Tuesday, March 25, 2014

Turnabout is Fair Play - Why University of Illinois Students, Faculty and Alumni Should Question the Dean of Medicine about Novartis' Ethical Misadventures

Since 2006, we have posted repeatedly about  what was then a new species of severe conflicts of interest.  This occurred when leaders of academic medical institutions or other health care non-profit organizations or non-governmental organizations (NGOs) also serve as members of boards of directors of for-profit corporations  whose products and actions have major effects on health care.

Most recently, we discussed the cases of the current CEO of the National Quality Forum and past CEO of the American Board of Internal Medicine who was found to be on the board of for-profit hospital group purchasing organization Premier Inc, and had been on the board of its privately held but for-profit predecessors.  We also discussed the case of the incoming president of the US Institute of Medicine and former Chancellor of Health Affairs at Duke University who was on the boards of Alnylam Pharmaceuticals, Medtronic and Pepsico.

We also recently posted about the first time these sorts of severe conflicts of interest issue have been addressed in a large circulation medical journal.  A commentary in JAMA called for many such conflicts to be banned.

The JAMA article, and much of the discussion surrounding the NQF and IOM cases focused on how loyalties to outside for-profit corporations could affect leaders of academic and other non-profit organizations.  However, we also noted (e.g., here and here) how company directors should be accountable for the actions of their companies, even if they also happen to also be academic or non-profit leaders. 

Thus, academic and non-profit leaders may find themselves in the awkward position of being held accountable for unethical or even illegal actions of the companies on whose boards they sit.  Such corporate actions may contradict the mission of the institutions whose leadership is their primary job, and whose mission they are supposed to uphold. 

While we were writing about these somewhat convoluted, but very important issues, a fellow blogger discovered yet another academic leader serving on the board of a health care corporation, while simultaneously the media reported multiple examples of that corporation's ethical misadventures on his watch.  Those who care about that academic institution ought to question whether a leader accountable for such misadventures is fit to continue to lead.  Yet so far, no one has publicly juxtaposed this leaders' responsibilities to his institution's mission and how the corporation over which he is supposed to exercise stewardship has been taking actions that contradict that mission

The Dean of the College of Medicine at the University of Illinois Is a Director of Novartis

Paul Levy, blogging on Not Running a Hospital, noted a print advertisement for the Intuitive Surgical daVinci robot.  The advertisement implied endorsements by academic surgeons at the University of Illinois.  Levy suggested that surgical faculty acting as salespeople for a device company appeared to violate the university code of conduct.  This concern was heightened by the status of several of the surgeons in the advertisement as clinical and academic leaders.    

Mr Levy then discovered that the Dr Dimitri Azar, Dean of the University of Illinois College of Medicine, to whom these surgeon report, was on the board of Novartis, the multinational pharmaceutical and device company.  Dr Azar's position is easily verified by consulting the Novartis web-site.  Mr Levy further discussed the case here and here.  Then he  reviewed  the extensive dealings between the University of Illinois and Novartis and its subsidiaries, raising suspicion that the Dean's known involvement with the company may have lead to its favorable treatment by the university.

But wait, there is another major dimension to this problem. 

Novartis' Recent Ethical Misadventures

Novartis, over which Dr Azar is supposed to be exerting stewardship, has made a series of ethical missteps according to recent media reports.  I will summarize them in chronological order according to the date of media publication.

Novartis, Roche Fined for Anti-Competitive and Deceptive Practices in Italy to Encourage Sales of Lucentis

According to a March 5, 2014 article in the New York Times, Novartis was fined for anti-competitive and deceptive practices, 

Italian antitrust authorities said on Wednesday that they had fined two Swiss pharmaceutical companies, Novartis and Roche Holdings, a total of $250 million for colluding to keep doctors from prescribing a relatively inexpensive eye treatment in favor of a more expensive drug.

The authorities said the two companies had sought to steer doctors away from Avastin, an anticancer drug developed by Genentech that has been used for years as an off-label treatment for common eye problems. Instead, they said, the companies had tried to 'channel demand toward the much more expensive drug Lucentis, through an artificial distinction between the two products,' essentially by overstating the dangers of Avastin use.

It is not the first time such substitution efforts have brought an unwanted spotlight: Genentech got into trouble in the United States in 2010, when it was found to be offering doctors secret rebates to prescribe Lucentis over Avastin.

Novartis, which holds the rights to market the two drugs outside the United States, has been fined 92 million euros by the Italian regulators. And Roche, which acquired Genentech in 2009, was fined 90.5 million euros, for a total of about $250 million in the Italian case. 

Given that many drug companies have been cited for marketing their products for unapproved, or off-label uses, it is ironic that in this case, Novartis managers said they were shocked, shocked by the ruling because it could encourage off-label use:

 Novartis said in a statement that the Italian decision 'openly encourages and promotes the widespread unlicensed intravitreal use of Avastin contrary to the requirements of European and Italian regulatory law,' and 'undermines the European regulatory framework designed to protect patient safety.'

The NY Times also reported that one method the two companies were alleged to use to encourage Lucentis rather than Avastin use was to launder their message through patient advocacy groups,

The Italian authorities discovered numerous messages between Roche and Novartis in which the two companies discussed what kinds of communications would be needed to induce doctors and hospitals to adopt the more expensive product.

According to one such message from early 2013, cited in documents in the case released Wednesday, growing cost pressure in Italy and France to use Avastin had 'reinforced the political dimension of the debate,' and 'further reinforcement of the Lucentis value proposition to all stakeholders is critical.'

Another message called for the companies to 'work with diabetes patient groups to increase voiced concerns about safety risks of unlicensed therapies' — a reference to Avastin — for an eye condition known as diabetic macular edema.

Novartis Paid Doctors to Act as Marketers for Starlix and Other Drug

After the New York state attorney general filed suit against Novartis, a March 15, 2014 Newsday article included interviews with physicians that suggested how the company turned them into disguised marketers:

Dr. Howard Brand says he had one goal when he gave a speech at a Miami hotel in the early 2000s -- to tout the diabetes pill Starlix for the pharmaceutical company Novartis. 

The giant Swiss drugmaker, which reported $57.9 billion in global sales in 2013, paid the Stony Brook endocrinologist $1,500 for his talk at a doctors' meeting, Brand said in an interview. Novartis also paid for Brand's airfare and his weekend hotel stay, he said.

'It was self-serving, but I also thought it was a benefit to patients,' said Brand,...


 Brand, the Miami speaker, said in an interview that investigators had not approached him about the payments he accepted.

He said Novartis paid him a total of $10,000 to $12,000 for speeches, mostly at restaurant dinners it sponsored. The payments, which Brand said he received before 2010, are not reflected on the Novartis website.
Even [with] the notion that we were paid solicitors, I think people really paid attention,' he said. 'Of course, a lot of doctors just enjoyed going to dinner.'

Brand said he accepted more than $60,000 in speaker's fees from drugmakers, including Novartis, in one two-year period.

Another physician allowed that Novartis furnished the material for his "educational" talks,

Dr. Howard Hertz, a Babylon internist, confirmed that he had received $4,000 from Novartis in 2010 and 2011 for talking about its hypertension drugs to colleagues. Hertz said he dealt with a Novartis sales rep who brought information about the company's pills to his office. 'He would educate me about the product, give me slides to study,' he said.

Hertz said the slides were on CDs and made him an expert on Novartis drugs such as Diovan, a blood pressure pill, Lotrel and Valturna. He said he spoke mostly about Diovan and Lotrel.

'We had dinners whereby I would speak about the products and speak to the colleagues,' Hertz said. 'I became somewhat of an expert in these products.'

Note that Dr Hertz's expertise seemed to come exclusively from information provided by a company salesperson, making it obvious that he was not hired for his prior expertise as a physician.

The prosecutors allege that Novartis' payments of some $65 million amounted to illegal kickbacks.  This is only an allegation.  However, it seems obvious that Novartis paid physicians to act as salespeople.  Newsday asked bioethicist Arthur Caplan about these actions,

'To even hear about it just takes my breath away,' Caplan said. 'It sounds like egregious, inexcusable violations of agreed upon legal and ethical standards . . . with an inexcusably complicit group of physicians,' Caplan said.

Japanese Hospital Investigation Alleged Novartis Manipulated Research

A March 17, 2014 article in FiercePharma stated that Japanese investigators found that Novartis had manipulated clinical research to make its results appear more favorable to the company's products,

Novartis employees were more involved in a Japanese drug study than previously suspected, a Tokyo hospital official said. In an investigative report released last week, the University of Tokyo Hospital said doctors not only let Novartis  employees collect patient data from various trial sites but also allowed the Swiss drugmaker into its records on all 255 trial participants, Japanese media reports.

Plus, at least one Novartis employee was involved in planning the trial, designed to compare side effects of multiple leukemia treatments, the hospital found, according to Japan's Mainichi news. Those treatments included Tasigna, the company's follow-up to the hugely successful Gleevec (imatinib).

In fact, according to NHK World, hospital director Takashi Kadowaki said Friday that Novartis employees were 'virtually managing the study.' 

According to Mainichi, this sort of clinical research manipulation is taken very seriously in Japan,

 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.

It is obvious this story is not from the US, because the drug company has already apologized,

 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.'

Indian Regulator Cancels Import License Alleging Fraud by Novartis to Market Veterinary Drug

A March 18, 2014 article in the New Delhi Business Standard told how Indian regulators accused Novartis of fraud, opening with,

Swiss drug maker Novaris is likely to face legal action for allegedly faking documents to seek registration of its veterinary product Tiamulin Hydrogen Fumarate (80 per cent granules) in India. The drug regulator, Drugs Controller General of India (DCGI)), has already cancelled the company’s import licences as well as existing registration certificate for the product.


So in just the last few weeks, evidence appeared that Novartis engaged in collusive anti-competitive and deceptive practices marketing drugs in Italy, paid physicians to act as marketers in the US, manipulated drug studies in Japan, and lost an import license in India due to alleged fraud.  By the way, in 2013, Novartis was fined for anti-competitive practices in its marketing of Fentanyl by the European Commission (look here), and in 2011 its Sandoz subsidiary settled allegations of misreporting prices in the US for $150 million (look here)   Other Novartis misadventures from 2010 and earlier appear here.  So Novartis has quite an impressive, if not infamous record of ethical failures.

While he is Dean of medicine at the University of Illinois, Dr Dimitri Azar is also a director of Novartis, and hence has a fiduciary duty for the company's stewarship.  While questioning Dr Azar's role in the participation of his faculty in advertising for Intuitive Surgical, perhaps those who care about the reputation of the University of Illinois and its ability to fulfill its mission ought to ask how the poor ethical track record of the company Dr Azar is supposed to be overseeing reflects on his ability to defend the mission of the university and the medical school.

While parties that enable or enter into arrangements that create conflicts of interest in health care may be thinking mainly of the advantages that they may accrue, many of these arrangements create accountability and obligations, even if they are honored mainly in the breach.  If leaders of academic medicine and health care non-profit organizations insist on becoming directors, and hence stewards of for-profit health care corporations, they ought to be held accountable for the actions of these corporations, and how these actions reflect on their primary obligations to the academic and non-profit organizations they have also pledged to serve.

True health care reform would make health care leaders accountable for putting patients' and the public's health ahead of their own self-interest.

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