University’s plan to pull report on Diovan a blow to Japanese research
July 31, 2013
Jikei University School of Medicine’s plans to pull a paper on the hypertension drug Diovan from a prestigious British medical journal due to “data manipulation,” which suggested it could help treat other ailments, will hurt the credibility of Japanese clinical research.
In addition, the controversy is putting the drug itself under a cloud with some hospitals moving to stop prescribing Diovan for patients, although no one is questioning its effectiveness in treating high blood pressure.
The university's decision to withdraw the 2007 paper in the Lancet would also hurt the reputation of the Swiss-based Novartis Pharma AG, raising ethical concerns about the company’s behavior concerning its best-selling hypertension drug.
An investigative panel formed by the university to look into the allegations of rigged data for Diovan told a news conference in Tokyo on July 30 it has concluded that the results were cooked.
The panel also said it strongly suspects an employee of Novartis Pharma KK, the pharmaceutical giant's sales arm in Japan, who was involved in the university’s study on Diovan that started in 2002, was responsible for the manipulation.
The panel said the individual, who has since resigned from the company, conducted statistical analysis of the data for the study on his own. But he denied it in an interview with the panel.
The university said it is “appropriate” to withdraw its research team’s paper on Diovan from the Lancet due to “the lack of reliability as a scientific paper” following the panel’s findings.
The withdrawal is expected to have far-reaching ramifications. The Japanese Society of Hypertension cites the paper in treatment guidelines, a key yardstick used by physicians in treating patients.
Novartis Pharma in Japan touted Diovan’s benefits for other ailments in addition to reducing high blood pressure, such as reducing the risk of stroke and angina, in literature presented to doctors based on the reports by the university and Kyoto Prefectural University of Medicine, which also conducted a clinical study on the drug.
In a market crowded with similar drugs, the reports by the two universities gave a tremendous boost to Diovan sales.
The drug took in 108.3 billion yen ($1.1 billion) in sales in 2012. It was introduced in the Japanese market in 2000 after the health ministry's approval earlier the same year.
In light of the growing research scandal, some hospitals are moving to stop prescribing Diovan. Saiseikai Central Hospital in Tokyo decided to discontinue the use of the drug from Aug. 5 out of ethical considerations.
Officials with some hospitals said they will switch to other drugs at the patient's preference.
A 75-year-old male patient in Yokohama who has been taking Diovan for six years said he will switch to a different drug.
The man said his doctor recommended Diovan as “the best hypertension drug.”
“I feel betrayed if falsified data was used to sell the drug,” he said.
The Jikei University School of Medicine is the second university to acknowledge impropriety in connection with Diovan.
Kyoto Prefectural University of Medicine admitted earlier this month that its data was manipulated.
But it stopped short of blaming the former Novartis Pharma employee for tinkering with the data.
The former employee was involved in similar clinical studies on the drug at three other universities: Shiga University of Medical Science; Chiba University; and Nagoya University. Investigations are under way at the universities to find out if data was also falsified in those studies.
Data was falsified apparently to draw a conclusion that Diovan appears effective in preventing other ailments, such as stroke and angina.
Novartis Pharma in Japan denied the allegations of data manipulation on July 29, citing the results of a probe by a third party that was commissioned by a law firm at the request of Novartis headquarters in Switzerland.
“No evidence has turned up to point to rigged data,” a representative from Novartis Pharma in Japan said.
The study in question at the Jikei University School of Medicine was conducted by a team led by Seibu Mochizuki, a former professor of cardiovascular internal medicine at the university. It covered 3,081 Japanese patients suffering from high blood pressure.
The team's paper published in the Lancet in 2007 said Diovan is effective in preventing stroke and angina based on its clinical study.
The university’s investigative panel compared data of blood pressure for the 671 patients the university still retained and the corresponding data used in the study.
Of the 671, there were discrepancies in 86 cases, or 12.8 percent.
The panel confirmed that the data kept at the university was identical to the figures entered at medical records for 485 patients.
The panel concluded that the data was manipulated at the stage of statistical analysis.
“Researchers at the university were not involved in (conducting data analysis),” said a member of the panel. “It was all done by the former employee.”
The panel said the former employee denied the allegation during the interview with investigators last weekend.
But the panel countered that it has evidence to prove otherwise.
“An individual can do (manipulation of data) easily,” said Kazuhiro Hashimoto, professor of cardiovascular surgery at the university, who sits on the panel.
The panel also said that the Japanese arm of Novartis Pharma’s assertion in the paper that the company had no part in designing the clinical study and data analysis on Diovan is false.
“Mochizuki’s responsibility for listing a false fact is grave,” the panel said.
In a report on the clinical study submitted by the former Novartis Pharma employee, he was listed as the representative of the body that conducted the data analysis.
The panel disclosed that Mochizuki’s lab received a total of 84 million yen in research grants between 2005 and 2007, when he retired from the university.
Novartis Pharma in Japan said it also provided research funds to the four other universities involved in the studies on Diovan.
The Ministry of Health, Labor and Welfare will establish a task force under the minister to launch an investigation into the scandal.
(Naoya Kon and Fumikazu Asai, a senior staff writer, contributed to this article.)