Boning Up On How Merck Marketed Fosamax
25 CommentsBy Ed Silverman // December 23rd, 2009 // 10:11 am
Did you know that ostopenia is considered by many physicians to be normal thinning of bones as aging occurs? And that in 1992 a group of osteoporisis experts met in Rome and decided arbitrarily who should be treated for ostopenia? Essentially, they created a new category and never imagined the term would become a marketing cry for Merck to sell Fosamax. But NPR reports that’s what happened.
Along the way, Merck wanted to increase the market for its drug, but that required scanning, an expensive and inconvenient procedure. So Merck created a nonprofit called the Bone Measurement Institute to push for alternative scanning solutions, such as smaller, cheaper machines. The drugmaker allegedly bullied makers of bigger scanners and offered financing to docs to encourage purchases of the newer, smaller devices it encouraged some companies to make.
Then, Merck successfully lobbied to pass the Bone Mass Measurement Act, a bill that changed Medicare reimbursement rules to cover bone scans, NPR reports. As a result, docs got reimbursed for buying or licensing the newer machines and for measuring bone density. The next step? Merck developed a lower, 5-milligram Fosamax dose that was intended for use by women with osteopenia.
“When millions of women are getting the word ‘osteopenia’ from the bone density test that they are getting in their 50s and 60s, they get worried,” says Steve Cummings, director of clinical research at the California Pacific Medical Center Research Institute. “When a clinician sees the word ‘osteopenia’ on a report, they think that it’s a disease. They want to know: What should I do?”
Medicare claims for screening exams jumped from 77,000 in 1994 to more than 1.5 million annually by 1999. The sale of peripheral machines rose more than 500 percent during that time. Studies in women with osteopenia show Fosamax reduces spinal fractures, but may not reduce other types of fractures more common in women with osteopenia, according to Cummings and Susan Ott, an associate professor in the department of medicine at the University of Washington.
Moreover, there are no long-term studies that look at what happens to women with osteopenia who start Fosamax in their 50s and continue treatment long-term in the hopes of preventing old-age fractures, NPR reports, adding that none are planned (here’s some background).
But Jeremy Allen, who devised Merck’s push, has no regrets. “I get a great sense of satisfaction that I was able to rejigger the marketplace so that women could be treated for osteoporosis before it got them,” he tells NPR. “That was a good episode of my life.” As far as he’s concerned, he helped save millions of lives. But Richard Mazess, which made the bigger machines and resisted Merck’s efforts, disagrees. “He was complicit in a plot to misdiagnose American women,” Mazess says of Allen.
Here is the full NPR report…
Salmon
The same thing is currently happening with the use of antipsychotic and mood stabilizing drugs in children.
Ed, you have reported that 1% of children on private insurance and 4% of children on Medicaid are on antipsychotic drugs.
Only 1% of adults will ever develop Type 1 Bipolar Disorder, i.e. full blown mania, and the drugs only appear to have any benefit over placebo in the sickest 50% of these patients or approximately 0.5% of adults. Thus it’s clear that there’s blatent overprescribing for these lethal drugs. Even when we quote that onset of symptoms may occur in 1/3 of patients between the ages of 15 - 18 yo we mean that in most of these patients mild symptoms or changes in behavior may be occuring that still don’t rise to the level of bipolar disorder.
In spite of this evem the FDA has been complicit in promoting the over diagnosis of BP and prescribing of these drugs. I say this as they have put in class labeling ADHD drugs to tell parents that if a child may be irritable that they may have bipolar disorder. Thus contributing to this blatent overprescribing of these lethal and dangerous drugs.
Salmon
Mike
Also part of the story:
The makers of the larger equipment didn’t want Merck to engage in this strategy because it disrupted THEIR strategy - to produce devices that were very expensive and were limited in the marketplace. Merck wanted inexpensive devices widely distributed. I think that Merck’s plan was better for consumers in the long run - even though their incentives were to increase drug sales.
patrons99
Get ready for the Flying Nun, now slightly demented and fully edentulous after loosing all of her teeth to osteonecrosis of the jaw, to appear in new DTCA promoting the bisphosphonates as, for example, cancer preventives, antivirals, and treatments for dementia. That’s how marketing minds work. When the data militate against their primary marketing indication, just manufacture some new ones. Doesn’t matter that they are off-label and illegal. The marketing “spin” is already revving up. Stay tuned. At the pharma-controlled CME sites, you can already see their reactionary moves, almost in real time.
Condor
More on the NPR story — including graphics — here:
http://shearlingsplowed.blogspot.com/2009/12/solid-deep-dive-on-fosamax-via-national.html
In any event, it is deeply concerning to me that pharma now thinks it okay to “build” a blockbuster (from what was originally only a niche drug — at best — like Fosamax®), rather than letting the pure evolving practce of medicine (and solid, independent science) drive it to blockbuster status. . . .
Namaste
pharmavet
Don’t forget about all of the radiologists who saw bone mineral densitometry as a cash cow, bought tons of expensive scanners, and had to recruit lots of “patients” to pay for them.
riv
Don’t forget about all the women who don’t have osteoporosis. A lot of us are called First Nations. Funny about that. There we are living our lives in the Land of the Midnight Sun, not having much of an acquaintance with milk, or doctors for that matter, and as far as my kin are concerned (and we are many) there’s not an osteoporotic “skin” among us, well over 60 years of age.
It’s not only the drug that’s a con.
YRLR
More on the comment by Salmon as it relates to Bipolar Disorder over-prescribing and as it also relates to Osteopenia.
I have had the little ankle test (which was hard to take seriously) and, much later, the big hefty hip and lumbar vertebrae scan.
The ankle scan done for free at the doctors office, as a sort of clinic that only included that one test, led immediately to a conversation about bone saving drugs. Didn’t think to wonder why the clinic was there or who was conducting it- way back then.
Anyway, Osteopenia confirmed by the big scan.
It is a trade off that people taking (cough) Bipolar drugs need to consider. Though, if you are lucky like me, Fosamax probably shouldn’t be taken with (geez) Bipolar medications because of the kidney disease indication. Here’s why…
_______________________________
The new thing I have to consider in the trade off between brain and body is what has now been diagnosed as a VERY dramatic and rapid increase in antinuclear antibodies.
Essentially this means that my body is attacking it’s (otherwise) healthy tissue. Excruciating pain and much illness. After a slew of tests to eliminate all of the usual suspects- it is suspected that my epilepsy (erm Bipolar) medication is the cause.
I sit here thinking which is worse, to resume seizures or continue to poison my body. You might think Stop Poisoning Yourself! You probably have never been terrorized by seizures. I sure as hell wouldn’t take them for anything less. But yeah, it’s time to give them up, I have no choice. No idea how to deal with quitting them, except to say that, at least they have become crappy enough that it makes the thought more desirable.
Everyone should read this page as it relates to so many different types of drugs (you might be surprized which ones).
What is going on?
Read the cases and Just Say No!
http://patientsville.com/symptoms/antinuclear-antibody-positive.htm
I’d report it to MedWatch but they are like backed up or something. Maybe my doctor has.
YRLR
Your Resident Lab Rat
Anonymous
This is all very sad….
Doc
Because company marketing departments are the true power center in pharma today, this should be no surprise to anyone. Marketing even drives what scientific studies to do, all in light of what will give a sales edge in the field.
Anon
Marketing has been the true power center for many years.
I worked at Merck and my colleague in the next office was working on Fosamax. She had come from P&G where she had worked on Actonel. She told me that the main reason Merck beat P&G to market (and by years) is that P&G placed marketing people in charge of the Actonel development team and they thought they could just follow FDA guidances and get it approved without even understanding what those guidances and the regulations meant in terms of required scientific studies.
Atlex
Condor,
I don’t know why you are so against innovation. As with almost every new innovative drug (or other medical therapy), initially it starts as niche treatments and builds to blockbuster status as indications broaden, medical practice changes, new diagnosis and treatment systems are developed, and, importantly, physicians become more comfortable with the treatment and its value (effectiveness, safety profile, etc.). Osteoporosis is an incredibly debilitating disease/condition. Once bone loss occurs, it is very hard to reverse course. Being able to identify high risk patients in their 50s and 60s prevent problems from occurring 15 or 20 years later, resulting in significant morbidity and mortality, as well as huge costs (LTC, surgery, etc.). You might root for “the pure evolving practice of medicine”; I’d argue that this doesn’t exist. Someone with an incentive to do so has to develop the drug, the diagnostic, the system of care, and the reimbursement mechanism. Unless Merck hid data or promoted off-label, I can’t see that they did anything wrong. They saw an opportunity, developed an innovative solution, and reaped the benefits of innovation.
Moreover, while Merck benefits financially for a few years, it will inevitably lose exclusivity and the price of the medicine will drop to pennies a day. Merck, of course, will lose almost all of its sales, while women will still benefit from better bone health and less morbidity and mortality.
Atlex
Condor
As often seems to be the case between us, Atlex, we start from wildly diverging views.
I think Fosamax actually causes, or is a contributing cause to ONJ, or necrosis of the jaw bone — and perhaps, is causing an increased incidence of spiral fractures in the femurs of otherwise healthy older women taking it.
Now, true enough, their spines are straighter, and as measured, stiffer (there are fewer spine fractures in the treated group) — but at what cost?
Note that I am a ardent capitalist — I am for innovation — REAL innovation. Is this real innovation? I am unconvinced.
Moreover, on the other hand, I am not so wild about expanding Fosamax scrips to the “osteopenia” population (perhaps not a disease, at all — as Ed’s links teach us) — especially if these otehrwise pretty healthy, mature women suffer femur fractures, or jaw bone death, as a “side effect”.
So — CREATING a disease, out of thin air — simply to sell a niche pill to a wider class of Medicare-reimbursed US female patients. . . is beyond the pale — especially if it is doing them documented harm.
That wouyld seem criminal.
Namaste, and Merry Christmas, just the same!
patrons99
An article by Dr Neil Burman MBChB, MRCP, from February 4, 2009, titled
“Debunking the myth of bisphosphonates: time for class action,” is an interesting read, which supports my view that not all so-called “innovations” are good for society.
http://healthspanlife.wordpress.com/2009/02/04/more-death-knell-for-bisphosphonates-for-osteoporosis-breast-cancer-time-for-class-action-against-bisphosphonate-damage/
“Is it an overstatement to say that bisphosphonates are clearly even worse chronic disaster than statins – where the damage is usually insidious but reversible- or NSAID class drugs- which can simply kill by thrombosis or bleeding; or SSRIs- which can trigger suicide? The other modern drugs (after thalidomide) do not, like bisphosphonates, disfigure and maim.”
“Osteoporosis is like diabetes, hypertension, obesity, cancer, cardio/neurovascullar, arthritic, mood and dementing diseases, a multi- $billion-dollar a year target for the designer drug industry -let alone the diagnostics and invasive medical industries. For these industries, lucrative drugs, tests and surgery far outweigh the boring counseling about lifestyle and lowcost micronutrient preventatives- which would make designer drugs, costly tests and surgeries – hospitalization- virtually obsolete for medical conditions except for those who live to be the oldest of the old.”
Atlex
Condor,
Again, you just miss the point, either intentionally or unintentionally. Osteopenia is not a disease; however, we do know that a certain percentage of women who experience osteopenia will continue down the path to osteoporosis. This is similar to high cholesterol; that is also not a disease. However, we do know that it is highly correlated to future cardiovascular disease and that the treatment of high LDLs with statins significantly lessens morbidity and mortality. In fact, high cholesterol is a great analogy given that Merck helped to create the market for the condition and worked with a number of outside groups to ensure that Medicare and insurers paid for the laboratory tests (both cholesterol and liver panels).
One side note to patron99. Your citation of “Dr. Neil Burman doesn’t help any argument you try to make. He is a self-described expert “complementary health products” and the owner of a business selling those products. Not only is that in itself a conflict of interest, there are NO (ie, zero) placebo controlled, blinded studies proving the clinical value of any of the products he touts. On the other hand, there are innumerable studies proving the clinical value of the drug classes he disparages.
Atlex
patrons99
Atlex,
I would love to see prospective, double blinded, head-to-head comparison between the bisphosphonates and high dose Vitamin D3. I don’t believe that such studies are needed, however, because the safety data have already dealt a knock-out to the bisphosphonates. It’s really just a matter of time.
patrons99
Atlex,
At the risk of straying a bit off-topic, I’d just like to respond (briefly) to your mention of the statins:
I have never been completely enamoured with statins as the “be all and end all” that they are hyped-up to be by pharma. The statin proponents are so single-minded in their advocacy that I’m sure they would recommend adding statins to our drinking water. Perhaps we should begin to ask whether there might be some long term safety issues as to the wisdom of driving LDL’s down ever further with a parade of progressively more “potent” statins. For a long time I have believed that the mainstream theory of atherogenesis should be reexamined.
The promotion of vytorin and zetia is based on the theory that cholesterol blood levels are key determinants of atheromatous plaque formation in arteriosclerotic vascular disease. This theory may be wrong.
An alternative theory is the hemorheologic-hemodynamic theory of atherogenesis. This theory holds that atherosclerosis is a disease of stasis of blood, which promotes the organization of a thrombus into an atherosclerotic plaque. Risk factors for atherosclerosis create larger areas of decreased shear (flow) by increasing blood viscosity, arterial stiffness, or both. The name reflects the fact that the interaction of hemorheologic, i.e., blood flow, and hemodynamic, i.e., blood velocity, pulsatility, and arterial geometry, factors lead to atherosclerosis.
For a quick overview of the topic see Wikipedia at this link:
http://en.wikipedia.org/wiki/Atherosclerosis
Personally, I would love to see a study or studies which validate the hemorheologic-hemodynamic theory of atherogenesis. Placebo-controlled, hard clinical endpoint studies might only partially support the theory because even if the treatment works, it may work via a different mechanism - as may be the case with the statins. Also if the treatment did not work it would not completely invalidate the theory because the treatment might not have an adequate effect on viscosity or tendency to clot.
Why not undertake head to head, double blinded, placebo controlled studies comparing statins (the present standard of care) with active control arms that might include molecular entities (both new and old) which alter the hemorheologic and hemodynamic properties of blood? For example, we might discover that the efficacy of omega fatty acids, niacin, and vitamin C, can be better explained in terms of their effect on the hemorheologic and hemodynamic properties of blood, i.e. its viscosity and tendency to clot. There may be an ethical problem with relegation of a placebo control group to no treatment.
Justice in MI
There are, indeed, a lot of folks who think “statin” is “satan” spelled backward. I’m not one of them. I think they’ve proved themselves in secondary prevention pretty definitively, regardless of mechanism. Most preventive cardiologists _also_ recommend fish oil and, more and more, vit. D. Niacin is obviously getting a boost in some recent studies.
Personally, I do worry about the effects of long-term use of statins. A lot of this we simply don’t know, but the all-cause morbidity/mortality data are not entirely reassuring.
Worst, though, I am not confident that we will get data that _may_, in fact, be available until more than simvastatin is generic. Sorry to say that on this Merry day, but consider it one example of the “trust gap” that CEO Kindler spoke about.
I would say it to him directly: “I do not trust Pfizer to tell us everything it knows, and suspects but avoids finding out more definitively, about long-term use of Lipitor. Please prove me wrong.”
pharmavet
Having reached the age of requiring dental implants, my friendly prosthodontist shares with me the horror stories of total jaw reconstruction he has had to do on women who developed osteonecrosis from bisphosphonates. Quite nasty, and I have a pretty strong stomach.
Atlex
JiM,
There is a really, really big hole in your assessment. Once a product goes generic, we tend to have a bigger gap in knowledge. Is there anyone really tracking simvastatin effects in a comprehensive way. Like it or not, Merck had a much better handle on the entire simvastain picture when it controlled the market.
I know you speak of a trust gap and I don’t argue that, but we now have 20 years or more of experience to demonstrate their safety and overall strongly positive risk-to-benefit ratio. Given the large numbers of patients on these products, it doesn’t take terribly long for even rare side effects to emerge–eg, Baycol. Could something still emerge–sure, anything is possible, but it remains unlikely. Moreover, the chances of a side effect emerging that would shift the risk-to-benefit ratio significantly is even more remote.
Finally, we also don’t know the long-term effects of high dose niacin. Sure, we’ve been taking niacin for many years, but high dosages are a more recent phenomenon. There are similar issues with almost every other “natural” product on the market place. Plus, for most of them, no one is truly tracking the negative effects.
Atlex
Justice in MI
Hi Atlex,
Appreciate your thoughts. So as to be clear, I did not say that I believed there _was_ a “cover-up”/diversion/distraction re: long-term statings–only, sadly, that I do not entirely trust that there is not.
Baycol may be exactly the example. Depending on which account you believe, Bayer knew several years before withdrawal that there were problems with increased rhabdo relative to other statins, and especially with concommitant fibrate use. They did a great deal to obviate this–knowingly promoting to docs in ways that exaggerated benefits (thus creating a false benefit/risk impression); burying data they themselves generated about rhabdo rates in Baycol relative to other statins; in that context, bringing out higher and higher doses of Baycol; in same context, low-balling, suggesting they were going to bring out a Baycol/fibrate combo product, apparently to divert attention to the known risks of precisely that combination. And so on.
OK. One company. One drug. But it still took years, and not a small number of lives, before the fuller truth emerged. (The FDA was mostly asleep at the switch, and Bayer knew it and, seemingly, counted on it.)
So what does this have to do with other companies and other statins? It leaves the following questions (as questions, not conclusions):
1. How unique was Bayer’s handling of Baycol relative to other companies’ handling other statins? What reasons to do have to believe we that Bayer was, in any significant way, a “worse actor” in this regard?
2. Even if Baycol’s problems were harder to conceal for a _very_ long time, they were concealed long enough. What reason do we have to believe that problems easier to conceal are _not_ being so?
That is the trust issue–that one would even ask such questions and whether the history, as we know it, makes it unreasonable to do so. Again, the issue is the reasonableness of raising the questions–not presuming to know their answers.
Re: tracking generics, yes, another inadequacy in our system of post-approval surveillance.
JaT
At the risk of being repetitive and for sure off-topic. This is impossible to ignore.
“Re: tracking generics, yes, another inadequacy in our system of post-approval surveillance.”
____
Yes generics, and also, every branded drug that has been represented by an ANDA for approval under the same rules as generic drug applications.
Ie: dissolution/absorption tests when an ingredient is changed or when a manufacturing process is changed.
There are generally no post-marketing commitments either way.
It would be interesting to know which branded drugs have not been represented by an ANDA or two or more.
Silly to think one abbreviated application is any more valid than another. The difference may be that a generic maker (trying to gain a first time approval) is more scrutinized. And that a doctor will know that a generic is new. Where he may not know that a branded drug has been altered- so that when a patient presents with a new issue it is not clear where the new problem originated. Drug makers don’t exactly advertise when they make changes to the products you are swallowing.
I think Orange Book has to list them (I may be wrong), but your doctor sure isn’t going to have the time to research every medication every time he writes a refill.
A Greek to English translator might be helpful in making this point. I’ve made it in every way imaginable. Am I wrong?
patrons99
Are we missing the boat as to drug toxicity in general? I’d like to propose a unifying theory, which might further the discussion. I’ll give it a name. The cummulative, synergistic, pleiotropic theory of drug toxicity. Such a theory may help explain why, it sometimes takes years before a clear pattern of toxicity emerges.
http://www.holtorfmed.com/topics/statinsssribisphosphonates/use-most-popular-osteoporosis-medications-associated-with-brittle-bones-osteonecrosis-jaw-disintegration-heart-damage-and-muscle-pain
I found an article [link is provided above] titled “Use Most Popular Osteoporosis Medications Associated With Brittle Bones, Osteonecrosis (Jaw Disintegration), Heart Damage and Muscle Pain” to be of particular interest, which I will excerpt here:
“There are a number of studies that demonstrate that the use of bisphosphonate are associated with an increased risk of heart
arrhythmias (1-4). This includes a large study of 1700 women published in Archives of Internal Medicine that demonstrated that current and past users of bisphosphenate
medication such as Fosamax , Actenol, Reclast and Boniva had significant increased risk of potentially fatal heart arrhythmias. It was shown that any individual who had ever used these meds (could have stopped many using many years prior) had a 300% increased risk of
abnormal heart arrhythmia and a 575% increased risk of sustained arrhythmia. In addition, the risk was higher if the mediations were used by those who also had diabetes mellitus or were currently taking statin medication. There are also increasing reports of muscle and joint pain due to bisphosphonate use.
1. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356: 1809-1822.
2. Alendronate and atrial fibrillation. N Engl J Med 2007; 356:1895-1896.
3. Compston J. Treatments for osteoporosis—Looking beyond the HORIZON. N Engl J Med 2007; 356:1878-1879.
4. Use of Alendronate and Risk of Incident Atrial Fibrillation in Women. Arch Intern Med. 2008;168(8):826-831.
Why should the risk of arrhythmia be higher in patients who were currently taking statin medications? In my day-to-day medical practice, I often see patients on literally dozens of prescription pharmaceuticals at any given time, a problem often referred to as “polypharmacy”. The burden on kidneys and liver to metabolize and clear many of these drugs is well-documented. Drug-drug interactions have been well-documented. Are these toxicities synergistic?
pharmavet
To extend Patrons99 argument, not only would it take years to detect “cumulative, synergistic, pleiotropic effects to establish some sort of pattern, there are also those drug toxicities that are completely idiosyncratic, without any dose dependency or pattern of causation. By definition, an idiosyncratic drug toxicity obeys no laws of pharmacotoxicology, and would defy pattern behavior. But if we could do a better job with those toxicities that patrons99 describes, it would be a good start.
Justice in MI
Clearly, there are many reasons why uncommon AEs both happen and may not be picked up for some time.
I would add the importance of study designs, in which surrogates are used for M&M as well as for benefits. The saga of the arrythmic drugs that Tom Moore has retold is perhaps the most dramatic example.