How Pharma Funds Then Runs Clinical Trials, an example

http://mainichi.jp/english/english/newsselect/news/20140315p2a00m0na006000c.html

University of Tokyo admits giving Novartis Pharma patient info without permission

The University of Tokyo Hospital gave copies of questionnaires from 255 patients in a clinical trial to drug company Novartis Pharma K.K. without permission, the institution admitted in a mid-term investigative report released March 14. "It was a serious mistake, and this situation hurts the reputation of clinical tests," University of Tokyo Hospital Director Takashi Kadowaki told a news conference the same day. "We sincerely apologize to the patients. (The clinical trial) should be stopped."

Professor Mineo Kurokawa, who was in charge of the clinical trial, proclaimed during questioning by the hospital that he didn't know until December last year that the questionnaire copies had been given to Novartis Pharma, the Japanese subsidiary of Swiss pharmaceutical giant Novartis AG. The doctor working under Kurokawa who passed on the copies reportedly said they did not think sharing the information was inappropriate. The university will continue to investigate the issue and consider disciplinary action.

The sharing of patient information without permission was not the only problem announced by the hospital. It also admitted that a salesperson from Novartis Pharma handled the collection of patient data from medical facilities for the clinical trial, even though the trial involved the company's own leukemia drug. Furthermore, the hospital admitted that a Novartis Pharma employee or employees were involved in creation of the plans for the drug trial and the agreement form for patients, and that the research team used a slide made by Novartis Pharma with data analyzed by the company for an announcement at an academic society.

The clinical test, a comparison of the side-effects of multiple leukemia drugs, began in May 2012 and involved 22 medical institutions, with the University of Tokyo Hospital taking the central role. Novartis Pharma's patent for its leukemia drug imatinib --known by the brand name Gleevec and one of its main products -- is nearly expired. The company used the clinical trial's mid-term report in advertisements for its new leukemia drug. "The researchers were aware of the possibility (the trial data) would be used for advertisement purposes," admitted Kadowaki.

The university hospital furthermore revealed that an additional four clinical trials with connections to Novartis Pharma staff had been discovered at Kurokawa's lab, and these will also be investigated. The hospital stated that for the three years from when the clinical trials on leukemia drugs began, Kurokawa's lab received a total of 8 million yen in scholarship money donations from Novartis Pharma.

Senior Ministry of Health, Labor and Welfare officials called the case a serious situation and said the researchers involved showed a lack of ethics. They called for a detailed investigative report from the hospital and are considering punitive measures. The ministry will consider a new law to prevent corruption in clinical tests in the wake of a scandal involving the clinical trial of antihypertensive drug Valsartan.

A representative for Novartis Pharma's PR division said, "We want to apologize to patients and doctors. We must refrain from comment on the investigation, which is being handled outside our company." [But this is the norm and hiring a CRO (contract research company0, only makes the problem worse, because their production of the desired results is a de facto condition for future contracts.]

March 15, 2014(Mainichi Japan)

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The scandal started with a government investigation of advertising being passed off as science. The Japanese press carried the story and a series of at least 5 other stories as the investigation uncovered more dirt on Novartis. Novartis is the world’s largest pharmaceutical company with 2013 sales of $58 billion in drug sales—not counting other areas of business such as making GMO seeds.

http://www.fiercepharma.com/story/japan-files-criminal-action-against-novartis-exaggerated-diovan-advertising/2014-01-08 January 8, 2014 | By Tracy Staton

Japan files a criminal complaint against Novartis for 'exaggerated' Diovan advertising

The Diovan data scandal in Japan has spawned a criminal action against Novartis ($NVS). The country's Health Ministry lodged a complaint against Novartis today, accusing its domestic unit of exaggerated advertising.

It's the first-ever action of its kind against a drugmaker, the Japan Times reports. Under the country's pharmaceutical law, anyone found guilty of exaggerated advertising can face up to two years in prison or a fine of up to 2 million yen (about $19,400).

The criminal complaint isn't unexpected; Japanese authorities warned as early as September that Novartis could face criminal penalties for its Diovan promotions. The advertising in question was based on studies suggesting that Diovan (valsartan), a drug for high blood pressure, could prevent strokes and angina.

The problem is that a former Novartis employee had been involved in reporting the stroke-prevention data--and did not disclose his affiliation with the drugmaker. Tokyo's Jikei University School of Medicine retracted its Diovan research, published in The Lancet, after determining that some of the data was fabricated. Kyoto Prefectural University of Medicine also said its Diovan data was incomplete.

Novartis has said that it wasn't aware that the studies included fabricated data. But the company cracked down on its Japanese operation in the wake of the scandal. In October, Novartis pharma chief David Epstein cut local executives' pay by 30% and apologized publicly. "I would once again like to apologize for Novartis' involvement in this issue," Epstein said at the time. "Controls have been put in place to ensure this cannot happen again."

Authorities say Novartis has cited the questionable data, supporting Diovan as a preventive tool, about 700 times in ads since 2006.

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http://www.japantimes.co.jp/news/2014/01/08/national/ministry-targets-novartis-claims-for-legal-action/?#.Uycy5fldV8G

Novartis advertising probe intensifies with Tokyo office raid

Prosecutors came knocking at Novartis' ($NVS) Tokyo offices, stepping up their probe of the Swiss drugmaker's Diovan advertising. The Japanese authorities raided the local unit as part of an investigation into allegations that Diovan data was manipulated, and advertising for the blood pressure drug relied on that rigged data.

Japan's health ministry filed a criminal complaint against Novartis KK last month, citing the country's laws on truth in advertising. Prosecutors said that ads citing data from now-disputed Diovan studies could put Novartis on the wrong side of that law.

Exaggerated advertising of drugs in Japan can be punished by up to two years in prison, a fine of up to ¥2 million (about $19,600) or both.

The data scandal has been dragging on for months, since evidence surfaced that a former Novartis employee had been involved in reporting the stroke-prevention data--and did not disclose his affiliation with the drugmaker. Tokyo's Jikei University School of Medicine retracted its Diovan research, published in The Lancet, after determining that some of the data was fabricated. Kyoto Prefectural University of Medicine also said its Diovan data was incomplete.

Japanese authorities warned as early as September that Novartis could face criminal penalties for its Diovan promotions. The advertising in question was based on studies suggesting that Diovan (valsartan) could prevent strokes and angina.

Japanese media has reported that Novartis cited the questionable data, supporting Diovan as a preventive tool, about 700 times in ads since 2006.

If any employees are personally fined, it won't be the first time local workers have suffered financially from the scandal. In October, Novartis Pharma chief David Epstein actually cut Japanese executives' pay until the data probe is resolved. Sales of Diovan have declined since the scandal broke, Epstein said during the Oct. 3 press conference, but Novartis is more worried about the fallout's effects on its global reputation.

- see the story from Agence France Presse

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By JK: Can we trust clinical trials? Mountains of evidence point to numerous flaws, for example, with psychiatric drug trials 80% of patients and 87% physicians in double blind studies figuring out correctly if they are a in the placebo or drug cohort (see Prof. Irving Kirsch The Emperor’s New Drugs 2010). This phenomenon is called “breaking blind”. Others flaws from a long list include changing endpoints of studies to produce desired results, selecting participants quite different from the normal treatment group so as to produce favorable results, suppressing negative results. This is the norm since corporations have a financial interest in the outcome, and the corporations they hire firms (CROs) to distance themselves from exposure of violations of scientific research standards. These CROs have an even greater incentive to please their customers because their very existence depends upon their reputation of delivering results.

And it gets worse: a comparison of the raw data compared to the published articles found consistent positive bias in journal articles. In a truly rare case a group of professors obtained the FDA submission by pharma for psychiatric drugs. The difference between the published journal articles based on these trials and the raw data averaged a positive bias of 32%. Al 74 journal articles had positive bias, from 11-69%. The journal do not receive the raw data, thus the peer review is always flawed. Click on link for the article published in the NEJM.

There is a fundamental flaw between research and marketing. Patients are harmed when a less effective or dangerous drug is through marketing science “shown” to be best. This is what we have in our corporatist world where regulatory agencies function to promote pharma’s marketing goals. Investigations and fines don’t get at the core of the problem: it is just part of the façade of public protection and a cost of doing business. With pharma doing research, with pharma running the required continuing education classes of physicians, and the corporate media committed to pleasing their largest advertisers, the health care system is in shambles. Everything is cooked. For example, in 53 journal published results of laboratory research on promising targets for cancer treatments, 47 of them could not be duplicated, Begley & Ellis, see also Ben Goldacre, Bad Pharma, p. 32.

What follows below is not atypical, but the norm. It is the product of a system that rewards the, maximization of profits. Novartis was simply protecting their investment by making sure that the clinical trial provided favorable results. Novartis was involved in all aspects of the clinical trial. What is atypical is the press in Japan exposed the practice, and followed up with more articles. How many of you know that the block buster Vioxx killed caused over 125,000 heart attacks between 1999 and 2005 of which a 55,000 were fatal in the U.S.? The Vioxx horror became widely known among doctors thanks to a whistle blower, Richard Graham. Merck had already decided to withdraw the product because of an article published a meta-analysis on Vioxx in the Lancet on Nov 5^th 2004. How many of you know that Celebrex is a me-too version of Vioxx, and is still a heavily advertised block buster, even though in the high dose taken long-term for arthritic pain, Celebrex high dose increases the risk of a heart attack by over 3 fold? Over the years the Wikipedia article on Vioxx has been rewritten--as is the norm. The apple is rotten to the core.

And this core includes the corporate press, which in our country does minimal coverage of bad pharma, and tainted drugs from China and India. The core includes our government and those around the world which legislate pretend fixes and have pretend regulatory bodies.