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Study Finds Altering of Data for Diovan in Japanese Research

Data altered in Japanese research for Novartis blood pressure drug

TOKYO, July 12 -- (Kyodo) _ Data employed in a clinical study on Novartis Pharama K.K.'s blockbuster blood pressure lowering drug Diovan were found to be manipulated, the Kyoto Prefectural University of Medicine announced Thursday.

The research based on around 3,000 Japanese with high blood pressure was started in 2004 by Hiroaki Matsubara, a former professor at the university, who released papers between 2008 and 2012.

His study concluded that Diovan, generically known as valsartan, is more potent in reducing angina and brain strokes than other antihypertensive medicines.

At a news conference, a university official said its investigation showed "it is highly likely that this conclusion was erroneous." The university said it does not question the drug's intended efficacy of lowering blood pressure.

Asked if Matsubara could have deliberately tweaked data, University Vice President Shinji Fushiki said, "Those involved in the research give accounts that do not match up with each other, so we don't know who did manipulation where."

Matsubara requested that his papers be withdrawn, citing "data problems" in December 2012, after data in his study were questioned.

Altering data in such a large scale clinical study is thought to be rare in Japan. The university is believed to be considering filing a criminal complaint.

Rei Hashiguchi, a lawyer representing Matsubara said, "We are surprised by what was said at the news conference. We would like to withhold any specific comments at this point. (Matsubara) has not been involved in the manipulation."

His research on this drug has been called into question on other fronts as well. A Novartis Pharma employee was involved in analyzing statistical data but the employee's affiliation was not indicated in the papers. Matsubara's research team was also known to have received more than 100 million yen in grant from the drugmaker.

Novartis Pharma, a unit of the Swiss pharmaceutical group Novartis, said in a statement that it "cannot confirm if there had been any deliberate acts" of data manipulation in the course of research because of inadequate account in the university's report.

The university's report said Novartis Pharma refused a request for an interview with the employee in question. On this, the drug company said that the request was not met at the strong request of the person. The employee has retired from the company.

While noting the university's acknowledgement about its drug's effect of lowering blood pressure, the company said it regrets that the case is causing tremendous concern among university officials and patients. Diovan is one of the company's flagship products, generating just over 100 billion yen in revenue in Japan.

The university's investigation focused on incidences of stroke and heart failure of 223 patients whose hospital medical records have been confirmed.

It found that a total of 34 cases where an illness not listed in the medical records was cited in the analysis data used for the professor's papers or one found in the records was not in the analysis data.

Data changes were made to reduce incidences of illness among the group of patients who were administered Diovan, while they were increased among the group that was not given the drug. The university said there could be manipulation of data in cases handled by other hospitals.

Matsubara's study was intended to explore better ways of prescribing the approved antihypertensive drug in preventing serious cardiovascular diseases typical among people with high blood pressure.

It is not believed to have posed any danger to patients as a result of the data manipulation but it may undermine public trust in clinical studies.

Clinical study data are typically analyzed by a third-party institution and it is normally inconceivable that an employee of the seller of the drug is involved in such analyses. Some experts noted the need for oversight by public authorities and stiff penalties against such involvement.

The Novartis employee in question was also involved in Diovan research at Tokyo Jikei University, Chiba University, Nagoya University and the Shiga University of Medical Science. These universities have said they will also conduct investigations to see if there were any problems.

Posted: July 2013