TOKYO ­– The controversy in Japan surrounding Novartis Pharma KK's blood pressure drug Diovan (valsartan) grew more intense over the last week following the arrest of a former employee and a raid of the company's offices.

Japanese prosecutors showed up at Novartis' Tokyo offices on June 12, a day after authorities arrested Nobuo Shirahashi, 63, who had earlier appeared on Japan's national broadcaster, NHK, denying that he had falsified data related to clinical trials of Diovan, the company's best-selling drug used to treat blood pressure.

Novartis acted quickly to apologize publicly for the recent fiasco. The company posted a statement on its website apologizing for "causing great worry and trouble."

As it has done in previous statements, the company has pledged "to fully cooperate with the investigation and authorities" but has not admitted any wrongdoing.

These events come six months after Japan's Ministry of Health, Labour and Welfare filed a complaint with prosecutors alleging that the company exaggerated benefits in its advertising of Diovan. This could result in criminal charges against the Japanese subsidiary of the giant Swiss pharmaceutical firm for violating drug marketing laws.

Diovan is an angiotensin II receptor antagonist that keeps blood vessels from narrowing, thus lowering blood pressure and facilitating blood flow.

"The Novartis saga goes on and on, when it will stop no one knows," said R. Reed Maurer, president of the Tokyo-based life sciences consultancy, International Alliances Ltd. (IAL). "Obviously an arrest of a former employee takes it to a new level. The whole affair has a negative impact on Diovan sales in Japan."

In fact, Maurer told BioWorld Asia, his own doctor switched him off Diovan, and instead gave him a drug from Daiichi Sankyo Co. Ltd., of Tokyo. Diovan also has been taken off the menu for other patients, sometimes at the patients' own request.

"The end result of all this should be tighter regulations on conflicts of interest between medical institutions and pharma companies," Reed said.

In addition, Iwao Kuwashima, director of Proper Evaluation Studies on Clinical Research, said that "the Japanese public has lost confidence in the medical community because of the arrests over the unethical way the medical research was conducted. This is what happens when you combine physicians with companies. Again, collusion will take place when you mix companies and doctors. We need to know what happened here."

The whole affair started last July when Novartis Pharma KK admitted that a former employee had created a conflict of interest by participating in clinical studies of Diovan conducted by five Japanese medical schools, while concealing his affiliation with the company. Several studies were retracted after investigators concluded that data had been manipulated to skew the results.

According to some reports, a substantial amount of blood pressure data used for analysis did not match patient records, indicating deliberate manipulation. It would appear that this fudging of the data occurred during analysis, rather than at the time the data was collected.

A representative of Kyoto Prefectural University of Medicine, where some of the clinical research was performed, issued a statement on June 17 that said: "We want to say that we regret the arrest of former employees of Novartis and we will continue to cooperate in the investigation by the prosecutors and want to strive to prevent this from ever occurring again."

The company's advertisements, however, featured the studies, claiming that the use of Diovan reduced the risk of heart attack and stroke in hypertension patients better than alternative medications.

If the company is found guilty of having breached Japan's false advertising laws, there is the potential for fines to be levied against Novartis and there is an outside chance that executives could face penalties of up to two years in prison.