This is Why Nobody Trusts the Pharmaceutical Industry, Part 2: A few days ago, I posted in response to a Wall Street Journal article concerning clinical trials for a blood substitute developed by Northfield Labs. The crux of the story is this: in an earlier (though not recent, as I initially said) trial, 10 of 81 patients who received the fake blood suffered a heart attack within seven days. As current trials proceed, however, “several hospitals have told community meetings that previous trials showed PolyHeme to be safe, failing to mention the 10 heart attacks in their printed materials.”
It was—and remains—my position that pharmaceutical companies should adhere to the ethical principle of informed consent, which means that they have an absolute moral obligation to share any information regarding fatalities in a previous clinical trial with patients. In this case, patients are generally in extremis when treatment is required, and unable to give their consent at that time. So that means the companies have an absolute moral obligation to share the information proactively with the community, so that people can opt out, if they wish.
The article provoked an interesting response from at least two readers, both of whom—doubtless they have their reasons—elected to remain anonymous.
The first provided examples of the information being shared with the communities in two trial centers, presumably in an attempt to rebut my argument that they were not fully informed. In fact, the community information is worse than I had imagined. Not only is there no mention of the 10 in 81, there’s no mention of the word death. The language used—“serious cardiovascular adverse experiences”—is so vague, the only reasonable conclusion is that it’s deliberately misleading.
This deception is explained—if that’s the right word—with the information that “the company involved, the surgeons involved, and the FDA concur that the blood substitute was NOT responsible for the cardiac problems.” By all means, share those conclusions with the patient population. But those conclusion are not an excuse to refuse to provide them with the facts. One of the hallmarks of a democracy, and of true free markets, is that regulators (and companies) do not presume to decide what is good for us and what is not. People should be given the facts and then trusted to make those decisions for themselves.
Even more telling are the words of the second anonymous poster, who writes that I must be “caught up in the angry, self-righteous anti-pharmaceutical company mood” of the times. Leaving aside the fact that I have been accused of being an apologist for the pharmaceutical industry far more often than I have been accused of being a critic, I have always believed that this kind of ad hominem attack (the word “self-righteous” pops up three times in one paragraph) tell us more about the writer than they do about his (or her) subject.
A strong subset within the pharmaceutical industry is so convinced of its goodness that it is impervious to criticism. It sees the world in black-and-white terms and its thinking runs something like this: “We make products that save or improve lives. We are therefore the good guys. Anyone who criticizes the good guys must be a bad guy. Therefore, all critics are bad guys. Therefore all criticism is necessarily wrong.”
I now understand why my friends in the pharmaceutical PR industry are so frustrated. They offer sound public relations advice. They counsel greater openness and honesty. They suggest that when it comes to disclosure, the pharmaceutical industry should err on the side of providing too much information rather than not enough. They provide advice designed to improve the industry’s image—which is exactly what I did. And they are accused of being angry and self-righteous.
The difference is, they’re being paid to save the industry from its deceptive, authoritarian and arrogant impulses. I’m not.
It was—and remains—my position that pharmaceutical companies should adhere to the ethical principle of informed consent, which means that they have an absolute moral obligation to share any information regarding fatalities in a previous clinical trial with patients. In this case, patients are generally in extremis when treatment is required, and unable to give their consent at that time. So that means the companies have an absolute moral obligation to share the information proactively with the community, so that people can opt out, if they wish.
The article provoked an interesting response from at least two readers, both of whom—doubtless they have their reasons—elected to remain anonymous.
The first provided examples of the information being shared with the communities in two trial centers, presumably in an attempt to rebut my argument that they were not fully informed. In fact, the community information is worse than I had imagined. Not only is there no mention of the 10 in 81, there’s no mention of the word death. The language used—“serious cardiovascular adverse experiences”—is so vague, the only reasonable conclusion is that it’s deliberately misleading.
This deception is explained—if that’s the right word—with the information that “the company involved, the surgeons involved, and the FDA concur that the blood substitute was NOT responsible for the cardiac problems.” By all means, share those conclusions with the patient population. But those conclusion are not an excuse to refuse to provide them with the facts. One of the hallmarks of a democracy, and of true free markets, is that regulators (and companies) do not presume to decide what is good for us and what is not. People should be given the facts and then trusted to make those decisions for themselves.
Even more telling are the words of the second anonymous poster, who writes that I must be “caught up in the angry, self-righteous anti-pharmaceutical company mood” of the times. Leaving aside the fact that I have been accused of being an apologist for the pharmaceutical industry far more often than I have been accused of being a critic, I have always believed that this kind of ad hominem attack (the word “self-righteous” pops up three times in one paragraph) tell us more about the writer than they do about his (or her) subject.
A strong subset within the pharmaceutical industry is so convinced of its goodness that it is impervious to criticism. It sees the world in black-and-white terms and its thinking runs something like this: “We make products that save or improve lives. We are therefore the good guys. Anyone who criticizes the good guys must be a bad guy. Therefore, all critics are bad guys. Therefore all criticism is necessarily wrong.”
I now understand why my friends in the pharmaceutical PR industry are so frustrated. They offer sound public relations advice. They counsel greater openness and honesty. They suggest that when it comes to disclosure, the pharmaceutical industry should err on the side of providing too much information rather than not enough. They provide advice designed to improve the industry’s image—which is exactly what I did. And they are accused of being angry and self-righteous.
The difference is, they’re being paid to save the industry from its deceptive, authoritarian and arrogant impulses. I’m not.
posted by Paul A. Holmes @ 9:37 AM
5 Comments:
At 12:36 PM,
Anonymous said…
From at least a third “Anonymous.” There is something very important to understand that hasn't been discussed: the Wall Street Journal article left out, either intentionally or through serious blunder, the single most important body of fact. Wouldn't any reasonable person think that before allowing a large controlled trial like this, the FDA would require data on similar patients (trauma victims) using the same protocols? It does this for every other drug or substance, why not here? The journal article certainly makes it look like this all-important work was not done. Instead, it obsesses on a largely unrelated trial on a very different (very sick, with serious vascular disease) patient group using a very different infusion protocol, with clear implications that the FDA used this as the only real basis for approving a current and darkly dangerous study. Forget for a moment that the FDA agrees that a (pretty weird, actually) protocol was far more likely to blame for any serious problems in that unrelated study. Pay attention, instead to the fact that while focusing intently on this study, Journal reporter Thomas Burton astoundingly failed to discuss compelling data from one other, far more significant, highly detailed, highly related study that was, in fact, fully completed, and conducted on same kind of patients now being given polyheme – otherwise healthy trauma victims, similar protocol.
Yes, before the current double-blind trauma trial was approved, a more preliminary trauma trial WAS conducted, in much the same way that such trials are routinely mandated for other drugs, and, in this case, with very compelling, and very positive results. Wouldn't have a clue from reading Burton's piece.
That trial, on some 170 patients, not only demonstrated safety when used under this protocol, it produced powerful indications of efficacy – that lives were saved. For an easily accessed discussion of these results, you can find a review article on blood substitutes here at the site of a scientific journal: http://www.akuttjournalen.com/pages/aj/pdf/2005_13-2/Synthetic%20blood.pdf. Burton could have easily found this too, a well as more detailed elucidation of results from this study in the journal “Trauma” (1997:43:325-332). The strongest item mentioned, in my mind: 12 of the patients in this closely-related trauma study lost so much blood that their own hemoglobin levels dropped to LESS THAN HALF the very low level where medical practice has shown that death must occur, due to lack of oxygen to the brain and other organs. All of these people, in other words, were vastly beyond the point where they would have been incontrovertibly dead, dead, dead from blood loss. (With red blood cell levels, as the article put it, at levels so low as to be “incompatible with life.”) Yet, astoundingly, 9 of them survived. (And who knows what other trauma injuries the remaining three had?). This seems completely unambiguous: zero chance of survival under normal ambulance protocols, yet a 75 percent survival rate when given polyheme, with it's oxygen-carrying polymer.
In fact, one would have to do some serious reading between the lines in the Journal story to know that this work had been done at all. Only in a sort of backhanded, drive-by mention, deep in the article, does the reporter note that some work was done with retrospective data on Jehovah's Witnesses who had refused blood, comparing their survival to “earlier research on... trauma patients.” That's it. Why not even a shred of additional information about this “earlier research”? Why does this remain hidden? Burton completely fails to discuss any of the published results of that very closely related trauma-based study, including the fact that safety, at the very least, was firmly established before the FDA gave the go-ahead.
By the way, it's no surprise that the FDA wouldn't issue a marketing approval based on the results of a comparison with the retrospective J.W. data. As compelling as it looks, FDA doesn't like studies with retrospective aspects if there's any way to avoid them, virtually always insists on a gold-standard double blind experiment, as difficult as that can be in cases like trauma. Nevertheless, this comparative work did provide some highly useful clues: it strongly suggests even at blood loss levels not quite as serious as the horrific example of the 12 patients cited above, polyheme saved additional lives. You might simply want to load up the PDF at that web address, and peek at the stunning graph plotting death and survival in the two study arms, polyheme vs. the J.W.'s who refused transfusions. Then ask yourself this question: if someone you love is deep in shock, unconscious, almost certain to die due to lack of oxygen to his or her brain, would you rather, absent their ability to give consent, that EMTs in an ambulance infuse only salt water? Up until now, that was all they could do: no way, no time to do blood typing, no good way even to carry an adequate arry of refrigerated fresh blood, so trying to keep fluids up was the only frantic short term answer, even with death inevitable. Or, still absent consent, would you rather they be able to infuse an oxygen-carrying fluid that has already demonstrated compelling overall safety in such victims, with strong indications that it's a life-saver?
I can't take issue with you for being generally outraged after reading a highly misleading article. I can partly buy your argument that the public education effort should have included information about the problems in the unrelated aortic aneurysm study, but as a PR professional, you'd have a good sense of just how difficult it is to explain complex science accurately and fairly in this kind of exceedingly convoluted instance in a way that provides accurate information without falsely scaring the wits out of people (which could, in turn, cause them or their children, say, to lose their lives. Yes this is that big a deal.) Might you have been tempted to boil it down to, say, simply telling the relevant truth: that for trauma indications, this product has proved to be safe in earlier trials and that there is, in fact, no scientific basis to believe that polyheme has ever caused harm, and certinaly not when used this way? And that a team of highly qualified doctors at the local level 1 trauma center, and at several others, have, along with the FDA, reviewed all relevant data and believe this product will be safe. And, at this point, that after multiple safety “looks” in the current trial, with a great degree of statistical “power” (500 data points) the product continues to show safety. (In point of fact, even in the less related study, there's no evidence that polyheme was a problem, and plenty of medical reason to believe that it wasn't. That situation so complex that it defies any easily understandable explanation)
The reasons why the Journal story went so awry is beyond me, beyond knowing that including even a few sentences of moderately accurate detail about the most relevant earlier research would have completely demolished the “investigative” aspect of the story, and knocked it off the front page, if not killing it outright. Maybe it was just momentary incompetence by the reporter. If not, I guess Judy Miller taught us all a lot about what misdirected, grasping and possibly unethical ambition can do.
Full disclosure of the “reasons of my own” for taking the time to write this: after a lot of research by a three person investing team working both individually and together, I joined my two very well qualified friends in nibbling at NFLD stock after the final, 500 enrollee safety “look” last fall. So I've got a “grasping” interest of my own, in that it is most annoying to see my retirement account take a temporary hit as a result of bad business journalism in the nation's leading business newspaper. I also have developed a pretty strong emotional and intellectual attachment to the notion that we may be on the verge of a new, lifesaving medical miracle.
At 6:24 AM,
Anonymous said…
Mr. Holmes -
I am the "anonymous" responsible for the first two responses to your initial posting - call me VOS if it makes things easier for you. My reason for choosing to have my post identified that way is that the registration process is cumbersome and meaningless, nothing more.
It's obvious you've paid attention and done some additional homework since your first broadside; my only comment would be that I believe the phrase "severe cardiac adverse experiences" is quite descriptive and more easily understood by the general public than 90% of the information printed on the data sheets that accompany each prescription filled. The legal community may very well be more involved here than the researchers in determining phraseology.
Having said that, I'd like to pose a few tangentially relevant questions to you: Do you now believe the Wall Street Journal article painted a well researched, accurate, unbiased picture of the situation? Do you believe that a journalist who won a Pulitzer Prize for an article on a subject very closely related to the first aborted trial did an acceptable job of reporting this story? In light of the price action in Northfield stock since the WSJ piece first appeared do you believe an investigation may be in order to determine if improper influence may have been exerted on the stock by Mr. Burton or any of his sources that may have assisted in preparation of the article?
As a public relations expert, where is the line of propriety effectively drawn between a news story and a spinmaster's work?
At 10:11 AM,
Anonymous said…
Mr. Holmes said, " So that means the companies have an absolute moral obligation to share the information proactively with the community, so that people can opt out, if they wish. "
Wih all due respect....that's what Northfield has done!!
In North Carolina there were many meetings and newspaper coverage.
Frank and honest sharing of the previous clinical data occured. In order for Duke to particpate, they also had to face the withering fire of a UNC ethicist, whose shrill anti-"non-consent " comments were widely publicized.
Ultimately, locals were offered the opportunity to opt out of the trial. VERY FEW folks ever requested the bracelets!!
I have found nothing to indicate Northfield has been anything but
completely forthright with the public. Anyone can conjure up a "better approach." What counts is a premise of honesty and transparency.
My concern is that the ruckus raised by the media may in fact hinder the development of a product that can save the very lives of those so critical!!
At 8:57 AM,
Paul A. Holmes said…
Sorry for the long delay in response. Obviously, there are some areas where we are going to have to agree to disagree.
One question that deserves a response is what I think of the Journal's reporting. Obviously, it's not as strong as I assumed it to be when I wrote the first post based on the story. In fact, it seesm to be a pretty good example of agenda-based reporting.
But... there are reporters with agendas everywhere, and smart companies conduct their business on the assumption that an agenda-based reporter will one day get ahold of the facts and put as bad a spin on them as he or she can. Smart companies make it difficult for a reporter to do that. This company made it pretty easy.
At 9:39 AM,
Anonymous said…
From Anon 3, (the long-winded one with the typos.) Mr. Holmes, your final point is well made, and well taken. The company could have, at the very least, pushed the data analysis hard enough (statistics and analysis ain't a matter of just counting heart attacks, though, it can get expensive) to get a poster or conference paper done. Belately, this is apparently now set to happen at a medical science conference in April, I take it by an outside expert. (I know enough about how scheduling presentations for such conferences work to know that this paper was certainly well in the works long before the WS Journal story, so at least they did eventually get to it.) However, some of the scientists quoted in the Journal piece may be carping about the data analysis not being formally published, meaning in a peer reviewed science journal. This kind of grumbling about unpublished data goes on all the time among scientists. Problem is, while it's easier to get a simple conference paper accepted, it can be impossible to get a journal to accept an inconclusive study that the company ultimately cancelled, with enrollment far too low. By the way, Northfield's CEO has admitted outright that they should have devoted resources to getting the aortic aneurism data and analysis out in some fashion (even though they had decided to focus on trauma after the successful safety trial) so even they appear to ruefully agree with you. I remain appalled by the poor quality of the Journal story, and saddened by how such a piece of self-serving garbage can take on a life of it's own. I found myself wondering if this could lead to a cascade of events, based on serious misinformation, that could bring in the lawyers and get the trauma trial halted. Based on the compelling evidence that this stuff saves lives, I think I'd be prepared, if this nearly-complete trial got halted due to misplaced public hysteria, to travel on my own expense to the Chicago Bureau of the WSJ and puke in Thomas M. Burton's lap.
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