The "Prevention" Bait-and-Switch: Inverse Benefit Rides Again

I recently suggested that we should rename the so-called "risk-benefit ratio" the harm-hope ratio:
http://brodyhooked.blogspot.com/2013/11/welcome-to-harmhope-ratio-alternative.html


I suggested this because it matters what we call things. The names we use over time shape our thinking.


In a similar vein I have been pondering the significant change in the way we use the term "preventive medicine." This change is extremely important because we have granted prevention in medicine a status right up there with motherhood and apple pie. All sorts of things that would never pass the sniff test otherwise are swallowed whole so long as we call them "prevention." So prevention "creep" is potentially quite a serious issue.


Once upon a time we understood exactly what preventive medicine meant. We should live healthy lives, and thereby prevent ourselves from getting sick in many instances. To do this we mostly had to adopt healthy lifestyles.


When we regarded preventive medicine in this way, two important implications followed. First, there are numerous advantages to healthy lifestyles, so even if we failed to prevent a particular, feared outcome, such as heart attacks, the individual patient was very likely to accrue significant health benefits. Put in today's statistical terms, the number needed to treat (NNT) for some sort of patient benefit was very low, i.e., favorable. The second implication was that healthy lifestyles are quite safe as a rule. It was quite unlikely that we'd cause anyone's health to deteriorate by promoting this sense of "prevention."


Well, that was then. Today, we seem to equate "preventive medicine" with swallowing a boatload of pills.


Speaking to this topic are my colleagues Meta Kreiner and Linda Hunt of the anthropology department at Michigan State, whom I introduced a while ago:
http://brodyhooked.blogspot.com/2012/09/inverse-benefit-in-trenches-primary.html
Drs. Kreiner and Hunt continue to report on the same study of primary care practice I mentioned in that earlier post, this time in a sociology journal (subscription required).


The authors looked especially at hypertension and diabetes diagnoses in these clinical practices. The physicians tended to swallow current guidelines completely and were eager to diagnose "pre-diabetes" and "pre-hypertension." But far from encouraging lifestyle changes for people at risk for progressing to more serious problems, they saw these "pre" states as demanding aggressive drug therapy. Drs. Kreiner and Hunt attribute a  lot of this impulse to the wide use of NCQA guidelines to track individual physician performances, so failure of one's patient to hit a target blood pressure or glycohemoglobin level quickly could jeopardize one's "report card" and perhaps deny one a bonus payment.


They also discovered that the patients generally failed to distinguish "pre" from "real." So far as patients were concerned, they had a dread disease and the physician was doing them a big favor by throwing a bunch of meds at them. While attributing a good deal of what they saw to the ascendency of evidence-based medicine,they apparently saw no sign in any of these encounters of providers explaining NNT to patients or giving them any choice in deciding how aggressively they needed to jump on mild deviations from normal in otherwise healthy people. Meanwhile, many of these patients encountered severe adverse reactions to their meds, which usually meant that more meds were added on to counter the adverse effects.


Drs. Kreiner and Hunt prefer an analysis that shows all this as an inappropriate slide from a population health perspective to an individual patient perspective.  They suggest that from a public-health standpoint it makes perfect sense to try to reduce the total load of diabetes and hypertension in the population. Trouble is, "An individual walking into a doctor's office does not come there with the intention of improving the health profile of the population, but is there to pursue betterment of their own health. To enlist them unwittingly into the project of prevention, while exposing them to potential harm,...raises serious ethical concerns."


The authors add astutely that another problem with this system is its fallaciously self-justifying nature: "Should the patient experience increasingly poor health, it is taken by both clinician and patient as confirmation that early or incipient disease had been identified. On the other hand, should the patient never develop illness, it is viewed not as diagnostic error but as a triumph of preventive medicine over disease." The fallacy here is the same as overdiagnosis through cancer screening tests such as PSA--the patient who has a high PSA level, and who then undergoes radical prostatectomy and ends up impotent and incontinent, never reasons that he could have lived all the rest of his life with no symptoms from his so-called "cancer" and instead credits his surgeon with having saved his life.


While the authors cite Don Light's and my paper on the Inverse Benefit Law:
http://brodyhooked.blogspot.com/2011/01/inverse-benefit-law-making-sense-of-how.html
--my own take on their observations would be slightly different. Instead of focusing on the public vs. individual health, I would more directly apply the ideas of NNT and inverse benefit. I would, in the process, blame drug industry marketing for a large part of the problem they have so well described. It's not an accident that we have so come to de-emphasize lifestyle interventions and focus instead solely on medications. It's no accident that we've expanded the definition of "at risk" to include populations where the NNT gets higher and higher (less and less favorable). It's no accident that when we throw medications at patients with very high NNT, the chances for adverse reactions far outnumber the chances of benefit. It's no accident that accumulating evidence that chasing arbitrary target numbers with more and more meds fails to produce good medical outcomes is systematically ignored by physicians. All of this reflects a concerted, coordinated drug marketing juggernaut that sees huge profits in convincing previously healthy people to take more and more drugs.


By physicians and the public at large so uncritically adopting the shibboleth of "preventive," we created a huge opening for the drug industry merketers, and they proceeded to drive the proverbial truck through it.


Kreiner MJ, Hunt LM. The pursuit of preventive care for chronic illness: turning healthy people into chronic patients. Sociology of Health & Illness 2013; doi: 10:1111/1467-9566.12115 (epublished ahead of print)

Tilting at Straw Windmills: Medical Writers Defend Pharma

I'm grateful to Dr. Michael Altus, a frequent contributor of thoughtful comments, for sending me a copy of the December 2013 issue of Medical Writing, the journal of the European Medical Writers Association (available to members only according to the website). The major theme of the issue is "Good Pharma" and the various authors, most of whom express pride in working for the pharmaceutical industry, want to defend that industry from the unfair slings and arrows recently aimed in its direction. I'll focus on just a few of the articles, which sadly suggest that these folks would rather defeat straw men, or tilt at windmills, or choose your cliché, than take on seriously the criticisms raised by us pharmascolds. (I'll mention one possible exception at the end.)

Two editorials, by Adam Jacobs and Wendy Kingdom, set the tone. The points they jointly make should be very familiar and by now quite threadbare:

• The drug companies have admittedly committed some misdeeds, which no person of good character would want to defend.
• On balance these misdeeds are heavily outweighed by all the good done by the industry.
• A few bad apples work for the industry, but most of the employees are decent, hardworking people.
• The tight regulations under which the industry functions leave little room for any of the misdeeds alleged by critics.

Perhaps the most ridiculous would-be defense of the industry is this, from Kingdom: "In the particular case of the pharmaceutical industry, the company's medical director is at personal risk of criminal prosecution for any breaches of the advertising code, which is an effective incentive (if one were needed) for ensuring that any claims made in marketing materials can be substantiated."

Now, as Dr. Roy Poses over at Health Care Renewal has gone blue in the face repeating, and as this blog in its own humble way has tried to confirm, count up all the times in the last decade that a drug firm has been found to be criminally responsible for marketing practices. Then count up the number of individual executives in those firms that have suffered any criminal penalties whatsoever, personally. (Hint: You don't need the fingers of any hands to do this.) So whence comes this nonsense that drug execs run any personal risk of punishment for false marketing? Mostly they seem instead to be at risk for higher bonuses.

Another straw man thrown into the mix is that maybe it's just that we pharmascolds are ignorant of basic human biology. We apparently don't realize that it's the case that drugs have possible side effects. So when, unfortunately, a patient suffers from one of these side effects, we decide immediately that the industry is evil.

Now, it's one thing to say that unfortunately, good prescription drugs have occasional, ideally rare, side effects. It's quite another thing, as we've recently discussed, to address the sobering data suggesting that prescription drugs, taken correctly, might be the 4th or even the 3rd leading cause of death in the U.S. That latter possibility is nowhere addressed or even hinted at by these highly skilled medical writers.

To add a bit of scholarly heft, the issue includes a piece by a professor of English in the U.S., Robert Blaskiewicz, who has studied conspiracy theories. He characterizes the current wave of attacks on the drug industry as a typical conspiracy-theory exercise. I read through the piece looking for evidence of conspiratorial thinking from any of the prominent pharmascold writers that I've had occasion to quote in this blog, but found none. Eventually Prof. Blaskiewicz gets around to giving a concrete example of what he has in mind--the claim that the industry has actually discovered cures for dread diseases like cancer, but has suppressed these cures so that they can go on selling today's generation of expensive, imperfect drugs. I agree that such thinking counts as conspiracy theory, but I cannot recall any legitimate pharmascold ever making any such claim. To find fault with today's drug industry, you hardly need to go to such lengths.

I promised that I'd get around to something a bit more substantive. An article by Art Gertel accuses those of us who complain about ghostwriting of medical journal articles being simply out of date--he claims that these practices have effectively been dealt with and essentially are no more. I can see a potential justification for such a claim. Since drug firms don't exactly take out ads to announce ghostwriting, the way such practices commonly come to light is through legal discovery of company insider documents during litigation, and such litigation commonly addresses activities that were carried out several years earlier. If, in fact, ghostwriting is now a thing of the past, it would probably take the rest of us a while to find out that this was so--especially if we are inclined, for what I believe are solid reasons, to distrust the public proclamations of the industry as to its own bona fides.

As an apparent counterpoint to Gertel's piece, the magazine reprints the only true pharmascold, scholarly paper in the collection--one we reviewed previously, by Stern and Lemmens proposing legal remedies for ghostwriting (http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001070). Now, if what Gertel says is true, then Stern and Lemmens, who presumably looked into the issue at some length, would have had no reason for writing their paper. Be that as it may, I will try to contact Gertel and see if he can provide any backup for his claims, and if so will pass the word.

On the European Front: Yet More Industry Corruption

I've so far restricted my periodic reports of settlements and guilty verdicts against the big drug companies to US-based actions. Dr. Roy Poses over at Health Care Renewal--
http://hcrenewal.blogspot.com/2013/12/the-camels-aching-back-johnson-and.html
--being a more cosmopolitan sort of guy, picked up this news item, which he says got very little play in the US media.

Johnson & Johnson got hit with a more-than 10-million euro judgment and Sandoz with a 5 million euro judgment for anti-competitive activities around the fentanyl opiate-pain-killer patch. The patch was about to go off patent and Sandoz was poised to offer a generic equivalent, but instead, the two companies entered into a so-called cooperation agreement, which meant that J&J paid off Sandoz to delay their generic so that prices could stay high on the brand-name patch. This is a form of "evergreening" that we've seen frequently in the US, and apparently the Europeans don't like it any better than we ought to.

OK, so as we have seen in the past, a few million dollars is chickenfeed to these big firms. Dr. Poses goes into some detail on his blog about the former CEO of J&J, on whose watch this breach occurred along with numerous other illegalities, and how he retired with huge bonuses and a ton of J&J stock; and how the current CEO is already pulling down a big paycheck with no indication that any changes are occurring in how the company is managed. So far, same ol' same ol'--we have covered many times, as did Dr. Poses even more times, how no actual individual ever seems to be to blame for these misdeeds, and somehow the misdeeds just keep happening as a result.

But for our edification, Dr. Poses adds a bit of a new twist by reminding us of a partial rundown of the J&J board of directors:

• Dr.Mary Sue Coleman, the president of the University of Michigan
• Dr. Michael M.E. Johns, Chancellor of Health Affairs Emeritus at Emory University
• Dr. A. Eugene Washington, Dean of the medical school and Vice Chancellor of Health Sciences, UCLA 
• Dr. Susan Lindquist, Professor of Biology at MIT, former director, Whitehead Institute for Biomedical Research
• Dr. Mark McClellan, former head of both FDA and Center for Medicare and Medicaid Services, senior fellow, Brookings Institution

Dr. Poses suggests that even if the various corporate types on the rest of the board don't give a hoot about integrity or the well-being of patients, these people are supposed to have a set of values that takes such things seriously. But presumably the wrongdoers in high executive positions at J&J could not keep committing their sins, and then being richly rewarded for them, unless all these board members acquiesced in the practices. Which, in turn, suggests that the leaders of health care and of academic research cannot be distinguished from corporate execs these days. All these folks appear simply to take it for granted that once you rise to a certain level of power in the system, it's okay to extract all the money you can, no matter what the impact on public health or well-being.

What’s in the “Free” Sample Closet? Very Little of Value

I’ve blogged about the issue of sample drugs in doctors’ offices mostly in the earlier years of this blog, except for one post this past spring:
http://brodyhooked.blogspot.com/2013/05/recently-i-posted-on-report-suggesting.html

Now we can add a study published a while ago by a medical student, Kari Evans, from University of Arizona, and Drs. Steven Brown and Gerald Smetana:

http://www.jabfm.org/content/26/4/380.long

 The folks (I’m guessing they sent the student) snooped into 10 sample closets of primary care offices in Phoenix and made a list of 23 different medications that they found in 7 or more of the closets. They then asked: Is this medicine novel? Is this medicine useful? They had formal criteria for judging each of these variables. They found that 22 of the 23 had a cheaper generic medication available for the same condition, and that only 3 medicines had scientific evidence of superior patient outcomes.

In short, had the docs not had these samples to give out to patients, it’s hard to imagine that the patients would have been any worse off, or that the docs would have missed a chance to become informed about an important breakthrough in medical science.

The study also nicely illustrated why companies give out “free” samples. The mean cost of a month’s supply of the 23 drugs was $178, with the highest-cost drug ringing up a bill of $749. If a patient can be hooked on these meds with free samples, and then the prescription is continued later on, you see how much the company stands to gain—especially knowing that almost all the meds have cheaper generic alternatives.

 
Just a bit more evidence as to why the sample closet ought to go—and if you’re interested in the issue in any depth, the article provides an excellent review of the previous literature.

GSK Announces Major Changes--Is This for Real?

Hot news coming off the NPR wires:
http://www.npr.org/blogs/health/2013/12/17/251965775/why-glaxo-wont-pay-doctors-to-sell-its-drugs-anymore
Normally I like to take a while to report on breaking news, to be sure that things are as they seem and also to gather reactions from other observers, but this is big enough to warrant immediate comment in my view.

GlaxoSmithKline has already made history within the drug industry by changing its practices in the US for paying its sales reps--no longer paying bonuses purely on volume of sales. Now the firm announces that it is changing global practices--no more paying reps on volume anywhere; no more hiring doctors as paid speakers; no more paying doctors to attend medical meetings.

In short, the company has announced that it is discontinuing many of the business practices that industry critics have held most responsible for threatening the professional integrity of medicine, and in turn making pharmaceuticals a public health threat rather than a benefit.

Why now? asked NPR. Some theories--no point launching huge marketing campaigns when there are fewer important new drugs rolling off the industry pipeline anyway; pharmascolds have been successful in getting more docs to pull back from schmoozing with sales reps and taking their bribes; the Internet is turning out to be a more effective way of getting industry-friendly information to docs without the expense of a big rep sales force; the looming Federal Sunshine Act will cause docs to think twice about accepting industry largesse in the very near future.

Are we to take this announcement at face value? It's hard, when the industry has such an extensive track record of lies, to believe that at long last, Lucy is going to hold the football and actually allow Charlie Brown to kick it. Yet folks like me have been preaching for some time now that this is what the industry should do, and that it might even be in the industry's interests to do it. So it hardly seems appropriate then to take potshots at the industry if they actually do what we've been asking. If it's real.

We need, in short, better research on what's actually changing. For example, the last big "ethics" reform of the industry took place in 2009 when the US firms voluntarily gave up handing out the pens emblazoned with drug logos and all the other "reminder" items that used to clutter physicians' offices. And what was the actual impact of those changes? I can't point to any research studies that tell us. Of course, if change occurs today, it will naturally take a while for an investigator to do the research on the consequences, and even longer for the results to then be published. So we can cautiously welcome GSK's latest statements while withholding judgment till we see the evidence.

Congratulations, Pfizer, You Are Now Officially a “Racketeering Influenced Corrupt Organization”

Thanks yet again to Dr. Roy Poses over at Health Care Renewal—
http://hcrenewal.blogspot.com/2013/12/blogscan-us-supreme-court-turns-down.html
--for picking up from some of our fellow bloggers this latest news tidbit about drug giant Pfizer.

In the past I have blogged (again thanks to Dr. Poses) about Pfizer’s rather amazing record of criminal wrongdoing:

http://brodyhooked.blogspot.com/2012/12/doing-it-again-after-pomising-not-to.html

I have also agreed that the word “corruption” is the correct term for much of what we see in today’s drug industry:

http://brodyhooked.blogspot.com/2013/09/special-journal-issue-institutional.html

And finally, I recently commented on the book by Dr. Peter Gøtzsche in which he compares the drug industry with organized crime:

http://brodyhooked.blogspot.com/2013/11/deadly-medicines-over-top-or-overdue.html

So, by way of commentary for anyone who thinks that all the above is unjustified piling on, Dr. Poses reports that the U.S. Supreme Court has refused to review a 2010 conviction of Pfizer in which the company was found guilty to violating the RICO law, and therefore was found to constitute a “racketeering influenced corrupt organization.” With the high court’s refusal to hear an appeal, the original verdict now stands for all time.

As Dr. Poses has repeated until he is blue in the face (as probably most people in New England are these days given the weather they’re having), when an organization is found guilty of RICO violations, one normally expects that some of the people who run the place are going to end up in jail. We are of course still waiting for that day to come to the drug industry. In the meantime all the big execs will presumably continue to take home their multi-million-dollar bonuses.

More on Cholesterol Guidelines: Cochrane Lets Us Down

Dr. Roy Poses over at Health Care Renewal did a nice post on the cholesterol guidelines—
http://hcrenewal.blogspot.com/2013/12/how-manipulated-clinical-evidence-could.html
--that have been the subject of my two previous posts:
http://brodyhooked.blogspot.com/2013/11/new-cholesterol-guidelines-part-two.html
http://brodyhooked.blogspot.com/2013/11/new-cholesterol-guidelinesthe-devil-in.html

The basic question, you’ll recall, is: how did we end up with supposedly “evidence-based” guidelines that read like a script written by the drug industry to sell statins, when the most accurate and dispassionate reading of the actual scientific literature arguably tells us that 1) statins are way overrated as a way to prevent heart disease and 2) that to the extent that statins do work, it’s not at all clear that they work by reducing cholesterol levels?

Well, one way this happened is that a couple of meta-analyses (which don’t do any new research but rather re-evaluate studies previously conducted) which come from supposedly neutral and respectable sources have recently set up a big cheer for statins as effective primary prevention (prevention for people who don’t yet have established cardiovascular disease). One is the CTT that we’ve already gone over in some detail, for instance:

http://brodyhooked.blogspot.com/2012/05/statins-in-water-supply-continued-why.html

The other is a recent review from the Cochrane Collaboration. This organization is supposed to be the world’s gold standard for evidence-based systematic reviews. I tell medical students that they should generally look first to Cochrane if they want reliable evidence as to how well any medical treatment works. But for all the great work Cochrane does, and their generally impeccable results, they occasionally slip up, and some reviews have been discovered in the past to have been done by people with unreported conflicts of interest.

The review of statins for cholesterol seems to be one of their flops. Dr. Poses’ post, above, provides details as to why the methods used in their review are questionable. It has also been reported that at least one Cochrane review author had financial ties to the drug industry.

This has not stopped the pro-statin crowd from running with Cochrane as their main evidence for how wonderful statins are. Last week’s JAMA featured an editorial (subscription probably required) “Accumulating Evidence for Statins in Primary Prevention,” by an author who lists about a dozen financial ties to drug-makers. The editorial and the article on which it comments both rely heavily on the Cochrane review as their evidentiary centerpiece.

Normally, when pharmaceutical marketing reaches the level of “irrational exuberance,” we can depend on Cochrane to rein in the excess enthusiasm. It is very sad to see Cochrane instead pouring gasoline on the fire.

Robinson JG. “Accumulating Evidence for Statins in Primary Prevention.” JAMA 310: 2405-6, Dec. 11, 2013.

ADDENDUM 12/20/13: I have been waiting for some backup on the cholesterol guidelines issue from people who actually have the expertise to crunch the numbers. Here's a reply by our old friend Dr. John Abramson (Overdo$ed America) to a response offered to an earlier opinion piece that he co-authored, by the authors of the Cochrane review mentioned above. The reply further develops some of the criticisms of the Cochrane review.
http://www.bmj.com/content/347/bmj.f6123/rr/678736