A health ministry panel is questioning Novartis Pharma K.K.’s use of clinical research data in promoting the sale of Diovan, its drug to lower blood pressure, saying it “could constitute misleading advertisement” after revelations that some of the data were manipulated.
The Japanese unit of Swiss pharmaceutical giant Novartis AG promoted its product, released in Japan in 2000, by claiming it works better than competitors’ rival drugs in reducing strokes and angina, according to the panel’s interim report.
While the panel expressed concern that the scandal may have tainted the credibility of clinical research conducted at Japanese institutions, there appear to still be many hurdles in getting to the bottom of the case.
Diovan, generically known as valsartan, was a blockbuster for Novartis. In Japan, its annual sales topped ¥100 billion in the five years after its 2000 release, and peaked at ¥140 billion in 2009. The drug accounted for nearly half Novartis Pharma’s entire annual revenue at one point.
In one of the company’s ads published in a medical journal, Novartis described Diovan as the “world’s most-prescribed drug.”
“Diovan was the star drug,” a sales employee said.
To reach out to medical professionals, the drug was promoted by publishing magazine articles featuring panel discussions by experts as well as lecture meetings.
Brochures for physicians and handouts for lecture meetings often featured research papers by Jikei University School of Medicine and Kyoto Prefectural University of Medicine, where clinical data for Diovan were later found to have been manipulated.
Since 2006, these research papers were cited around 700 times, according to Novartis Pharma. These citations were purported to boast the superiority of Diovan over rival manufacturers’ drugs.
“Research papers have their own ranks. The more they get published in authoritative Western medical journals such as Lancet, the greater their impact,” said a source close to Novartis Pharma.
The source acknowledged that the company greatly valued papers by the two universities that were published by prestigious medical journals. The universities have retracted the papers in question after the data manipulation surfaced.
Since the clinical studies in question were found to contain errors, Novartis Pharma’s claims in promoting Diovan’s efficacy could be construed as misleading. The study panel of the Health, Labor and Welfare Ministry cited “the need for more detailed investigations based on the Pharmaceutical Affairs Law.”
Noting this suggestion, an official at the ministry said, “The key point is whether Norvatis as a company was aware the contents of the research papers were false.”
The official indicated tough action could come from the government, saying, “We haven’t issued a penalty in the past on the grounds of advertisement regulations alone, but we don’t care whether there has been a precedent or not.”
The Pharmaceutical Affairs Law, however, offers limited investigation authority. A fine may be imposed to those who do not comply, but the law does not provide for mandatory raids or seizures of documents.
The law’s investigatory scope is also limited to pharmaceutical companies. Former employees are out of bounds. In the two universities’ clinical studies, a former Novartis Pharma employee was involved in the clinical studies as a statistical analyst without the person’s professional affiliation being revealed.
Jugo Hanai, a member of the health ministry panel and a representative of a liaison group of advocacy organizations for victims of pharmaceutical drugs, suggested the issue should also be examined in the context of high drug costs.
“Patients are forced to buy expensive drugs and insurers are forced to pay (high) insurance costs,” Hanai said.
The report said the issue should be examined by the Central Social Insurance Medical Council, which advises the ministry about pricing medical services and products.
Elsewhere, the scandal may overshadow Japanese clinical research. The interim report said Japanese scientists may have to clear “higher hurdles” in presenting their studies to overseas science journals from now on.
If that turns out to be the case, it could be a hindrance for pioneering fields such as Japan’s stem-cell research or development of new drugs.
On Sept. 26, Health, Labor and Welfare Minister Norihisa Tamura summoned David Epstein, a division head at Novartis AG, and sharply criticized the firm for triggering the latest scandal at a time when Japan is focused on boosting its strength in innovative medical technologies.
Speaking at a news conference at the ministry, Novartis Pharma President Yoshiyasu Ninomiya said the company was offering its “full cooperation” to the investigation.
Asked about the data manipulation, Ninomiya said, “I feel responsible for creating circumstances where such a thing could happen after the fact.”
Ninomiya categorically denied that the company as a whole was involved in the data manipulation, claiming an in-house probe did not point to such behavior. The company’s investigation even exonerated the former employee engaged in statistical data analyses.
“There is no evidence that (the former employee) was involved in data manipulation,” it said.
On this point, the ministry panel said the firm has a responsibility to provide more explanations.
“Our investigation has its own limits,” Ninomiya said. “We would like to cooperate with the investigation under the guidance of the health and labor ministry.”
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