There are sources of information I inclined to accept with minimal questioning.  I do not have time to examine everything in excruciating detail, and like most people, use intellectual short cuts to get through the day.  If it comes from Clinical Infectious Diseases or the NEJM, I am inclined to accept the conclusions without a great deal of analysis, especially for non-infectious disease articles.  Infectious disease publications I have to read more closely; its part of passing as an expert.

Outside of medicine, I am predisposed to accepting at face value many of the articles in Skeptic and Skeptical Inquirer. They are trusted sources.  Some topics, like haunted house or Big Foot investigations, I barely skim. After all these years, I doubt there will be any new insights into the subject.  Other topics, depending on my interest, I may read more carefully.

I  often read longer articles  many times.  First a quick skim to see if it offers anything of interest.  If it does, then I may read it carefully.

This months Skeptical Inquirer had an article called  Seven Deadly Medical Hypotheses by Reynold Spector.  Just seeing the title and knowing the magazine, I was primed to accept the content at face value.  I enjoy a well reasoned, thoughtful rant. I relish a clever diatribe, even if I do not agree with the topic.   So I gave it a quick skim.  I was discomfited.  My first gut check was ick.  But I was uncertain why.  So I read it slowly and carefully, and still ick.  But why?There is a degree of self absorption in being a blogger.  I can write about what I want any way I want (I remain amazed at how much I can get away with).  The process of writing about a topic helps me clarify in my own mind issues with articles.

The author of 7, as I shall refer to the article,  has over 200 published articles, is a former executive vice president in charge of drug development at Merck and oversaw the development of 15 drugs and vaccines.  I am nobody from nowhere who just takes care of infected patients for a living.  He wins the argument from authority; I am the E. coli evaluating the human.  Oh well,  this is more an exercise for me to enlighten myself; you are the innocent bystander.

Overall the tone of 7 ? It reminded me of the Health Ranger at NaturalNews.com. Really.  Lots of dramatic statements, no qualifiers, no buts, no subtlety, no nuance.  To me, what marks good medical writing is an understanding that there is far more grey than black and white and that generally people are doing the best they can within numerous limitations  One of the many characteristics of the Health Ranger is hyperbole without nuance.  The Health Ranger has a belief system and sees the medical industrial complex through that lens; information is used to support a predetermined conclusion.  Health Ranger is a bombastic style that is both self assured and self referential.

Let us see what 7 has to say. It begins

A chronic scandal plagues the medical and nutritional literature: much of what is published is erroneous, pseudoscientific, or worse.

I’ll grant the first.  I am an Ioannidis convert.  The second seems hyperbole and exaggeration. Pseudoscientific?  Like homeopathy, psi and astrology?  Sorry The author is 17 words in and he has lost me.  I already question his veracity and judgement.  I read the literature. Hundreds of papers a month. I know the literature, and Sir, it is not pseudoscientific.  Suboptimal, often, but not pseudoscientific.  The third?  What could be worse than pseudoscientific?  Oh yeah.  Wakefields Lancet article.  But fraud  is a very rare exception in the over 20 million references on Pubmed.  The author’s opening salvo strikes me as someone more interested in polemic than truth. If done with verve and panache, and above all wit, I like a good polemic. Pomposity with hyperbole, not so much, and calling the medical literature erroneous, pseudoscientific, or worse leans towards the latter.

Two major factors account for a large proportion of this problem.  First, many medical and nutritional hypothesis are ill-conceived.

Are they?  Over 20 million references in Pubmed.  A few, perhaps, were ill conceived before they are tested. Say, measles vaccine induced gastroenteritis causing autism?  Not even that.  If approached honestly and competently, it would be a long shot, but you never knows unless you look.   That is what a great deal of medical research is about: looking around to see if an etiology or intervention or medication will be effective.  Most ideas, I would guess, go nowhere.

Second, the methods used are often epistemologically unsound.

Got me there.  What is epistemologically unsound?  Even after looking epistemologically up on the interwebs, I am uncertain what it means.   I expect the comments will school me on the meaning of epistemologically unsound. I guess that is why I am a lowly clinician.

Moreover, the same unsound methods are often repeated multiple times on the same tired hypotheses with the same incorrect results.

Isn’t that three major factors?  Or is that the unsound epistemological I cannot understand?  I shouldn’t quibble about counting, but I feel a rising tide of ridicule and scorn, and I am not one to hold it back.

I am not even done with the first paragraph, and the author has epistemologically lost me. Maybe there is good reason to be unsettled with the article.   And in the first five sentences, there are four references, all to works by the author, to justify the position.  I tend to prefer external references in my literature; the hyperbolic self-validation is what I expect from the Health Ranger and his ilk.  But again, who am I to question (1)?

… there is an epidemic of published studies that do not follow the principles of sound medical science- the principles demanded by the US Food and Drug Administration for the licensure and sale of medications.

Well, most studies are preliminary and exploratory.  The rigor demanded by the FDA is the final step in a long process starting with basic principles and, perhaps, epidemiology.  I can’t imagine we should jump to huge randomized, placebo controlled trials for every therapy and to answer every question.  Seems a wee bit excessive to me. Start small and build.  The downside is that there will be dead ends and false conclusions.  The upside is that in the end, a close approximation of Truth will be determined.

The resulting “findings” of such misleading or erroneous studies are often hyped by the news media on the day they are reported or published without any additional, careful analysis.

Hyped “findings”?  Nothing like that in the first two paragraphs of the this essay. Nope.  Nothing to see there but a well reasoned, careful, nuanced prologue for the body of the  essay.  “I” am always “mistrustful” of people who use “quotes” as a form of “sarcasm” when sarcasm is not used for good “effect” like “humor” because it otherwise comes across as “supercilious”.

Now I am starting to understand my discomfiture. Still, that’s just the first two paragraphs.  The body will better, right?

The author then proceeds to the background of how to do a good study: generate a plausible, testable hypothesis and test it.  He uses the Scandinavian Simvastatin Survival Study as an example of medicine done right (a Merck product if you care) and bemoans that not every study meets this high standard.

Too many published studies fail to adhere to these high scientific standards and lead to faulty, and even dangerous, conclusions.

Which is true and to my mind understandable, since there are not the resources to do perfect studies of every hypothesis.   Not every car is a Lexus, not every restaurant has a Michelin three star rating. You can’t always get what you want (2).  The issue to my mind is not that there are suboptimal studies; they are often used to find search for hypothesis that can be tested in better trials.  A large part of research is flailing about looking for something interesting to investigate in further detail.  Not everyone has the resources to test everything using the ‘hypothetical/deductive method” to answer all out questions, like the FDA demands.  Although this is not always the preferred method of generating ideas to test.  I don’t need quotes to cast aspersions on the validity of information or generate guilt by association.  I have learned a thing or two from reading the Health Ranger.

I wonder how many suboptimal studies it required to get to the point of the Scandinavian Simvastatin Survival Study?  The concepts to be tested did not appear from the void, fully formed.  The author does not, as will be seen, pay attention to the history and context of the evolution of medical ideas.

The author then proceeds to his 7 deadly hypotheses. Well, one deadly,  6 not so much.  But guilt by association is a game played by the author of 7 as well.

1) the investigator does not need a specific hypothesis and/or can use an inadequate method to test hypothesis.

He uses the example of epidemiology generated by case-control and cohort studies (the kind of studies that lead to the simvastatin study) and the effects of hormone replacement therapy.  He points out that these epidemiologic studies, for a variety of reasons, can lead to erroneous conclusions. Fine.  The other option?  With no preliminary studies jump straight to a huge trial?  And sometimes epidemiology can lead to important results: that a certain water pump is the epicenter of cholera or that chimney sweeps have more testicular cancer. Or that lowering cholesterol is associated with a decrease in vascular deaths.

Epidemiology is part of a continuum of understanding and evolution of medical knowledge.  But strawmen are easier to burn than recognizing the stuttering, somewhat chaotic progress of medical knowledge.  If proving a point is more important than understanding complexity, this is how you argue.

He then proceeds to genome-wide association studies (GWAS) that have been a disappointment for  elucidating genetic causes of heart disease and Alzheimer’s. The author considers GWAS a failure.  I suppose if you have a narrow perspective, yes it has been a failure. So far.  Huge amounts of information about the genome have been generated, and I am always a fan of knowledge for knowledge sake.  In the world of infectious diseases, there are single gene polymorphisms in the immune system that can increase or decrease a patients risk for a variety of infections.  Is it of clinical relevance yet? No.  Is it interesting? Oh, yes.  Will it lead to a new treatments and diagnostic interventions in the future? Who knows. But trying new ideas may fail but still  lead to insights that may lead to better interventions. I would wonder what secondary advances in technology and understanding were accomplished as a results of the GWAS studies.

It is like complaining that the Apollo program only put 12 people on the moon so the program is a bust since we are not going to the moon for vacation.  Here is a dirty little secret from a mere clinician.  I learn far more from failure than I ever have from success.  “The most exciting phrase to hear in science, the one that heralds new discoveries, is not ‘Eureka!’ (I’ve found it!), but ‘That’s funny…’ -Isaac Asimov.”  If you are a clinician, it is not ‘That’s funny,’ but ‘Oh shit’ that really drives change and knowledge.

2) If women replace these missing hormones post menopausally with HRT, they will remain “youthful” and not suffer from heart disease, dementia, vaginal dryness, hot flashes, and fractured bones.

I remember the late ’80′s,  a time that was the heyday of HRT, when I was in my internal residency training and discussing the issues at length not only in clinic, but with my mother.  I remember discussing the epidemiologic data and the worries of cancer.  The author states that

…based on these  (biased) studies, false claims were made the HRT protected against cardiovascular disease and dementia.

As if we knew it was false at the time. It was the best guess based on the data, and epidemiology can give insights that can be later confirmed  by better studies.  He also says

“the proponents…ignored the well-documented fact that estrogen is a carcinogen that causes breast cancer that can kill women” and that “HRT caused a 25% increase in breast cancer.”

I do not know where the author was practicing, but I remember talking with patients (I know, flawed memory) and my mother about the relative risks of cancer and fracture from HRT.  And 25%. Increase.  That’s bad.

What was the study?  On “16 608, patients, there were  more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases  [0.34% per year]…and the estrogen group had higher mortality (25 deaths [0.03% per year] vs 12 deaths [0.01% per year].”

That is bad.  Equally bad was the way the author presented the data, the same author who complains in the opening paragraphs about complex data being presented as looking “superficially adequate to the unsophisticated reader,” but I know when someone is presenting information in an manipulating manner designed to blow smoke out a usually inaccessible area.

In a section worthy of the Vaccine Council or Dr. Mercola, it sounds like people deliberately ignored cancer risk to push estrogen to kill women.  Someone mention hype?  I know it is important to make a point, but those who were investigating HRT and prescribing it, as I did once upon a time, were doing it carefully and with knowledge that there could be risks.

Information does not exist in a vacuum.  When talking with my patients and Mom in the late 1980′s, I basically said, based on the odds, how do you want to live your life?

Lifetime risk is a useful way to estimate and compare the risk of various conditions. Hip fractures, Colles’ fractures, and coronary heart disease, and breast and endometrial cancers are important conditions in postmenopausal women that might be influenced by the use of hormone replacement therapy. We used population-based data to estimate a woman’s lifetime risk of suffering a hip, Colles’, or vertebral fracture and her risk of dying of coronary heart disease. A 50-year-old white woman has a 16% risk of suffering a hip fracture, a 15% risk of suffering a Colles’ fracture, and a 32% risk of suffering a vertebral fracture during her remaining lifetime. These risks exceed her risk of developing breast or endometrial cancer. She has a 31% risk of dying of coronary heart disease, which is about 10 times greater than her risk of dying of hip fractures or breast cancer. These lifetime risks provide a useful description of the comparative risks of conditions that might be influenced by postmenopausal hormone therapy.

That was the kind of information and conversations about HRT I was having with patients in my clinic as I completed my residency, the years the author was at Merck developing drugs.  Many patients were far more worried about the disability and pain of fractures than they were of breast cancer.

In continued hyperbole that is totally disconnected from what I remember, he calls HRT a “flagrant example of the harm done by straying from the principles of hypothetical/deductive approach and sound clinical science.”

Really?  Did this guy ever take care of patients?  Has he ever had to make decisions based on incomplete information?  We are only into number two of seven and he last lost me with the hysteria.  I wonder how he would suggest exploring the effects of waning estrogen on the health of women?  Jump straight to a large trial?  Do no preliminary work?  Ignore any potential leads?  What is the alternative to the incremental, and sometimes erroneous, results of medical understanding?  How about fluoride and tooth decay?  So many insights start with a guess and a little epidemiology. Sometimes it pans out, sometimes it doesn’t.  But you do not know unless you try.

3)  if small dosages of vitamins are good for humans, very large doses would be better for everyone.

He then notes the studies that show the hypothesis was wrong.  But this was only known after the fact, after the studies,  and perhaps using vitamins like drugs would have beneficial effects.

Then the odd summary: ” megavitamin therapy tested in properly controlled trials either does nothing or is harmful (except in a few well defined exceptions).”

So it does nothing except when it does.  And how would we know the well defined exceptions unless we did the trials?

He goes from complaining about the science to complaining about the regulatory and commercial issues of megavitamins, changing arguments in midstream.  Is it the science or how the science is used?  Two different issues.

This is getting tedious, even for me.  I will soldier on, although the re re re reading 7 is increasingly painful. The closer I read it, the greater the errors and manipulations; a Mandelbrot set of manipulative medical writing.  Soon I will find the indefinite articles and pronouns suspect.  I try to skim the Health Ranger for a few chuckles; that is not why I read SI. And when is their swimsuit issue?  Oh. Wrong SI.

4) Screening tests beyond the standard medical examination are necessary for identifying disease and the risk of disease in apparently healthy, asymptomatic adults.

I will leave this issue to the more knowledgeable hands of Dr. Gorski.  His argument seems to be based on the 20:20 vision of hindsight, which is apparently the primary argument in all seven cases.  We thought screening would be effective,  studies showed it wasn’t, so the hypothesis was flawed and we should not have suggested screening or done the studies.

The author does not show in this, or other examples, why the ideas were wrong in the context of time the ideas were first offered. It is only viewed through the all powerful retrospectoscope that the author finds his deadly hypothesis. It is ever so easy to predict the past.

He also seems to argue that since our understanding of the ramifications of screening are not perfect, they are suspect, referencing himself for issues with PSA and mammograms (1).  The author argues in part that since our understanding is imperfect, it is a deadly hypothesis. I have always been comfortable with making decisions based on incomplete information, as that is the only kind of clinical information we ever have, save for the results of the occasional autopsy.  The perfect always being the enemy of the good.

He also complains about genetic screening. He notes that few people with high risk genes will develop disease and they can’t do anything about it, so why bother?  I wonder if the author has had much direct patient care.  What  most patients dislike is uncertainty about the why of their disease and most prefer as much understanding and certainty about their health as they can gather.  That is why they bother. And todays why bother may be tomorrows critical insight.  I have discussed how the show Connections made an impact on my view of the serendipity underlying advances. It may not be cost effective or useful currently,  the author does note that for some patients (breast cancer) it may have utility. Again, it is a deadly hypothesis except when it isn’t. So much sound and fury.

But how do you know until after you have done all the studies and see what works and what doesn’t?  His argument still seems to be since in some patients genetic testing has been shown to be of no utility, in the past they should not have done the work to show it is not useful. Except where it is.  Sort of like going back in time to kill Hitler as a child because he was found to be evil in the future, even though you could not tell that the babe in the crib was going to be the source of Goodwin’s law. And far worse.

Circular argument much?

I do not get the impression the author is one for thinking outside the box.  Usually new ideas lead nowhere, but again, you never know unless you try. Nothing ventured, nothing gained vrs nothing ventured, nothing lost.  It is often not the results of studies that are the issue, but how they are portrayed in the media, as noted by the author, and, probably not intentionally, his entire article is a superb example of just that concept.  Maybe 7 is really meta.

5) Manipulating one’s nutrition can prevent cancer.

As he says,  “In retrospect,  this hypothesis does not seem plausible.”

The whole crux of almost every one of his arguments. Repeat after me. In retrospect. In retrospect. In retrospect.  In retrospect everything is clear.  I have had MD after my name for 27 years, and I remember the uncertainty and interest in all his 7 mostly not so deadly hypotheses.  In the beginning, it was not so clear as he makes it out to be.  The past is easy to predict.

6)  Personalized medicine will greatly advance medical care.

His argument is the same: it hasn’t worked except where it has.

“Personalized medicine has only been shown to be cost effective in a few well defined situations.”

How did we find these well defined situations?  Doing a ton of studies that show benefit in some cases and none in others.

I think the solution to this problem is being able to see the future and know in advance which research ideas will bear fruit and which will be a bust.  Precognition is apparently the only solution. Miss Cleo may be available to help review research proposals, I understand that her readin’ is free.

7) cancer chemotherapy has been a major medical advance.

Of course, in some cases it has been extremely effective, but the war on cancer has not been what it was promised.  Again it seems his argument is the same hindsight argument:  when cancer therapy has been effective, it is great, and when it is not so good, we should not have done the work to show that wasn’t effective.   Again, I leave the details to Dr. Gorski should he choose to cover the topic.

And of course the author doesn’t have a dog in the fight (and there are those quotes, so commonly used by the dispassionate):

“When one dispassionately weighs the minimal prolongation of ‘good’ life in patients with metastatic cancer versus the very distressing side effects of chemotherapy with ‘targeted’ drugs, the case is close.”

I’m convinced,  He is dispassionate.  And Jenny isn’t anti-vax, just pro-safe vaccine. Here is my hypothesis to be tested.  Anyone who argues they are dispassionate isn’t. They are fooling themselves and trying to fool others with their alleged practice of arei’mnu.  Me? I am never dispassionate; although sometimes I do not care, but there is a difference.

Some of his conclusions are reasonable: we need to do our science as best as we can.

The author argues that all these errors and  expenditures of his 7 mostly no so deadly hypotheses could have “been avoided if the hypothetical/deductive method had been applied rigorously.”  I am not convinced, since most of his arguments are based after the fact.  I would be far more impressed if, by using only the hypothetical/deductive approach (no epidemiology, no early studies, no preliminary clinical data, no basic science) if he would predict 7 hypotheses that warrant jumping straight to large, randomized, placebo controlled clinical trials so beloved by the FDA. The Randi prize awaits.

We all need that god like perfection and prescience, unlike those

“guilty of perpetuating worthless practices include “scientists” who repeatedly employ flawed methods and then publish them, government agencies who fund such practices, editors of journals that publish pseudoscience, the USDA and NCI bodies that perpetuate unscientific regimens…”

My. God.  The Health Ranger was right.  The conspiracy has incorporated itself into every aspect of the Medical-Industrial  complex.  A different conspiracy than the one we get from the woo world, but  everyone is involved.

Putting scientists in quotes. A very Health Ranger thing to do.  I don’t suppose he is referring to the “scientists” at Merck who repeatedly employed flawed methods and then published them.

“Approximately 250 documents were relevant to our review. For the publication of clinical trials, documents were found describing Merck employees working either independently or in collaboration with medical publishing companies to prepare manuscripts and subsequently recruiting external, academically affiliated investigators to be authors. Recruited authors were frequently placed in the first and second positions of the authorship list. For the publication of scientific review papers, documents were found describing Merck marketing employees developing plans for manuscripts, contracting with medical publishing companies to ghostwrite manuscripts, and recruiting external, academically affiliated investigators to be authors. Recruited authors were commonly the sole author on the manuscript and offered honoraria for their participation…

This case-study review of industry documents demonstrates that clinical trial manuscripts related to rofecoxib were authored by sponsor employees but often attributed first authorship to academically affiliated investigators who did not always disclose industry financial support. Review manuscripts were often prepared by unacknowledged authors and subsequently attributed authorship to academically affiliated investigators who often did not disclose industry financial support.”

I see people doing the best they can with the tools at hand.  Mostly honest people (I say mostly not knowing what their IRS forms show), working within many limitations, to advance medical understanding.  They do not deserve quotes applied to their work or the title of pseudoscience.  Not everyone is able to achieve the peerless, perfect knowledge bestowed on  a Professor of Medicine and Merck Vice President.

We need “honest” corporations.  Ironic from a former Merck executive;  casting the first stone and all that. I do not need quotes to show my snotty superiority.  We need better regulation of “unsafe and unproven products.”  Like Merck’s Vioxx?.   Ohhh, snap. The Merck shots are cheap shots,  I know. But they made me laugh, and above all I like to make me laugh. It is all about me.

Like the Health Ranger, I see someone with a bee in their bonnet, selectively and histrionically arguing in circles, hoping that if the same cognitive errors and circular reasoning are repeated they will be believed as fact.  I am not enthusiastic about the conclusions and arguments used, being significantly more flawed than the research he rails against. It is not far in style and content from being in the Natural News.  Science, at least,  is ultimately self correcting.  This article, probably not so much.

Of course, I am nobody from nowhere. Not a professor or scientist or a vice president.  I am a clinician and citizen who has to trust his sources of information.  I was raised to judge a man by the company he keeps.  When the NEJM published garbage on acupuncture, my trust in the Journal fell a notch.  The Lancet has always had a reputation of being flaky, it is part of the British charm and I have never held it against them; I just factor it in when reading a paper.  The Annals of Internal Medicine has been untrustworthy for years. Clinical Infectious Diseases remains unsullied.  Now the Skeptical Enquirer (sic) has slipped a bit as well.  7 was primarily deadly for my confidence in its editors. Oh well, at least I can still trust the material published by DC.

Rationalizations

(1)  Crislip et. al.  I said it here before, so it must be right.

(2) And if you try sometime you find/You get what you need.

The Supreme Court of the United States made a ruling the other day that has profound implications for the health of millions of children. Since October 12, 2010, The Court has been quietly deliberating the case of Bruesewitz v. Wyeth, inc. The case centers on Russell and Robalee Bruesewitz’s allegation that their 18 year old daughter, Hannah, was irreversibly injured by a DTP vaccine she received when she was 6 months old. What is important about this case is not the allegation itself (I will discuss its merits, or lack thereof, in a moment), but the ramifications the ruling has for the future of childhood immunization in this country. The Supreme Court’s ruling against the Bruesewitz’s and in favor of the U.S. vaccination program was the right one, and safeguards our children from the irrationality of the anti-vaccine movement. Some important background is necessary here to understand why this is so.

Prior to the development of effective vaccines, diphtheria, tetanus, and pertussis were common diseases, terrifyingly familiar to all parents. Death records from Massachusetts during the latter half of the 1800’s indicate that diphtheria caused 3-10% of all deaths. In the first part of the 20^th century, these dreaded organisms still caused illness in hundreds of thousands of people each year in the United States. These are devastating diseases which, if not resulting in death, often produced severe and permanent damage to those afflicted. In the 1920’s, vaccines against each of these scourges were finally developed, and in the mid 1940’s the combined DTP vaccine was introduced. The vaccines were so effective that cases of these deadly infections were practically eliminated. Today, few parents know the terror once routinely wrought by these pathogens.

Despite the effectiveness of the original DTP vaccine, it did frequently produce reactions in the children who received it. Fever (and fever seizures in those genetically predisposed), irritability, and sometimes frightening hyporesponsive episodes were seen. The side effects of the DTP vaccine were attributable to its pertussis component. The vaccine was produced using the whole pertussis organism in an attenuated state so that it could not cause the disease itself. Utilizing the whole organism, however, exposed the child to a large number of proteins, some of which were responsible for the fever and other side effects the vaccine produced. These deleterious reactions certainly paled in comparison to the dangers of the diseases themselves. Nonetheless, as the diseases prevented by the vaccine disappeared, parents began to take more seriously these annoying and often frightening reactions. Because some of these reactions were so frightening, including febrile, or fever seizures, many people began to believe the vaccine was responsible for more serious side effects, including brain damage and even death. As outlined in an earlier SBM post, the side effects of the original “whole cell” DTP vaccine (DTwP) were not, however, life-threatening and produced no long-term problems in those receiving it. In 2006, a retrospective case-control cohort study of more than 2 million children concluded there was no increased risk of developing encephalopathy following administration of the original DTwP vaccine¹. But when encephalopathy or a new onset seizure disorder occurred in temporal association with the receipt of the DTwP vaccine, causation was often ascribed to it.

It was the escalating, yet unfounded fears surrounding the original DTwP vaccine that led to the emergence of the modern-day anti-vaccine movement in this country. In 1982, the shockumentary “Vaccine Roulette” appeared on a local NBC TV affiliate. It purported to show the child victims of the DTwP vaccine, housed in a dark and dismal chronic care facility, damaged by doctors and forgotten by society. The show awakened the nation to the alleged dangers of this vaccine, and the fear quickly spread like wild fire. Fear of the DTwP vaccine and of vaccines in general enveloped the nation, and lawsuits against vaccine manufacturers over a host of alleged reactions rained down upon the courts. This torrent of legal action threatened the future of the vaccination program in this country. While in 1979 there was only 1 DTP-related lawsuit, by 1986 there were 255, with a total of over $3 billion sought by claimants. This clearly was not sustainable for the vaccine industry, and in fact manufacturers went out of business. In 1967 there were 26 US manufacturers of vaccines. By 1980 this number had dropped to 15, and by 1986 there were only 3 companies still making vaccines in this country. Vaccine prices skyrocketed, and manufacturers found it difficult to obtain liability insurance.

With the future of our vaccination program at risk, Congress passed the National Childhood Vaccine Injury Act (NCVIA) in 1986 and established the National Vaccine Injury Compensation Program (NVICP). Funded by an excise tax on each vaccine component administered, the NVICP was designed as a no-fault, expedited process to compensate families who claim their child has suffered a vaccine-related injury. No proof of causation is necessary to be eligible for compensation. A child simply has to have a documented problem that occurred in the specified time frame following a vaccination, and that problem has to be on the table of problems recognized by the NVICP as potential vaccine adverse events. Cases are reviewed by a Special Master, who makes a determination based on minimal evidence, with the primary goal being a prompt resolution. If a claim is successful, compensation is granted for medical, rehabilitation, counseling, special education, and vocational training expenses, and $250,000 when the claimed outcome is death. Patients may accept the ruling or take their case through the usual tort process by suing the manufacturer. However, a major aspect of this process, and the one which saved the vaccine program from total collapse in the 1980s, is the significant liability protection granted to the vaccine manufacturers. Before suing a vaccine manufacturer, a claimant must first go through the NVICP process, or the so called “Vaccine Court”. But if a parent rejects an NVICP ruling and decides to sue in court, the vaccine manufacturer is immune from liability, assuming they have complied with all regulatory requirements and have not committed outright fraud or other crimes in the manufacture of the vaccine. Most importantly, the NCVIA stipulates that,

No vaccine manufacturer shall be liable in a civil action for damages arising from a vaccine-related injury or death associated with the administration of a vaccine after October 1, 1988, if the injury or death resulted from side effects that were unavoidable even though the vaccine was properly prepared and was accompanied by proper directions and warnings.

Setting aside for the moment the fact that there is no evidence the DTwP vaccine can cause any of the adverse events listed in the original table, the statement above gets to the heart of the Supreme Court’s ruling. Specifically, the ruling centered around the words “unavoidable” and “even though” in the above excerpt. In April 1992, when Hannah Bruesewitz received the vaccine that allegedly injured her, her diagnosis “residual seizure disorder” had just been removed from the NVICP vaccine injury table. Her claim was denied by the Special Master, although she was still awarded $127,000 for legal fees. The family rejected this decision, and instead brought the case against Wyeth (which had acquired Lederle) to Pennsylvania state court. The Breusewitz’s asserted that the vaccine was defective, that the manufacturer knew it could cause harm, and that they had knowledge of a safer vaccine but failed to develop or use it. The Pennsylvania court rejected this claim, citing that such design-defect claims were preempted by the Vaccine Act. The case then ended up in The Supreme Court which finally, this past Tuesday, upheld the intent of the NVICP to protect the vaccine supply by preventing lawsuits based on design-defect claims. The Supreme Court’s opinion, delivered by Justice Antonin Scalia, interpreted the word “unavoidable” as written in the Vaccine Act, to apply to the specific vaccine administered to a claimant, and not to other hypothetical, alternate vaccines that might or might not be more or less safe and effectve. Justice Scalia argued that the use of the words “even though” in the excerpt above implies that the unavoidability referred to in the Act applies to the specific vaccine that was administered, and not to some other potential vaccine. In other words, the Breusewitz’s claim that their daughter’s condition was avoidable because a safer alternative vaccine could have been given was ruled to be a misreading of the Vaccine Act’s intent. The Opinion asserts that exclusion of design defects from the Act was intentional. The fact that the NCVIA and the FDA spell out in detail the manufacturing method and the warnings and directions that must be provided by a vaccine manufacturer, while making no mention of vaccine design requirements is a clear indication that such an exclusion was intentional. It was the Court’s opinion that any other reading of The Act would require very difficult determinations of relative vaccine safety and efficacy. Justice Scalia points out that these determinations are rightly the domain of the FDA and National Vaccine Program experts, and not the courts.

The Supreme Court’s ruling in this case was a huge victory for the health and well-being of our Nation’s children, and the Court should be applauded for its good sense and clarity on the issue. Undoubtedly, those who eschew rationality and oppose vaccines will find fault with the ruling, and cling to the mantra of conspiracy and collusion. Sadly, the fear and misinformation spawned from the DTwP-era lives on today. As technology improved, a version of the vaccine containing an “acellular” pertussis component did eventually become feasible. The DTaP vaccine, as it was called, was introduced in 1996 and nearly eliminated reactions to the vaccine. But the damage was done. As the media and a splintered cadre of like-minded conspiracy and anti-establishment groups took up arms against vaccines in general, a new anti-vaccinationism took hold. We’ve since been through the Wakefield crisis, the thimerosal debacle, and many other dangerous vaccine myths, nourished along by the media and the anti-vaccine cartel. The consequence of this spreading fear is an increasing distrust of vaccines, and the development of pockets of underimmunization around the country. We are now seeing outbreaks of completely preventable childhood disease, and children have died as a result. This was an important ruling, but we have a long way to go before we can bring rationality to the public discussion and understanding of vaccines in this country.

¹Pediatr Infect Dis J. 2006;25:768-773

Dr. Mehmet Oz is one of America’s most influential doctors.  Just ask him.  He has a TV show and everything.  And in the past, much of his advice had been practical and mundane, the same advice you might hear from your own (perhaps less charismatic) physician.  But lately, he’s been giving out frankly bizarre medical opinions.  Not all of Oz’s recommendations are over-the-top strange, but even some of his less-bizarre stuff is hyperbolic to the point of being—in my opinion—deceptive.  Let’s explore one example close to my heart, diabetes.  As an internist, one of my most important tasks is the prevention and treatment of diabetes.  I know something about it.  As a heart surgeon, Dr. Oz deals with one of the most serious complications of diabetes, coronary heard disease, so he must know a bit about it as well.

So I was a bit surprised to learn from his website that I’ve  been going after diabetes the wrong way.  Unknown to me is the “prevention powerhouse” of coffee and vinegar.  He recommends heavy consumption of these miracle foods to prevent diabetes and to help the liver and cholesterol, whatever that means.  Reading this, two questions come to mind (a few more, really, but two that we will focus on): is this plausible, and is this true?

There are a few epidemiologic studies that support the idea that coffee consumption is in some way associated with diabetes risk.  (For a bit of background on different types of studies, see here and here.)  There are a few bits of basic science that could explain this relationship, if it turns out to be causal.  But these large studies simply show relationships.  They have found that people who drink more coffee (regular or decaf) were less likely to develop diabetes during the study period.  Most of these studies tried to control for confounding variables (for example, caloric intake) but none of these truly shows cause and effects.

The two biggest potential problems here are recall bias and confounding variables.  Do people reliably report the data we ask them to?  We aren’t directly measuring it, so this is critical.  Do coffee drinkers simply have smaller appetites?  Or other habits that reduce the risk of diabetes?  These studies give us an interesting starting point.  The next step to look for actual cause and effect would be a randomized controlled trial (which obviously could not be double-blind), that takes non-diabetics and randomly has half drink coffee and half abstain, and follows them over a several year period.   The idea that coffee can affect blood glucose metabolism and the development of diabetes is not nuts, but the available data don’t allow us to go any further than that.

The data support the plausibility of the question of coffee and diabetes, but not the truth of the statement.   But let’s pretend it is true.  The next questions are are how much risk reduction is there, and at what cost?

We know that some drugs and proper diet and regular exercise reduce the risk of diabetes.  How do these interventions compare with coffee or vinegar?  Is one of them 100 times more potent than the other?  One thousand?  One fifth?  And what are the hazards of caffeine consumption?  Not that great in general (and lessened by drinking decaf), but even small amounts of caffeine can cause significant acid reflux, sleep problems, heart palpitations, headaches.

What Dr. Oz is suggesting is using an unproven drug (coffee or dilute acetic acid) that isn’t needed.  We have safe, effective ways to prevent diabetes.  Our biggest failure is in providing people with the education, health care, and other tools to follow through.

References

Salazar-Martinez E, Willett WC, Ascherio A, Manson JE, Leitzmann MF, Stampfer MJ, & Hu FB (2004). Coffee consumption and risk for type 2 diabetes mellitus. Annals of internal medicine, 140 (1), 1-8 PMID: 14706966

VANDAM, R., & FESKENS, E. (2002). Coffee consumption and risk of type 2 diabetes mellitus The Lancet, 360 (9344), 1477-1478 DOI: 10.1016/S0140-6736(02)11436-X

Tuomilehto, J. (2004). Coffee Consumption and Risk of Type 2 Diabetes Mellitus Among Middle-aged Finnish Men and Women JAMA: The Journal of the American Medical Association, 291 (10), 1213-1219 DOI: 10.1001/jama.291.10.1213

van Dam, R. (2006). Coffee, Caffeine, and Risk of Type 2 Diabetes: A prospective cohort study in younger and middle-aged U.S. women Diabetes Care, 29 (2), 398-403 DOI:10.2337/diacare.29.02.06.dc05-1512

Pereira MA, Parker ED, & Folsom AR (2006). Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women. Archives of internal medicine, 166 (12), 1311-6 PMID: 16801515

Dam, R., Dekker, J., Nijpels, G., Stehouwer, C., Bouter, L., & Heine, R. (2004). Coffee consumption and incidence of impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes: the Hoorn Study Diabetologia, 47 (12), 2152-2159 DOI: 10.1007/s00125-004-1573-6

Last week David Gorski wrote a excellent post about why we have not yet cured cancer. It turns out, cancer is a category of many individual diseases that are very challenging to treat. We have made steady progress, and many people with cancer can now be cured – but we have not discovered the one cure for all cancer. I personally am not convinced that we will discover a single cure for all cancer, at least not with any extrapolation of current technology. But if we continue to make progress as we are cancer will become an increasingly treatable and even curable type of disease.

This topic also brings up a meme that has been around for a long time – the notion that scientists have already cured cancer but the cure is being suppressed by the powers that be, to protect cancer as a source of income. In the comments to David’s article, Zuvrick writes:

So we can find a cure. It has probably happened multiple times. But nobody wants to cure cancer. Too many researchers earn a living seeking a cure by remaining inside a narrow, restricted channel of dogma. Their institutions get grant money and survive from the funding. Big Pharma makes big bucks selling chemotherapy drugs, surgeons remove tumors and various radiation devices employ radiologists and firms making these machines. MRI and CT scans would not be needed for cancer if Rife technology were available today.

I have heard or read some version of this claim since before I entered medical school.  Superficially it may sound like profound wisdom (cynicism is a cheap way to sound wise) – but the idea collapses under the slightest bit of logical scrutiny.

First, as David thoroughly pointed out, the claim is implausible. Cancer is a complex set of diseases that defy sincere attempts at a cure. Those who promote the notion of the hidden cure often simultaneously promote wacky pseudoscientific treatments that they claim work – and Zuvrick is no exception. He believes that Royal Rife cured cancer 70 years ago. Rife was essentially a copycat of Albert Abrams who promoted his radio frequency devices. The concept is to use radio waves to alter the vibrations of cells in the body. This is pure nonsense. Here is a quick summary from Stephen Barret:

One of Abrams’s many imitators was Royal Raymond Rife (1888-1971), an American who claimed that cancer was caused by bacteria. During the 1920s, he claimed to have developed a powerful microscope that could detect living microbes by the color of auras emitted by their vibratory rates. His Rife Frequency Generator allegedly generates radio waves with precisely the same frequency, causing the offending bacteria to shatter in the same manner as a crystal glass breaks in response to the voice of an opera singer. The American Cancer Society has pointed out that although sound waves can produce vibrations that break glass, radio waves at the power level emitted a Rife generator do not have sufficient energy to destroy bacteria.

But let’s explore the logic of the hidden cure a bit further. Given that cancer is such a complex set of diseases, there is a vast and evolving science exploring the causes and behavior of cancers. This research takes place in numerous labs around the world. A cure for cancer would likely emerge from a collaboration among many researchers, in different labs and institutions, and even in different countries. Even if one lab made a significant breakthrough, it would be the capstone on top of a large body of research that was available to the entire community (and in fact the public). It would be impossible to keep other researchers from replicating the final steps that lead to a cure.

Often the hidden cure conspiracy idea is framed around the claim that a pharmaceutical company would hide such a cure to protect their profits from other cancer drugs. This claim fails not only for the reason above but for a separate practical reason. It would take about 100 millions dollars of research (if not more) to prove that a drug was actually a cure for one type of cancer (let alone all types of cancer). Why would a pharmaceutical company spend that kind of research money on a drug they know they have no intention of marketing, just so that they can suppress it? Also – where would they do such research? How could they get past all the regulatory hurdles to perform human research without revealing what they are doing?

Often those who claim that “they” are hiding a cure for cancer have only a vague notion of who “they” are. They generally have an image of the “medical establishment” as monolithic, but nothing could be further from the truth. The medical establishment is composed of universities, professional organizations, journals, regulatory agencies, researchers, funding agencies, and countless individuals – all with differing incentives and perspectives. The idea that they would all be in on a massive conspiracy to hide perhaps the greatest cure known to mankind is beyond absurd.

For those who think the profit motive is sufficient explanation, not all of the people and institutions named are for profit. And what about countries with socialized medicine who could dramatically reduce their health care costs if a cancer cure were found? Is Canada, the UK, all of the European Union, in fact, in on the conspiracy to protect American cancer treatment profits? It’s as if hidden cure conspiracy theorists forget that there are other countries in the world.

Hidden cancer cure conspiracies also are premised on a simplistic notion of how medicine and medical research progresses. The practice of medicine is constantly evolving in a process of creative destruction. New technologies render older ones obsolete. Resources ebb and flow to diseases as they emerge and are reduced or cured. There used to be entire hospitals dedicated to the chronic treatment of tuberculosis – and now, after antibiotics, those hospitals have been repurposed. Researchers, specialists, hospital space, and other resources shift over time to where they are needed.

If a cure for cancer were discovered it would not be as disruptive as is claimed by the conspiracy theorists. It would take years if not decades of research to explore how effective the treatment was for every type, grade, and stage of cancer. We could not assume that it cured all cancer even if it cured one type. And what about people who did not respond to the treatment, or could not tolerate it for some reason? (One might assume a 100% effective and side effect free cure for all cancer, but this gets progressively more unlikely.) Further, any real breakthrough cure would likely tell us something profound about the nature of cancer itself, and this would spawn entire research programs.

Research funding and researchers themselves would shift their focus where it was needed. Some might shift their skills to other diseases entirely, and perhaps fewer doctors and researchers would go into cancer research if a cure were already found. As with any other significant medical advance, the medical infrastructure would adapt.

Conspiracy theorists also tend to ignore the huge incentive to find a cure. For the researchers involved, it would mean fame, fortune, Nobel prizes and an enduring legacy within the halls of medicine. It is safe to say that it is every cancer researcher’s dream to be part of the team that finds the cure for cancer (or at least as big a breakthrough as is plausible).

The institution would also gain fame and prestige, which translates into more donations, better applicants, and also part ownership of any patents. A company that discovered the cure for cancer would make billions, even if it meant it would make existing drugs obsolete. Patents on drugs are finite, so companies are always looking for new drugs anyway. And imagine the public relations boon for the company that cured cancer – their name would forever be “Pharmaceutical Company – We Cured Cancer!” Even if the new treatment could not be patented, it would still be an enduring profit stream for the original company to market it – it would become their Tylenol, only bigger.

And of course the health care systems around the world would rejoice at the potential reduction in health care costs, which are now threatening to cripple the system. Doctors, hospitals, researchers – pretty much everyone, is making less money than they were a couple decades ago because of rising health care costs. The system is now being threatened by further cuts and restrictions to tame rising costs. A significant reduction in overall costs, by curing an expensive disease, would ease the pressure on the entire system, and free up resources for other diseases.

Finally, there is the human element. A hidden cure would require individual people to know that a cure for cancer is available but to deny this cure to dying patients in order to protect their or someone else’s profit. There may be people in the world who are that callous and evil, but think of all the people who would have to be that evil, over years or decades, to maintain a hidden cure. These are people who also have loved-ones who are likely to get cancer at some point in their lives, and who themselves are at risk for cancer. I would not casually assume that the medical establishment is full with such cartoonish maniacal villains.

Conclusion

The grand conspiracy of the hidden cancer cure is a meme that I wish would go away, but for some reason persists. It is like an urban legend – it appeals to some ill-formed fear or anxiety produced by the complexity of modern society. It gives a focus to these anxieties, and gives the illusion of control. No one wants to feel as if they are being deceived, and so assuming there is a conspiracy feels like a good way to avoid being duped. But ironically it is the conspiracy theorists who are being duped, or who are doing the deceiving.

The notion of a hidden cure is also dependent on seeing institutions with which one is not personally familiar as faceless and monolithic organizations, comprised of obedient drones. But these institutions are made of people – ordinary people with flaws and feelings and families just like everyone else.

…Steve Novella, who will be featured as the guest on a live chat with Trine Tsouderos discussing alternative treatments for Alzheimer’s, ALS and other neurological conditions at noon CST. Be there, aloha.