Aducanumab Approval, Part 2

So how did a drug with such dubious benefit get approved? At best, another clinical trial might be warranted, but certainly not approval. It's a result

1. of a huge campaign by a company (Biogen) that would not accept the failure of its drug
and
2. of pressure from patient organizations like the Alzheimer's Association (which receives major money from pharma, including Biogen and its Japanese partner, Eisai).

The company campaign began in spring 2019, after its Phase 3 trials were stopped for futility after an interim review. A long, detailed, and excellent STATnews article published this week, drawing on insider sources, tells a fascinating but troubling story. The last-ditch effort to get approval was originally called "Operation Phoenix," but was re-titled "Operation Onyx." Biogen managed to get Billy Dunn, Director of the Office of Neuroscience at the FDA, on their side, to the point that he worked closely with them to provide a roadmap for approval, very inappropriately.

After the groundwork was laid for an approval of aducanumab despite the negative advisory committee recommendation, and prior to the announcing of a final decision, the patient organization campaign was carefully timed. In early May, the Alzheimer's Association launched a big campaign seeking to build grassroots support for drug approval. The "More TIme" campaign worked to pull at heartstrings with celebrity endorsements and poignant personal stories. Full-page ads were taken out in the Wall Street Journal and USA Today, and focused on what "more time" would mean to Alzheimer's patients and their families. There were google search ads, Facebook and Twitter and Instagram and LinkedIn posts. The campaign succeeded in getting over a million people to express support in petitions.

After the approval, the Alzheimer's Association spoke of victory:

As the first FDA-approved drug that delays decline due to Alzheimer’s disease, the approval of aducanumab (Aduhelm™) is a victory for people living with Alzheimer’s and their families.

Comments on articles including this one give the flavor of the passion with which some people want to try this unproven therapy.

Denying a medicine which might work is far more worse than approving one that might not work! Do you agree in the case of Alzheimer’s?

The negativity of these old fashion mentality is what has driven new discoveries to a halt. I don’t suffer from Alzheimer’s nor know anyone close to have been dx w it but we need to start somewhere. Prescribing the pharma will only help w research. Get in line MD.

Alzheimer’s is a horrible disease. If the medicine has a chance of success then prescribe it.

And public officials seem to be buffaloed. A Politico article said that not only are public officials mute about the approval, they are hesitant even about making a fuss about the pricing (about which more in another post):

[Politicians are] worried they’ll be seen as dashing desperate patients’ hope for an Alzheimer’s treatment — even one that may provide little or no benefit. The FDA’s controversial approval of Biogen’s drug, known as aducanumab or Aduhelm, has caught both political parties flat-footed ...Everyone is a bit terrified by Alzheimer’s, so the average person hears about the FDA approval of a treatment, and they don’t know about the controversy over whether it works or not,” said Craig Garthwaite, a health economist at Northwestern University’s Kellogg School of Management who lambasted FDA’s Aduhelm approval. “They hear there’s a new treatment and, that’s great, it’s a sign of hope. Do you want to be the politician who says, ‘I want to take that away from you?’”

Evidently, the public opinion campaign with its drumming up of support for this bogus drug has had its desired effect, creating cowardice to speak about the realities. Subsequent to the publication of the Politico article, two senators did speak out about pricing, but were careful to praise the drug:

Even as they criticize the price, however, Cassidy and Warren still stopped short of directly criticizing Biogen. They offered praise for the drug’s approval, too, calling it a “historic, watershed moment” in the history of the disease.

Public Citizen - who does not have to get elected - did not share this hesitancy. Their long public letter to HHS Secretary Xavier Becerra - which I recommend reading in full - begins as follows:

Public Citizen is writing to express its outrage over the Food and Drug Administration’s (FDA’s) indefensible decision to approve Biogen’s aducanumab (Aduhelm) for treatment of Alzheimer’s disease despite the lack of evidence that the drug provides any meaningful clinical benefit plus the fact that the drug has a well-documented risk of potentially serious brain injury. The FDA’s decision to approve aducanumab for anyone with Alzheimer’s disease, regardless of severity, showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.

They go on to ask for resignation of key officials in approving aducanumab, including FDA acting head Janet Woodcock and Billy Dunn. They also ask that the Office of the Inspector General for HHS investigate the relationship and "close collaboration" between the FDA and Biogen prior to Aduhelm approval. In addition, they want rescission of the bogus approval:

You should direct the next Acting FDA Commissioner to consider whether the agency’s approval of Biogen’s BLA for aducanumab should be withdrawn.

Those who pushed for approval seem eager to foreclose any discussions of rescission. In an interview, there was this question and answer with Acting FDA Head Janet Woodcock:

Question: "There’s been some reaction that every time this criticism comes up, the FDA just dismisses it outright and doesn’t really meaningfully engage on it —doesn’t do soul-searching. … Should the FDA do some soul searching? Should you and the FDA be trying to respond more directly to these critics?" Woodcock's reply: "I think we will have some more public soul-searching type of discussions on accelerated approval itself, but the soul-searching when a decision is made goes on before the decision, and once we’ve made the decision, we’ve made the decision."

Similarly, the head of the Alzheimer's Association wants to end discussion of the approval:

Harry Johns is ready to stop talking about whether or not the Food and Drug Administration should have approved Aduhelm, the divisive new Alzheimer’s treatment that got the green light last week. “Dwelling on the approval at this point is not productive for those who can benefit from the treatment,” said Johns, the CEO of the Alzheimer’s Association. The “negative voices” focused on criticizing the decision, he said, are “not pro-patient.”

But, if the aducanamab approval is not rescinded, what will happen and what are the consequences? More on that in another post.

Is the Cystic Fibrosis Foundation a Charity or a Venture Capital Firm?

We have often discussed how health care organizations now seem prone to diversion from their stated missions, often when money is the object.  While the organizations in question are frequently academic, teaching hospitals, academic medical centers, or medical schools in particular, in May, the Milwaukee Journal Sentinel presented an example of a disease specific charity.  This article deserves considerably more attention than it apparently initially received.

Background

The background was,

What happens when a disease-fighting charity dives into venture capitalism?

In the first case of its kind, the results include one of the planet's most expensive pills, huge sales projections for a drug company and windfalls for executives who sold stock in the glow of enthusiastic news releases about the drug.

Kalydeco is a breakthrough drug designed from knowledge of the genetic roots of cystic fibrosis, a lung disease that kills most victims before they reach middle age. Developed by Vertex Pharmaceuticals with a $75 million investment from the Cystic Fibrosis Foundation, it is an early example of 'venture philanthropy,' where a nonprofit helps finance development of a treatment in return for a cut of sales.

Remember that while disease specific charities often sponsor basic and clinical research, in this case, the CFF sponsored drug development.  In fact, much of the research on which this development was based was sponsored by charities and the US National Institutes of Health:

In the 1980s, Francis Collins, now director of the National Institutes of Health, was a researcher at the University of Michigan and on his way to becoming a renowned gene hunter.

Collins and a team headed up by Lap-Chee Tsui at the Hospital for Sick Children in Toronto collaborated to identify the gene responsible for cystic fibrosis. That breakthrough involved funding from the NIH, the Cystic Fibrosis Foundation and the Howard Hughes Medical Institute, said Collins.

Another decade of intense basic science followed, much of it funded by NIH.

The Price to Patients 

Despite, or perhaps because of the funding provided by CFF, Vertex chose a stratospheric price for its new drug.

 Yet it costs each patient $307,000 a year to take two Kalydeco pills a day - a price borne by taxpayers through Medicaid and other government programs and by the workers and companies who finance employee health insurance plans.

In 2012, with less than a full-year on the market, Vertex sold $172 million worth of Kalydeco....

To put that in perspective, the yearly cost of Kalydeco is approximately six times the median family income in the US.


Minimizing the Harms

To put it further into perspective, keep in mind that for the moment, the data from the single best published clinical trial on Kalydeco suggests that while the drug seems to help the average patient, it is not without risks, and it is certainly not a cure.

The largest published trial that followed patients for a reasonable amount of time appeared in 2011 in the New England Journal of Medicine.  [Ramsey BW, Davies J, McElvaney G et al.  A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011; 365: 1663-1672.  Link here.]  The study followed 161 patients for 48 weeks.  The patients treated with Kalydeco on average showed improved lung function (increase of FEV1 [forced expiratory volume in one second] of 10% compared to essentially no change (-0.2 percent) in the placebo group.  Treated patients were less likely to have an exacerbation of their pulmonary disease requiring hospitalization (31% vs 49%).  So the drug certainly seems to have benefits at least in the short term.  The number needed to treat to prevent one exacerbation requiring hospitalization in one year is five, which seems quite respectable.

On the other hand, the drug may have significant harms, even thought the report of the study seems to have attempted to minimize them.  The article stated

there was a lower rate of serious adverse events in the ivacaftor [Kalydeco] group than in the placebo group (24% vs 42%).  

However, this statement depended on a rather peculiar definition of severe adverse events.  In particular, pulmonary exacerbations of cystic fibrosis were included among severe adverse events.  Yet these are, as the term suggests, manifestations of the disease that is being treated.  Reduction of pulmonary adverse events should be and was considered a measure of efficacy.  So placing exacerbations within the definition of adverse events essentially double counts these incidents. 

Furthermore, the presence of these within the category of adverse events swamps out other events which may in fact be adverse results of the study drug.  If one subtracts pulmonary exacerbations and hemoptysis from the counts of serious adverse events, what remains is that patients on Kalydeco were more likely to have a serious adverse event (10%) than those on placebo (4%).  Thus the apparent number needed to harm was 17.  Thus, using this peculiar definition of adverse events appears to be a way to manipulate the analysis to minimize the apparent harmfulness of the drug.

While the study did appear to show that more patient received the benefit of avoiding a hospitalization due to a pulmonary exacerbation of cystic fibrosis than had a serious adverse event, the study did not show that the drug had overwhelming efficacy, or tremendous safety.   The study did not last long enough to show long term advantages, or to rule out rare but severe side effects.

This is the only drug available of this type, and it may well provide benefits that outweigh harms, at least over the short-term, but it is not a wonder drug, and the rationale to charge so much money for it, other than that is what the market will bear, is not obvious.  

A Windfall for Corporate Executives, and a Question of Insider Trading

The drug's approval has lead to a lot of financial success for stock holders, particularly Vertex executives:

 Last month, news about success of the drug sent Vertex stock soaring more than $6 billion in a single day. That surge and a similar one last May allowed top executives and directors of the company to sell stock and options worth more than $100 million.

The executives' lavish windfall occurred in somewhat questionable circumstances:

Vertex and its executives have benefited greatly from Kalydeco and foundation funding.

Last May, when Vertex and the foundation reported positive results from a clinical trial involving Kalydeco and whether it could be combined with another drug to treat more patients, the company's stock jumped more than 70%, from $37.41 to $64.85 a share.

Five executives and two directors sold off more than $35 million in shares, mainly at prices from about $55 to $64 a share. Many of the options were priced between $16 and $40 a share.

Three weeks later, the company said it overstated the effectiveness of the drug in that trial and the stock dropped about $7 a share, ultimately falling back under $40 by December.

Vertex spokeswoman Nikki Levy said in an email the company does not comment on individual stock sales.  She said the executive stock sales either were part of pre-existing 10b5-1 plans or followed the company's internal stock trading policy. A 10b5-1 plan is an automatic trading tool in which executives specify timing or pricing of sales to avoid questions about inside information the seller had at the time.

U.S. Sen. Chuck Grassley (R-Iowa) wrote a letter to the U.S. Securities and Exchange Commission, saying it could appear that Vertex executives took advantage of the situation, knowing the overstated clinical trial results would eventually be made public and cause the stock price to drop.

The letter said the stock sales were troubling for industry investors and the federal government, which pays billions of dollars a year for drugs through Medicaid and Medicare.

Judith Burns, a spokeswoman for the SEC, declined to comment on the Grassley letter.

Last month, the company's stock shot up more than 60% again, from $52.87 to $85.60, after positive early data from a clinical trial of Kalydeco and another drug it is developing with funding from the foundation. On April 19, the day after the news was released, the company's market value jumped by more than $6 billion.

That same day, two company executives sold huge chunks of stock options. Executive Vice President and Chief Financial Officer Ian Smith alone sold 745,685 shares worth more than $60 million. Most shares were sold at $81.50, with options purchased from $29 to $39.

So at least Senator Grassley raised the question of whether Vertex executives may have taken advantage of their insider knowledge to personally profit even more from this useful but not miraculous drug meant to be used on vulnerable patients.

Keep in mind that those huge trading gains were layered on top of already lavish compensation.  The 2013 Vertex proxy statement, the total compensation and stock holdings of its top executives in 2012 was:

Jeffrey M Leiden, CEO                                $5,656,684      441,160 shares
Ian F Smith, CFO                                           $3,109,193      795,434
Stuart A Arbuckle, Chief Commercial Officer   $4,808,697         66,477
Kenneth L Horton, Chief Legal Officer             $2,802,735         41,161
Peter Mueller, Chief Scientific Officer              $3,614,890        997,651
Matthew W Emmens, Former CEO                  $6,896,029    1,486,748
David T Howton Jr, Fomer Chief Legal Officer $3,447,898           3,105



So the top executives of Vertex, while their company got $75 million from an ostensible charity to develop what became an extremely expensive drug, got very rich in the process, although how they got rich may yet attract attention from the SEC.

A Windfall for the Cystic Fibrosis Foundation and its Executives

Furthermore, it appears that the supposedly charitable Cystic Fibrosis Foundation also made quite a bit of money, and its executives, while not getting quite as rich as their associates in Vertex, did not do at all badly.

As the Journal Sentinel noted,

the foundation cashed in by selling future royalties from the drug to an undisclosed firm for $150 million.

Keep in mind that since the CFF was to receive royalties, the money it gave for drug development was not a grant, but an investment.

Furthermore, according to the Foundation's 2011 form 990 (the latest available), its executives received the following total compensation from the foundation and its affiliated organizations:

Robert J Beall, CEO                                                      $1,073,725
C Richard Mattingly, COO                                              $759,799
Preston W Campbell MD, Exec VP of Medical Affairs     $736,031
Vera H Twigg, CFO                                                         $445,183
Ann Palmer, Senior VP                                                     $276,029 
Daniel Klein, Senior VP                                                    $277,300
Gregory August, CIO                                                       $262,698
David McLoughlin, Senior VP                                          $316,122
Glen Goldmark, VP                                                          $253,215
Amy DeMaria, Senior VP                                                 $241,672
Mary Dwight, Senior VP                                                   $246,232

These compensation amounts may be much lower than the gargantuan pay dealt out to for-profit health care corporate executives, but they are very high for those who are managing a supposed charity meant to help vulnerable patients.

A More Complex Web

While profiting from its underwriting of the development of Kalydeco, the CFF also sponsored guidelines about the treatment of cystic fibrosis, with not unexpected results.

Last month, new treatment guidelines for doctors who handle cystic fibrosis patients strongly recommended use of Kalydeco. The guidelines were funded by the Cystic Fibrosis Foundation.

Three of the 10 authors of the guidelines were employees of the foundation and four others worked for institutions that received grants from the foundation. The chairman, Peter Mogayzel, is a professor of pediatrics at Johns Hopkins University, which foundation tax records show received more than $2 million in grants from 2009 through 2011.

These guidelines hardly look like they would be deemed trustworthy according to the Institute of Medicine's standards (look here).  However, they certainly look like they might help sell ivacaftor, and hence help justify higher pay for the executives listed above.

Criticism of Venture Philanthropy

Merriam-Webster online suggests one definition of a charity is an institution funded by a gift for public benevolent purposes.

The Cystic Fibrosis Foundation appears to be such a charity, but now one that functions more as a venture capitalist.  In this case, it did provide venture capital to develop a new drug for its disease of interest.  However, the foundation appeared to have done so not to provide public benevolence, but to generate a  return on its investment.  It is using that return not for public benevolence, but to provide more venture capital to other drug companies, presumably with the goal of getting further returns.  Meanwhile, its executives make generous compensation for people who are supposed to be running a charity.  Finally, the drug has an astronomical price, and its pricing has helped make investors in and executives of the company supported by the CFF very rich.

This has not been lost on some dissidents, per the Journal Sentinel,

'The concept of a charitable, not-for-profit taking on the role of a venture capitalist is new and difficult to digest at the moment,' said Paul Quinton, a cystic fibrosis researcher at the University of California, Riverside and the University California, San Diego.

Quinton, who has cystic fibrosis, is one of 28 doctors and scientists who sent a letter to Vertex calling the price of Kalydeco 'unconscionable.' A copy of the letter was provided to the Journal Sentinel and MedPage Today. Kalydeco, the doctors wrote, costs 10 times more than what a typical cystic fibrosis patient pays in total drug costs.

'This action could appear to be leveraging pain and suffering into huge financial gain for speculators, some of whom were your top executives who reportedly made millions of dollars in a single day,' the doctors wrote.

Vertex responded with seeming contempt,

 Since receiving the letter last July, Vertex has raised the annual price of Kalydeco another $13,000.

The funding by the supposedly charitable CFF of guidelines that promote the drug it financed has also drawn criticism,

 'It is definitely a conflict of interest,' said Eric Campbell, an associate professor at Harvard Medical School who has researched conflicts of interest in patient treatment guidelines.

In the past, drug companies have been criticized for funding treatment guidelines that recommend their drugs. It is no different if the guidelines are funded by a foundation that gets royalties from drug sales, Campbell said.

Also,

'It is concerning that the organization now stands to profit when patients choose to use the drug,' ... [Prof Lisa Schwartz of Dartmouth Medical School] said. 'Financial entanglement with industry, even with the best of intentions, creates a conflict of interest.'

However, the very well paid CEO of the CFF pooh poohed concerns about conflicts of interest,

Robert Beall, president of the Cystic Fibrosis Foundation, said that without its financial support, drugs such as Kalydeco would never get to patients. Neither insurance companies nor patients have voiced any concern to him about conflicts of interest, he said.

'They applaud the decision and our business model to the utmost,' Beall said. 'The patients are excited.'

He rejected the idea of using the royalty money to help patients pay for the medical care, noting that the foundation needed the money to entice drug companies to get involved in risky cystic fibrosis drug research.

One wonders when patients would ever have the opportunity to voice any "concerns" to Mr Beall, who also disdained any restraints on the price of the drug,

.Beall said the foundation did not ask Vertex to price the drug more affordably.

'That would have been a deal-breaker,' he said.

That seems to put making money ahead of patients' needs.  Was this venture philanthropy, or vulture philanthropy? 

 Summary

We have discussed numerous cases in which non-profit health care organizations seem to put short term revenue ahead of their missions to further patients' and the public's health.  In this case, a disease specific charity seems to have foregone its mission to directly support patient care, teaching, or research to provide venture capital, an action which lead to a profit for the organization, huge profits for a drug company, large rewards for the charity's executives, and even greater wealth for the drug company's executives.  It did also lead to the marketing of a beneficial drug, but at a breathtaking price that no middle-class patient without exceedingly good insurance could afford.  

Where is the public benevolence here?  Where is the charity?  How much is about patients and how much is about  making insider executives wealthy? 

As we have said until blue in the face, true health care reform would ensure health care organizational leadership that upholds the health care mission, not their personal finances.  

Astroturf Grows in Britain

This is just in case anyone thought this was only an American pheonomenon. As reported by the Independent.

The rising tide of protest over the refusal by the NHS to provide expensive drugs for cancer and other conditions is being funded by the pharmaceutical industry, an investigation by The Independent has revealed.

Patient groups that have been among the most vocal in spearheading attacks on the National Institute for Clinical Excellence (Nice) over decisions to restrict access to drugs on the NHS depend for up to half of their income on drug companies, but details are often undisclosed.

Protests have been launched by charities including the National Kidney Federation, the Arthritis and Musculoskeletal Alliance, the National Rheumatoid Arthritis Society, Beating Bowel Cancer, the Royal National Institute for the Blind and the Alzheimer's Society. All of these charities received sums of up to six figures from drug companies in 2007.

The extent of the drug companies' support for the smaller charities has led to criticisms that supposedly grassroots patient organisations are puppets of the pharmaceutical industry, being used to bludgeon Nice into making the drugs available on the health service.

Yet none of the charities named has criticised the high prices charged by the pharmaceutical companies for their products in their recent campaigns.

The National Kidney Federation (NKF) accused Nice of taking a "barbaric, damaging and unacceptable" decision when it turned down four kidney cancer drugs for NHS use this year and pledged to campaign against the decision. It did not criticise the cost of the drugs, at more than £3,000 for a 30-tablet pack. Half the NKF's £300,000 budget comes from the pharmaceutical and renal industries.

The Arthritis and Musculoskeletal Alliance (Arma) organised a protest letter from 10 professors of rheumatology, published in The Sunday Times last month, over a recent Nice decision to restrict access to arthritis drugs. The letter made no mention of the cost of the drugs but Ros Meek, chief executive, admitted that "half, or more" of the charity's £147,000 income came from the drug industry.

The National Rheumatoid Arthritis Society described the same Nice decision as "another nail in the coffin" for arthritis treatment and launched an appeal against it this week, with Arma and three drug companies. The society received 49 per cent of its £300,000 budget from the pharmaceutical industry in 2005-06, reducing to 26 per cent of its £472,000 budget in 2006-07.

We have heard physicians and leaders of not-for-profit organizations funded by pharmaceutical companies and other commercial health care organizations protest again and again that their activities and decisions are uninfluenced by the source of their money. For example, we recently posted about the President of the US American College of Cardiology who revealed that this medical society receives 38% of its funds from the pharmaceutical industry, but has "firewalls" that prevent this sum of money from having any effect on how the organization operates. Yet, as the saying goes, "he who pays the piper calls the tune."

The current example, from the UK, highlights how organizations that get substantial commercial support never seem to manage to criticize the policies or actions of those who provide the support. One would think a charity devoted to the interests of patients with a particular disease might protest when drug companies charge outrageous prices for treatments for that disease, but as noted above, not one of the charities listed above did so.

So in the absence of transparency, accountability, and clear and enforced codes of ethics, those with health care goods or services to sell are more than happy to plow substantial funds into non-profit, "grassroots" organizations with the not unreasonable hope that such organizations will then promote the requisite marketing or policy agenda. Thus these supposed "grassroots" organizations are really astroturf, and allow their sponsors to engage in stealth health policy advocacy.

Hat tip to Ed Silverman on PharmaLot.

Advocacy in Whose Interest? - The Pharmaceutical Industry, the Epilepsy Foundation, and Generic Anti-Epileptic Prescribing

Just in time for another lazy summer weekend comes this article from the Wall Street Journal about another instance of cozy ties between the pharmaceutical industry and a disease-specific not-for-profit organization. (We posted about another such instance here.) The article's focus is how the Epilepsy Foundation has been campaigning against generic anti-epileptic drugs on a state level, while accepting significant funding from and leadership by pharmaceutical companies that make name brand anti-epileptics. First, the background,

Four major brand-name drugs used for epilepsy are expected to lose patent protection and face generic competition between next year and 2010. Those four drugs generated $5 billion in U.S. sales last year.

When a doctor writes a prescription for a brand-name drug, pharmacists are usually permitted in most states to make an automatic switch to a generic judged equivalent by the FDA.

In the late 1990s, the national Epilepsy Foundation, based in Landover, Md., raised concerns about anecdotal reports that some patients experienced seizures and side effects after switching epilepsy drugs. Some of the episodes involved patients who had been switched to a generic from a branded drug. The foundation also worried about cases in which patients were switched from one generic version of a drug to another generic version of the same drug.

The foundation theorized that some generic pills had a meaningful difference from the brands. This difference, it postulated, meant patients were getting more or less of the drug in their blood, causing some of them to have seizures or side effects. Foundation officials floated the idea in a 1999 meeting with the FDA.

The FDA's response: 'Show us the data,' recalls Sandy Finucane, who oversees state and federal policy for the foundation. The agency, unpersuaded by what it saw, stood firm in its long-held position that the difference was too small to have a tangible impact on patients.

In early 2006, the issue re-emerged as legislation requiring doctor permission for switches was proposed in Illinois.

In May 2006, the national Epilepsy Foundation convened a committee of medical experts to examine the question. The committee found a lack of authoritative studies showing that such drug switches cause problems, says its chairman, Steven Schachter, a Harvard Medical School neurologist. Nonetheless, it recommended that doctors give explicit approval for switches, citing anecdotal reports of seizures and noting that such attacks can be serious.

Now, about those ties among the foundation and pharmaceutical companies.

The foundation and its state affiliates receive funding from the epilepsy-drug makers. GlaxoSmithKline PLC and UCB SA donated $500,000 to $999,999 each in fiscal 2006 to the national foundation, according to its annual report. Abbott Laboratories and a Johnson & Johnson unit each contributed $100,000 to $499,999. Representatives of four drug companies sit on the foundation's board, as does PhRMA chief Billy Tauzin.

The foundation says its diverse funding base shields it from undue drug-company influence, and the industry executives on its board didn't participate in discussions of the drug-switching issue. Foundation leaders note that the state bills would generally require doctor permission for several kinds of switches, including when a patient goes from a generic to a brand.

'These are people's lives that we're talking about -- nothing about stock options and stock value and how this would affect [companies'] bottom line. That would be insulting to us to have discussions like that,' says Sindi Rosales, the head of a foundation affiliate in Texas, one of the states that weighed legislation this year. She says pharmaceutical companies are 'fabulous partners' and their help in several areas 'has been amazingly tremendous,' but the companies leave it to the foundation to call the shots.

For their part, company executives describe their lobbying role as limited and say the bills were primarily an initiative of the foundation, although they acknowledge in certain cases that company officials have gotten directly involved. Executives say the aim of these activities is to protect the health of patients.

Here we go again. We have noted before that conflicts of interest may not consciously affect human decision making, and how people affected by conflicts may be genuinely indignant when confronted with suggestions that the conflicts consciously influenced their decision making. But, "people who have conflicts of interest often find giving clear advice (or opinions) particularly difficult" (see post here).

However, there is ample evidence that conflicts may affect how people think and what they do. Try a thought experiment. If you knew that your organization were getting a large amount of money from donor x, would you be more likely to take a position that directly goes against the interests of donor x, or the opposite?

In any case, this case appears to be yet another example of stealth health policy advocacy or stealth lobbying, and one that may succeed in keeping the costs of drugs rising ever higher.

See Pharmalot's related post here, and the Wall Street Journal's Health Blog's here.