No, Pharmascolds Are Not Worse Than The Pervasive Conflicts Of Interest They Criticize
Let’s start with a quick poll:
Which is worse?
- A. The pervasive influence of industry on medicine, which has undermined the independence and altruism of physicians.
- B. The critics of industry influence, who have created a paranoid culture of distrust which has undermined the partnership of industry and physicians that has brought medicine to its current heights.
If you chose B then you are going to really love Lisa Rosenbaum’s 3-part series in the New England Journal of Medicine in which she argues that the reaction against the influence of industry has proved to be far worse than any damages those conflicts of interest (COI) have actually produced.
I think Rosenbaum is almost completely mistaken in her views, but first let me state that she has some legitimate points. Undoubtedly there are some “pharmascolds” who have gone too far, and it is always legitimate to raise questions about reformers, their motives, and their effects, intended or otherwise. But it is also important to keep in mind the totality of the issue and place these legitimate questions in a broader perspective. Unfortunately, in her articles Rosenbaum completely fails to draw the larger picture. To use a highly imperfect analogy, Rosenbaum’s focus on the imperfections of industry critics without fully appreciating the full magnitude of industry influence is akin to focusing on the imperfections of the extreme anti-slavery abolitionists in the 19th century while ignoring the overwhelming tragedy of slavery. Or, to use another imperfect analogy, it’s a bit like focusing on the extreme activities of a group like Greenpeace while ignoring the much larger and more important problem of climate change.
Responding to Rosenbaum isn’t easy, since the articles, though beautifully written, do not present a coherent and cogent position. Instead, hidden behind the flowing prose is an outpouring of irritation and distaste for industry critics and their influence.
At numerous points in the series she admits that there has been an enormous amount of unethical and illegal behavior by industry and physicians, but time and again she fails to follow through. Rosenbaum admits, for instance, that industry has given gifts to physicians, which she herself describes as “a practice that smacks of bribery.” But, she writes, this practice has not been shown to harm patients. Instead, she asks, where is the evidence that these illegal and unethical behaviors have caused harm? Where is the evidence that this has resulted in physicians losing sight of the interests of their patients?
But does she really want to argue that we shouldn’t be disturbed by evidence of corruption because there is no objective assessment of its harm? By that logic, we should repeal all laws prohibiting bribery of public officials until we can empirically demonstrate the disastrous effects. By then, I’m afraid, it will be too late. The absence of evidence is not, decidedly, evidence of absence, notes James Stein, a cardiologist at the University of Wisconsin who has thought long and hard about COI. ”Harm is very hard to show, especially in a sociological context,” he observes.
Rosenbaum begins her series of articles with a discussion about statins, complaining that the evaluation of these drugs has been poisoned by undue COI concerns which have buried the crucial point that statins are “the best drugs we have to prevent cardiovascular disease.” Even though many members of the guideline committee that recommended statins had industry ties, she writes, it is clear that they were working in the best interests of everyone. In fact, she correctly observes, nearly all statins are now available in generic forms so industry interest is quite small at this point.
She’s right, but she misses a bigger point. Except for a few fanatics very few people have questioned whether statins are valuable drugs. We all know they are good drugs. The question is in what patient population are they truly valuable? When are they cost effective? The debate isn’t about whether people should take statins. There is absolutely no serious debate that there will be millions of people taking these drugs. The debate is instead about identifying the best possible population. To help resolve that kind of question requires people who are not preprogrammed to prescribe pills to nearly everyone. When the guidelines came out these were the kind of reasonable questions that were raised. But in Rosenbaum’s cartoon glasses she sees a ”rush to conclude that the guidelines were part of an industry plot,” and further evidence of “industry greed.”
“The question is not were the guideline writers good people,” said Stein. “I know them. They are ethical people and physicians. The question is if they were unduly and subconsciously influenced by their relationships with pharma. Empirical social science research shows that such bias often is unconscious and self-serving. In fact, research shows that humans are susceptible to bias even if the bias is at random– and clearly the payments and industry trelationships were not made at random. They were highly targeted. Bias does not make you “bad”– it makes you human.”
Calcium Channel Blockers
After considering the statins Rosenbaum goes on to recall the controversy over another class of drugs, the calcium channel blockers (CCBs), in an attempt to illustrate her views. CCBs, you will recall, were among the most successful drugs in the golden age of pharma in the 1980s and 1990s. An enormous controversy– one that served as a prototype for the more recent Vioxx and Avandia episodes– exploded when several prominent “pharmascolds” questioned the safety of CCBs and claimed that these safety concerns had been hidden by investigators with COIs with the CCB manufacturers. Writes Rosenbaum:
“…the physicians who favored the use of calcium-channel blockers were right. Subsequent randomized trials demonstrated both the safety and efficacy of calcium-channel blockers, and they thus remain a common treatment for hypertension. Why is no light being shined on this relevant fact?”
But I think Rosenbaum has chosen an unfortunate example. The fact that the CCBs proved safe– ie, didn’t cause cancer– is only a small part of the story. Just because the safety concerns proved unfounded doesn’t mean it wasn’t legitimate to raise the concern. It has become painfully obvious that we need to be vigilant about the safety of drugs, especially when they are so widely used in millions of people.
Furthermore, is there any question that the CCBs were massively overused? For many years they were the dominant antihypertensive agent. It wasn’t until after a very large government trial, which industry did everything in its power to discredit, that the less expensive generic diuretics became, again, the first choice agent to lower blood pressure. In addition, due to the efforts of industry-fuelled research and key-opinion-leader (KOL) physicians on the big time industry payroll, CCBs were widely prescribed for “silent” ischemia, angina, acute coronary syndromes, heart attacks and even heart failure. These are all indications that have now been largely debunked or fallen out of favor. The difference now: all the CCBs are now generic. Back in the day the CCBs were probably the single biggest industry-supported gravy train. When Rosenbaum writes that “the physicians who favored the use of calcium-channel blockers were right” she is really quite wrong.
I don’t want to be misunderstood here. CCBs represent a great advance, and they would not have been possible without the partnership between industry and physicians. But the CCBs are also an example of how COIs can distort medical practice and priorities.
Fear and Sunshine
Rosenbaum writes that the strident voice of the “pharmascolds” silences “honest discourse” and discourages “productive collaborations.” She cites people she interviewed who were afraid to say positive things about industry on the record. But, once again, she misses a much larger and more important point, and she confuses cause and effect. It’s really important to realize that the movement toward sunshine and COI disclosure was motivated in large part because the vast proportion of industry’s relations with physicians was so completely and thoroughly hidden. The movement for transparency was a response to the completely opaque nature of industry-physician relations in the past. Blaming silence about the topic of industry influence on the critics of industry influence is disingenuous at best.
Rosenbaum correctly claims that there are many forms of bias which have nothing to do with money or industry. By focusing on bias from industry she argues that we may be missing more important or dangerous forms of bias. But two wrongs don’t make a right and no one would reasonably disapprove of efforts to understand and possibly curb one form of bias just because other forms still exist. The different types of biases are neither mutually exclusive not competitive. To think otherwise is a classic rationalization of bad behavior.
Rosenbaum digs up extreme examples to support her view. She ridicules a medical student who employed language used to describe rape and child abuse to describe the experience of being subjected to listening to an industry-funded faculty member extoll the benefits of statins. Of course that type of reaction is silly. But the extreme exaggeration doest mean there isn’t a legitimate underlying problem. Does Rosenbaum really want to argue that it’s unreasonable to ask whether medical education should be in the control of doctors who are largely funded by industry? (Most people don’t realize but at many medical schools a significant portion of faculty income comes from industry. Academic salaries are notoriously low– at least by comparison with the salaries of doctors outside of academia– and many faculty members receive a substantial portion of their income by consulting, performing research, giving talks, etc.)
A Wall Street Journal Article
A significant portion of Rosenbaum’s long and convoluted argument is devoted to decrying “the desire for retribution against ‘bad pharma’… in a way that obscures the possibility that we are obstructing medical advances.” She suggests that this desire for retribution has created a kind of McCarthy-like demonization of industry supporters. But she never actually delivers any cases of concrete damages.
One case that she does cite fails to support her case upon careful examination. She is highly critical of a front page Wall Street Journal article that focused on a well-known cardiologist (David Kandzari, though Rosenbaum doesn’t mention his name) who did research for Boston Scientific (and other companies) and also served on an FDA advisory panel that evaluated a Boston Scientific product (but not the one Kandzari had worked on).
Rosenbaum rightly explains that the WSJ article failed to include a lot of important details. She notes, for instance, that “we are told that he received $ 100,000 in industry payments over 5 years. No mention is made of how much of it went to his employer or to research, or of the strict institutional de minimis requirements he followed.” Although Kandzari voted in favor of the Boston Scientific device (the Watchman), he was joined by other panel members without COIs and, according to Rosenbaum, despite “appropriate clinical justification” the article insinuated that “his true motive was financial.”
Now I actually agree with Rosenbaum that the WSJ article was over the top. It failed to consider the nuances that Rosenbaum mentions. But let’s be clear. This is not an example of yellow journalism or a McCarthy-type attack. Rosenbaum greatly exaggerates the danger: ”At best, the endless gotcha quest simply ruins some reputations unfairly.” But Kandzari’s reputation wasn’t ruined. He’s not a pariah in medical circles, roaming the earth like the Ancient Mariner telling his tale of woe and hubris. He remains the director of interventional cardiology and the chief scientific officer at the Piedmont Heart Institute in Atlanta. He’s still a highly visible and respected cardiologist who speaks at conferences and runs clinical trials. But he is a public figure and so he is subject to open discussion and criticism. (Full disclosure: I’ve known Kandzari for 15 years, since he was a cardiology fellow at Duke. He’s one of the smartest guys I know and I quote him often. But I am also aware that he works a lot with industry and I try to find alternative perspectives when necessary.)
Woulda Coulda Shoulda
Rosenbaum speculates about the potential dangers of the demonization of relations with industry but fails to imagine alternate scenarios that don’t fit her predetermined perspective. For instance, she writes:
Perhaps effective therapies are adopted more slowly when industry representatives are banned from our workplace.
But she fails to consider the alternate fact (not possibility) that ineffective therapies have been rapidly adopted due to the presence of industry in the workplace. (Here’s just one out of many possible examples: the rapid introduction and success of the heart failure drug nesiritide from Johnson & Johnson.)
Rosenbaum raises another possibility:
Perhaps we miss opportunities to understand complex medical topics because experts aren’t permitted to write about them.
But she fails to consider that in fact we miss opportunities to understand so much of medicine because there is simply no commercial backing for these parts. Why don’t medical students and physicians learn more about nutrition and exercise? What would happen if even a small portion of the money spent on developing new drugs and devices was allocated to testing and finding effective diets, exercise, and lifestyle interventions?
And Rosenbaum suggests yet another possibility:
Perhaps life-saving therapies whose development requires the combined talents of clinicians and industry scientists don’t materialize.
But she fails to consider the host of drugs and devices that were thought to be “life-saving” but that have turned out to be nearly worthless. For instance, as a society we’ve now spent tens of billions of dollars on new diabetes drugs, yet the only thing we know so far for sure is that these drugs don’t save lives. And, to mention just one other example, until an enormous scandal emerged, largely due to concerns about improper COI, stents were being routinely implanted in people who thought they were receiving a life-saving therapy when in fact as we now know they were only receiving palliative therapy.
Kool Aid or Water
Rosenbaum is concerned that we’ve all been drinking the anti-industry Kool Aid. Perhaps some of us have. But Rosenbaum might want to take a closer look at her surroundings. I love the little David Foster Wallace’s parable that Susan Molchan summarized in her response to Rosenbaum:
An older fish had swum by and asked a couple of younger ones, “How’s the water boys?” After a few minutes, one asked the other, “What the hell is water?”
Rosenbaum raises some valid questions but I think a more compelling story is the pollution of the ocean in which she’s been swimming. Maybe as she grows older she’ll begin to realize she’s been swimming in polluted water all along.