Medical Journal retracts study claiming cancer treatment is more effective when given in the morning

Earlier this year, an article in a medical journal caught the attention of cancer patients and doctors worldwide because of its extraordinary conclusion. Simply changing the time of day when immunotherapy was administered appeared to provide amazing benefits for lung cancer patients.

According to results from a clinical trial in China published in February in the journal Nature Medicine, those who received intravenous infusions in the morning were kept at bay twice as long as those who received them in the afternoon. The study also reported that patients lived almost twice as long.

Several oncologists said they and their hospitals have received numerous calls in recent months from patients inquiring about switching to morning infusions.

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

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

The issues the journal cited in its retraction notice included: Records that were supposed to be locked before the study began were changed midway through. There were discrepancies between the Chinese version of the curriculum and the translated version. Every patient remained treated and monitored for the first year of the study, and no one withdrew from the study due to side effects – highly unusual in an oncology trial. And unusual patterns were noted at the timing of follow-up visits.

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

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

China has pumped money into its hospitals and pharmaceutical companies, leading to a flood of patents, publications and new clinical trials. In just a few years, the country has quickly become a drug development powerhouse, a shift that some U.S. 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 China’s research results, similar to studies in the United States, cover a wide range of quality: Some Chinese scientists conduct their studies to the most meticulous standards. Others are said to have cut corners.

Dr. Yongchang Zhang, the study’s senior author, said in a statement that an internal review “confirmed that some of the study conduct and manuscript preparation may not have met the standards for publication in a reputable journal.”

Dr. Zhang, a researcher at the Chinese hospital where the study was conducted, added: “We acknowledge these shortcomings and sincerely apologize for any inconvenience caused to the journal and its readers.” He did not provide an explanation for the problems cited by the magazine.

The study involved 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 immunotherapy — Merck’s blockbuster drug Keytruda or Tyvyt, which is not approved in the U.S. — either before or after 3 p.m

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

These “were numbers we typically associate with new blockbuster drugs, not with planning decisions,” Dr. Gilberto Lopes, an oncologist at the University of Miami. And rescheduling a patient “costs nothing,” he noted.

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

“If we believed in the impact, it would be misconduct not to do it,” he said.

But just a few days after the study was published in Nature Medicine, online detectives and doctors like Dr. Makam to raise 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 Thursday, Dr. João Monteiro, editor-in-chief of Nature Medicine, published by Springer Nature, said: “We are grateful to the research community for bringing these concerns to our attention.”

Some scientists have long been fascinated by the idea of ​​harnessing the body’s circadian rhythms to make drugs more effective or less toxic. For example, enzymes that the body uses to break down certain medications are more abundant at certain times of the day.

But critics of the Chinese study argued that immunotherapy works very differently than fast-acting drugs like Tylenol. The drug Keytruda remains in the body and takes effect over several weeks. The study failed to identify a biological reason for a difference in treatment timing that would provide such a significant benefit.

“There was no sound scientific reasoning behind it,” said Dr. Roy Herbst, the new director of the Dartmouth Cancer Center in New Hampshire and Vermont.

In March, a team led by European researchers reported the results of an analysis that examined whether more than 3,000 cancer patients in eight studies had received immunotherapy in the morning or afternoon. Their study, funded by drugmaker Roche, which sells a range of cancer drugs, concluded that timing was “probably not a determining factor” in how well patients fared.

Other studies looking at the results have found a link between the time of day patients receive cancer immunotherapy and their health status. But the why remains unclear.

Doctors said it’s possible that more energetic and healthy patients might opt ​​for morning slots. Poorer or rural patients who live far from an infusion center and who tend to be worse off may ask for afternoon slots because they have to spend the morning traveling to their appointment.