TOKYO—Claims made for the beneficial effects of a leading hypertension drug continue to unravel. A second medical school in Japan has found data manipulation and an undisclosed conflict of interest in a paper resulting from a large clinical trial of valsartan.
The main results of the study, known as the Jikei Heart Study, were published in The Lancet in April 2007. But "the scientific paper is fundamentally flawed, the lack of reliability cannot be denied," concludes an interim report (in Japanese) released today by an investigating committee of the Jikei University School of Medicine in Tokyo.
In a statement distributed at a press conference here, Seibu Mochizuki, the Jikei cardiologist who led the study and was the paper’s corresponding author, wrote "I take full responsibility." He also said that he has requested the paper's retraction.
Valsartan, marketed by Novartis, the Swiss pharmaceutical giant, was originally approved in Japan for the treatment of high blood pressure in 2000. In a postmarketing clinical trial, the Jikei Heart Study followed more than 3000 patients for 3 years with participants taking valsartan or an alternative hypertension drug. In their Lancet paper, the researchers claimed that patients taking valsartan not only saw improvements in their blood pressure, but also had reduced risk of stroke, heart failure, and other cardiovascular complications.
The Jikei investigating committee, however, found that a substantial amount of blood pressure data used for analysis did not match patient records, indicating deliberate manipulation. The report states that this manipulation was not done by anyone associated with Jikei, but occurred during data analysis.
The report also notes that an employee of Novartis Pharma, the Japanese subsidiary, was a member of the research team but his affiliation was not disclosed. The investigators concluded this was "a significant conflict of interest," according to the report.
The report states that "Mochizuki bears a heavy responsibility" as the study’s leader and primary paper author.
But it also notes that the Novartis Pharma employee, who is no longer with the company, was in charge of data analysis. According to the report, the employee met members of the committee and claimed to have had only minimal involvement with the data analysis and never saw the final paper. The committee concluded that the statements of the former Novartis employee “were, on the whole, not credible," the report states.
On 11 July, investigators at Kyoto Prefectural University of Medicine announced finding data manipulation in a similar clinical trial of the benefits of valsartan known as the Kyoto Heart Study. The paper reporting the main findings of the Kyoto Heart Study was retracted by the European Heart Journal in February. Three other medical schools are now investigating valsartan clinical trials.
At a 29 July press conference, Novartis Pharma President Yoshiyasu Ninomiya apologized for the trouble caused to patients, their families, the medical profession, and the public. The company also released a summary of a third-party investigation into the incident based on company records, e-mails, and interviews with key former and current employees. The report notes that one former Novartis employee was involved in five valsartan clinical trials and another former employee participated in at least one of those trials, activities that the company acknowledges were improper. But the investigators could not find any evidence that company employees manipulated data, though the report notes that investigators did not have access to computers owned by the former employees.
A health ministry official tells ScienceInsider that the ministry expects to finalize plans for its own investigation within the next 10 days. Novartis's Ninomiya promised full cooperation with any further investigations.