Thursday, July 27, 2006

Why is testing saw palmetto's efficacy different from testing Reiki's

Robert G. Newton in his book "The Truth of Science" (Harvard University Press, Cambridge, Massachusetts, 1997) talks about the Criterion of Coherence.

Newton said that "the most important criterion for ascertaining the truth of a statement is its coherence with a network of assertions that are also regard as true."

In regard to the often made accusation of proponents of unorthodox ideas ( parapsychology,etc) that scientists are inappropriately dismissive of their ideas and are elitists or closed minded he says:

"Researchers justifiably refuse to listen to these claims,to examine them or refute them in detail,because they are incoherent with the rest of our scientific knowledge."

Reiki and distant healing and homeopathy-to name a few-fall outside the boundaries of the coherent web of scientific learning while the possibility that a given herb or root might have some active pharmacological effect and be beneficial does not.In regard to the later there are numerous examples while the former violate too many well accepted and established and coherent scientific principles to seriously expend research time, money and brain power to bother to refute them. Manipulation of an undetectable energy force that is capable of healing any and all diseases,the mastery of which has to be taught by a master should not have to be investigated by a dubious controlled clinical trial.So the difference between testing saw palmetto and Reiki is the difference between testing something that is considered possible in the wide web of scientific knowledge and testing something that is just absurd.

Thursday, July 20, 2006

Clinical trials underway to evaluate Reiki

Several clinical trials are being funded by the government to investigate the efficacy of Reiki.
Details can be found in the above link.

Cleveland Clinic received 371,500 for a study involving Reiki and prostate cancer.

My favorite is the 1.8 million study at the University of Michigan studying the effect of Reiki on diabetic patients with numbness in the feet and legs.

This is an interesting endeavor. Since there is no way to test for or measure the transfer of the Reiki energy which purportedly is the basis for the healing, a controlled trial was devised.
One arm will involve treatment administered by a person claiming to have the power to heal by manipulating a undetectable energy force (the "real" Reiki master) and the other arm involves someone who claims to be someone who claims to have the power to heal by manipulating an undetectable energy force (the "fake" Reiki master). Money well spent.

Another NIH sponsored trial is the " Efficacy of distant Healing in Glioblastoma treatment". In this trial "healers"-who come from various schools of distant healing will received a photograph of the patient and will send "mental intentions for healing and well being" for one per day for three days per week. Apparently, here there is no control arm in which fake healers would pretend to send a mental intention.

Dr. Steven Barrett was quoted in a Medscape book review of an IOM report on CAM:

"Methods that are plausible should be tested with well-designed clinical trials. The rest should be discarded"

Can someone explain why the NIH is funding such trials?

Wednesday, July 19, 2006

Still more about Ketex (telithromycin) and a glimpse into the FDA

The July 19,2006 edition of "Morning Edition" on NPR revealed internal e-mails from the FDA concerning the discussions about the approval-or continuing approval-process for Ketex. Dr. David Graham who will be remembered for his role in the Vioxx issue was quoted as saying ( I paraphrase) -Ketex offers no unique benefits relative to other drugs in its class and other drugs with the same type of hepatotoxicity profile as Ketex were removed from the market by the FDA-such drugs as Rezulin and Trovan.So he is saying that the benefit do not trump the risks.Incidentally, Dr. Graham was actively involved in the recall of those two drugs as well as others.

I've written before about the vigorous promotional effort to sell Ketex as an antibiotic that purportedly offers a mechanism to mitigate the development of microbial resistance.Ghost writers and thought leaders put forth the effort that in part have apparently lead to Ketex developing a respectable market share.

It will be interesting to see if this media-induced transparency will lead the FDA to reconsider its position. There are now 4 fatal liver toxicity cases in the U.S. and the public is being made aware of Dr. Graham's argument for not continuing approval and reminded that a clinical trial that was supposed to demonstrate safety was riddled with fraud and fictional patients.

Tuesday, July 18, 2006

Medicare D patients now enjoying the "Hole" while Pharma companies enjoying the profits

One of the interesting features of Medicare Part D is the so called dough-nut hole, the time when the savings go away and the patients pay for the entire cost of meds until another threshold of medicine cost is reached and Medicare kicks in again covering most of the cost. The profit boost to pharmaceutical companies comes from the fact that previously those so called dual-eligible patients ( those who were eligible for both Medicade and Medicare) are now receiving their drugs solely from the Part D program. Under the states' administration of the medicaid program they were able to and did negotiate lower prices on the drugs paid for under that program but the federal government is not allowed to do that under the rules of part D. This is all explained with numbers in a recent NYT article on the subject.

This windfall is, of course, occuring while CMS has enacted more cuts in professional fees for medical services performed for Medicare recepients.Pay less to the docs ,more to the drug companies, can you guess who really knows how to lobby.

Sunday, July 16, 2006

NEJM article -time to event analysis and still more on the Vioxx matter

In the July 13, 2006 issue of NEJM, S.W. Lagakos, a statistical consultant for the journal, writes about time-to-event analysis for long term treatments in the context of the APPROVe trial. This was the trial to see if Vioxx could prevent the recurrence of colon polyps and which demonstrated an increased risk of cardiovascular events in the treated group and which in all likelihood both Merck the NEJM wishes never happened.

The article is found in the perspective section and labeled "statistics and medicine".Dr. Lagakos discussed some of the issues involved in a time-to-event analysis such as the appropriate period of follow-up and the assumptions of the proportional hazards technique and the log rank test and monotonicity.If the purpose of this article was to inform readers so that they could read studies with these tests in an at least semi-informed manner,I am not sure he succeeded. I read it twice and still do not have a good sense of the statistical issues.However,I doubt a didactic motivation was operative.

He does make it clear that-in his opinion-that one cannot conclude that rofecoxib poses no increased cardio-vascular risk in less than 18 months. This 18 month threshold has become an issue in some of the many law suits pending in the courts.

The throngs of plaintiff attorneys involved in Vioxx cases could not be more pleased.The NEJM seems to be still trying to compensate for publishing the APPROVe trial in the first place.

Friday, July 14, 2006

Does value=quality/cost ?Is it immoral not to measure value?

I suspect we will be hearing more and more about paying for "quality" since the recess appointment of Dr. Donald Berwick to be the head of CMS. His views on central planning of medical care are the subject of much discussion. The following is a lightly re-edited version of a commentary I wrote several years ago on "measuring" quality and value.

Dr. RobertWachter, Professor of Medicine at UCSF , tells us that "value=quality/cost" and we have a moral obligation to "solve" equations for various clinical services. I reference his comments in the ACP observer as he replies to a letter to the editor commenting on the interview he gave discussing the overseas out-sourcing of medical services.(ACP Observer,July/August/2006 pg4) Dr. Wachter says in part:

Health care will be judged by its value: i.e.quality/cost...It is immoral not to seek ways to provide high quality care at more affordable costs"

It seems to me that this "equation" presupposes an intrinsic theory of value in which value is considered to be something that can be objectively measured and is an intrinsic property of a good or service much like the specific gravity of a liquid or the density of a compound.

Since the Austrian School of economics popularized the subjective theory of value most mainstream economists reject the intrinsic value theory.

The same service may be more or less valued by a given person as her circumstances and desires change. No two individuals need value the same thing to the same degree though they may.Value to most economists is not an intrinsic measurable number but rather value is subjective and is in "the eye of the beholder". Thomas Sowell ( pg 51,Knowledge and Decisions,Basic Books, 1966) puts it this way:

"Value being ultimately subjective, it varies not only from person to person but from time to time with the same person, and varies according to how much of the given good he already has."

Advocates of the subjective value theory would argue that to define value with the above equation is to erroneously claim that value (or in this case "quality" which along with "cost" determines "value") is an objectively measured entity. Are the medical quality experts( as best I can tell this is a self proclaimed designation) who are able to or claim to be able devise means to measure quality merely substituting their preferences-dressed up as objective measurements-for the value judgments of others?

Wachter continues saying:

"Patients, payers and policy makers now expect us to tap into actual clinical data to assess a physician's quality of care.I suspect once we truly figure out how to do that..."

I take this to mean that exactly how to measure the quality of care has not yet been "figured out". Somehow, I think that compliance with guidelines and adherence to protocols will play a big role in this-it has so far- and I doubt if patients will be asked what it is they value. I agree that payers and policy makers want quality data to use as a cost containment tool, the gatekeeper concept now largely abandoned, but patients want a physician who will spend time with them,care about their problem and be more interested in doing what the doc and patients agree on as the right course for that person and not adherence to some guideline that the patient has probably never heard of and does not take the particulars of his situation into account.

I believe "quality" which is now the main rhetorical tool of the cost-containment movement has become a classic bait-and-switch term. Everyone, docs and patients alike,would naturally say we want to give/receive good care or "quality" care. But the quality guidelines so often turn out to be what some self-appointed quality guru, committee or task force says is an quality indicator and are often no more than simplistic, easy-to-count, check-off list items, some of which may have counterproductive or harmful effects.

I have no doubt there are many well-intentioned physicians working hard to improve medical care- if you will improve quality- but much of the quality movement and arguably its major motive force is to contain costs.

The movement to contain costs is the result of so much of medical care being paid for with other people's money. We are not instructed about the moral imperative of providing high quality legal services, or haircuts or home repairs at more affordable costs because the people who use these services pay for them themselves.

Some may rejoice in the passage of Obama care as a golden opportunity to improve the quality of medical care while the more cynical think of the legislation with unparalleled power placed in the hands of various governmental agencies as the mother of all opportunities for what economists call rent seeking in which various interested parties ( now known a stake holders) seek special privilege.

Wednesday, July 12, 2006

Still more on LABAs, asthma and the Annals meta-analysis

I was eagerly awaiting the replies to the recent Salpeter meta-analysis (MA) posted about here.

I suspect the rapid responses are available only by subscription, so here are some of the critical comments paraphrased:

1.The MA was basically a warm over of the SMART trial since about 3/4 of the data in the MA was derived from SMART and apparently all of the mortality data. I have commented before on the inadequacies of the SMART trial and how it may well be a poster child for how not to do a large RCT.

2.Since SMART was not able to answer the big question (i.e does the use of inhaled corticosteroids (ICS) protect from any putative harm derived from the LABAs),neither can a MA based largely on SMART. There was a one sentence summary in the analysis section that purported to show that ICS were not protective but no tabular data was presented and a conclusion that important should have been explicated further.

3.Salpeter's recommendation of inhaled anti-cholinergics to replace LABAs in asthma treatment was ill-advised as there are no clinical trial data showing its efficacy and safety in asthma treatment (as opposed to COPD treatment).

4.Concern was expressed that patients would be stopping their LABAs on their own based on the lay press's reporting of this article.One group of letter writers said exactly that had happened with the resultant exacerbation of patients symptoms.

5.Salpeter's comment that 4,000 of the 5,000 U.S.Asthma deaths per years could be blamed on LABAs was criticized by several letters.Two writers commented that the CDC data indicate that in 1996 asthma deaths were about 5,600 and by 2,003 ( the last year for which data is available) it had decreased to about 4,800. Salmeterol was introduced in the U.S. in 1994. Although this data does not at all prove salmeterol introduction decreased asthma deaths it is consistent with that interpretation and does not support the opposite conclusion. But, in any event the comment that 80% of asthma deaths are due to LABA is unwarranted hyperbole at best.Another letter supplied British data also showing a decrease in asthma deaths in the era following the intoduction of a LABA.

Just as the controversy over the Salpeter article grows, even more disagreement is likely to be generated by a recent article by the Salpeter father and daughter combo concluding that LABAs and short acting beta-agonists also increase the mortality in patients with COPD.

Monday, July 10, 2006

FDA gives continuing approval to Ketex-fatal liver disease notwithstanding

The FDA, after reviewing the fatal cases of liver disease associated with use of telithromycin( Ketex) decided to continue to allow its use. It is approved for mild to moderately severe respiratory infections including community acquired pneumonia,bacterial sinusitis and exacerbations of chronic obstructive lung disease.

It has been promoted heavily by the manufacturer and uses as a promotional hook the purported theoretical arguments that it is less prone to induce bacterial resistance.It range of activity seems about the same as Biaxin and Zithromax and a side effect profile in the same general range as these two well established and safe drugs with the exception of the fatal liver disease complication

Earlier I had blogged about allegations of possible fraud ( fabrication of data) in some of the treatment trials involving Ketex, quoting Health Care Renewal and the Wall street Journal.
The drug was approved by the FDA in April 2004 and has been advertised heavily and promoted by "thought leaders" in various CME and pseudo-CME forums.Most recently, a RCT using Ketex in asthma patients showed some indications of improvement. In June 2006, Sanofi-Aventis suspended enrollment in pediatric studies that were using Ketex for respiratory infections. With the reported liver disease cases, I doubt we will see many doctors recommending telithromycin to "improve" asthma or to treat children.

Both the manufacturer and some ID specialists appropriately concerned about the antibiotic resistance issue had high hopes for Ketex. It seemed to offer good defenses against the mechanisms by which bacteria were developing resistance to the macrolides. But I can see no indication for a drug that in the individual patient offers nothing that a macrolide does not offer and runs the risk of serious liver toxicity.There are too many other good antibiotics to use in respiratory tract infections to risk fatal liver disease.

Sunday, July 09, 2006

Retired Doc's suggestion for med school curriculum Part 13

Had I been aware of the degree to which CAM (complementary and alternative medicine) has been accepted, taught,and practiced in at least some medical schools, I would have made this suggestion as Part 1 of the suggested curriculum series. Logically it should be Part 1 because to learn the science and art of medicine,which is supposed to be what medical schools teach, one should be able to know how to distinguish between science and pseudo-science.

I would have thought that college graduates entering med school would know well the distinction between the two and I suspect most do on entry. However, after learning their med school has a CAM clinic, CAM instructors and practitioners and that the NIH funds CAM research and that the FDA uses less stringent standards of evidence in evaluating alternative therapies,their understanding of the distinction may become blurred.

To mitigate that potential blurring, here is some material (not intended to be comprehensive) to include in the "what is science, anyway?" lecture.

The discussion might well begin with Einstein's comment regarding the development of western science which he said to be based on two things' The invention of the formal logic system by the Greeks and the discovery of the possibility of finding causal relationship by systematic experiments.

A discussion of Karl Popper's treatment of the problem of "demarcation" should be included. To Popper this was the basic issue of what is the difference between science and psuedo-science.
He said:

"...the criterion of the scientific status of a theory is its falsifiability,or refutability, or testability."

If a theory cannot be stated in such a way as to allow for its refutation, it is not science.

Edward O.Wilson is his book ,"Consilience, the Unity of Knowledge" says this about the difference between science and pseudo-science;

Science... is the organized systematic enterprise that gathers knowledge about the world and condenses the knowledge into testable laws and principles.

Wilson's diagnostic features of science are ( I paraphrase a bit)

2.economy-abstract the information into its simplest form
3.mensuration-measure it
4.heuristics-the best science stimulates further discovery
5.consilience about which Dr. Wilson says that the explanation most likely to survive are those that can :

"be connected and proven consistent with one another."

Mention needs to made of the importance of reductionism wherein that which is thought relevant to the problem at hand is walled off and for the time being the rest ignored.This is a major difference between western scientific thinking and eastern holistic thought which is prevalent in the fables of some forms of alternative medicine. The few folks who read this on their computers can do so because of the accomplishments of western scientific thought and not the efforts of those who believe that everything is related to everything and the methods of western scientific thought are no more valid than say the undetectable "lifeforces" of reiki.

I became more convinced that a lecture or lectures on what is science and how well it has worked needs to be part of the curriculum when I read this June 18, 2006 posting by Dr. RW on the activities of the SAMA.Based on their statements they seem to believe that it is not clear what "type of science" is needed to evaluate CAM.It is hard to believe that medical educators have failed so badly .

The above suggestions are not intended to be all inclusive but the main point is that the powers that be in medical education need to make sure that their students know the difference between science and pseudo-science, teach them about the former and stop promoting the latter.

AMA recommends mandatory medical insurance-Is this "boil the oceans redux?

The AMA passed a policy resolution supporting mandatory medical insurance for those persons and families that can afford it and subsidies for those who can't.

Here is how I understand how the AMA perceives the issue.

The problem is too many people do not have health insurance.
Therefore, those individuals and families who can afford the insurance will be forced to purchase it. There should be subsidies for those who cannot afford it.

Who will decide if a family can afford it? The government will. Who better to decide how one should spend their money than the government.

Where will the subsidies come from? The government. Where will they get the money? From the individuals and families who can afford health insurance. The government gets all its money from the people who make money. One of the AMA's arguments for this proposal is that "cost shifting" has become a problem and the system has no more elasticity to allow for further shifting as if this proposal is not cost shifting itself.

How will the folks be forced to buy insurance. Well although AMA left many details to be worked out they favor the enforcement to be carried out by the tax structure. I think this means the IRS. I guess IRS does not have enough to do already.

Predictably, the libertarian CATO Institute opposes the mandated medical insurance proposal, both on practical and philosophical grounds.Michael Tanner, in Cato's policy analysis number 565, points out the difficulties in implementing such a program. He analyzes how relatively ineffective mandatory auto insurance has been with the uninsured rates in states with mandatory insurance being little different from those states without such laws.He writes in detail about the problems associated with various possible enforcement techniques.

On a philosophical level they echo AMA delegate, Dr. David McKalip who said " What you're doing here today will results in a single payer system"

Cato puts it this way:
An individual mandate crosses an important line: accepting the principle that it is the government's responsibility to ensure that every American has health insurance. In doing so, it opens the door to widespread regulation of the health care industry and political interference in personal health care decisions. The result will be a slow but steady spiral downward toward a government-run national health care system.

Does the AMA resolution confuse " Wouldn't it be nice if..?" with "Lets pass a law making it happen"?

When Will Rogers was asked how to implement his suggestion regarding the German U-Boat problem by boiling the oceans, he replied that he would leave that up to the detail men and that he was a policy man.Some of us feel uneasy encouraging the government to work out the details of our health care policy but it seems now the AMA does not.

Tuesday, July 04, 2006

NEJM Health Policy report-employee sponsored medical insurance

Since employer-sponsored medical insurance is the cornerstone of health care in the U.S. physicians will be well advised to be aware of-at least- the basics of the history of that phenomenon. A non-exhaustive primer can be found in the July 6,2006 issue of NEJM written by David Blumenthal.("Employer-Sponsored Health Insurance in the United States-Origins and Implications"NEJM 355:1,p.82)

We are told that it may have been the opposition from the then apparently much more powerful AMA and possibly Roosevelt's friendship with his in-law Dr. Harvey Cushing that led to the omission of national health insurance from the Social Security law.

The relationship of the price and wage controls from WW II and the rise of employee hospitalization insurance ( people apparently went to the hospital back then when they were sick) is discussed, along with the ruling that such benefits should be considered part of the wage package and therefore part of union contract negotiations. Tax code provisions made employer medical insurance plans beneficial to employee and employers.

One example of [presumably] unintended consequences is the effect of the 1974 passage of ERISA leading to many large employers becoming self insured and thereby being largely exempted from state regulation of the coverage and small employers facing higher costs to provide insurance.

Much less well know is the 1990 ruling by the Financial Accounting Standards Board (FASB),which is the group that sets the rules for the accounting industry.By ruling that companies who covered health care of retirees had to carry those future liabilities on their balance sheets , the assets of many companies were reduced, stock values fell and as a result a number of firms stopped the practice of offering such coverage.

Another useful overview of how we got to where we are now can be found at the University of Nebraska web site in their video library of grand rounds in which Dr. Lynell Klassen discusses " The Practice of Medicine in 2011".

For a reader who has the time and energy to dive deeper into this issue, Paul Starr's book "The Social Transformation of American Medicine" is still in print and appears to be an obligatory reference for any review of the subject.

Sunday, July 02, 2006

Australian authors berate academic medicine for not calling the absurd "absurd"

A 2005 Medical Journal of Australia article pulls no punches as it decries the rise of CAM (complementary and alternative medicine) in academia.

The authors,Wallace Simpson and Kimball Atwood iv,discuss how something as absurd as much of CAM has gained an alarming degree of respectability in medical schools. They speak of :

"The guardians that usually keep the institution of medicine from reeling off into irrationality are social contracts built into medical science and ethical behavior. The academic community guards the contractual borders of science, while laws and regulations encode our ethical system. For the Absurd to have advanced, there must have been some breakdown of these social guardians."

So, why did the medical academics (collectively) fail in this role?

The authors suggest that the rise of Postmodernism is a factor. I cannot help but think that the availability of federal and foundation research money to " investigate"- or more commonly promote-CAM has to also be a major factor. Why else would medical schools sponsor CAM clinics and conferences?

For whatever reasons, it seems that medical schools ( many of them ) have lost their way. It used to be about teaching the science and art of medicine not the science, pseudoscience and art of medicine. What is the compromise between science and pseudo science? There is none.