What we offer in response to this confident pro-industry advocacy is often pretty mealy-mouthed. We fear being dismissed as Luddites and cranks if we deny that new drugs are largely useful. So we say, "New drugs are largely useful, but..." and then try to get on to our main point.
Well, there is nothing at all mealy-mouthed about my esteemed colleague Dr. Donald Light, medical sociologist and health policy expert based at University of Medicine and Dentistry of New Jersey and visiting professor at just about every place he can buy a plane ticket to. I will soon post about Dr. Light's new book (to which I conributed a chapter); but the text for today's sermon is a paper that Dr. Light delivered recently at the American Sociological Association annual meeting in Atlanta, August 17 (session 487), entitled, "Pharmaceuticals: A Two-Tiered Market for Producing 'Lemons' and Serious Harm." The paper is thoroughly documented and supported and I would like to see a Pharmapologists' factual rejoinder.
The entire paper is worth reading and I hope Don will get it into print soon. By way of trying to summarize, Dr. Light builds the paper around an economist's idea, Akerlof's theory of "a market for lemons." The idea is that when there is an imbalance in the information available to buyer and seller, sellers can take advantage by pushing inferior products off on buyers. This leads to a general distrust, with buyers being unwilling to pay top dollar because they fear getting a lemon. If you have a good product but know you can't get top dollar for it, then you will take your product elsewhere to be sold. Eventually, predicted Akerlof, the market will simply fall apart. Dr. Light shows why pharmaceuticals don't exactly follow the Akerlof prediction, and how it can work that a more or less permanent market for lemons characterizes the U.S. pharmaceutical business.
In the market that Akerlof originally looked at, used cars, we don't see any car company trying to produce lemons. Says Light: "[T]he pharmaceutical market for 'lemons,' differs from other markets for lemons in that companies develop and produce the lemons. Evidence in this paper indicates that the production of lemon-drugs with hidden dangers is widespread and results from the systematic exploitation of monopoly rights and the production of partial, biased information about the efficacy and safety of new drugs. The institutional practices differ profoundly from car manufacturers working tirelessly to produce safe cars but inadvertently discovering a serious problem, like Toyota discovering its sticking accelerator problem in 2009. The massive reaction, Congressional investigations, and recalls [in the Toyota case] involved less than 1/10,000 as many deaths as are attributed to prescription drugs every year." Light adds that the information asymmetry also characterizes the relationship between the drug companies and the government regulators, who now rely havily on industry user fees to fund their own operations, assuring that the FDA has little power to impede the "market for lemons" and instead becomes a sort of enabler, providing additional cover for the companies because they can always point to FDA approval in their own defense.
If one dispassionately surveys this institutional landscape, says Light, then it is easy to predict the outcome: "Companies will design and run their clinical trials to minimize evidence that their drugs cause adverse reactions and maximize evidence that they are not inferior to or [are] better than a placebo for the target indication. And companies will also learn from the regulatory body how to game accelerated approvals and condition[al] approvals with post-market studies by cutting corners and submitting partial evidence in order to get drugs on the market faster and put the regulator under pressure to approve and not to later rescind." Light might have added here that any company in today's highly competitive market that does not get good at playing these games will quickly lose market share and be put out of business, or gobbled up in a merger.
What, then, is the evidence that this account of Pharma's institutional environment is correct?
- It has been documented numerous times that of all the so-called "new drugs" put onto the market annually, only a few are actually novel chemical structures, and of those, only a handful are real advances over existing drugs. An estimate of 10-15 percent actually being significant advances in one way or another would be highly generous.
- With 85-90 percent of new drug discoveries not counting as real advances, it is herefore clear, as Light notes, that "company R&D goes largely to a marketing strategy that does not meet societal needs or the needs of patients."
- Drug companies constantly whine that they spend so much on R&D, taking huge risks of wasting money on drugs that don't work, that their profitability is always in jeopardy. Garbage, replies Light. R&D in the US drug industry rose during the decade between 1998 and 2008 from $18.9B to $47.4B. Societally speaking, this was a huge waste as so few real drug innovations resulted as noted above. But drug industry profitability did not suffer at all during this period (even though, as I reported in HOOKED, it looked a bit grim for a while in the early years of the 2000s).
- Extrapolating from the best available figures, the US suffers about 111,000 deaths annually from adverse drug reactions (that is, drugs prescribed and administered correctly, and leaving aside deaths from medical errors), or more than twice as many fatalities as from auto accidents. This puts adverse drug reactions as the 4th leading cause of death, and besides, adverse reactions lead to about 1.5M hospitalizations per year (the total damage toll being underestimated because we lack good data for nonhospital settings).
- If the industry produced drugs, many of which offer no real advantage over existing drugs, and then urged the maximum possible caution in their use, we could perhaps avoid some of this swath of death and destruction. But such, of course, would hardly suit the company bottom line; so instead we have what Light calls the "risk proliferation syndrome." Company-sponsored research talks up the efficacy and the safety of the drug. Marketing then tries to get physicians to prescribe the drug to as many patients as possible, including those (such as the elderly) inherently at higher risk for adverse reactions, and those who have less and less chance of actually benefiting (because their disease is mild, or for whom nondrug therapy would work better, etc.) The industry does everything possible to speed up FDA approvals of new drugs and to slow down any threatened FDA action to remove an unsafe drug from the market or to restrict its use. The end result is that as many patients as possible are put at risk, while revenues go steadily up. (More on this particular phenomenon later on when I have the chance to blog about a paper that Dr. Light and I co-authored, which is currently awaiting publication.)
- The financial power of the drug industry allows it to "colonize" medicine in the same way that it has effectively taken over the FDA. This means that more and more of medicine turns into a commercial enterprise placed at the service of industry profits. New diseases are "discovered" that require drugs to treat them. The medical literature becomes indistinguishable from the industry marketing juggernaut. And so on, as this blog has documented ad nauseam.
Bottom line: Let's put the burden of proof where it belongs. When anyone says that the drug industry, in its present form, is a benefit to society, we ought to reply, "prove it." Or, to put the matter in another (and perhaps kinder and more moderate) way, we must not mistake the level at which the bad stuff happens. When new drugs end up killing people instead of healing them, it is not something that just happens around the edges. The reasons for those bad outcomes are much deeper into the structure of the industry today than most of us (even pharmascolds) want to admit.