Tuesday, September 30, 2014

The Disappearance of Generic Drugs

(My source for this post is Elisabeth Rosenthal's article in the New York Times:
--which has actually published almost a year ago, but seems to have some important information that others besides me may have missed.)

Once upon a time, we knew that almost all drugs would eventually turn generic. Under the influence of the Hatch-Waxman Act of 1984, most drugs made the transition from expensive brand-name to cheap generic after 20 years (which actually amounted to 10-12 years after a drug first came onto the market). Walmart inaugurated the sales pitch of the "$4 generic" and generally generic drugs were quite affordable.

During the first decade of the twenty-first century, savings picked up. More and more older drugs went generic, and the companies had fewer brand-name drugs to replace them with.

Or so it was supposed to go. Rosenthal tells us what has actually happened. She focuses her story on asthma drugs.

Very few new asthma drugs are on the market, so treating this common disease should be cheap. It is certainly cheap in other countries, where the government intervenes to keep medicine affordable. But in the U.S., virtually every inhaler costs what we'd expect to pay for brand-name drugs, even if the active ingredient is as old as the hills.

One of the oldest drugs for asthma is the basic bronchodilator, albuterol. You'd think that you could get a simple albuterol inhaler for a few bucks, right? That was true until a few years ago when the FDA got environmentally conscious and demanded the drug companies remove chlorofluorocarbon propellants from inhalers because they harmed the environment. The companies were happy to do so--and were promptly issued new patents for their drug products, despite the fact that the basic drug was the same. So now we're on another 20-year rollercoaster until these drugs get cheap again (pending whatever new wrinkle the companies can throw at us in the meantime).

The FDA says that "difficult, longstanding scientific challenges" make it hard to measure drug activity deep in the lung and so assure that a new propellant or other vehicle really produces the same drug product. Meanwhile, other nations have managed to demand that drug companies sell these inhalers at much lower than brand-name prices, and nowhere in the world, to my knowledge, have any medical difficulties arisen because the dose of a drug from a new inhaler is actually different than the old dose. The US is basically the only country in the world where these drugs cost so much. (Many European countries have forced the common asthma drugs over-the-counter.)

Rosenthal writes, "The Centers for Disease Control and Prevention puts the annual cost of asthma in the United States at more than $56 billion, including millions of potentially avoidable hospital visits and more than 3,300 deaths, many involving patients who skimped on medicines or did without."

As usual, the uninsured in the US pay top dollar for these drugs. As Rosenthal notes, "Lawmakers in Washington have forbidden Medicare, the largest government purchaser of health care, to negotiate drug prices. Unlike its counterparts in other countries, the United States Patient-Centered Outcomes Research Institute, which evaluates treatments for coverage by federal programs, is not allowed to consider cost comparisons or cost-effectiveness in its recommendations.....California's Medicaid program spent $61 million on asthma medicines last year, paying more than $200--not far from full retail price--for many inhalers."

A few years back, the generic drug market appeared to be one of the areas where the large drug manufacturers were losing their clout. Now, at least for some medical conditions like asthma, they seem to have their way again.

Sunshine Act Goes Live, Sort Of

According to ProPublica's Charles Ornstein--
--as the Sunshine Act (of the 2010 Affordable Care Act) finally goes live today, some 18 months after the scheduled first release of data, we still can't expect all that we had anticipated.

Recall that the Sunshine Act was supposed to list all payments from drug companies to individual physicians so that consumers could check on which doctors were receiving which sorts of money.

Ornstein lists the current complications:
  • The current release of information only covers August through December, 2013.
  • Data on payments related to new products, and sometimes new uses for existing products, are held back for as long as 4 years.
  • Some practitioners are not included--despite more frequent company payments recently to nurse practitioners and physician assistants, they're not on the bus.
  • Because of initial errors with similar physicians' names, etc. up to 1/3 of data is not being released currently.
  • Many different sorts of payments are included and they have different ethical implications--expect it to be a while before we can make sense of all the numbers.
  • As usual, expect errors.

Ornstein puts in a good word for ProPublica's own website, Dollars for Docs:
--which currently lists about half of all drug company payments to physicians and is current through the end of 2013.

Tuesday, August 26, 2014

The Anechoic RUC: Some Small Efforts at Reform

I have previously written about the Resource-Based Relative Value Scale Update Committee, or RUC:

Now, along comes a long and thoughtful synopsis of RUC from our friends over at Health Care Renewal:
--which in turn highlights a piece in Politico by Katie Jennings:

When I asked Dr. Roy Poses of HCR about RUC, his reaction was: "It's amazing how little traction this issue has gotten, despite its importance, and the fact that there is something in the RUC for nearly everyone to hate..."

Now, what's it about the RUC that should make people hate it?
  • Is it the fact that it's run by the AMA on a nearly-secret basis, despite the fact that it more or less sets Medicare and Medicaid policies?
  • Is it the fact that it overwhelmingly represents specialty societies who generally manage to practice "you scratch my back, I'll scratch yours" as a way to assure good payments for procedures?
  • Is it the fact that primary care specialties are woefully underrepresented and usually end up with the short end of the stick when it comes to payment--assuring that primary care will continue to pay well below average and drive away med students despite the great need?
  • Is it the fact that these high medical prices for procedures fit in well with the corporate interests that continue to dominate medicine?
I'll let Dr. Poses speak to this issue at some length in his conclusion:

"So since 1992, the RUC has had an outsize role controlling what Medicare pays physicians, and hence physicians' pay in general.  Over this time, the playing field has become increasingly tilted in favor of procedural services and away from cognitive services, especially primary care.  The result is that the US has the most expensive health care system in the world, but hardly the best health care or health care results in the world. 

"Economists have beaten us over the head with idea that incentives matter.  The RUC seems to embody a corporatist approach to fixing prices for medical services to create
perverse incentives for physicians to do more procedures, and do less conversing with and examining patients, examining the best clinical research evidence about their problems, and rigorously thinking about how best to help them.  More procedures at higher prices helps physicians who do procedures.  It may help even more the corporations that provide the devices and drugs whose use is necessitated by such procedures, and the hospitals who can charge a lot of money as sites for performance of procedures.  It may even help insurance companies by driving ever more money through the health care system, and thus allow rationalization for higher administrative expenses as a function of overall money flow.

"Yet incentives favoring procedures over all else may lead to worse outcomes for patients, and more costs to patients and society.  If we do not figure out how to make incentives given to physicians more rational and fair, expect health care costs to continue to rise, while access and quality continue to suffer.

"Since we started writing about the RUC in 2007,  there have been some small changes in the RUC.  It has slightly more primary care representation, and its membership is no longer secret.  That is, however, about it.

"As I wrote last time, hopefully the Politico article, added to all the other attempts to shine light on the RUC, will succeed in increasing awareness of the RUC and its essential role in making the US health care system increasingly unworkable.  Of course, such awareness may disturb the many people who are making so much money within the current system.  But if we do nothing about the RUC, and about the ever expanding bubble of health care costs, that bubble will surely burst, and the results for patients' and the public's health will be devastating."

Dr. Poses' blog is based on a central metaphor which for some reason I find mildly irritating, the anechoic effect--the idea that something happens but it never leaves an echo, and so it gets ignored. (Why I find that irritating can be left for elsewhere.) But RUC seems to be a great example. It does all sorts of things wrong, in a huge way, and it just keeps rolling and rolling on the same pathway, and whoever criticizes it seems to be talking to nobody and never gets an answer. The basic factor favoring RUC is that even most physicians have no idea that it exists.

Saturday, August 23, 2014

Not-So-Personalized Medicine

Jack E. James, who appears to hail from either Reykjavik University in Iceland or the National University of Ireland in Galway, or both, kindly sent me a copy of a paper published in June in the European Journal of Epidemiology:

The paper addresses "personalized medicine" from the perspectives of Julian Tudor Hart's "inverse care law" and Don Light and yours truly's "inverse benefit law":

James starts off reminding us of the promise of personalized medicine: instead of "one size fits all," we will have "the right drug to the right patient at the right time." Instead of 100 people getting a drug, and 5 of them having a nasty allergic reaction to it, we'd get the message in advance that these particular 5 folks should not be given that drug. Personalized medicine seems to be quite effective nowadays, for example, in breast cancer treatment, where patients are tested and their tumors are found to be sensitive or insensitive to various chemotherapies before they are administered.

James goes on to discuss personalized medicine in some depth. Why the gap--why, at least so far, has personalized medicine seemed to hover just beyond reach? Theoretically, there's the problem that personalized medicine is yet one more way we've devised to believe in a false genetic determinism, when as James reminds us, "disease and health are the result of complex interactions between networks of genomic and epigenetic processes, behavior, and the environment." On a more practical level James suggests that personalized medicine depends on clouds of billions of data points for each individual, which would first be extremely expensive, and second, more importantly, would not guarantee that any resulting associations would have either a large effect size or a high predictive probability.

There's a difference, for instance, between our ability to "prove" that high blood pressure causes more cardiovascular disease, which is consistently true at the population level, and our ability to make predictions at the individual level, where many low-blood-pressure folks continue to develop heart disease and high-pressure folks remain healthy. James summarizes, "Empirical evidence across a range of medical conditions indicates that prediction based on individual genomes compares poorly in clinical value to that of clinical risk markers currently employed in conventional medicine."[1] He also noted, "When identical DNA samples were sent to leading commercial suppliers, a comparison of genomic test results found that the information supplied about individual risk profiles was not merely without clinical value but that the level of risk reported differed markedly between the companies."[2] Thus those firms that claim to be able to assist one in obtaining personalized medicine results seem incapable of this--yet quite capable of pocketing their fees.

The story so far at least seems to be that some genetic traits, which are now mostly well known (such as Huntington's disease and cystic fibrosis) have a clear and significant linkage between one's genes and one's medical prognosis, and tests are now available for many of these. By contrast, what has come forth since the mapping of the human genome is genome-wide association studies, which (for instance) have shown numerous small associations related to one's risk of developing type 2 diabetes, but even in higher-risk groups these have been mostly worthless in predicting individual risk. James adds that no group has yet been shown to have a different life span due to the cumulative effect of genome-wide associations with increased risks for coronary artery disease, type 2 diabetes, or cancer.[3]

James then turns to the two "laws." He states, "To the extent that health expenditures draw upon finite resources, development of the genomic and information technologies that underpin personalised medicine will have the unintended consequences of diverting resources away from other healthcare priorities. The inverse care law predicts that any such redirection of resources will disproportionately disadvantage those with lowest income and greatest healthcare need, who in turn have fewer resources to offset shortfalls arising from any diminution in existing healthcare."

He then addresses the inverse benefit law: "Whereas the inverse care law elucidates harm that exposure to market forces may have on the distribution of healthcare, its generalisation in the form of the inverse benefit law illustrates market-related harm of a different kind; namely, the treatment of ever more healthy populations." He gives the example (only one of many possible) of shifting treatment from osteoporosis (bone mineral density 2.5 times or more below population mean) to osteopenia or "pre-osteoporosis" (BMD as little as 1.0 SD below mean). This leads predictably to two outcomes--first, treating many more healthy people with drugs that will do them no good, and second, exposing many more of them to the risks of adverse drug reactions. James notes this amounts to drug treatment for those "at risk of being at risk."[4]

James summarizes, "the extreme levels of human and material resources required by the genomic and information  technologies upon which personalised medicine is based threaten to disproportionately disadvantage those with greatest healthcare needs (inverse care law)... while simultaneously posing harm to ever larger populations of health individuals (inverse benefits law)....A mix of excessive confidence in personalised medicine,  high expectations of benefits, perceived commercial opportunities, and insufficient attention to harmful consequences has the potential to 'colonise the future' of healthcare...wherein attention and resources are captured at the expense of alternative behavioural and social pathways that have the potential to effect greater improvements in population health."

I would, in all this, stress the role of commercial interests.

[1] Smolen JS, Aletaha D. Forget personalised medicine and focus on abating disease activity. Ann Rheum Dis 72:3-6. 2013.
[2] Adams SD, Evans JP, Aylsworth AS. Direct-to-consumer genomic testing offers little clinical utility but appears to cause minimal harm. NC Med J 74:494-499, 2013.
[3] Beekman M, Nederstigt C, Suchiman HED, et al. Genome-wide association study (GWAS)-identified disease risk alleles do not compromise human longevity. Proc Natl Acad Sci 107:18046-18049, 2012.
[4]Alonso-Coello P, Garcia-Franco AL, Guyatt G, Moynihan R. Drugs for pre-osteoprorsis: prevention or disease mongering? BMJ 336:126-129, 2008.

Overall: James JE. Personalised medicine, disease prevention, and the inverse care law: more harm than benefit? Eur J Epidemiol 29:383-390, June 2014.

Monday, August 18, 2014

Research on Pharmaceuticals: From Confidence to Commercialism

The main thrust of this commentary comes from Dr. Roy Poses and:
--which in turn draws on two prior posts:


A little background: HOOKED described a major shift in pharmaceutical research. Initially, the vast majority of drug trials were conducted by universities. Over the past 30 years, companies found that universities were too slow in doing this research for maximum financial gains, and so gradually, contract research organizations replaced universities as the major players. Dr. Carl Elliott (first of two prior posts) has been one of the major writers about the fallout from these policies.

Dr. Elliott describes in some detail a group of subjects who can be found in typical contract research organizations, who talk openly about their ways of qualifying for research trials, and also of dodging the painful and burdensome procedures that typically form a part of some trials. It seems quite clear that the money, and not any goal of contributing to science, is the main and indeed the sole motivator. Dr. Elliott had previously described this "guinea pigging" in earlier published work.

The second prior post, by Peter Aldhous, describes some of the physicians who run the contract studies, and focuses on those who have been censured and who have various licensure problems. Aldhous admits that these misfits count as a minority of all the doctors running the contract research organizations, but adds, "My trawl netted dozens of doctors selected to work on clinical trials over the past five years who had previously been censured by state medical boards. Thousands of doctors are hired each year to test experimental drugs, making this a small minority. But most doctors have clean records, so companies should have few problems finding recruits without red flags against their name."

Aldhous concludes, "Some experts argue that the FDA’s entire rulebook for clinical trials, with its talk of things like 'institutional' review boards, reflects the academic past of clinical research—not today’s industrial juggernaut of for-profit clinical trials firms and for-hire review boards, which oversee a workforce of doctors drawn from regular medical practice. 'They are regulations for a world that doesn’t exist anymore,' says Elizabeth Woeckner, president of Citizens for Responsible Care and Research, which campaigns for the safety of medical research volunteers."

Dr. Poses then notes: "So given the push to do research rapidly at the lowest cost, the lack of supervision and regulation by the FDA, the hiring of physicians with problematic backgrounds, the willingness to take vulnerable patients desperately motivated by money, can we trust that the nice, clean, detailed descriptions of clinical trials implemented by contract research organizations presented in research articles and trial registries have anything to do with the reality of what went on? If not, what then should we make of the validity of the results of such trials?...This is yet another reason to ask whether we need to take research on human subjects meant to evaluate commercial products or services out of the hands of the companies that make those products and provide those services."

In other words, bait and switch. Get everyone used to research on human subjects while research institutions are running the shop and people who sign up as subjects have at least some motivation to behave in the interests of science. Then gradually change the system so that it's all about money and one can no longer trust the results. The money affects different players in different ways-- the companies and the CROs have their financial motives, the "guinea pigs" have theirs--but the one thing we can count on is that the money plays a role that's different from the ideal of scientific research. The end result is that things look legitimate up front, and all the people involved have strong motives to do what's less legitimate behind the scenes. We have no idea how that plays out in terms of scientific rigor.

And this is now how drugs are tested before we use them.

Monday, August 11, 2014

From Christopher Gregory: What's Wrong with Profits in Medicine?

Now I'm turning the blog over to Dr. Christopher M. Gregory, a fellow Texan who runs the DocOnomics blog (http://www.doconomics.com/blog/). He sent an e-mail recently which so nicely, and briefly, captured a large issue that has perplexed me that I couldn't help but ask him to reprint, and he kindly consented:

This Modern Healthcare article Another Year of Pay Hikes for Nonprofit Hospital CEOs galls me. Almost as much as this article that reported the director of interventional cardiology at NY Mt Sinai was paid almost $5 million a year for being the rainmaker there, where far more stents are done than the national average.    

As I consider the proliferation of waste in the form of freestanding ERs, urgent care clinics, and shiny new hospitals popping up, and more doctors being bought off into economically forced subservience, I see nothing but the extreme excesses in our system. And for that there is a small group of these so-called “not-for-profit” CEOs getting pay packages that would choke a horse. Boards and compensation consultants continue to cite market forces—the need to keep up with peers to hold onto skilled healthcare leaders—as the main reason for the increases. The market forces they refer to are the market forces of excess, waste and profits that continue to make life increasingly intolerable for the group of physicians – primary care physicians – that would make this system much better if we let sanity retake the high ground. These high-talent CEOs are especially valued for the business smarts needed to make sure we are continuing to pay such disproportionate amounts for the unnecessary, costly care in this country .

To be precise, these pay packages are needed to keep these high-power hospital businessmen in the business of maintaining the well-oiled machine that is swallowing up nearly 20% of our GDP. And yet, millions of Americans can’t afford to get the care they need.  

Total cash compensation grew an average of 24.2% from 2011 to 2012 for the 147 chief executives included in Modern Healthcare's analysis of the most recent public information available for not-for-profit compensation. Of those 147 CEOs, 21, or 14.3%, saw their total cash compensation rise by more than 50%.

I talked with Dr Bob Kramer this morning. He said that it will be an uphill battle getting ologists to passionately endorse a cutback in the sorts of conspicuous consumption that nets them many multiples of what PCPs are paid, and continues to siphon off the ranks of potential primary care doctors in training. We are going to reap a medical, economic whirlwind for all of this foolishness as we continue to lose the numbers of physicians who would serve us best on the front lines. If only we could overcome the entrenched stupidity of organizations like the AMA and the RUC, that keeps PCPs from making the economic and care-centric progress that would make our healthcare system run so much better.

What can be done – what group of physicians around the country – will stand up and make a definitive statement that the intensifying black hole of the overheated healthcare “business system”, with its goal for more money and more influence, is taking us in a terribly wrong direction? As my Canadian healthcare friend once pointed out, there is a healthcare noose around our national neck, and the “system” is the hangman. 

Christopher M. Gregory
1705 River Birch Drive
Flower Mound, TX 75028

From Health Care Renewal: The Free Market and Drugs

Let's see what's going on over at the Health Care Renewal blog, courtesy Dr. Roy Poses.

Dr. Poses has been noting that there are some pharmaceutical developments that could easily help us out in the case of Ebola virus, which seems right now to be expanding its presence and going out of control in West Africa. Unfortunately, while new vaccines and other drugs could be helpful (even if drug treatment is a small part of the immediate response to the deadly virus), the world's pharmaceutical industry has largely tuned out. From a capitalist standpoint, this is simply not an attractive investment. Not enough people with enough cash in their pockets are at risk for coming down with Ebola to make it profitable for any company to develop the necessary drugs.

Dr. Poses has been comparing the real human needs posed by Ebola virus with the made-up needs which are met, at great profit, by the drug industry. His latest case is Acthar gel, an obscure drug made from pigs' pituitary glands. The use of this drug, made by Questcor, has grown more than 20-fold between 2008 and 2014, reaching about $220M on Medicare. (Notice that as a million- and not a billion-dollar drug, Achtar is not even on many people's interest lists.)

Here's Dr. Poses' summary of this drug and its implications:

  The sorry case of Questcor and Acthar reveal how crazy the costs of health care in the US have become, driven now by a system that itself now seems crazy.  Through clever use of regulatory loopholes, the company acquired rights to an old drug whose efficacy was unproven, hugely increased its price, began aggressive marketing even though the drug's efficacy was completely unproven, while remaining largely silent about the drug's substantial risks.  Fueled by hundreds of millions of dollars in revenue thus generated, mainly from the US government, the company richly rewarded its top hired executives, who then have decided to sell it to a company outside of the US in a deal that will make these executives millions more.  So patients received a drug whose benefits are unknown, and whose risks may be much higher than they were told, at a cost of hundreds of millions of dollars, much of it borne by US taxpayers, while company executives got rich.

 Just coupling for now the story of how we spent hundreds of millions on Acthar to enrich company executives with the story that we have no money to develop vaccines or treatments for Ebola virus... demonstrates the massive failure of our experiment to turn our health care system over to market triumphalists and laissez faire mercantilists.  As long as we let the health care system be run by people who put their own enrichment ahead of patients' and the public's health, things will only get crazier.

Dr. Poses also added that many of the docs who are busy prescribing this questionably-useful drug to their Medicare patients are being paid by Questcor. He noted that if a proposed sale of Questcor to Mallinckrodt goes through, 6 top execs at Questcor stand to make an additional $63M. So they have every reason to portray Acthar in a solid light, and particularly to hide any ill effects caused by the drug.

Meanwhile, there's Ebola, for those silly enough to be worried about such things.