.

The study had enrolled 210 patients with advanced lung cancer at Hunan Cancer Hospital in Changsha, a city in south-central China.

Patients were randomly assigned to receive infusions of an immunotherapy – Merck’s blockbuster drug Keytruda or Tyvyt, which is not approved in the United States – either before or after 3pm.

The study reported that tumors did not progress for 11 months in patients who received the earlier infusions compared with six months for those given the later infusions. Patients receiving the earlier infusions lived for 28 months, compared with 17 months for those infused later in the day.

Those “were numbers we usually associate with new blockbuster drugs, not scheduling decisions,” wrote Gilberto Lopes, an oncologist at the University of Miami. And rescheduling a patient “costs nothing,” he noted.

Anil Makam, an epidemiologist and health services researcher at the University of California, San Francisco, said that such a drastic benefit, if real, would have prompted infusion clinics to overhaul staffing and scheduling to shift appointments to earlier in the day.

“If we believed the effects, it would be malpractice not to,” he said.

But within days after the study’s publication in Nature Medicine, online sleuths and physicians, including Makam, began raising concerns on social media and in blog posts. Less than three weeks after the study was published, the journal published an editor’s note saying it was investigating the issues.

In a statement on June 25, Joao Monteiro, chief editor of Nature Medicine, which is published by Springer Nature, said, “We are grateful to the research community for bringing these concerns to our attention.”

This article originally appeared in The New York Times.