"Me," "We," and the FDA
Your wife is dying of cancer and you read about a drug-maker developing a product that could slow the progress of the disease. Her doctor says it shows promise; the price of the company’s stock has tripled in just six months. But the new drug has not yet won FDA approval.
Your spouse wants to try it. But her doctor tells her that it’s too late to enroll in an ongoing clinical trial. You could apply to the FDA and the company for access under a “compassionate use” provision, but this is a bureaucratic process that could take weeks, or months—time your wife doesn’t have. In the meantime, the FDA won’t let you buy the drug directly from the manufacturer.
Shouldn’t your wife be able to buy it --even if it doesn’t have the FDA’s imprimatur? After all, the life she would be risking is her own. How can a government bureaucracy stand in her way?
This is exactly what a patient-advocacy group known as Abigail’s’s Alliance” argued last April before a U.S. Court of Appeals in Washington. A year earlier, the Alliance won its case before a three-judge appellate panel, and the FDA appealed. The full appellate court is expected to rule later this year.
Abigail’s Alliance for Better Access to Developmental Drugs commemorates Abigail Burroughs, who died in 2001 of head and neck cancer at age 21 while struggling to gain acess to drugs not yet approved by the FDA.
The alliance, which was co-founded by her father, is demanding that the agency allow dying patients to buy experimental drugs from the manufacturer. The Alliance also argues that drugmakers should be able to profit from these sales.
Last year, when the three-judge panel ruled in Alliance’s favor, Judge Judith Rogers wrote:. "A right of control over one's body has deep roots in the common law. The prerogative asserted by the FDA ... impinges upon an individual liberty deeply rooted in our Nation's history and tradition of self-preservation."
The FDA’s supporters were appalled. They say that if the full court finds in Alliance’s favor this time around, the rules of the game about how we test drugs could change radically in ways that, according to oncologist and ethicist Dr. Ezekiel J. Emanuel, “threatens the very research process that gets drugs tested and quickly delivers safe and effective ones to the most people."
Emmanuel worries that if indivdiuals can buy experimental drugs without waiting for FDA aproval, the pool of patients willing to participate in randomized clinical trials in which only half receive the new nostrum will dry up. Who will be willing to risk receiving a placebo or a conventional therapy instead of the “breakthrough” drug?
After all, most patients—and many doctors—tend to assume that the “lucky patients in a randomized clinical are the ones who get the “new, new thing.”.
In truth, a recent study shows that fully 42% of the products that make it to the third, and final phase of FDA trials ultimately fail because they prove ineffective and/or unsafe. http://www.mckinsey.com/clientservice/pharmaceuticalsmedicalproducts/pdf/why_products_fail_in_phase_III_in_vivo_0406.pdf.
How do so many lemons get so far? The study suggests that once a drug company has invested a certain amount of money—and reserachers have invested a certain amount of time and ego—it becomes difficult to admit failure. Moreover, as long as investors think a drugmaker has a new product in the pipeline, the stock will stay afloat.
Meanwhile, Wall Street hype about a "life-saving drug" tends to spill over into the media where it fans faith in the miracle drug, a phenomenon I’ve written about here http://www.tcf.org/Publications/HealthCare/healthbeat.pdf. in a story about a prostate cancer vaccine.
So physicians like Emmanuel have reason to fear that if patients could buy the drug, it could become difficult to mount the full-scale randomized trials needed to establish firm evidence of a drug’s efficacy and safety. “The Abigail Alliance approach would eliminate the kind of careful monitoring on larger groups of patients [that we need] before widespread access becomes available,” Emmanuel argues in The New Republic. “Instead, unproven drugs would be tested for safety in fewer than 80 people [in phase I trials] and then could be sold to patients. The benefit of a few desperate patients would come at a steep cost for the rest of us.” http://www.tnr.com/doc.mhtml?i=20060703&s=emanuel070306
Others make the libertarian case for individual rights. In the newest issue of Reason, Kerry Howley writes: “Drug trials are rooted in centralized authority: trial slots are numbered, subjects handpicked, control groups maintained, patients monitored. Maintaining this level of precision requires not only the cooperation of willing test subjects, but the coercion of the general population. To preserve pristine testing conditions, the federal government curtails our freedom of exchange and our right to take risks . . .” http://reason.com/news/sKow/120763.html.
Howley acknowledges that physicians and patients’ advocates like The American Society of Clinical Oncology and the National Breast Cancer Coalition oppose Abigail’s Alliance. But she points out, the Alliance is willing to let the FDA insist that patients apply to clinical trials first, before trying to purchase the experimental drug. Then, if they are turned away (because they don’t meet eligibility requirements) they should be free to purchase it.
However she also quotes the amicus brief submitted by the American Society of Clinical Oncology on behalf of the FDA, arguing that such a requirement would only give patients an incentive to appear ineligible: “Their physicians could easily help them game the system by, say, ordering a round of chemotherapy, which disqualifies patients for many Phase II and Phase III trials.”
Finally, there is a question of equity. If drug-makers are allowed to sell experimental products at a profit, who will buy cancer drugs at $50,000 a pop? Wealthy patients. Others will have to wait for FDA approval.
Meanwhile, if an individual who uses the drug outside of carefully monitored trials dies, there is a real risk, as a drugmaker in this WSJ story http://online.wsj.com/article/SB117798196751887629.html.
points out, that the FDA will halt randomized trials until the company can investigate what happened. This means more delay for the less affluent.
In the end, the questions the debate raises remind me of the point Michael Moore made in “Sicko”: In other countries, people think about healthcare collectively, in terms of “we.” In the U.S. we think of healthcare individually—in terms of “me.” This is one reason why our heatlhcare system is broken.
Interesting. I'd be somewhat concerned about getting in the way of trials, but your case study indicates that the trials were underway and closed; so one could always have a qualifying rule like that. Thus someone who wants a drug could get it either by joining a trial or, provided the trial were closed, otherwise.
But I'd also be worried about the end run around FDA approval. We're often worried that the Bushies are allowing companies to rig the game now, so that a drug doesn't have to have any advantages to gain patent protection. And the approval process is supposed to keep the companies from peddling useful or downright dangerous drugs. If we allow drugs to be sold without approval, what does approval mean? Does it mean anything at all, when the discretion is left to the buyer? Does it cede all power to marketing, where all of health care becomes like that insidious "ask your doctor" in the ads?
I'm serious when I say these are real and not rhetorical questions. That is, I'm speaking from the gut and would love your expert thoughts.
John
http://www.haberarts.com/
July 26, 2007 1:34 PM | Reply | Permalink
You've outlined the issues pretty clearly. The problem with new drugs is that they tend to treat increasingly rare diseases (I'm talking about real breakthroughs, not me-too drugs).
Finding an adequate sample to use for testing becomes difficult and sometimes the results are ambiguous. Another problem is that side effects may only occur in a small percentage of people. If an adverse reaction happens in one out of a thousand and the sample is a hundred the chances are it won't be observed.
Presently there are few new drugs which have such a dramatic effect that giving them to a terminal patient will reverse the course of the disease. When things like this do happen, the experimenters usually terminate the trials early and say that it is unethical to deny the drug to those getting the placebo.
Desperate people with little understanding of science have been having too much influence on policy recently. No ethical doctor will deny treatment when it is clear that it will do good (that's the job of insurance companies).
Finally I don't think this is an American problem, drug trials now take place worldwide and the protocols are pretty much the same. If there is a weakness it is in permitting the drug companies to keep their research data private, rather than allowing it to be examined by others.
It's funny that this segment used to be called the "ethical" drug sector. Now it seems to be the prescription drug sector. No more ethics, I guess.
--- Policies not Politics
Daily Landscape
July 26, 2007 1:39 PM | Reply | Permalink
Where's the money in developing drugs for increasingly rare diseases?
Let the government do that.
The smart money is developing the newest viagra, or a safe weight loss drug, or a hair restoration or skin rejuvenation drug. Yeah. Imagine the market for that stuff.
That's a lot more important.
July 26, 2007 2:32 PM | Reply | Permalink
John and rdf--
First, John--I do think that if companies are allowed to sell drugs at a profit without FDA
approval we would be "ceding all power to [direct-to-consumer marketing.
That said, I should point out that many drug companies are not enthusiastic about Abigail's Alliance because, under the law, an individual who buys an experimental drug can turn around and sue the company if unhappy with the results.
Amazingly, there is no waiver that a patient can
sign relieving the company of all responsibility. (Under the law no such waive would stand up in court.)
But if the company could sell the product at a high enough profit and was quite certain that any side effects would be mild (even if it wasn't certain that the drug was effective--or any more effective than what is on the market) then this could be a good deal for the company.
We need the FDA to protect people from companies selling risky, over-priced and ineffective drugs. WE need the FDA to protect Medicare from being forced to pay for risky, over-priced and ineffective drugs.
RDF-- You're right that it can be hard to mount a randomized clinical trial for "orphan drugs"--used to treat rare diseases. I don't think that all drugs have to be subjected to randomized clinical trials--sometimes it's just not possible.
But randomized trials remain the gold standard, and in this piece I'm talking about the "blockbuster drugs"
aimed at dying patients (like Provenge for patients dying of prostate cancer.) In fact, as you say, these drugs do not reverse the course of the disease. Typically, they may give the average patients a few more months. But they are touted as "life-saving" and patients who do not want to face the fact that they are dying cling to the idea that if they can just win a few more months, maybe something else will come along that will cure them.
I totally agree that "Desperate people with little understanding of science have been having too much influence on policy recently."
Finally, while this problem is not unique to the U.S., I do think that our fear of death is greater than in some other cultures. In Italy, a friend died of cancer a year ago. When his doctor told him that nothing could be done, he accepted it. His doctor sent him home with morphine which his wife administered. In a few weeks he died, as he wanted to, in his own home.
As it happens he was a very wealthy, intelligent businessman in his late 50s; it is hard to imagine a comparable American who wouldn't have
flown around the country, going from doctor to doctor saying YOU HAVE TO DO SOMETHING. I CAN"T
DIE.
I am, of course, making gross generalizations about Americans and other cultures. But I would note that other countries have many more hospices than we do. Many of us just don't accept the idea of dying. Some would call that our "American optimism."
July 26, 2007 2:34 PM | Reply | Permalink
Great discussion here so far. So many complexities I can't say that I come down on any side with any great conviction, though I'm leaning towards a conclusion:
My healthcare really is a "me" issue. Access to healthcare is a "we" issue but when I'm sick or in pain, I want to be made to feel better. I'm not particularly adept at, nor am I particularly willing to, tough it out or lay down and die on the advice of one doctor.
And, I have had (minor) conditions successfully treated by one doctor when another says "You'll have to live with it."
I think I come down on the libertarian side when it comes to access to experimental drugs. I assume that patients aren't making this decision, their doctors are. So the issues of scientific expertise are probably mitigated. Meanwhile, the FDA has simply not acquitted itself well over the last few decades. It's been approving copycat drugs at an alarming rate. I guess that keeps the FDA from taking too many risks.
thosethingswesay.blogspot.com
July 26, 2007 2:56 PM | Reply | Permalink
Thanks, Maggie, that was really informative and just what I needed to know. Fascinating about the limitations on waivers.
John
http://www.haberarts.com/
July 26, 2007 5:48 PM | Reply | Permalink
This resonates with a discussion I had with my medical surrogate about my durable power of attorney. With her, it's a situation where we have significantly different views about mainstream and alternative medicine, but I can trust her to follow my directions.
One question I was asked was "if you had cancer and the doctors gave up, wouldn't you want to try this (referring to an herbal mixture)." I read the book on this particular herbal, and it reeked of quackery, although probably sincere. The proponent was "too busy saving lives" to go not only through clinical trials which she was offered by a distinguished and sympathetic researcher, but even to have her mixture analyzed. I know too much pharmacology not to know that some plant-derived preparations have significant biological activity, but I also know about the high variability of the raw forms.
Rather than throw myself desperately at something that had only anecdotal evidence, I'd rather stay with comfort measures that I had confidence that would work. I'd rather have a competent hospice team than false hope.
I've been quite explicit about comfort measures only, and very well defined comfort measures, if I had an irreversible dementia and, for example, developed pneumonia. My only exception is to give advance consent for Phase I or later trials of treatments for dementia, not that I'd hold out much promise, but we aren't ever going to advance without test subjects.
Let me go gentle into that good night if there's nothing that can be accomplished, but let me also follow the model of someone I much admire, who rages against the dimming of the light. He is a master in his field (culinary & ornamental herbs), and has early-onset Alzheimer's Disease. As his memory fades, he works with coauthors, trying to get a lifetime of experience written before it is lost forever. There's no greater form of courage.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 26, 2007 7:51 PM | Reply | Permalink
Howard, one of the leaders of the Indian occupation of Alcatraz was a Mohawk named Richard Oakes. In 1970 he was bashed in the head with a pool cue in a bar room brawl, Indians v. Samoans. This left him in a coma, and the doctors at the SF hospital treating him had given up hope. The brain injury had caused all the muscles in his body to spasm - I forget the name - when your muscles extend, not contract and not clonis. So Richard, unconscious, was litterally exhausting his body to death. The doctors figured that in a couple of days he would expire.
However, a couple of Indians from Alcatraz took it upon themselves to travel to New York, and plead for help from the Indian doctors. The Tuscarora leader Wallace Mad Bear Anderson listened, and he went across the border and solicited the help of a doctor from the Cayuga reserve, Peter Mitten. On their way to San Francisco they picked up a Hopi leader, Thomas Banyaca. The three arrived at the hospital and demanded that they be allowed to treat Richard Oakes.
Of course the doctors at the hospital thought it was an outrageous proposition. But Richard's wife, Annie, argued that since they had given up hope on saving Richard, the "Indians" ought to be given a chance. Ultimately the hospital agreed - but you can imagine how nervous they were about it. When Peter Mitten was preparing his "medicine" (which included singing and praying) the M.D.s kept asking what it was and what he was doing. Mad Bear (Mitten refused to acknowledge the English language) would tell them "You wouldn't comprehend."
Then Mitten took his mixture, which resembled really dank and dark sewer water, and injected it into Richard's IV tube, and they all watched it go down the tube and into Richard's body. The doctors were obviously horrified, but they didn't interfere. But then they noticed Richard, whose skin was pale and white from the effect of his muscle spasms, and around his heart color began to return to his skin, and the color gradually spread out to his whole body. And as the color returned, his muscles relaxed, as if he was sinking into his matress. Mitten turned to the doctors and said something in Iroquois, which Mad Bear translated "He is very tired. He will rest for two days and then come back to us. And that in fact was what happened.
I know this story because the three Indians traveled to the Pit River tribes land in Northeastern California the next day, and I was among the people there who listened to their account. It was sort of strange, too. Someone had brought a couple of buckets of Col. Sanders Kentucky fried chicken for dinner, and we were all sitting around outdoors at Willard Rhoades place eating it as the story was being told. Willard had a bunch of chickens himself - those Japanese Bantams with the feathers on their feet. As we listened and ate, we would throw the bones on the ground and Willard's Bantams would dive on the scraps to have their feast too. Dirty little cannibals.
Neoboho
July 26, 2007 9:08 PM | Reply | Permalink
Maggie,
I am grateful that you bring up a truly insoluble problem but I take exception to this:
Approved drugs are sometimes later found to be unsafe and/or inefficacious.
Just so abandonment of drug development may be for reasons other than lack of efficacy or safety. The costs of drug development are enormous, unnecessarily so. The reasons for ending development range from the idiocy of the hidebound rules of entrenched bureaucracy to highly charged terror stories that concentrate nearly exclusively on safety.
What you do not take up, what is seldom whispered about anywhere, is the case of abandoned drugs.
I could probably locate the sad tale of a woman executive with breast cancer who had been in a clinical for cancer vaccine. The trial failed miserably and the vaccine was abandoned but it seemed to help that one lady. Enlisting the aid of various VIP's and with considerable effort and expense, the woman finally managed to gain access to some quantity of the vaccine that collected dust on shelves.
So why was development abandoned? Was the vaccine truly worthless? My feeling is that the vaccine certainly helped some but the Phase III trial was cursed by particularly poor design. Other reasons beside expense include regulatory obstacles thrown up by the political scientists at the FDA. For an obvious example think of cannibinoid drugs but that is just the tip of the iceberg.
I have no quarrel at all BTW with the argument that development of some drugs should be abandoned sooner than they are but I offer the counter example of thalidomide that has currently been found to be a very useful drug for treating cancer. Somewhat more startling is that technology is available that might clean up the manufacturing to purify the drug of contaminating enantiomers to make it safe for pregnant women.
The terrible bureaucratic mess at the FDA is mainly good for the Pfizers and Mercks as well as newspaper columnists and other purveyors of sensational hysteria. Dying patients count for even less than wounded soldiers from worthless wars.
Best, Terry
July 27, 2007 2:47 AM | Reply | Permalink
Wow, that was a beautifully rational and persuasive article.
So glad Mahar is at TPMC.
July 27, 2007 5:03 AM | Reply | Permalink
The government does do that. In fact, the government funds the research for 23 out of 27 cancer drugs.
July 27, 2007 6:48 AM | Reply | Permalink
I think she's fantastic. She doesn't shy away from complexities and she always offers a great mix of liberal and libertarian thought. It's as if she's a "do it yourself" liberal who believes both that society should do a better job taking care of people and that people need to be free to follow their own ideas.
She's kind of a step forward who has managed to avoid paternalist liberalism and yet she remains a liberal. It's really refreshing.
Also, as a TPM writer she's the best at jumping into the muddy comments and answering us when we debate with her.
thosethingswesay.blogspot.com
July 27, 2007 8:29 AM | Reply | Permalink
Good points, and let me clarify. I'm considerably more comfortable with alternative medicine when it involves a tradition and a provider, rather than some of the herbals I've described, which simply are in an old book and do-it-yourself.
In this case, it does help, I believe, to be a patient with exposure to the traditions. As to other forms, I'd hesitate before calling meditation and visualization even alternative. I've seen acupuncture and moxibustion have positive effects on pain.
Still, there is a point, with allopathic or alternative medicine, for acceptance. There's a difference between palliative care and keeping alive someone with no quality of life.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 27, 2007 8:59 AM | Reply | Permalink
Thanks to all of you for your comments. This is a great thread, thanks to you. Let me offer some responses.
Terry--Actually, the study was looking at drugs that never made it past Phase III, not drugs that were later found to be
too risky or not that effective.
Regarding abandoned drugs, I'm sure that there are some drugs that have been abandoned because the manufacturer blew it(poor design of the study) of because a bureaucrat at the FDA got in the way.
But I think the solution is to continue studying the drug--not to put it on the market and see what happens. As for the cancer drug that helped just one woman (or very few people in a study) it's quite possible that something else caused her to get better. I'd want the company to continue studying it (and include her in the clinical trial so that she has access to it) before putting it on the market
Also, I would point out that the problem in our health care system is not that we don't have enough drugs. We're awash in new drugs. And as a nation, we are overmedicated.
The big problem is that at this point, most of tne new drugs are at best, partially effective, while many of them offer neither comfort or cure--just false hope and more suffering. I'm thinking in particular of the overuse of various types of cancer therapies that may give the patient a few more months, but no cure, and no relief from pain.
I'm with Howard (hcberkowitz) on this one.
His comment seemed to me an excellent example of thinking in terms of "we"--especially his willingness to be part of a trial studying treatments for dementia. He doesn't think it would help him--we're too far from understanding the disease--but if people don't sign up for trials we'll never make any progress.
Going back to the FDA, it did some very good work in the 1990s when David Kessler was the director. Since then, morale within the agency has really slid.
destor 23--I don't think anyone should lay down and die on the advice of one doctor. I, too, have had the experience of being told "there's nothing we can do" (about a fairly minor ailment) and then found another doctor who knew how to do something else.
But there is a point where you have to accept death. My Italian friend had liver cancer. There is no cure.
Moreover, thinking in terms of "we", when
people spend the last months of their life on futile treatments they cost all of us millions of dollars. Insurance companies don't give anything away for free. If they cover $60,000 dollar drugs that give the average patient an extra 10 days (the FDA has actually approved such a drug) they pass on the cost to all of us in the form of higher premiums. And when Medicare covers these drugs (which it virtually always does if the FDA approves them) we can all look forward to higher co-pays and premiums--and perhaps the end of Medicare.
Unfortunately, some doctors and hospitals make huge profits on futile treatments. They may not consciuosly think they are in it for the profit, but they know that they cannot cure the patient, only cause him more pain. Yet some cruelly encourage the patient to go on--"Don't give up. Think of your family, etc.You're a fighter, aren't you?" Such doctors should be lying in the bed, in excrutiating pain themselves.
What such patients need is a palliative care specialist--a doctor trained to help dying patients sort out their priorities in a honest, frank discussion of their options.
One very honest oncologist has told me that after one or perhaps two rounds of chemo, he
often says to his patients "I don't think I can make you well--but I know I can make you sick. Think about this--how do you want to spend the time you have left in your foreshorted life--with me and my staff, having chemo treatments? Or is there something else you would like to do with what remains of your life?
That's what I would want a doctor to say to me.
neoboho--that was an amazing story. I think that there is a great deal that we don't understand about medicines and therapies used in other cultures. I'm a big fan of acupuncture, for instance. But I'm also very very wary of alternative treatments because so many hucksters have gotten into the business of selling them . . .
Finally for those of you interested in how the FDA approves drugs and the pressures on the agency, you might be interested in a story about a prostate cancer drug that I posted recently on www.tcf.org. The two doctors on the FDA panel who voted against the drug ultimately had to hire bodyguards!
July 27, 2007 9:26 AM | Reply | Permalink
Completely Off Topic But:
Currently reading Money-Driven Medicine -- great book.
Now, ideas that seemed "intuitively obvious" to me actually have empirical validation. And some ideas not obvious are introduced into my already bursting cranial lumber room! ;-)
On the current topic: Well, it's another case in which the "obvious" answer doesn't withstand scrutiny. Hmm, kind of like "market forces" in medicine. The problem with advocacy groups like this is general -- they don't care about long-term or ancillary impact. The other item I believe should be noticed is that if pharma is not indemnified against bad effects, it probably is not indemnified against no effects, either. Somebody is certain to sue because the "experimental" drug did not save their loved one's life.
Thanks.
mp
With the supermarket as our temple and the singing commercial as our litany, are we likely to fire the world with an irresistible vision of America’s exalted purpose and inspiring way of life? -- Adlai Stevenson
July 27, 2007 9:54 AM | Reply | Permalink
Maggie,
From personal experience as well as more general knowledge of medicine, there are factors other than pure profit, such as ego. Around 1975, my mother, beyond any interventions (see below) was transferred from a community hospital to a VA hospital. She had breast adenocarcinoma with brain and widespread bone metastasis.
While I had power of attorney, especially in a VA hospital, this was still unusual, and the staff ignored DNAR. Within a few weeks of the transfer, her mind was gone, with nothing left of higher consciousness than the ability to moan and scream. There was a point at which the person I knew was gone, although her basic functions continued. Even in that state, the staff would not give what we would now consider adequate opioids, for "fear of addiction".
Given the real-world figures on resuscitation, it amazes me that she came back twice from cardiac arrest. Of course, the closed-chest compressions had pulverized her already damaged ribs.
With salaried physicians, it couldn't have been profit driven. There can be complex factors, as with a beloved cat of mine, who, if we could get the second-stage chemotherapy induced, had the chance of a significant remission. Still, euthanasia earlier might have been more kind, and I held on too long.
Again with the singular of data not being anecdote, I went through this with my mother while she was in the community hospital, where medical oncology was really new. For an assortment of factors in hospital politics, it had gotten to a point where I was given full chart access, and was coordinating care more than was her primary physician.
One day, she called me, annoyed that the nurses, as she said, wanted to give her IVs to "build up her strength". This puzzled me, as she was already getting IV treatment.
Soon, on getting her labs, I called around to find out what was really happening. She had immediately life-threatening hypercalcemia, as a reaction to the chemotherapy. The oncologist and the primary care physician couldn't decide what to tell her. I had much better rapport with the oncologist, who said his recommendation was not to treat the hypercalcemia, which is a gentle way to go. There were very few possible treatments left.
Still, I insisted that since she was still lucid, she had a right to make a decision. It fell to me to lay out her options, making it clear that I would support whatever choice she made. One was not to do anything, which would mean she would get sleepier and sleepier, and then never wake up. The other was to try a hormonal treatment that had, at best, a 30% chance of getting some regression. She chose to treat. In the same situation, I don't know if I would have asked for that, unless I had some things I very much wanted to finish.
Ignoring any emotional cost to myself, at least I had the skills to understand the situation, present her options, and try to support her--and we had a pretty bad relationship. I wonder how many other physicians have abandoned that sort of discussion and not had a family member able to take on the task.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 27, 2007 10:15 AM | Reply | Permalink
But geez, Maggie, that is exactly my point.
Because development of drugs ceases does not mean they were inefficacious or unsafe. That's what the statistics imply.
In some cases the time simply begins to run out on patents as the FDA adds obstacles.
Also, I would point out that the problem in our health care system is not that we don't have enough drugs.
Certainly is a shortage if you have cancer or many other deadly diseases.
The system is geared more to produce mostly copycat drugs with minor improvements to health at best rather than develop new platform drugs.
But I think the solution is to continue studying the drug
Time and money run out and patents expire. So do patients expire. The benefit is to the big drug monopolies.
As for the cancer drug that helped just one woman (or very few people in a study) it's quite possible that something else caused her to get better. I'd want the company to continue studying it (and include her in the clinical trial so that she has access to it) before putting it on the market
But, Maggie, the government cannot mandate a small biotechs somehow continue development. Many of those biotechs simply head off to Biotech Heaven.
The particular problem with cancer vaccines has probably been in individual differences. The FDA doesn't like personalized medicine. It wants one size fits all. And there is the rub. I was attracted to Barack Obama because he is the author of a bill directing the FDA towards looking at personalized medicine; i.e., genetic differences.
Best, Terry
July 27, 2007 11:57 AM | Reply | Permalink
I know it's not the same, not exactly, but I can't help remembering Thalidomide and what lessons we learned from that tragedy.
Can I add my kudos for one of the most stunning essays I've read on TPM in recent memory. (Maybe the last stunner was also a Maggie Mahar piece--I suspect it was.) I'd love to use this in a University Civic Engagement class. It is so incredibly rich and thought provoking. I caught my self deciding "x" then saying "but wait a minute" probably half a dozen times. So bravo and again bravo, and maybe you might think of compiling a series of these...public issue pieces fraught with ambiguities and hard choices. What a learning tool it would be.
aMike
July 27, 2007 11:57 AM | Reply | Permalink
Consider adding the lesson that thalidomide is now back in use, for completely different purposes than its original, somewhat me-too role as a sedative. Reapproved, with enormous warnings, for leprosy, it gave insight that the damage done by leprosy is largely a hyperimmune reaction caused by tumor necrosis factor alpha (TNF-a). TNF-a is, as the name suggests, a part of natural defenses against cancer, as well as infection.
Too much TNF-a, however, is involved in a wide range of diseases from Behcet's Syndrome to septic shock and probably multiple sclerosis. A different means of TNF-a inhibition was a breakthrough in rheumatoid arthritis.
In any drug policy, one needs to allow for the drugs that can have major benefit but also present major risks, or, as with thalidomide and retinoids, extreme risk in a specific situation such as pregnancy (even through semen). The selective COX-2 inhibitors, such as Vioxx (withdrawn) and Celebrex (still marketed), IMO, still have a role, when all other reasonable alternatives have been tried, in disabling musculoskeletal disorders.
There must be thoroughly informed consent for a drug such as Celebrex, which, to my shock, still is in direct-to-consumer TV ads. Other policy tradeoffs get involved here: if the issue is pain alone, not anti-inflammatory effect as well, long-term opioid use may a rational alternative -- but too many physicians fear prosecution. They are unaware that DEA and the American Academy of Pain Medicine have worked out "therapeutic contracts" and charting criteria that will be considered documentation of appropriate use.
Indeed, I am actively involved in a drug tradeoff with policy implications. The class of thiazolidinedione drugs really got my diabetes under control, but my previous endocrinologist had been reluctant to prescribe them with my history of heart disease. Adding Avandia to my insulin had enormous benefit, but there are an increasing number of studies showing Avandia is much higher-risk than other drugs in its class. Switching to another, which probably is therapeutically better while simultaneously lower in risk, I was shocked to find the list price of Actos at about $485 per month. Avandia was substantially cheaper.
There are all sorts of questionable micromanagement techniques. I don't think anyone will argue that the ideal in diabetic management, with insulin, is frequent measurement and small increments, but my insurer won't cover the test strips for more than 2-3 tests per day.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 27, 2007 12:33 PM | Reply | Permalink
I'm afraid that medicine man story didn't instill much confidence in me. The world's full of inexplicable events, events with multiple potential causes, placebo effects, ordinary physician error, and thoroughly unreliable accounts of them all. Who's to say what's at stake here? I'm not going to change my plans next time I'm sick because of tales of healing by touching fragments of the true cross either.
The reticence of those involved doesn't make things any better, whether one calls that the strength of rooting alternative treatments in tradition or not. In practice, it just means denying the one redeeming feature of alternative therapies. That is, drugs have, as Howard noted, often begun from observation of remedies (or recreational substances) found in nature, which makes them worth studying. But they're still chemicals, and they still need to subject to modern standards of openness, shared knowledge, and testing before they can be trusted and harnessed. When I hear the usual religious story that conveniently ends by making that impossible, alerts go off. Unlike religion, science is not a dogma.
John
http://www.haberarts.com/
July 27, 2007 12:34 PM | Reply | Permalink
The Wikipedia article to which I gave the link has the leprosy story in it. :-)
aMike
July 27, 2007 12:48 PM | Reply | Permalink
There are some interesting trends of old drugs, not as dramatically as thalidomide, that have gone out of production, but go back in demand. For example, streptomycin, the second antibiotic in clinical use, is a fairly toxic and can only be given by injection. Along with another drug, PAS, it was the first antibiotic found effective against tuberculosis.
Superceded by other drugs, it turned out to be useful again against certain multidrug-resistant TB strains. Long off patent, the Centers for Disease Control issued a contract to make more, and dispenses it as it tracks such strains. CDC also will provide physicians with a wide range of drugs useful for tropical parasites, which there would be no economic basis for a company to have approved in the US.
There are examples here of both how a government program can deal with drug production, and also the tracking of infectious patterns. Discussing such could lead into the very challenging area of new antibiotics that may be the only drugs that will hit resistant strains, but the manufacturers are tempted to "push" for other than the most necessary purposes.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 27, 2007 12:58 PM | Reply | Permalink
It doesn't tell the real story.
Not much leprosy going around these days.
Thalidomide was taken through the approval process for a symptom of leprosy so it could be prescribed for cancer. Lots of cancer going around.
An approved drug may be prescribed in any way the doctor sees fit. Well that is unless the drug warriors object but that is an entirely different story.
The FDA has tried to prevent doctors prescribing drugs for any but approved uses. They have been slapped down by superior Divines - the Supremes.
the FDA has a byzantine empire that raises costs enormously and costs many their lives and health. Many concerned citizens do more harm than good by ignoring the workings of the empire and adding to its complexity.
The first thing one might consider is that clinical trials are barbaric. There is no way around controlled trials today but one might first recognize that basic fact.
Best, Terry
July 27, 2007 8:49 PM | Reply | Permalink
I don't buy it. Patents last 20 years. The only situation when a patent running out interferes with drug company plans is when they launch a study to get approval for a new use for an already-existing drug.
July 27, 2007 10:53 PM | Reply | Permalink
So?
Meet Prof. Sumner Burstein.
http://www.umassmed.edu/bmp/faculty/burstein.cfm
The last time I saw Dr. Burstein he was one very angry man. Not without cause I think.
Dr. Burstein is the inventor of ajulemic acid. Ajulemic acid is a synthetic cannabinoid that eliminates psychotropic side effects.
Elimination of the fun stuff from the dreaded weed may not be all good, except to drug warriors, if you really think hard on it. Be that as it may, Dr. Burstein's baby has the potential to give far more potent dosage than is available from a joint. Certainly it is not like the long-approved synthetic, marinol, that gives a high that patients find objectionable over measured puffs on a joint. (I can only speak from reports BTW. I have never smoked the stuff.)
There was a successful small trial long ago in Germany treating neuropathic pain. And then - nothing.
The drug was licensed to a small biotech with high hopes and little money. Then it was sold to another biotech that specialized in dump picking, according to the CEO himself. The CEO stated frankly that all the drugs Indevus bought had "something wrong with them." That something was mostly aging patents. Some drugs even had expired patents. (There is a provision for 3 years protection of drugs without patent protection taken through trials. Obviously it is seldom needed.)
Your drug is very hard to fabricate the scientists at Indevus told Prof. Burstein while I was there.
I have never made any ajulemic acid or any other drug. Would have no more knowledge of where to begin to make ajulemic acid than Mark Twain had in building a bridge. I can only tell you that Prof. Burstein, a chemist, told me that such an excuse was ludicrous.
No patient with a lifetime of neuropathic pain beyond that handful in Germany long ago are likely to ever get relief from a superior drug without the high. Cancer patients will have to just sneak a puff on a joint if they can. Same for glaucoma patients trying to prevent blindness. MS patients can just keep shaking and quaking.
The story is told and retold with all manner of drugs. Some of the drugs are of little consequence, if they are even of value, but some promise huge benefits, even to the point of being life-saving.
Big drug companies and their Naderite allies have only little concern. Above all, the power and majesty of the FDA must be preserved at whatever cost in lives and health - and, not so incidentally, additional cost to our bankrupt health care system.
Tough luck, Prof. Burstein. Just go away and die or learn to suffer, patients. Take an aspirin or something. See a counselor.
Drug development can be very lengthy, especially for very deadly diseases. The cost is enormous, far above what it might be. Many drugs could save on health care with outpatient treatment and surgery.
But as you say, who cares? (Isn't that what you said?)
Best, Terry
July 28, 2007 3:44 AM | Reply | Permalink
Terry--
On whether we have enough cancer drugs.
First, we are not counting on for-profit corporations to find new cancer drugs. As Bev M.D. points out " the government funds the research for 23 out of 27 cancer drugs."
For-profit corporations get involved only when they see some hope of a product they coudl sell. Then they piggyback on government research.
Oncologists complain that there are too many cancer drugs on the market--too many to keep track of (read all of the literature, etc.) and very, very few that are actually very effective.
(I have written about this in a piece titled "Can there be too many cures for Cancer?"
on www.thehealthcareblog.com.
Scroll down on the first page to "Spotlight on Maggie Mahar" and you'll see it listed.
We are still a very long way for finding a cure for most cancers. Customized medicines may help, but again this is a new science. Wall Street hype tends to make us feel that a breakthrough is just around the corner, but, sadly, that just
isn't true.
For a very good article about the problems in the way we reserach cancer, see Clifton Leaf's piece in Fortune a few years ago http://72.14.205.104/search?q=cache:r4T6UJ69lU4J:blog.aperio.com/articles/Fortune_Cancer.pdf+%22Clifton+Leaf%22+and+cancer+and+Fortune&hl=en&ct=clnk&cd=7&gl=us. (If the link doesn't work, google his name, Fortune and cancer and scroll down a few items to get the full article. The main point, I think is this: in our for-profit-health care system, reserachers don't collaborate, they compete, claiming that their reserach is "proprietary.")
Also, see Howard's (hcberkowitz)most recent post above--he gives a good example of the CDC making good use of an older drug. The nice thing about the CDC is that it doesn't have to worry about turning a profit on the product. . .
Naugiedoggie--You're exactly right--"the supermarket as our temple" really does go to the heart of the problem.
Howard--You're right many health care providers are driven by ego as much as (or even more than) money when overtreating. I can't emphasize enough the need for palliative care specialists.
If anyone is every involved with hospitalizing a dying friend or relative, if at all possible, ask if they have palliative care doctors and nurses. I think it would be worth travelling
a distance to find a hospital that provides this service.
Then ask to see the palliative care specialists.
They will talk to you and the patient. They will
not try to force you to do anything you don't want to do. They won't end treatment unless you ask them to. They will talk to other doctors or surgeons who may be bullying you (however well-meaning they may be) to continue treatments you don't want. Finally, palliative care specialists
will do their very best to make sure that the patient is not in pain.
jhaber--I'm not at all certain I find the medicine man story credible either. But I do think there is more to healing than western medicine understands.
amike--thanks
mm
July 28, 2007 8:29 AM | Reply | Permalink
Did Bev mention that it might be the 4 out of 27 that are the most important?
How far?
For sure basic research needs government funding but government funding didn't get the Wright Brothers in the air and government funding isn't responsible for some of the most exciting and promising developments in medical research.
We will make our annual trek to New York City this winter to hear again how many mice were cured of lung cancer and septicemia and glaucoma by the "Death Switch." We will hear again how the infarct area was reduced in strokes and heart attacks.
We were on the ground floor when the company only wanted to grow superior bananas and tomatoes and flowers that lasted longer when picked. Then the genes that grew better plants were found to be ubiquitous in animals as well as plants. An artistic success has naturally been a financial disaster.
The initial funding came primarily from the Forbes rather than government agencies. The discoverer is a university professor.
How will it all work out?
Don't know, of course. It was rather bizarre talking to an unassociated doctor at the meeting last year about the advantage of a "drug" that would cure (not just treat) all cancers. Even the like George Bush might be able to understand that.
Too much of those kinds of drugs you think? Are you sure?
The problem is that people concentrate on copycat drugs with only incremental improvement in treatment at best and ignore revolutionary treatments that offer huge benefits.
One of our sons would almost surely not be alive today without advances in surgery in just the last few years. Another might be alive if we knew decades ago what is common knowledge today. I probably would not be alive today without advances in medicine but that might be regarded as not an unmixed blessing.
Regulators and fright mongers inhibiting research and marketing hardly aid in advancement of science. They do fine work for the big pharmaceutical monopolies. I am not making an argument that there should not be regulation and protection of innocents from dangerous drugs but rather that it should be consistent with the best interests of advancement of science.
Cancer vaccines incidentally trace their roots to the 5th Century in China. Parke-Davis sold a version of "Coley's Cocktails" as late as the 1950's before the more primitive slash-and-burn chased them out. Are you certain progress is too swift?
Every mother on the face of the earth knows that her children are different from all others, that they have needs and allergies different from the general population.
The FDA doesn't.
BTW blood typing before infusion of donated blood is not exactly new.
We have a basic disagreement, Maggie.
An FDA commissioner has the ability to kill more people in one morning than George Bush can in a lifetime. Some, like David Kessler notably, are most likely to do harm rather than good. I have witnessed the results of his good works and note that after his tenure even he talked up reform a good deal but not when it counted.
Again I thank you for the opportunity to present my views. I think I understand yours well enough but perhaps not. For sure we are talking past each other. Of your goodwill I have no doubt at all. We surely agree on some of the evildoing by Big Pharma.
Best, Terry
July 28, 2007 7:03 PM | Reply | Permalink
Knowledge is a significant factor: a good friend of mine took an unconventional route -- call it fifth or sixth pathway -- through medical school(s). This worked out such that he had a summer free, which I think was between the third and fourth year. He already had a master's degree in biomedical engineering. Volunteering for Nader's health group, the director made it very clear to him that interns, typically social science students, were there to support the group's positions, but independent scientific research was not welcome.
Litigious culture, significantly involving Nader and others, led to a risk-averse culture at FDA. At the same time, financial market pressures, I believe, led to greater secrecy in clinical trials, as well as far too many me-too drugs.
Thalidomide, while a new chemical class, was introduced as a sedative, and only a marginally better one. Ironically, it hit the market at about the same time as the first benzodiazepine, which, other than the yet-unrecognized fetal damage, didn't demonstrate clear superiority for anxiety and sleep.
I don't have a simple answer to the right balance. My most recent experience with FDA is not in drugs, but in a relatively new development, of 510(k) approval not just medical devices, but information systems for managing information systems. So far, I find the people at FDA to be professional and fair, but the particular area is not a huge market. I think that some regulatory approval there is appropriate, although there are competing forces for patient care information systems. For example, JCAHO and FDA want software version control and regression testing, which implies the software stays stable -- which weekly Microsoft upgrades do not help. We have had more atability with open source LINUX based systems. Telomere manipulation? In an interested way, I might not understand it, as I don't see all cancers as having the same cellular mechanisms. -- Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 28, 2007 7:55 PM | Reply | Permalink
Telomerase is far more likely to cause cancer than suppress it.
But all cancers, like all life forms, utilize some of the same mechanisms to grow, propagate and die.
The research began with genes that imparted superiority to plants that could better resist heat, drought, salt, cold and thrive on poor soil. Reistance to parasites was quite interesting. Unlike the mean green which poisons the enemy, the plant simply did not wilt when attacked by predators, that then sought out the weaker plants.
The same basic mechanism applied to stroke or heart attack helped preserve brain and heart cells. A turn of the "Death Switch" on cancer induces apoptosis. The superior genes imparted to mice allowed the overwhelming bacterial infection of septicemia to be overcome by most. Glaucoma was and is a mystery to me.
All science fiction? Not at all but one should understand that there is no "drug" fully characterized as such. Delivery depends on RNAi, which has captured the fervor of the mob, not to mention Big Pharma, but is about as easy as containing nuclear fusion for useful purposes.
I had been hoping that concentration would focus on agriculture where plants are bred with better genes rather than attempting the very difficult feat of delivery. Naturally it was not to be. The pull of the legendary cancer cure is too strong.
Investors, of course, want results now or at least a good pump. The government is hardly immune.
A story that might interest some here:
A CEO of a struggling biotech told me proudly of a visit by Hillary, who was very interested in their novel "artificial heart." [A very crude characterization for brevity.]
The CEO was enchanted by Hillary's obvious intelligence and interest and probing question. The CEO even later made a donation to her campaign. A government grant didn't hurt. {BTW I am not making an accusation of any quid pro quo and, in fact, deny it.) The CEO mentioned writing down some notes for Bill, when requested. Bill tucked them away in his pocket. I asked if they were in the same pocket next to Bill's heart with his little black book.
There is much cutting edge science with enormous possibilities being carried on far from the purview of the general public. Most will fail and maybe more often because of the demands of the juice racketeers and the disinterest of the establishment than the science. The pump's the thing as I guess it is in real life.
Best, Terry
July 28, 2007 8:54 PM | Reply | Permalink
That's your personal wish scenario having nothing to do with reality.
Drug companies get involved with cancer drugs at the end of research, as marketing agencies, not as developers. I.e. drug companies do mass production and marketing and that's almost all they do.
The only reason they're given the R&D for free at the government's expense, is the assumption they're the entities best suited to bring drugs to the for-profit drug market.
However, the only reason we have a for-profit drug market is the presumption that the companies involved will be motivated to develop the best drugs.
So, basically the state is developing the drugs and giving them away to for-profit drug companies, who then market them and drive costs up tremendously, and sell them back to the public at hugely inflated costs, after the public has already paid for the drug R&D. And becasue marketing the drugs government gives them is so much more profitable than paying for the R&D themselves, they've become almost entirely marketing operations and slashed R&D budgets tremendously, and have huge Wasgington lobbies to ensure the sweet deal continues.
A real nice scam to essentially loot the economy.
July 29, 2007 3:17 AM | Reply | Permalink
It might be helpful if you restrained your blind rage long enough to read what is written.
I write about companies that mostly have no revenues at all except interest on funds held in reserve. Occasionally they get grants from the government but their source of funding is generally from stock sales and partnerships with the behemoths you hate.
Much valuable research decays on shelves because of folks that would rather live in darkness than glimpse the sunlight.
Government funding of academic research tends more to support the interests of the big drug companies than novel drug platforms.
A brother-in-law was hospitalized some years ago with necrotizing fasciitis ("flesh-eating bacteria"). He lost 3 days in delirium under heavy sedation as the infection climbed up his arm at maybe an inch or two an hour. Doctors cut away the rotting flesh and fought the common staph bacteria on steroids as best they could with the drugs available.
About half of those who are attacked by these baddies have it happen internally after operations. I can't imagine how that is dealt with.
Not much research on how to deal with necrotizing fasciitis. Happens to only a handful. But most could be ended with a vaccine against strep. Such a vaccine was banned for a couple decades because the vaccine caused one of the very diseases it was meant to prevent: rheumatic fever. Strep is not the only cause of necrotizing fasciitis but it is solely responsible for about half and implicated in others.
So how are things going with the vaccine?
Slow. Very, very slow.
Like with most all vaccines but especially a strep vaccine that has the potential to cause a disease it is designed to prevent.
Vaccines have done far more to combat disease than any drug. It is still a backwater for funding and development.
You see R&D, like Willie Sutton, goes where the money is. A new headache pill, an acne preparation, a copycat cancer drug, these are the things that light the fire in the belly and loosen the wallets of Big Pharma and Big Government.
It is often claimed that an effective malaria vaccine would have long ago been developed if economically advanced countries still suffered the ravages of that deadly disease. (One cause given for the decline and fall of Rome is malaria. Malaria was once endemic in North America.) The annual body count is enormous.
How's your government doing? Compared to, say, the Bill and Melinda Gates Foundation?
BTW how many drugs has your government developed and put on the market?
Best, Terry
July 29, 2007 6:00 AM | Reply | Permalink
Truth is rarely black and white. Let me go back to some older drugs and compare how they came to market.
All of these were introduced at a time when there was little advertising. Pharmaceutical companies still called themselves "ethical" and appeared to mean it. Even in the early sixties, it was still difficult for nonphysicians to get drug information, even to find what had been prescribed for them.
The financial markets and tax structure was very different at the time. Be it broadcasting or pharmaceuticals, many corporations -- certainly not all -- believed that part of their mission was public service, as opposed to maximizing shareholder value.
All of these examples, of course, were well before the explosive advent of molecular pharmacology, a discipline coming first from academia with government support. The now obsolete methicillin was probably the first antibiotic synthesized for a particular clinical reason, but more of the semisynthetic and synthetic antibiotics started coming online in the seventies and eighties, slowing in the mid-nineties, with some new classes again being introduced.
So, one has to look at the pharmaceutical industry in the light of changes in government policy and tolerance to business concerns.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 29, 2007 10:01 AM | Reply | Permalink
"Government funding of academic research tends more to support the interests of the big drug companies than novel drug platforms."
I'm not sure what Terry is talking about. Two major advances on "novel platforms" Gleevac and Avastin were extensively financed by government funds before taken private by drug companies.
In the case of Gleevac the drug was one of the rare cases of being an order of magnitude more effective than previous approaches to Chronic Myelogenous Leukemia. It required minimal clinical testing and was almost immediately approved--it sells for $50,000/year.
The antiangiogenesis research by Judah Folkman that led to Avastin was financed by you and me for over 20 years. It was taken private and we now have the privilege of paying up to $100,000/year for this drug alone. Parenthetically it's only maginally effective in most patients extending life a median of a few months in cases of advanced disease.
Drug companies are pricing themselves out of the market. Single drug costs/year exceed that of new autombiles and over a lifetime can exceed the cost of homes. This is irresponsible and requiries some adjustment of patent regulations and or insistance that the drugs originally developed under government funded research be fairly priced (Dole-Bayh). This regulation has never been enforced.
It's pay us or die.
July 29, 2007 10:04 AM | Reply | Permalink
Antiangiogenesis is a cancer therapy to suppress creation of blood supply to fast-growing tumors. The reverse, however, is potentially beneficial in cardiology, if the heart can be encouraged to enlarge coronary capillaries to "self-bypass" blockages.
I've been in a long-term clinical research project at NIH Clinical Center, in which active drug management of my heart problems, with eventual full failure of angioplasties and partial failure of bypass grafting, let my heart significantly repair itself. That my heart had the ability to "collateralize", remolding the blood vessels, is almost certainly genetic.
One of the research studies is doing a genetic analysis, over a significant number of patients, to correlate genetic markers with good and bad bodily responses. For example, I have bad genetics for cholesterol metabolism, but good genetics for collateralization.
No one is predicting when the genetic basis of collateralization, or useful angiogenesis, will be understood. It's a reasonable expectation that it eventually will be, and even later turned into a treatment. So far, a good part of the research is government funded or, in my case, in a government research hospital.
Your points about cost are well taken. With safety questions arising from one of my diabetes drugs in spite of my own positive benefits, I was switched to a safer one in the same class. The list price, however, at least tripled. Without the Massachusetts plan, I could not currently afford a long list of drugs -- this is not even strictly a insurance payment issue, but that I would be otherwise uninsurable.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 29, 2007 10:19 AM | Reply | Permalink
One thing that is being ignored in all of this discussion is that medicine is an international undertaking. Many people are criticizing the FDA and/or drug companies for policies that may inhibit research or promote profit over innovation.
There is no reason why research has to depend upon the US. Just because the US is a large market it is not the largest (just the most profitable). In fact many recent breakthroughs have taken place elsewhere (Korea and the UK come to mind).
If the US is not supporting medical research properly then others can step into the breach. I think an examination of the whole international market would be useful. Imagine what would happen if China developed a cure for cancer. They could chose to sell it to the US at any price they desired or they could chose to withhold it completely. In either case the US would be an economic disadvantage. Either we would be sending them our money or they could lower their cost of production since they now have a healthier population. This then would lower their costs and make them more competitive on the world market.
The discussion needs to be broadened.
--- Policies not Politics
Daily Landscape
July 29, 2007 10:57 AM | Reply | Permalink
There's no question that appropriate research needs to be supported, and it's a public policy question if that is to be done by direct research subsidies. Before making that call, it's also appropriate to see the basis of commerically provided drug prices. If, as in some cases, marketing budgets exceed research budgets, it may be a cost-effective argument to subsidize less market-driven research centers. Researchers themselves are not necessarily the beneficiaries of huge biotech investments.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 29, 2007 11:14 AM | Reply | Permalink
Perhaps a lingering social effect of the war effort as well as tax structure, but it was apparently more satisfying to be productive and successful professionally than to be simply rich. Not that wealth was bad, it was just more incidental to social status in the majority of society. (I except certain enclaves of old money.)
July 29, 2007 12:11 PM | Reply | Permalink
Which makes me wonder why we ain't getting our share of the $100,000.00. Actually I don't wonder, I have a pretty good hunch. Private investors "finance" in expectation of a return on the investment. Maybe the government should do so as well... It takes a risk on the research that flops, which is what it should do given free market theology. Why not make a buck when the research succeeds? Seems like one should practice the whole theology or none of it. :-)
aMike
July 29, 2007 12:39 PM | Reply | Permalink
I've been away for the weekend, and at the same time my home computer was out for repair.
But I've been reading the comments on a friend's computer---the discussion is going deeper and deeper in very interesting ways.
Monday, when I'm back in my office, I'll respond at greater length. But for now, let me say, I
find rdf's comment intriguing, and probably right:
"There is no reason why research has to depend upon the US. Just because the US is a large market it is not the largest (just the most profitable). In fact many recent breakthroughs have taken place elsewhere (Korea and the UK come to mind).
"If the US is not supporting medical research properly then others can step into the breach. I think an examination of the whole international market would be useful"
And hcberkowitz' most recent comment is also looking ahead to what we might do in the future:
He says: "If, as in some cases, marketing budgets exceed research budgets [at for-profit drug companies] it may be a cost-effective argument to subsidize less market-driven research centers."
[Here, it strikes me that it might be better for the government to subsidize
research centers at universities rather than
letting for-profit companies have so much influence on what resarch scientists at universities do. That's the way it was, say,
30 years ago. mm]
These are not the only comments that I plan to respond to on Monday, but for now, what do the rest of you think about these two suggestions?
July 29, 2007 1:46 PM | Reply | Permalink
Both seem relevant. I'll be out of contact from Tuesday through Saturday.
Drug manufacturing, while it has challenges in scaling up from pilot plants, still is a reasonably understood part of chemical engineering. Government owned contractor operated facilities have long been part of defense, and, with appropriate oversight, can be economic and reliable.
A number of medical groups are now blocking pharmaceutical representatives from directly briefing physicians. Instead, the representatives brief staff pharmacists, who distill the information, along with independent judgment on practice needs, and present their findings to clinicians.
There will always be room for innovation, and it should be rewarded -- but not usoriously.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 29, 2007 2:10 PM | Reply | Permalink
Imagine what would happen if Cuba developed a treatment for cancer.
Well actually they did and some controversy attends to the attempts to introduce three Cuban cancer vaccines into the U.S. market.
What people should try to understand is that a large part of the cost of drugs is the very thing that some liberals want more of.
Frost & Sullivan once estimated the cost of introducing a new drug at $1.8B. The figure given is normally below a $1B.
Clinical trials themselves are ghastly affairs. Patients with deadly diseases often search for something other than blinded, controlled trials for obvious reasons. Wouldn't you?
I communicated for years with a volunteer with Stage IV breast cancer who had no way of knowing if she had received the cancer vaccine or a placebo vaccine. She had gotten the real vaccine it later turned out. The trial ended in failure - perhaps because of design deficiencies. The vaccine is still alive in a modified form.
Surely I agree with those that don't think America's ill should be supporting the world's sick.
Biotechs around the world often look to America for their fame and fortune and are for that reason willing to accept the heavy burden of dealing with the obstreperous political scientists at the FDA.
Something is definitely wrong. The prescriptions of the Naderites are more venomous than helpful IMO. One might guess it did not take $1.8B/ea for Cuba to develop its vaccines nor cost as many lives. While Cuba too has a lot of lives to waste if it so desires, it has somewhat fewer pesos.
Best, Terry
July 29, 2007 2:43 PM | Reply | Permalink
Should we freeze out, say, the Bill and Melinda Gates Foundation you think?
One biotech depends largely on R&D sponsored by the Gates' Foundation, which Warren Buffett has now offered to donate the bulk of his assets to. The Gates not only paid for the research but for the clinical trials and are expected to pay for distribution of drugs in many countries if development is successful.
In general the experience of biotechs that rely almost solely on university R&D is not great.
I asked the biotech CEO why they would seek FDA approval for the most advanced drug for african sleeping sickness (trypanosomiasis) that is endemic only in poor African countries where it is transmitted by the bite of the tsetse fly. The answer was that was the requirement of the Gates.
Incidentally the company was proscribed by yours and Bush's fine government as one of the companies that had dealings in The Sudan. Their dealings in The Sudan consist of running pivotal clinical trials in the Darfur region. That must be fun. Which university would you suggest take on that task? Maybe Bush would blacklist them too unless it was Yale.
Best, Terry
July 29, 2007 3:00 PM | Reply | Permalink
Not all noncommercial research centers are necessarily fully university affiliated; there are quite a few government-owned contractor-operated (GOCO) with an academic flavor. Especially in the physical sciences and engineering, you have centers that might have started with MIT, but then went their own way, such as Lincoln Labs and Mitre. Mitre then spun off the Mitretek civilian-side group. On the nuclear side and again spinoffs, there are Los Alamos, Lawrence Livermore, Sandia, Lawrence Berkeley, Fermilabs, Oak Ridge, Brookhaven, etc. NASA GOCO include JPL and APL (latter also military). A good deal of the National Cancer Institute is GOCO.
--
Howard
*equal opportunity offense to both extremes*
"Those who cannot remember the past are condemned to repeat it" [George Santayana]
July 29, 2007 5:52 PM | Reply | Permalink
lol. :rolleyes:
Lay off the sauce.
July 30, 2007 8:14 PM | Reply | Permalink
Join the club. Terry is about as coherent as Limbaugh on meds. Lot's of rhetoric and market-shamanism, real slim on facts and reason.
July 30, 2007 8:18 PM | Reply | Permalink
Cycledoc makes an essential point: "drugs originally developed under government funded research should be fairly priced (Dole-Bayh)." Even on Wall Street some analysts believe that drug companies are pricing themselves out of the market. Eventually, they predict, the government will put a cap on drug prices. (I quote a Morgan Stanley analyst saying as much in a piece now on www.tcf.org titled "WAll Street, Cancer and the FDA.")
I agree that government should subsidize
not-for-profit research (whether in universities or elsewhere) that is not market-driven.
For-profit drug companies decide what to develop based on what they think they can sell for the highest price possible. There is a saying in the drug industry:
"A pill that cures is good; a pill that you have to take every day is better." Thus, they have put a lot of energy into developing antihistamines, etc.
For a long time they didn't spend as much money on trying to develop cancer drugs in large part because every cancer is different, and the patient population for a particular cancer drug is relatively small (compared to the number of potential customers for an allergy medication.)
Also, since so many cancers prove fatal, many patients don't live long enough to take a cancer drug for ten or fifteen years.
But then the large drug companies figured out that there is virtually no limit to how much they can charge for a cancer drug, and as a result, they can make a fortune selling these drugs to even a relatively small number of customers (A June 4, 2006 story in the NYTimes describes how big Pharma became interested in cancer: http://www.nytimes.com/2006/06/05/business/05drug.html?ex=1186027200&en=56dc95abed195887&ei=5070.
July 31, 2007 7:52 AM | Reply | Permalink
Thanks to the FDA because without it we cannot determine whether the foods we eat are safe or not. Let me give you an example. Cheerios is one of the best selling breakfast cereals of all time, if not the best selling. They are a virtual institution in and of themselves. The FDA has decided to take aim at Cheerios, for making claims that Cheerios lowers cholesterol and so have declared Cheerios a drug. That's right, the U.S. Food and Drug Administration have declared the General Mills breakfast cereal a drug, because of the labeling of said benefits for several years. If what they say is true, it would mean a way to improve heart health without needing a no fax cash advance. The company will likely change the labeling, as the idea of installment loans for the clinical trials of Cheerios seems a little ridiculous.
May 19, 2009 1:46 AM | Reply | Permalink
According to the FDA, Cheerios is a drug! You have to remember, this is the FDA, after all, and they aren't the greatest authority on getting people access to the treatment they need. Those clinical trials, done by pharmaceutical companies are the avenues towards those companies getting patents that more or less mean billions in annual revenue to Big Pharmaceutical. Am I suggesting that government agencies charged with protecting the public good are in bed with big business because money is involved, and that usually will mean a lot on campaign contributions and golf junkets to Scotland for politicians? No, and I also wouldn't be further suggesting that quite frankly the FDA and numerous other agencies wouldn't allow products known to be toxic to enter the market place with a "don't ask, don't tell" policy when it comes to tainted drugs, food, or other products for the same reason. No, far be it from me to suggest those things, and holding a government agency or private company to any sort of standard where doing things known to be harmful to people or the environment in any way shape or form is un American. (I'm laying the sarcasm on pretty thick at this point.) They also wouldn't do anything to artificially inflate the price of generic prescription drugs to make profits would they? Surely not.
A person has a right to self defense, and that should, and does, include using non-FDA approved drugs for treatment of life threatening illnesses. The corporate profits of Pfizer or any other drug company who makes enough already should be the last concern of the FDA or the courts - people should be allowed access to save their own lives. We're allowed to shoot a burglar in defense of our homes, we should be able to take a few pills.
May 20, 2009 6:59 PM | Reply | Permalink