I do want to raise some potential issues here, however, not because I am against the idea--I am for it--but because there is a danger that the government seal of approval may become far too powerful. Governments do not have the obvious conflict of interest that plagues some pharmaceutical industry research. But they have different problems, some more prevalent in government because there is no countervailing market discipline to weed them out.
- Perhaps the most obvious problem is that we won't entirely eliminate the financial motive--government workers sometimes leave their agencies, and the obvious place for them to go is to the companies they regulate. If you wall off this lucrative avenue of escape (say by dictating that they can't work in a regulated company for 1-5 years after they leave their agency), you may have trouble recruiting good people in the first place, because working for the government will become something like a prison sentence.
- Science isn't always cut and dried, but government reports are supposed to produce answers. There's a danger the bureaucrats will be more definite than the science calls for. This is a risk in the private sector, too, but private sector errors of this sort are rarely as powerful as government errors of the same kind. Once the government establishes a standard of care, private companies will probably follow, even if they are wrong, because it's
- Easier than doing their own analysis
- A lot easier than getting sued
- Possibly cheaper than the more effective treatment
- Government agencies are much more vulnerable to interest group pressure than private companies. Researchers will come under tremendous pressure to say that things work when they don't--not just from big, bad Pharma companies, but from patients who do not want their insurance company to cut off access to the treatment. And see above: a government report saying snake oil might work has more impact than a dozen private company reports saying the same.
- Government power can perpetuate a bad paradigm. I'm currently reading a book called Cure Unknown by a science journalist who believes she and her family are suffering from chronic Lyme disease. I don't know if Chronic Lyme Disease exists, or is a figment of the imaginations of people with some unspecified systemic or psychological problem. But some of the things she's angry about ring true to me because they sound a lot like other episodes from the history of science.
Weintraub makes a compelling case that these sorts of hard-and-fast diagnostic rules have, at the very least, left some indisputable cases of Lyme undiagnosed, including that of Weintraub's son. The CDC has turned this into a major problem, since of course most physicians do not pour through the journals themselves; they glance at the CDC criteria, which are quite restrictive. It's pretty clear that scientists who have a lot vested in the current model of Lyme (their careers, possible malpractice accusations), have at least for now won the debate. It's not quite so clear that they should have. And the government imprimatur has done a lot to seal the fate of the dissidents. This is all standard stuff to anyone who's read The Structure of Scientific Revolutions. But those revolutions happen because there are multiple possible centers of power. The government has the ability to potentially shut the revolutionary centers down.
The spirochete that causes Lyme is hard to detect, so treatment guidelines focus on the "bullseye rash", not because there's any particular reason to think it must follow infection by the borrelia bacterium, but because it's easy to diagnose, and . . . it's part of the diagnostic criteria. Everyone who has "real" Lyme disease has the rash, because the definition of "real" Lyme disease is having a rash. This, of course, makes it hard to test the theory that the spirochete might cause symptoms other than a rash.
As I say, I am in favor of doing the research. But the dangers of this sort of government sanction are not quite so far off and imaginary as Matthew Yglesias and Hilzoy seem to think. I don't think conservatives have done a very good job of articulating those dangers (and don't get me started on the pharmaceutical industry!) But I still think they're worth keeping in mind.
Non-profit oncology research groups have been doing this kind of research for at least 20 years now; that's what many of the recommendations for treatment by the American Cancer Society are based upon.
And even then, outdated treatments are frequently prescribed simply because it's what a doctor is familiar with.
These is a pretty nice theme, but I disagree with a lot of stuff (what else is new?).
1- Comparative effectiveness studies are going to be applied science. The Structures of Scientific Revolutions only deals with fundamental science, because that's where "revolutionary science" a la Copernicus, Newton or Dalton, occurs. No need to invoke for these studies. Or for most of the medicine field. Simple vested interests will do very well.
2- A lack of a "cut and dried" answer is an answer. If a study is inconclusive, that's the conclusion. I don't think there is particular pressure for "bureaucrats" being very definite. Bureaucrats already run basic science, with pretty good results.
3- Scientific paradigms are not associated with particular structures of power nor are they overthrown by competing centers of real power. "Government power" is not a threat. On the contrary, most non-medical research is financed by the government, and many sworn enemies in science are funded by the same agencies. Generally, what prolongs the duration of an inadequate paradigm are not vested interests (though they surely help), but a widely consensual way of approaching a particular problem that makes it very difficult for people in a particular field to think of alternatives.
Bureaucrats already run basic science, with pretty good results.
On what are you basing this assertion? We have nothing against which to compare these results. Maybe they aren't good at all compared to what is possible. We might have warp drive and a cure for the common cold if not for these bureaucrats.
I have some personal knowledge about research, mainly in neuroscience. Some grants are funded by private institutions and foundations. I have the impression that it doesn't make much difference. They don't fund better or worst scientists, or better or worst projects.
But I never really looked into it. I may be very well be wrong.
The problem with "comparative effectiveness" studies is that in this case they will be funded, controlled, and used by the political state. The reason that's a problem is simple, fundamental and can be stated in one word: coercion.
When the state has a coercive monopoly on health care, it will use CE studies to control costs. But biology is an infant science compared to chemistry and physics. Medicine is the field of applied biology (bio-engineering) and it's in its early, early days. But biology & biotech have entered a revolutionary era in which our knowledge of living systems and derivative technologies to improve human health are changing every week. New discoveries are happening everywhere. What was a cure yesterday, will be seen as blood-letting tomorrow.
Bureaucracies cannot keep up with a field undergoing such rapid (& revolutionary) change. In the guise of cost-cutting, CE will be used to stifle and bottle up advances in biotech and medicine that could extend the youthful extent of the human lifespan for many years.
Coercive bureaucracies, no matter how one dresses up their methods in fancy academic jargon such as "comparative effectiveness," are antithetical to innovation. Nationalized health care (which we've already got through control of funding and regs) is a killer. Literally.
There's no way BO and the feds can fund his attempt to extend the state's expropriation of health care. They're broke. There's no money. And they have not a clue (a practical clue, anyway) as to how to fund it.
Good points, well made.
Good points.
Actually not such a great point. Your beef is that if the gov't has a monopoly on purchasing health care (in other words a single payer system where individuals do not have the option to go out and purchase their own care out of pocket if they wish....) then yes bureaucracies will very well end up making inefficient decisions.
That, though, is a bad point about having a gov't monopoly on healthcare decisions. Not CE research. Monopoly or not it still makes sense to know more about what works and what doesn't than less.
As Megan said,
As Boonton pointed out, you're confusing comparative effectiveness research with government monopoly. CE research is just as important in the sort of system we have now. It just needs to be transparent.
I am very concerned about interest group pressure. I remember the first shot at nationalized health care (Hillary Care). A study had just come out showing that mammograms for women under 50 were not cost effective. Women's groups howled that mammograms should be paid for for any female. I think the "non-scientific" recommendation was adopted. Of course the demise of the Clinton proposals nullified the action.
More recently I read of a group of cancer patients who had participated in a clinical trial. The treatment was ineffective for most, but some patients went into remission. I'm not enough of a biologist to comment one way or the other, but these few patients were not going to get medicine that they thought helped because the study results were not generally favorable. Should the government fund or deny the treatment? Would your answer change if you were a relative?
Should the government fund or deny the treatment? Would your answer change if you were a relative?
I can answer both. The government should deny treatment, if the person wants it they can pay out of pocket, or purchase health insurance that would cover it. Your damn right I'd want it for a relative though. If I get to spend other people's money for a relative in the 0.01% chance that it could work I'd do it. However, if I had to pay for the relative's treatment out of pocket I'd not do it unless I was wealthy.
In short, the government is going to have to make harder choices on what it will pay for treatment with Medicare. Just because the government health care program doesn't cover a treatment doesn't stop anybody from getting it. It just means they won't be able to spend other people's money on a treatment not proven to work.
The mammogram issue is still at play. It's not like 'free mammograms' are an automatic win for women and only an 'economic' issue. Mammograms often pick up spots that are not cancer leading to unnecessary biopsies. It's not at all certain that more is always better for mammograms even if cost is not a consideration.
Regarding clinical studies. What sometimes happens when patients appear to benefit from a drug but the overall drug doesn't perform well in the study is that they will continue to receive the drug from the pharma company. Sometimes this is done by opening a pro forma 'long term study' for just the patients who seem to benefit.
But this depends on circumstances. Some drugs have are similiar to ones already on the market so in those cases the patient may be directed towards approved drugs. But even if the patient is allowed to continue on the drug, it still needs to be made. Producing a drug is not easy and at some point a company will stop once it is clear the science is not going to support the drug.
One situation that has arisen lately to show that government is not without problems is the recent HPV vaccine.
Most provinces in Canada put money towards the dissemination of the vaccine. The problem being that there was one vendor and the adoption was time critical for them. Also there wasn't any serious discussion of the effectiveness etc. The decision was 'womens health, prevent cancer, fund it'. Not to argue the effectiveness or appropriateness of the vaccine; in fact most arguments from both sides were not scientific but rather emotional and ideological. The marketing angle of the manufacturer depended on those emotions.
After the announcements and allocation of funding, serious questions from serious people started being asked.
Governments are political beasts. To suggest there isn't any bias or conflict of interest is nonsense.
And when the government says, it is law. They are a blunt instrument.
Another very odd thing has happened here. The British Columbia government was funding a group of doctors/scientist who looked at effectiveness of various drugs. Seemed to be doing good work. Their funding was dropped, some argue at the behest of some pharmaceutical interest. See, the province negotiates with the pharmaceutical interests for drug prices and supply.
On the other hand, groups have had to lobby government to pay for new treatments that are effective but expensive.
The idea that someone will pay for and make all the wise decisions for us is great. Hasn't worked yet.
Derek
This blog has a lot of discussion of CER and some of the pitfalls.
covertrationingblog.com
It's worth remembering that health care is one of several domestic policy challenges that could be ameliorated by enforcing our current immigration laws, and transitioning to an immigration system similar to that of, say, Australia: one that selects for immigrants with higher levels of human capital. These immigrants are likely to pay more in taxes than they consume in government benefits. If we enforced our current immigration laws, our uninsured population would probably drop by 40%.
Agree with most of the post... except the chronic lyme stuff (flame jacket on, as this seems to be an internet flame war starter).
Full disclosure: I am a first year intern interested in infectious disease, so I have a vested interest in this debate. Unfortunately, I think the IDSA (Infectious Disease Society of America)-- the chief villain in most of the chronic lyme stories-- has been cursed with terrible spokesmen. I listened to an NPR interview the other day and the IDSA person was just atrocious. I will try to write what I know in order to correct what I see as some of the problems with the debate. It needs to be said that I think that the patients who state they are experiencing long-term consequences of lyme disease need to be believed and respected. I think that there symptoms are real. I just think that the chronic lyme community is mistaken about a couple of things and it makes for some pretty nasty debates (see below for more info).
I have not read the book referenced in the post, although I just purchased it on amazon, so I will try not to assume too much about its arguments. Contra Megan, as I understand it, the major argument with regard to active infection with lyme disease is not diagnosis of active disease. Any physician with half a brain would tell you that any disease-- especially infectious disease-- can have protean manifestations (patients don't read the text books, etc. etc.) Unless the rash was absolutely characteristic with the right clinical history (e.g. tick bite with swollen tick), most physicians would not rely upon a rash to make a diagnosis. The "strict criteria" debate that she references is mostly a research concern; researchers want to be sure that they are studying actual lyme disease. Of course, denser physicians who are not experienced with lyme disease might rely upon these strict criteria. This is why you want smart physicians. In fact, one of the characteristics of Lyme disease is that it is a systemic disease with all kinds of weird manifestations. Physicians who care for patients who live in endemic areas need to have a high index of suspicion. Unfortunately, Lyme disease still gets missed all the time.
The sticky issue is, as I understand it, is treatment. The whole point of the chronic lyme story is that these patients feel that there infections have not been adequately treated (e.g. the antimicrobial treatment was not "aggressive enough"). After treatment, these patients experience what chronic relapses of various constitutional symptoms, including weakness, fatigue, depression, etc and they attribute these symptoms to "inadequate treatment" and persistent disease. This NPR interview had a series of very convincing stories about how whenever these patients go off the antibiotics, they experience devastating relapses. The chronic lyme patients (and some physicans) feel that antimicrobial regimens should stretch from months to years in order to fully eradicate the residual borrelia. After years of treatment, several of the patients stated that they were "cured."
The problem here is that there is no evidence-- none-- for this strategy. It is against everything we understand about infectious disease. The point of an antimicrobial agent is to kill the pathogen. Spirochetes, a family of bacteria that also include Syphilis and Rocky Mountain spotted fever, are exquisitely sensitive to some classes of antibiotics. After treatment, there are modern, very sensitive methods of detecting whether the pathogens are still present. One technique, polymerase chain reaction, can theoretically detect even ONE borellia in a given sample. Pathological specimens are also quite good. Although these techniques are not routinely used in clinical practice, they have been used in research and have been validated as detecting active infection. Researchers have looked for evidence of infection throughout all compartments of of these chronic lyme patients (e.g. patients who feel they have been inadequately treated) and have been unable to find ANY evidence of active infection. Furthermore, analogous diseases where the pathogen goes "dormant," is difficult to detect, and then reappears during periods of weakened immunity (e.g. chickenpox/shingles or Brill-Zinser disease (reactivated typhus)), it is extremely simple to detect the pathogen during the periods of recrudescence.
The question, then, is if there isn't an active infection, what are you treating with antibiotics? This is why there isn't really a scientific "debate" about the merits of the VERY long-term treatment strategy. There are real risks to this treatment, both from a patient-oriented and public-health standpoint and physicians who prescribe years worth of antibiotics should be chastened.
Still, the patients are experiencing real problems. I just don't feel that antibiotics are the answer. My speculation is that there is an underlying auto-immune component to the disease that has not been fully elucidated. Unfortunately, the nastiness of the subject precludes active research and I think these patients will continue to both suffer and feel betrayed by the medical profession.
As I say, I really can't comment on the science--Weintraub sounds convincing, but she also sounds like a disease advocate, and I haven't checked the studies myself. What she does claim is precisely that the diagnostic procedures developed for tracking--ELISA, Lyme blot, the rash--have, in the hands of at least some physicians, become treatment criteria. It's hard to argue when her son was not treated for years, until he developed a classic rash.
How common is this? Don't know. But I've spent enough time in the fun, fun world of autoimmune disease to know that harried GPs often prefer diagnostic tests to fuzzy attempts to treat a maybe problem. Hashimotos patients, the ones I'm most familiar with, know very well that they have to shop endocrinologists to find one who will treat their *@#! symptoms rather than a number on a test. If you're thirty pounds overweight, sleeping 11 hours a day, and your voice is still an octave too low, you should not have to fight to convince your doctor that your thyroid levels are not all right, even if your TSA is under four. But that is the situation that most thyroid patients, particularly women, find themselves in. And if your doctor is a GP? Forget it. They'll push your TSA to 4.8 and leave it there, even if you fall asleep on the table. Now, research endocrinologists are horrified by this, but the GP doesn't follow the research and make an educated decision--they read the guidelines and try to apply them as cautiously as possible. This is not true in every case. But it's true an awful lot.
Megan: Many -- all? -- of your objections seem to me to rely on the assumption that the research would be carried out by government employees. This isn't right -- some of it might be, but I'd imagine the basic model would be the NIH, which funds research carried out by others. (This is certainly true of the part of the CER budget that is actually given to the NIH.)
Is there any reason to think that your objections would hold if this is true?
Yes. The research I'm talking about was not conducted by government employees. I'm not trying to argue that government employees do crappy research--that may be true, but I have no reason to believe it is so; the NIH, as far as I know, has excellent researchers.
Rather, what I'm trying to say is that the government may, like the private sector, have bad incentives, that some of those incentives (like personal empire-building) are not blunted in government the way they are by market pressure in the private sector, and that the government's "Good Housekeeping Seal of Approval" can be a powerful force for bad as well as good, not because there's some big government conspiracy, but because whatever the government says will be given undue weight, and used incorrectly by rushed physicians.
That's not a reason not to do the research. It's a reason to monitor how it's being applied.
The danger with comparative effectiveness is that it uses aggregated data to then make individual treatment decisions. What works for most people doesn't work for everyone.
This is, or at least used to be, the reason that you'd build a relationship with a doctor. They'd get to know you, they'd respond to reactions (adverse or advantageous) that you were having to treatment and modify the treatment accordingly.
As treatment options become more and more complexx, however, those days are largely gone.
But that doesn't change the fact that using generalized treatment on an individual can be less than ideal.
I look forward to the day when biomarkers are more widespread and affordable. You should be able to swab a person's cheek and tell them the next day "you're not a candidate for NSAID's," or "this medicine is absolutely the best for you." Etc.
One point I thought of this morning re: lyme disease. If anything, many ID physicians would LOVE there to be such an entity as chronic lyme that was only responsive to long-term antibiotics. This would instantly create a very lucrative market segment for ID physicians, who currently have salaries roughly equivalent to general internists, despite longer training (they don't have procedures, unlike cardiologists/gastroenterologists, and therefore aren't reimbursed at the same levels). In some ways, it gives me some faith in science that you haven't seen too many ID docs out shilling for the chronic lyme community.
As far as the "treating the number," just classic crappy medicine. I'm sorry you have had to go through that. You are absolutely right to shop around and I hope that in my own practice I will never do that. James Fallows had a series of posts about the power of silence up awhile ago, and I think that just listening is one of the most powerful techniques in medicine. The sign of a truly awesome clinician is the ability to simply sit quietly (surprisingly rare and difficult to pull off in practice).
One thing about the CER proposal that isn't discussed as much as it should be is that I think that I think it dovetails nicely with one major, unequivocal positive in Obama's health care reforms: the subsidization of the switch to EMR. If all of the right precautions can be put in place (big if), the switch to EMR should represent a gold mine of data for researchers to use. The Dartmouth studies that both Orzag and Obama talk about (e.g. Medicare regional comparisons) actually use a pretty crude methodology. With access to better data, academics and government might be able to make meaningful conclusions about health care and, gasp, cut some of the treatments/procedures that don't do anything. Ultimately, I think this is a potential path to health care savings and would be worth the initial up-front investment.
Hi, I happened to notice this. I am the author of the book you are discussing --but I think you are not quite getting it right.
Long-undiagnosed or misdiagnosed Lyme disease --what my child had-- is NOT chronic Lyme disease, it is simply an infection that has never been diagnosed and treated.
We lived in Chappaqua NY in a house abutting a deer and tick-filled forest, in which my child played every summer. He had all the symptoms of Lyme disease --classic ones like swollen knees and heart block-- but was dismissed.
When he had a rash, it was a NEW infection, ANOTHER infection on top of what was probably the Lyme he already had. Not chronic, just untreated.
The rash should be diagnostic for the disease in endemic areas of the Northeast,but my child's rash was dismissed because it was not a bull's eye --even though any expert will tell you the erythema migrans does not have to be a bull's eye and usually is not.
He went misdiagnosed and untreated for TWO MORE YEARS --not with chronic Lyme disease, but with a very uncontroversial entity when you live next to a tick forest in Chappaqua --Lyme disease.
My point in the book is that the FIGHT over chronic Lyme disease has caused doctors in the community to pull back from diagnosing even classic Lyme disease, creating a large population of late stage patients who are harder to treat. My son was one of them. He is hardly alone.
I tried SO HARD in my book to differentiate between late-diagnosed, hard-to-treat Lyme and the controversial entity, chronic Lyme. It is dispiriting to be mischaracterized.
We had a complex situation. We lived in the ecosystem. We were reinfected. We had other infections from the tick. I myself continually relapsed until I was treated appropriately --and beyond the IDSA guidelines: But do I need to be called an advocate to state this? And is that relapsing infection chronic Lyme --or just a relapsing infection inappropriately treated?
These are questions I may ask --I leave it to the reader to decide.
I am not an advocate. I am a very longtime national science journalist and senior editor at Discover Magazine, and tried to present a balanced view in my book even while relating my own experience for full and honest disclosure.
I have traveled around the country interviewing mainstream scientists not involved in the political fight over Lyme but working with the organism and its pathogenesis at the lab bench at major academic institutions. The interviews with these scientists are in the book.
They have given me a very different view than that put forth by the Infectious Diseases Society of America.
I hope we are not at the point where a journalist must either spout the chapter and verse of a single but powerful body or be called an advocate.
I will be following this discussion and will be happy to participate.
To the doctor, I appreciate you not characterizing my book until you have read it in full.
Pam Weintraub
Senior Editor, Discover
Blogger, Psychology Today
Author, Cure Unknown; Inside the Lyme Epidemic
I'm sorry if I sounded like I was dismissing you; I'm not. First of all, sometimes disease advocates are right--but as you undoubtedly also know, sometimes they're crazy. Indeed, sometimes they are both crazy and right.
But more broadly, I've read one book on the topic, yours. I'm sure we all have had the experience of reading a powerful book, being completely persuaded--then reading another book arguing the opposite, and being completely persuaded by that. I know it's frustrating for you--I've felt the same way many times--but I can't jump to the conclusion you're right without reading other works on the topic. As I say, you're persuasive. And what you describe is certainly behavior that has been described of doctors in other contexts--Semmelweiss, the 48 human chromosomes.
RobM1981
The danger with comparative effectiveness is that it uses aggregated data to then make individual treatment decisions. What works for most people doesn't work for everyone.
Errr, well, this is like the entire field of medical science. Just about every modern drug out there sits on the shelves because 'aggregated data' says it works and is safe and doctors made 'individual treatment decisions' based on that data as it was presented to them in journals, conferences, speaking events and drug rep pitches.
I think Megan is unaware of some aspects of research (and I'm by no means an expert)....
1. Unlike the world of auditing and consulting, the 'Chinese Wall' is a lot thicker. A lot of drug research is unbiased. The selection of patients and collection of data is rigerous. Those collecting the data and processing it are 'blind' in the sense that they don't see the big picture so don't have an opportunity to 'manage' the end results.
2. The studies funded by pharma companies are reliable. They are rigerously audited and even without the FDA the liability issue alone provides a major incentive for this to be done honestly. I'm not going to say its impossible for a drug company to doctor the research to get approval but such a thing would be a big deal and would honestly be quite shocking. Perhaps Megan has been hanging out with that 'bad crowd' of finance types too much.
3. The issue with biased incentives in research isn't that the research is bad but that it is focused elsewhere. Companies want to establish that their drug works and is safe. That along requires a huge study effort that is very expensive and time consuming. Sometimes they do fund studies that establish "X is better than Y". Clearly this would be a desirable sales pitch and drug companies cannot make pitches without the FDa's approval. But the game theory here cuts against this. You can spend the money to do the research and if it turns out that 'Y is better than X' then you've not only wasted your money but given your competition their own sales pitch (you can't hide the study results because they are bad).
In theory HMOs, insurance companies and so on might do such studies themselves. If they learn that a generic blood pressure med works as well as a brand name one they could use that to push doctors to prescribe the generic or demand a discount from the brand name maker. But I there's a problem here. If one HMO funds the study to find this out, all the others will use the benefit of the knowledge without paying for it. Why would anyone fund such a study then?
Hi --No problem, I don't need you to agree with me at all. I was just correcting a misstatement that my son's long-MISdiagnosed Lyme disease was chronic Lyme on the front end. It was not. It was just a long-untreated infection. Chronic Lyme is something else --it is the disease that persists after treatment fails, for whatever reason. And it is true that my son needed to be treated for quite awhile for his symptoms to resolve, but his illness lasted for years because he was REINFECTED in the ecosystem: Again, this is not chronic infection, it is a real, new infection.
I do not know if you have finished my book --but the scientists I have interviewed --the workbench academics uninvolved in the political fight but at the top universities in the country-- generally point to a very low level persistent infection causing an outsized immune response.
Indeed the answer for this might not be antibiotic but some kind of immune treatment. Among scientists outside the IDSA this is not controversial, and you know: It is very rare that one rigid view is correct, or that we should embrace the scientist who says, "We know everything" and no more research is needed.
It was the great physicist Richard Feynman who said that when data conflicts with the paradigm, we keep the data and let the paradigm go.
The bottom line, to me, is that patients do fall outside the diagnostic guidelines --and this view is so widely held from the Mayo Clinic to Johns Hopkins it is not even controversial except to the nucleus of people holding to the IDSA Guidelines. When you speak to them alone, even THEY ADMIT that patients fall outside these parameters.
Because the Guidelines are so restrictive, many patients like my son are diagnosed late --and what could have been simple and easily curable becomes a bad hard-to-treat illness. That these late diagnosed patients often fail the standard treatment also is not really controversial --even in my interviews with the IDSA authors themselves, many said this to me --that about 20% of the late dx patients fail-- even if they do not say in in their guidelines.
So these patients are sick --what is the matter with them and how can we treat them? This is where we need research --the crossroads between very low level persistent infection or remaining antigens and outsized immune response seems to be a clue and one place to look. That is my view, actually --we need more and better science. Not sure this makes me an "advocate."
I AM interested in your discussion here and will follow along. I always appreciate the chance for intelligent discussion and debate.
Don't worry --am not offended here, but I would be interested if you conclude after reading more that the patients actually aren't sick and no more research is needed to find the problem. Because THAT is the view that would be opposite of mine.
All best, and thank you for this blog forum.
Pam Weintraub
"It is very rare that one rigid view is correct, or that we should embrace the scientist who says, "We know everything" and no more research is needed. It was the great physicist Richard Feynman who said that when data conflicts with the paradigm, we keep the data and let the paradigm go."
That's not the approach that liberals take towards Anthropogenic Global Warming. That is merely one of the reasons that conservatives are wary of government run "comparative effectiveness" research when we are on our way to single payer health care.
Ms. Weintraub,
While you are here (and I am waiting for your book), I was wondering how you felt about the long-term use of antibiotics? To me, this is the really sticky issue with "chronic lyme" (gonna use scare quotes to differentiate from chronic infections, like your son's). Do you think this is justified? I outlined some of my thinking above, but I think the point of forums is discussion.
Thanks,
Will Hahn
Dr. Hahn --Clearly it is never a good idea to take antibiotics for long periods of time. You will see that in my book I outline and quote experts on the dangers --and there are many, from yeast infection to antibiotic resistance to (in the case of IV) dangerous line infections.
As I was doing my interviews, I was alerted many times to these issues and took heed --I myself continually stopped antibiotics due to their danger as soon as I was better, and always relapsed, like clockwork, about two months later --no matter the season. I was not being reinfected, I was relapsing.
Hope springs eternal --I would be retreated, feel better, stop the antibiotic, and relapse... Antibiotics were not curative for me but without them I was too ill to function in my life.
This continued for four years until a doctor recommended a relatively short term treatment that put an end to the relapses, and that was five years ago. I have been off all antibiotics since.
I think that instead of arguing over long-term treatment --clearly the last thing you would want to do if you could help it-- we should ask about efficacious treatment. We need to treat early and aggressively --but what do you do if you have been diagnosed late? If you fail the standard treatment, what do you do if you cannot otherwise function --care for your children, do your job? You find yourself between a rock and a hard place. Retreatment and longer-term treatment, for such patients, may be the best they can do to stay afloat until science steps in to drill down into pathogenesis and find a short-term treatment that works for resistant later disease.
Indeed for patients long-misdiagnosed, as I was, the standard treatment recommended by IDSA is ineffective in about 20% (stats from peer review and IDSA members themselves, citations in my book.) For these patients --certainly anecdotally and it was true in my case--and antibiotics may be suppressive (for whatever reason) but generally not curative. Research from Dr. Steve Barthold of US Davis --albeit animal work, but very meticulous-- posits why. Barthold did the major animal model work at Yale for 25 years before he moved out West --a highly rigorous and respected scientist in this field.
The REAL problem is that we are not diagnosing patients early, when the disease is curable almost always. There is little controversy among the wide swath of researchers that the two-tier tests are mightily flawed --in part because of insensitivity but also because there are about 100 US strains, some of them do not even produce the antigens that the tests look for. This is work published by the Proceedings of the National Academy of Sciences and Emerging Infectious Diseases, not some advocacy blog.
Each strain might produce a different antibody pattern and even a different flavor of disease. Some strains cause only a rash, others mild disease and still others severe protracted disease that probably requires longer treatment. We need genomics and proteomics to sort this out --not the old technologies of the century past.
pw
To the issues noted in your post I would add that hopes for comparative effectiveness research leading to cost savings in a pain-free manner (that is, by identifying treatments currently popular but ineffective which can be eliminated free of cost) are unfounded. The concept is an attractive one but it hides some important difficulties; what is going to be compared to what? We can compare simple and cheap interventions to expensive pharmacotherapy (e.g. a Mediterranian diet to lipid therapy as regards the outcome of coronary events) and discover that diet works as well or better. Where does that leave us? Do we cut out funds for statins? Whereas if we compare things that are actually more comparable to one another, such as expensive competing drugs, then the scope for cost savings seems much reduced. And what, pray tell, is “effectiveness”? Is it QALY’s obtained per dollar expended? If so, goodbye to much current care offered to the elderly and disabled. Is it restoration to a given state of health? Is it success at managing a chronic condition as assessed by measures of subjective well-being? Any answer to the question leads us deep into political and philosophical waters and is bound to be controversial. It seems very likely to me that the govt functionaries answering these questions in funding and interpreting this research will do so not by way of dispassionate analysis but according to the budgetary exigencies bearing upon them. That is, we’re in for a rough ride when the rationing starts and comparative effectiveness research isn’t going to alter that.
They do have an interest if they're going to pay for it. Why else would they want to have an official registry of it?
Megan,
You and some of the commenters have made some valid points. But I think you're inappropriately relying on Matt Yglesias's and Hilzoy's mis-characterization of the "conservative" opposition. We in the free market movement have had no qualms about federal funding over the past few decades of comparative clinical effectiveness research -- what used to be known as evidence based medicine.
I've worked on food and drug regulation issues for over a decade and have not once heard of any conservative or libertarian opposition to such research being conducted de novo or aggregated from outside sources by, for example, the Department of Health and Human Services' Agency for Healthcare Research and Quality. But Yglesias and Hilzoy seem to believe, or would like their readers to believe, that free market advocates oppose this research per se. This is not true -- not in any sense generalizable across the "conservative" movement.
Instead, what many of us fear is that congressional Democrats have pushed for the creation of a new Federal Coordinating Council for Comparative Effectiveness Research for the express purpose of conducting comparative clinical effectiveness research "with teeth", to use Tom Daschle's words. That is, that this research is not merely intended to give physicians and patients better information, but that the Coordinating Council was created for the purpose of ruling some treatment options off limits. We fear this because the Coordinating Council's strongest advocates, such as would-be Obama Administration Health Care Czar Tom Daschle, have told us in no uncertain terms that this is its purpose.
Government (public) should fund the research since we all benefit from knowledge and dissemination of knowledge is almost free. Research results can be published in peer reviewed medical journals. It doesn't have to be a conclusive report from a governmental committee.
Ms. Weintraub,
Thank you for your nice reply. Just so we're on the same page, it feels weird to be called "Dr." (I graduated last weekend from med school). This is why I have time to hang out in internet discussions, as my intern year starts in mid-June (don't get sick next month!). I am interested in ID, so I have been peripherally involved in the care of persons with Lyme/chronic lyme/post-treatment lyme and I think it is very frustrating for all involved. Part of this discussion is to try and better educate myself from the patient's perspective, to try to learn maybe how to avoid some of this frustration.
First, I agree that the diagnostic laboratory tests used in general practice need to be improved (ELISA, western blot, etc.).
Still, my understanding was that ID researchers in more academic settings have chased post-treatment "chronic lyme" (again, apologies for scare quotes) with PCR (a much, much more sensitive assay) and/or biopsy and have been unable to detect the presence of the spirochetes anywhere. I have used PCR in my own research (for dengue, a virus) and it is pretty damn sensitive.
Also, from a clinical standpoint, there is at least one placebo controlled trial published that showed that patients with residual symptoms after standard treatment do not benefit from long-term antibiotics (Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. Jul 12 2001;345(2):85-92.) To my knowledge, there are no placebo controlled trials demonstrating the reverse. There was one abstract I found published in "Minerva Medicine" by a private practice doc in Connecticut that I could not access, so I will reserve judgment on its merits. There are a couple of trials, both in Europe and in the US, that underpin the current IDSA guidelines. I'll be interested to read your take on these in the book.
Still, I don't want you to think that I don't believe your symptoms resolved with antibiotic therapy. I can fully appreciate that there is nothing more infuriating than someone else telling you how you feel (and why!). I think that it is obvious that antibiotics helped someone like yourself. The question is why.
I think it is implausible that the bacteria "goes dormant." There just simply isn't any in vivo evidence-- even in vitro evidence-- for "resistance." Unfortunately, the reason for the prolonged symptoms remain a real mystery. Why some people improve with therapy is also a mystery.
I suspect that the "antimicrobial" nature of the therapy is not the answer. I can fully appreciate the need that patients feel to have a "real" disease, but I just think the "chronic lyme" community is mistaken in trying to posit that there is residual infection. There is a growing body of evidence that all kinds of infections-- from Q fever to parvovirus to chikgunya virus-- have long-term consequences after resolution that are not well understood. In none of those cases do is it necessary to posit dormancy/latency. Auto-immunity seems to be a much more plausible hypothesis and I hope that someone is looking at anti-inflammatory meds. Again, I can appreciate the frustration of not wanting to wait for a full understanding while absolutely debilitating symptoms continue but, to my mind, there is no greater sin as a physician than to knowingly offer a false answer.
Couple of quick points of clarification (for my own education):
1.) It sounds like you were off and on antibiotics for a while and then received a "relatively short term treatment." How long was this treatment?
2.) Were you on the same antibiotics for most of the time? Was there one that was more/less effective or was it a generalized effect?
Again, thanks for the nice discussion.
-Will
Will --Not sure this blog is the place to discuss my personal treatment which is, as I am sure you can appreciate, is anecdotal at best in any event --but I describe it in my book. Email me personally at pweintraub@discovermagazine.com for more info on this.
The NIH initiative that funded the Klempner study funded two others as well --Krupp and Fallon, also described in my book. Krupp in fact documented improvement with extended treatment for the entry symptom --fatigue-- but did not recommend the treatment because of side effects. We can all agree that extended IV abx is not ideal, but the answer is not to say treatment does not work --it is to find a SAFER treatment.
Fallon also documented resolution of a group of symptoms with longer treatment. These two studies were confirmatory to each other.
Barthold does indeed document dormancy in vivo --in my extensive interviews with many scientists, I have heard nothing but admiration for his work. The issue is NOT whether he documented it but whether what he observed is contributing to disease and whether it can be reproduced in humans (NIH is doing that follow-up study right now.)
Here is the Barthold citation:
1: Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008 May;52(5):1728-36. Epub 2008 Mar 3.
Keep in mind that Barthold was the MAIN scientist on the animal model work at Yale for 25 years, working right alongside Steere.
And you might also want to look at Straubinger dog studies, done at Cornell:
Summers BA, Straubinger AF, Jacobson RH, Chang YF, Appel MJ, Straubinger RK.
Histopathological studies of experimental lyme disease in the dog. J Comp Pathol. 2005 Jul;133(1):1-13.
2: Straubinger RK. PCR-Based quantification of Borrelia burgdorferi organisms in
canine tissues over a 500-Day postinfection period. J Clin Microbiol. 2000 Jun;38(6):2191-9.
On issue of seronegativity there is probably nothing better than the Luft azithromycin study.
All this said --could be that for these low-level dormant infections, immune treatments will work best. Barthold and his colleagues continue to seek antibiotics that will kill these quiescent spirochetes in mice. I suggest you read my book and then GO BEYOND IT by getting the original peer review that I refer to. I think it will at the least make you cognizant of the nuances. The things you are saying are not factually correct in the detal --they are overly broad and I sense perhaps you heard this from others and did not actually go and do an intensive lit search yourself. i suggest you read the material deeply and think it through logically --and don't neglect the strain work from Luft et al.
Pam