Sunday, January 26, 2014

The Inverse Benefit Law and Hypertension

I've mentioned many times the Inverse Benefit Law:
--that says that the public health effects of a drug worsen to the degree that the drug is more heavily marketed. While the Law can work via a variety of mechanisms, one common one is shifting the threshold downward at which we identify a "disease." Due to the way most biological traits are distributed in a population, the infamous bell-shaped curve, even a slight downward shift in a variable produces many more millions of "sick" people who suddenly become candidates for drug sales.

In past discussions we have often focused on cases like cholesterol and blood sugar. I've not said that much about hypertension because the data on the public health benefits of drug treatment of hypertension have seemed so unassailable--and hypertension can be treated very well with cheap generic drugs most of the time. It's therefore of interest to have a different point of view, from one of the most thoughtful commentators in British general practice, Dr. Iona Heath (subscription probably required).

Dr. Heath recounts the story of where today's hypertension guidelines came from. She recalls that the original recommendation was that we should start treating high blood pressure when the numbers exceeded 160/100. Even in that day, she argues, there were already excellent data to show that those numbers were not arbitrary--that there was good reason to believe that treating blood pressure at lower levels would produce no benefit and simply expose more patients to risks of adverse drug reactions.

Quoting one of the grand figures in British medicine, Julian Tudor Hart, Heath next describes three WHO symposia held on hypertension in the early 1980s. These were sponsored by Big Pharma and blatantly appealed to all in attendance to vote for a lower treatment threshold of 90 diastolic.

From that point on we've seen continued threshold creep as the numbers at which treatment was recommended dropped lower and lower and as we were presented with another dread disease, "pre-hypertension," that also required treatment--in every case, the guideline panels making these recommendations being awash in Pharma money. Dr. Heath illustrates how silly this has gotten by looking at a study of one county in Norway, showing that based on current European guidelines, half the population would be considered "at risk" by age 24 years and 90% by the age of 49 years. Yet Norway has just about the highest life expectancy of any nation on earth.

So now we get to the recent Cochrane review on hypertension treatment, concluding--guess what?--that one does not reduce either mortality or morbidity, according to large-scale clinical trials, if one treats hypertension at levels below 160/100, as we previously reported here:

Dr. Heath is pessimistic that practice will become truly evidence-based any time soon, as in the UK, for example, the lower thresholds have wormed their way into virtually all the crevices of the Health Service and are part of most guidelines and payment schemes.

Many people think that while it's quite dubious that we need to be treating high cholesterol in people with no existing heart disease, and high blood sugar in type 2 diabetes, at least we know that you have to be a bear about lowering blood pressure. It's sobering to be reminded that even with the poster child for disease prevention through pharmacology, things are not always as they seem, and drug money has been freely spent to be sure we don't realize that.

Hat tip to Primary Care Medical Abstracts (Drs. Rick Bukata and Jerry Hoffman) for calling this paper, from the excellent "Less is More" series in JAMA Internal Medicine, to my attention.

Heath I. Waste and harm in the treatment of hypertension. JAMA Internal Medicine 173:956-957, June 10, 2013.

Tuesday, January 21, 2014

"The Dark Side of the Sun": The Problem with Disclosure

"The Dark Side of the Sun" is the cute title of a 2011 paper in BMJ co-authored by Canadian bioethicist Mark Wilson. Wilson is now back:
--with a new short paper on the Sunshine Act that's part of the US Affordable Care Act and due to take effect later this year. Let's just say he's not a fan.

I've tried to take the position both in this blog and earlier in HOOKED that disclosure of conflict of interest is not enough by itself and we need to do all we can to eliminate COI. I have generally, however, supported Sunshine-type provisions as helpful steps in the right direction and especially as good tools for the few investigative journalists left these days, who have been able to use disclosures to piece together telling stories about physician misbehavior that in turn has probably exerted a useful chilling effect over too-comfy relationships with industry. Wilson's new paper raises the interesting question about whether the Sunshine Act, rather than being a partial step in a helpful direction, actually may do more harm than good.

Briefly, his case against disclosure policies is:
  • The current focus on disclosure as a cure-all has diverted critical institutional attention away from more meaningful (but difficult) COI reforms.
  • Wall Street provides an excellent example of the futility of disclosure. The COI's of the major accounting firms played a huge role in bringing about the Great Recession of 2008 (as I discuss briefly in my book, The Golden Calf). These firms proceeded to bestow triple-A ratings on worthless financial instruments while pocketing hefty fees from the purveyors of those instruments. The lobbyists for Wall Street have thus far fought off all attempts at real reform of this corrupt system, all the while acting as if mere disclosure solves things.
  • The Sunshine Act actually shifts the burden of "fixing" the COI problem off the shoulders of the institutions that might have the power and authority to do something, and onto the person with no power at all in the system, the individual consumer/patient.

Monday, January 13, 2014

Latest News from Health Care Renewal

Dr. Roy Poses put up only two posts this past week on his Health Care Renewal blog, but they are both about Pharma issues. First he passed on the bad news that the Pharmalot blog is no more:

I concur with his assessment that journalist Ed Silverman did a splendid job with that blog, and that it's a serious shame that the owner is not making the blog archives easily available.

Dr. Poses then tells us the story of the PR campaign to launch a new drug for a rare disease, pulmonary arterial hypertension:

The PR folks have concocted a smarmy account of how a mother's concern for her daughter led to this new drug, happily covering over the facts that 1) the drug probably doesn't work very well; 2) it causes serious side effects; and 3) to will be priced at as much as $150,000 a year.

Saturday, January 11, 2014

From ProPublica: There's Gold in Pharma Data

Thanks once again to Charles Ornstein at ProPublica:
--we're brought up to date on the big bucks generated by the firms like IMS Health called "prescription drug information intermediaries." Basically, these are the companies that (among other services) track physicians' prescribing and tell drug firms who's prescribing their products.

Without them, the drug rep approaching Dr. Jones would have no idea how much of what drugs he's prescribing. Dr. Jones could claim to be a heavy prescriber of the rep's product and the rep would never know if that was true or not. With firms like IMS, the rep probably knows not only every script Dr. Jones writes, but what brand of toothpaste he uses.

IMS was a publicly traded company until 2010, when it was bought for $5.2 billion by private equity groups. (Bloomberg recently guessed that the present value of the firm is $8 billion.) IMS recently filed to make a public stock offering, meaning that it once again had to go public with some of its financials.

As a result, here are some tidbits we now know:
  • IMS took in nearly $2B in the first 9 months of 2013
  • IMS claims its collection of data contains 85 percent of the world's prescriptions by sales revenue
  • IMS claims to process 45 billion health care transactions annually
  • All the top 100 global pharma and biotech firms are clients
  • IMS can provide general assessments of prescribing trends in 70 different countries, and detailed data about individual physician prescribing in 50 countries
  • IMS's total collection of data amounts to about 10 million gigabytes
Ornstein mentioned one irony in his article. When three states passed laws to limit the ability of these information intermediaries to collect individual physician prescribing data, the companies took their case to the U.S. Supreme Court, which ultimately ruled in their favor on First Amendment grounds. Several media companies, including ProPublica, filed a legal brief supporting IMS and the other firms, because of their shared concern for First Amendment rights.

ProPublica then turned around and, for research on some of the stories it was doing, tried to buy individual prescriber data from IMS and other firms--who refused to sell those data at any price to the press. So much for the First Amendment, I suppose. No point in offending your best-paying clients.

Friday, January 10, 2014

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:

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:
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:
--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)

Thursday, January 2, 2014

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 ( 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.