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Caveat lector: Reliance on Published Studies is Risky
Posted by Jackie
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Caveat lector: Reliance on Published Studies is Risky February 05, 2007 05:42AM |
Registered: 6 years ago Posts: 18,881 |
Dear Readers~ This is another lengthy post but one that is especially relevant to our group since we read studies and do research.
Caveat lector: let the reader beware.
So often we reference clinical studies published in respected medical journals to support or refute a finding on a health issue, a drug, a supplement, procedure or medical device. Today, this is a risky practice.
The focus of this report is to alert readers as to why we should view studies with a critical eye (perhaps skeptical) and to create awareness about the bias or spin now permeating our most respected medical journal publications as well as the commercialization of clinical trial material to create demand for pharmaceuticals or medical innovations.
A number of years ago, some of the forward-thinking physicians who expanded their knowledge to include expertise in functional and nutritional medicine issued a caveat about studies. They said, Follow the money trail to examine the bias. This is especially true today. More and more criticism is coming forth from mainstream medicine about the bias of studies and the failure to separate out vested interests.
One such person is a physician who became so alarmed about this data manipulation that he left his practice to write a book to get the word out. This report centers mainly around two hour-long teleconference interviews in mid- and late- 2006 along with book contents with author, John Abramson, MD. This is not new news, but its important to understand that reliance on published studies can offer a false sense of security, correctness, accuracy, safety or honesty.
Most of the conventional medical community is unaware of the bias nor has the time to sort through the data to learn the true facts. Because they rely on pharmaceutical companies for continuing education, they are fed misinformation and biased data that places patient safety in jeopardy.
Dr. Abramson points out that three quarters of published study data in our most trusted and respected medical journals the New England Journal of Medicine, Journal of the American Medical Association and Lancet, are commercially funded; and, says that studies show that when drug trials are commercially funded, the odds are 5.3 times greater that commercially funded studies will conclude that the sponsor drug is the treatment of choice compared to studies of exactly the same drugs that are not commercially sponsored.
ABOUT THE AUTHOR:
The book, Overdo$ed America The Broken Promise of American Medicine (Harper Collins Sept 2004) was written by John Abramson, MD, a Family Practice physician who left his practice to go public to create awareness among healthcare consumers and his own medical profession that the drug companies are funding and manipulating data so that the truth about clinical trials or study results is often obscure and the safety of the public is in jeopardy. What he reveals about his findings is appalling and irrefutable because its right there if one has access and digs deeply enough.
Dr. Abramson is quick to point out full disclosure. After his book published, he has since become a medical advisor to plaintiffs attorneys and often spends every day, all day, six days a week pouring through clinical studies and published FDA reports. The research for the book was done long before his association with plaintiffs attorneys.
Dr. Abramson has expertise in statistical analysis and comments that studies these days are made so intentionally obscure; it is wise to leave interpretations to the experts. He also points out that the abbreviated studies most people can access are inaccurate and highly shortened versions of the original study. Even the articles published in journals are mere fractions in length compared to the original document. He says the Internet is a double-edged sword when it comes to research as sometimes it lets the commercial messages get out further looking as if it is unbiased information.
He worked for two years in Public Health Service as a family doctor in Appalachia and for 20 years in private practice in a small town North of Boston (Hamilton, Mass). Dr. Abramson was a Robert Wood Johnson fellow and is currently a clinical instructor at Harvard Medical School where he teaches primary care to medical students. He served for seven years as Chairman of the Department of Family Practice at the very well known Leahey clinic, twice voted best doctor in his area by readers of the local newspapers and three times, selected by his peers as one of a handful of best family practitioners in Massachusetts.
About his Harvard teaching experience, Dr. Abramson says he thinks it is important to continue to work with medical students who are smart and keep us on our toes and its important to try to communicate to students that the biomedical model of medicine they are learning is necessary to be a good doctor but no way sufficient to be a good doctor. That there is an illusion that all things that are valuable for a doctor to know are scientific and can be observed from a third-person perspective, can be measured so-called objectively and reproducibly, and those are the kinds of things that science can investigated. What happens is the interpersonal or subjective or soulful, or spiritual side of the doctor-patient relationship gets discounted.
The fact is that about 70% of our health has to do with how we live our lives and if doctors and healthcare professionals really want to help patients and clients they have got to have the kind of interpersonal subjective encounter that will allow people to grow beyond the boundaries that are keeping them from achieving better health and thats not a scientific matter, thats an interpersonal matter.
He says, in fact the book I love to teach in a course at Harvard Medical School called Healing & Spirituality and in that the book I use I and Thou by Martin Buber is where the subjectivity of one meets the subjectivity of another person and is the space in which a lot of healing gets done. I would say the majority of healing that good doctors do is in that space. But you also need in your black bag all the science and medications that are available and to know how to use them wisely but its that combination and thats why its so important for me to stay in touch with students.
Right after his book published, Vioxx was withdrawn from the market and he was in demand for public appearances. He has appeared over 60 times on national television including two appearances on the Today Show and is often quoted in the NY and LA times. He lectures frequently to both medical and non-medical audiences discussing the core problems of American medicine and the opportunities to reclaim responsibility for our health. The topic of one of his recent lectures at Harvard Medical School was Healing the Critically Ill Healthcare System.
He is a doctor with integrity; believes in patients first, science first, and believes in truth.
To learn more, I urge reading Overdo$ed America as I can scarcely do the contents justice without reproducing it again right here. Nothing is irrelevant; all is eye-opening, discouraging and disappointing but very enlightening. Once again the trust, safety and well-being of the public the healthcare consumer (and most in the medical profession) -- is slighted in favor of marketing ploys strategized to improve the bottom line of already wealthy corporations.
When asked about why he decided to write the book, Dr. Abramson said he really began to write a book about healing relationships but our medical system is so screwed up that he couldnt quite get to that writing because Rome is burning and weve got other things weve got to talk about that are more important.
He says, Really what turned me from the book about healing relationships to Overdo$ed America which is a critical exploration of how the drug companies and other medical industries is the distorted science that doctors are trained to believe so doctors do things to the patients that are often not effective and sometimes harmful and virtually always expensive.
And what really turned me from the other book was finding the data on the FDA website that the manufacturer of Vioxx and the manufacturer of Celebrex submitted to the FDA the results of the big studies that were published in the New England Journal and JAMA, both studies showing that Vioxx and Celebrex were safer that the older anti-inflammatory drugs.
When I found data on the FDA website that said that was not true and in fact that Vioxx was significantly more dangerous than Aleve and no more effective and cost 15 times as much and the NEJM had published an article that left good doctors reading and believing the article perfectly left them believing that Vioxx was a safer drug and I couldnt convince my colleagues that they were being misled by their trusted journals, I realized I had to write this book. I started to get more and more of a sense of the bias thats in the literature that we docs have been trained to accept as fact, isnt always trustworthy. That let me do the research that led me to Overdo$ed America.
The magnitude of this problem is hard to believe but the best estimates are that between 40 and 60,000 people died from taking Vioxx - thats as many Americans as died in the Vietnam war and as many Japanese as died from the Nagasaki A-bomb. This is an enormous problem. This is one drug. Its an enormous problem there are 24,000 law suits and the score right now is 7 for Merck and 6 for the plaintiffs. It is unclear how this is going to play out whether the cost/benefit ratio for drug companies to cover up and spin the unfavorable results so that doctors are led to believe that drugs are more effective and safer than they really are. The jury is literally out now as to whether this debacle is going to end in a way that the message to drug companies is that it is good business to hide to hide your bad results.
More examples of the turning point that motivated Dr. Abramson to write Overdo$ed America:
EXAMPLES OF OBSCURITY IN STUDIES (quotes and paraphrasing)
As the 90s wore on, you could feel the commercial pressure coming in the journals and it was actually one event that opened my eyes. All of you in clinical practice know how draining it is to focus on your patients and clients needs so I would make a habit of sequestering myself in my office for about 15 minutes at lunch reading the journals and just relaxing.
One day in August 2000, I was reading the NEJM and happened to see an article called Pravastatin and the Risk of Stroke (Pravachol) and the article claimed taking Pravachol lowered the risk of stroke but when I looked a little more deeply, I could see that when the results were adjusted for other risk factors for stroke like diabetes, hypertension and smoking, that the correlation was no longer statistically significant. And when I looked a little further, and saw that the average age in the study was 58 and 5/6th of the people in the study were men, and realized that the average age of a stroke patient is 76 and most stroke patients are women the study was done on the wrong population and for the women in the study who took the Pravachol, they actually had 26% more strokes than the women taking the sugar pills.
For the people over 70 who took Pravachol, they actually had 21% more strokes than the placebo people, so it looked like the article was really upside down. It was in the NE Journal and it was sponsored by a drug company but Id never seen anything that was quite so commercially distorted, so I went to a research expert at one of the Boston Universities and said , look, I was a Robert Johnson Fellow 20 years ago, maybe my skills are rusty and maybe Im missing something and making more of this than should be made of it, do you see anything wrong with my analysis -- that this article seems to be touting the use of a drug when there really isnt any evidence that it will help our patients. He looked and said I dont see anything wrong with your analysis and I suggested writing a paper together we could go a long way in helping to immunize practicing physicians from this growing commercial bias in our research. And he said to me, well, Id rather not get involved; I do a little research for the drug companies and Id rather stay out of this.
And I realized at that moment in 2000 that we trust that the universities are going to be the ultimate backstop to insure the integrity of our knowledge in this case medical knowledge, and whats happening is so much drug money and commercial industry money that the universities are now dependent on both the universities and the researchers within the universities that the universities can no longer play that role so that the researchers are somewhat neutralized in the critical position by the drug company ties, and the universities are and the medical journals are and it became clear that in order to fulfill the mission that brings us all together which is to help people to achieve healthier and happier lives, that the right thing for me to do was start to look at what really was going on with our medical knowledge from the best sources, the most trusted journals and to do the research and to tell the story about how our most trusted sources of information are now being so heavily biased by commercial influence.
Which brings up the question about media manipulation.... I think there is no question that the amount of money coming into the media through drug advertising and other avenues of producing and influencing shows, there is no question that the media is not able to maintain an unbiased point of view. Look at the evening news being so laden with drug ads. At first you may think it is the demographics of the evening news because older people listen at that time and they are thinking more about drugs, but youve got to assume that the amount of time that the drug companies are buying in advertising is giving them some influence over the editorial policy.
Since the book came out (Sept 21, 2004), its been a real trip for me Its a pretty hard-hitting book about the drug industry and it didnt get much press from mainstream press in large part because of the issues just mentioned but a week after the book came out, Vioxx was withdrawn and my publicist at Harper Collins called and said the limousine will be there in 50 minutes and youll do 4 national TV shows out of Boston and then go to the Today Show in NYC. Since then, Ive learned a lot about the media. Fox news will give me a pretty long leash but NPR, not so long and the media issues are more complex than they appear to be.
Question: In the past the FDA has had strict standards for releasing drugs but strong lobbying is continual to reduce the strict standards because of research costs. For now, what type of profits are the pharmaceutical companies enjoying?
Answer: Good question, because we hear it costs $800 million to develop a new pill and there is some argument about the math in that but the bottom line is when all is said and done, all the R& D is paid for, the marketing and other costs are paid, the drug companies are earning 17 or 18% profit on their sales. The average Fortune 500 company earns somewhere around 4-4.5% profit. So net of all the expense including all the research, the drug companies are 3 4 times more profitable than the average other industries in the Fortune 500 group and thats very important to remember because 60% of the drug companies profits come from the United States. The drug companies argue they need to charge the high prices in the US to fund the ongoing investment in research which seems to be a bit exaggerated because they are making 3 4 times the profit of other companies and even with just twice the profit margin of the other Fortune 500 group, I doubt they would cease their research activities and in fact might even increase them.
In the US, price is clearly a problem. We have the highest cost for prescription drugs, and we all know the stories of going to Canada. When writing the book, I asked the spokesperson from Health Canada which is like the FDA if she knew of any instance ever of a counterfeit drug from a Canadian pharmacy imported into the United States and she said she was not aware that it had ever happened. It seems to be a fiction made up by the drug industry to dissuade Americans from importing drugs but more importantly, the importing of price control because the truth is that the biggest importer of drugs is the drug industry itself. They manufacture drugs off shore, import to the US and then send them out to other countries.
So one issue is cost with the drug industry, but the real issue or problem that we all need to focus in on is the quality of the knowledge from the best journals because three quarters of the clinical trials that are published in our best journals the Lancet, NEJM and JAMA are now commercially funded. And the studies show that when drug trials are commercially funded, the odds are 5.3 times greater that commercially funded studies will conclude that the sponsor drug is the treatment of choice compared to studies of exactly the same drugs that are not commercially sponsored.
So, when doctors are reading their best journals, that are the source of their scientific evidence more often than not they are getting infomercial-based medicine, not science-based medicine and I think thats the core problem in American medicine is that medical knowledge, itself, has been transformed from a public good into a commodity.
THE VIOXX/CELEBREX STORY
Another turning point for me was when I found the data on the FDA website that the manufacturers of Celebrex and Vioxx had turned over to the FDA (in Feb 01) (I found it in Aug 01) when I went over this study- Mercks own study the penultimate study of this drug the biggest study and the most authoritative, Mercks own data shows ..
.. that Vioxx is no more effective at relieving arthritis symptoms or pain than Naproxen or Aleve sold OTC. The reason Merck was touting for doctors to prescribe Vioxx was that it is safer on the stomach when in fact what Mercks own data shows is that Vioxx causes more cardiovascular complications heart attacks, blood clots and stroke, than it prevents stomach complications and the real bottom line of Mercks own big study is that if I as a family doctor gave Vioxx instead of Naproxen to 100 patients in a row, over the following year, there would be two and a half serious medical complications because I gave them Vioxx instead of Naproxen when the only reason to give Vioxx was that it was supposedly safer.
So doctors had read the NEJM article which was written by 13 authors all of whom had financial ties to Merck and they came away with the belief that Vioxx was a safer drug because it was gentler on the stomach when in fact the real data that Merck had turned over to the FDA showed that Vioxx was a significantly more dangerous drug than naproxen. The tragedy of this story is that after Merck and the FDA knew that Vioxx was significantly more dangerous than Naproxen, American doctors prescribed $7 billion worth of Vioxx that caused approximately 100,000 heart attacks and deaths after Merck and the FDA knew it was significantly more dangerous than Naproxen.
When I found this on the web and realized the truth about Vioxx was 180 degrees different from what doctors were reading in their best journals it became like an emergency for me to tell the story. So as not to be selective and pick on just Vioxx, let me just talk about Celebrex for a second. First a cost question - It is about a factor of 10 more to use Vioxx rather than Naproxen.
More important than the cost different is the fact that Vioxx was a significantly more dangerous drug and Merck knew it. Merck claimed because the bigger study looked at Vioxx vs. Naproxen and didnt look at Vioxx vs. placebo Merck claimed it wasnt Vioxx that wasnt more dangerous but rather it was Naproxen that prevented heart attacks the way aspirin does except that it would have to be 2.5 times more effective than aspirin to accomplish that a little detail that never got worked out. But Mercks claim was that the evidence did not show that Vioxx was dangerous but that Naproxen was beneficial.
Well, there are two problems with that. One is there was no scientific evidence that that was true and it turns out not to be true and the FDA told them that. The second problem is that the real structure of the study was a head-to-head study with people who had rheumatoid arthritis and the question isnt whether Vioxx is more dangerous than placebo because no doctor would ever give a patient with RA a placebo you are going to give them some medicine. So giving them Naproxen which was at the time, the most widely used anti-inflammatory drug was a good test a so called head-to-head test and Vioxx failed the test. And then Merck tried to do heads I win, tails you lose and they got away with it for a while. Hopefully justice will be served in a way that drug companies will be dissuaded from trying to cover up important science that shows dangers of their drugs in the future well see.
Celebrex is a similar story and Pfizer got lucky because Celebrex is just a useless drug for most people its not a dangerous drug and the article that appeared in the JAMA that led doctors to prescribe billions of dollars of Celebrex concluded that Celebrex used for six months causes fewer stomach complications but the fact of the matter was it was a 12-month study and the whole 12 months showed that Celebrex was no gentler on the stomach and Pfizer (it was Pharmacia at the time) just didnt turn over half of their data to the Journal of the American Medical Association. When the editors found out about this they said things like we are flabbergasted; we were operating on a basis of trust that perhaps wasnt there because the editors of the journals didnt know that it was a 12-month study. They were hoodwinked into thinking it was just a 6-month study and the doctors who were reading a trusted journal were misinformed about the truth of Celebrex.
The problem is that most of the information that is available about drugs and medical devices is coming from research that the companies themselves are sponsoring and the reason why they sponsor that research is to maximize their return on investment to their shareholders. So we have a system where research has been privatized and we dont have the mechanisms to oversee the integrity of that research because more than half the budget of the FDA that oversees drug safety is now paid for directly by the drug companies, and the universities are dependent on the drug companies and the medical journals are dependent on the drug companies. So its like playing a professional football game and having one side bring their own referees. It just doesnt work.
So the question comes up to what extent should the American public and the medical profession be trusting what comes out of agencies like the NIH and the FDA? The GAO accountability office just did a report on the FDA and found the FDA as currently structured is not able to oversee the drug safety of the drugs that Americans are taking.
We have a very serious problem. 20 million people took Vioxx and most took Vioxx after the information was in that it was dangerous so with the drug companies funding more than half of the division of the FDA that oversees drug safety, they are not able to provide an independent, critical oversight of the safety of our drugs. This is a real crisis. It is unclear yet whether legislators will rise to the occasion or whether they too are so addicted to drug money that they are not able to move on this.
Weve got a situation where the information we are getting is produced to serve these ends so the American people . The American doctors are being gullible. We doctors are taught to trust the journals, were taught that whats in the bottom line of the abstract is the evidenced-base medicine that we should be practicing so whats happening is like a perfect symphony its just that the people are being hoodwinked, its not just that there are two lobbyists for every legislator in Washington and they are being inundated with the drug companies version of the truth, and its not just that the doctors when they go to continuing education 70% of their continuing education is funded by the drug companies or that the medical journals are too influenced by the drug companies, its like a symphony so that all works in concert and the problem is that we havent figured out as a society how to create a representation of the public interest.
What is most concerning, even after these drug recalls and deaths from drugs, is that the American public still trusts everything they see and hear from the drug companies on television and the media and the FDA allows this to happen.
[My comment: Just recently (January 31,07), press releases indicate the FDA plans to address concerns over how it handles drug safety including issuing a regular online newsletter summarizing findings about drugs already on the market. We should watch closely how these safety reforms will be supervised and by whom. January 12,07- a press release reported on the FDAs deal with Big Pharma about revisions in user fees that drug companies pay the agency to review their products which will probably raise prices paid for these drug reviews.]
CHOLESTEROL & STATINS
Another key motivating factor to write the book concerns cholesterol and the fact that the National Cholesterol Guidelines keep increasing in strictness.
To set the stage about this situation: In year 2000, Americans were twice as likely to be taking a statin a cholesterol lowering drug as people of equal risk in Europe and of the 25 million people world-wide who were taking a statin, 13 million were in the US. So we were taking twice our share of statins and Americans were getting three times the number of cardiac procedures angioplasty and bypass procedures as were the citizens of the other industrialized countries. So twice as many statins; three times as many procedures. You might say thats evidence of high-quality medicine but the problem is that the death rate for heart disease in the United States ranked 19th among the industrialized countries and we were losing ground to most of them we were not getting better, we were getting worse.
In response to that, instead of saying wait a minute, time out, maybe were approaching heart disease prevention the wrong way and maybe we ought to be looking at the scientific evidence that shows that lifestyle and nutrition are the key factors in heart disease prevention not cholesterol and giving drugs. But instead of going in that direction, we went in exactly the opposite so that in 2001, the third iteration of the Cholesterol Guidelines recommended taking the number of Americans on statins from 13 million to 36 million almost tripling the number of Americans on statins in one fell swoop.
And the problem is that most of the people for whom statins were recommended --23 million people- most of those people did not yet have heart disease because we already understood that statins are beneficial for people who do have heart disease (that came out in the 1993 Guideline) so those 13 million people already had statins recommended for them. So the 23 million people for whom statins became recommended in 2001, didnt have heart disease.
This is such an outrage the guidelines say recent clinical studies show that statins reduce the risk of heart disease in women who dont yet have heart disease and they cite 7 studies. But not a single one of those 7 studies shows evidence to substantiate that statement but there is no way any practicing clinician would ever know that. I found that out because I was doing research for Overdo$ed America and I went through all the footnotes and checked them but the good ole boys just werent telling the truth. And in fact thats section 2 anyone can get them if you just want to Google NCEP or National Cholesterol Education Program youll get this 284 page guideline. Section 2, they make this misrepresentation about the studies that show these drugs are beneficial for women. In section 8 which is the very back of the guidelines they say Special Considerations for Women and say Clinical studies to show that statins are beneficial are generally lacking for women. So they admit they werent telling the truth. And then they go on and say These recommendations for women are based on extrapolation of data from men. Womens blood should be boiling about this issue.
That was 2001. In 1998, we had the HERS study published in JAMA and that showed that women taking combined hormone replacement therapy their bad cholesterol goes down, the good cholesterol goes up and if anything they had more heart disease not less. It is very clear there is a different relationship between cholesterol and heart disease in women than men and the folks who are writing these guidelines knew it.
And the same story for people over 65. They say that recent studies show that aggressive LDL lowering is effective and cite 9 studies to justify that statement and not one of the 9 actually shows it.
(Ref. p 246 of the book) The PROSPER study came out after the 2001 guidelines and is a well-designed study. Its a drug-company sponsored and it is designed fairly. It looks at the effect of lowering cholesterol with a statin drug in people from age 70 to 82. Its a fair mix of men and women and a fair mix of people who did and did not have heart disease. What the PROSPER study found is that people age 70 and over who did not already have heart disease, got no benefit from taking a statin.
There was no significant reduction in the risk of heart disease or mortality compared to the people who took a placebo. But they did have a statistically significant higher incidence of cancer. So that in this study of people ages 70 82, who took a statin short study 3.4 years, in that 4th year of the study, for every 70 people taking a statin drug, there was one extra case of cancer.
So youve got the majority of people who are taking statins, dont have heart disease, there is no evidence they are beneficial for people over 70 for people who dont have heart disease, and there is statistically significant evidence they increase by 25% the risk of cancer.
When there is no randomized control study that shows benefit and we have a drug-company sponsored trial that shows the risk of cancer goes up in an older population, this makes no sense. To be on a national campaign to get people to take more statins in this category, I find sinful. Just plain sinful. Significant evidence of harm and not evidence of benefit.
If you look at the entire mix of these people age 70-82 , it gets even more striking - half already have heart disease and looking at the whole study, there is no reduction in mortality, when these people are treated with a statin. And yet we know from another study done in Europe, if we look at older people who do four healthy habits exercise routinely, eat a healthy, Mediterranean style diet, dont smoke and drink in moderation - the people over 65 who do those four things have a 60% lower death rate than the people who dont do those things. Yet we are spending our time putting them on statins which increases the risk of cancer.
Statin drugs are the most heavily prescribed drugs hands down no matter what age but especially for seniors. [Statins are #1 in prescription drugs]
Is there science to support how and why these are prescribed especially for seniors? Answer there is some science and its really important to look at this. This is an especially important topic. Statins are the biggest drugs used and its enormously important example of whats going on in the United States. We have this huge campaign to lower cholesterol and what has happened is just like a master magician. We have our eye on cholesterol when the real goal is to reduce the risk of heart disease and stroke. Whats happening is that the statin drugs reduce cholesterol very nicely no question but there is not a single randomized controlled trial that shows that these drugs are beneficial for women who dont have heart disease or people over 65. Not a single trial and ¾ of the people who take these drugs dont have heart disease
Now, there are three groups of people men under 65, women under 65 and people over 65. For men, there are shades of gray. Very high risk men get some benefit from statins not as much as they would get from, exercise, nutrition, quitting smoking and controlling stress but there is some benefit. But for women, there is not a single randomized controlled study on file that shows that women who do not have heart disease or diabetes benefit from taking a cholesterol lowering drug. Not a one. And yet millions of American women are on these drugs.
Similarly, for people over 65, there is not a single randomized, controlled trial that shows that people over 65 who dont have heart disease or diabetes would benefit from taking a statin drug. In fact, the one study that does address older people the PROSPER study, published in Lancet in 2002, looked at people over age 70 an equal mix of men and women and equal mix of primary and secondary prevention meaning people who did not yet have heart disease and those who already had heart disease and for the primary prevention patients (who dont have heart disease), statins were not beneficial they did not reduce the incidence of cardiovascular disease or death but statins did increase the risk of cancer by 25% in an older population. So to be recommending statins and weve all heard the phrase, statins should be put in the water they are so good for people over 65 who do not have heart disease when we dont have a randomized control study that shows its beneficial and we have a drug-company-sponsored trial that shows that the risk of cancer goes up by 25% in an older population, it makes no sense.
This reminds me of the situation we were in back in 1989 when hormone replacement therapy (HRT) was being recommended for all post menopausal women and then the study came out showing a 26% increase in the risk of breast cancer in 1989 but this was just dismissed by the authorities by the experts who said were so sure that hormone replacement therapy is beneficial that we are willing to except this small increase in the risk of breast cancer. Well, that small risk of breast cancer led to 200-300,000 unnecessary breast cancers in American women.
At some point, we have got to catch on that when drugs are marketed that dont have a clear benefit and have a clear harm, we have got to take notice of that and stop falling for the hype. In the case of heart disease it is particularly important because we know how to prevent most heart disease; we know that exercising routinely, eating a healthy diet, not smoking, controlling weight, and controlling stress in your life we know that each of those things independently is more important than cholesterol or lowering cholesterol with drugs. So the headline here ought to be We can reduce 83% of the heart disease in women by doing those 5 things. But instead, the headlines are all about cholesterol guidelines and statins as miracle drugs.
We keep working down in the acceptable numbers for cholesterol levels.
HORMONE REPLACEMENT THERAPY
An article had just come out in JAMA in 00 or 01 that showed for women taking combined hormone replacement therapy, the risk of breast cancer went up by 8% for every year they were taking the combined therapy. A woman who had been diagnosed with breast cancer consulted with me and who was on HRT for 12 years so her risk increased 96%. She showed me the article and asked why doctors ignored this clear and present danger. It is an example of how we get into a mindset and we just assume that certain things are beneficial and we dont listen to evidence to the contrary. The hormone replacement story is mostly gone now and if menopausal symptoms dont respond to natural products, Im not opposed to very short term therapy with hormones, but not long-term therapy.
The Hormone story itself tells about or sets the pattern of what we see over and over again and I think it is worth looking at how the marketing evolved in HRT because it is the same with anti-depressants- the same with the cholesterol drugs, and the osteoporosis drugs and wherever you look, its the same game.
Estrogen was approved by the FDA in 1942- brand name Premarin called that because it is made from pregnant mares urine. It was a very effective drug for treating severe menopausal symptoms, hot flashes, etc that were upsetting womens quality of life. In the early 60s, the drug company that owned the patent on Premarin realized the market was limited on women with severe menopausal symptoms and they could sell a lot more drugs if they could convince doctors and female patients that menopause is not a natural process in fact that menopause is essentially an endocrine deficiency. Like diabetes being an deficiency disease of the pancreas not producing enough insulin, menopause was a disease of the ovaries not producing enough estrogen.
Robert Wilson was a gynecologist in NYC who wrote a book called Feminine Forever that was a best seller in the mid-60s that explained this theory to women that menopause was an estrogen-deficiency disease and they could maintain their youth and not suffer the ravages of this disease if they took hormone replacement therapy. Well, it turned out that Dr. Robert Wilson, as you may suspect, was receiving financial support from the drug companies and what they had done was re-frame a normal biological stage of a healthy womans life to a pathological process.
We found out in the 70s that Premarin given to women who had not had a hysterectomy and still had a uterus, increased the risk of uterine cancer, so sales fell off for a little bit but then the drug companies found that adding progesterone to the estrogen would prevent the uterine cancer problem. Sales picked up; we had national guidelines from the American College of Physicians which is the professional society of all the Internal Medicine doctors in 1991 recommending all post-menopausal women who dont have a contraindication should be put on HRT.
Well, it turns out in retrospect, that yes, adding progesterone to HRT did decrease the risk of uterine cancer, but it more than offset that by increasing the risk of breast cancer and the experts never looked to see if the total cancer burden caused by HRT by giving combined hormones would be better or worse and, in fact, was worse.
And, we didnt even learn that until the Million Woman study was published out of the UK. So the pattern we see of getting a drug that was effective, short term, for limited use for symptoms, getting marketed as good for everyone and then realizing there were unintended consequences that were very severe for many women and then coming to the truth of having HRT put into perspective but unfortunately, then we immediately get on the osteoporosis drugs and the statins, the anti-depressants and the cycle starts to repeat itself with different kinds of drugs.
NATURAL PRODUCT STUDIES
What about natural or nutraceuticals products and reliable studies?
There is good news: Unbiased natural product research comes out of Germany and studies on US nutraceuticals is fairly unbiased and are still fairly accurate in medical journals.
Take the Glucosamine study, for instance partially funded by NIH. They looked at Glucosamine for people with mild/moderate and severe knee pain. The result that got all the press was if you looked at the population as a whole, Glucosamine was not effective and Celebrex was but if you looked at the subpopulation of people with moderate or severe knee pain from arthritis, they did much better with the Glucosamine than the Celebrex. that wasnt reported because the study wasnt designed to look at the people with more knee pain.
Results can be biased in favor of the products of the sponsors which is typical with a company researching its own products; it can be biased against the product if it is a competitor or straight medicine looking at alternative medicine and the lines between those is getting blurred more and more as there are hybrid studies that have some public and some private funding and sometimes you only hear about the public side of the funding.
I dont have a black and white answer to say this is a good source of information but we have to a type of connoisseur and develop your own critical faculties as you examine the research.
I would suggest Pubmed to see what type of straight research is out there with the understanding that if it drug-company-sponsored research, they may have a bias against natural products but check the whole range of research but in the end you have to make your own decision.
OSTEOPOROSIS/OSTEOPENIA/OSTEONECROSIS
Remember we dont want to become duped on focusing on a surrogate endpoint. So its not really bone density that were treating what we are trying to do is prevent women from having clinically relevant fractures. When we got involved in bone density alone as the outcome measure, thats when we started to get into trouble.
I spoke to the Association of Healthcare Journalists Annual Meeting in Chicago and shared the podium with a Pulitzer Prize winning journalist and I started to tell the story about osteoporosis, and told the definition of osteoporosis bone density testing came out of a meeting that was organized by the world health organization in 1993 and that is when this thing about T-score of minus 2.5 being osteoporosis and minus 1 being osteopenia was developed and that there were three drug companies involved in funding that conference that came up with the definition that led to so many women having bone density tests and being put on these drugs. She corrected me, she said that had actually gotten these people who wrote the definitions to talk and she said it wasnt at that conference but that it happened in a bar on the back of a napkin that these guys developed this definition.
So whats happened is this: T score is the number of standard deviations that a womans bone density is below the peak skeletal density that a women achieves somewhere around age 28 or 29. So now whats happened is that normal skeletal aging has been reframed as a bone disease so that instead of doing bone density tests, lets say we measured how long it took a woman to run a mile and we found the average woman at age 29 could run a mile in 6 minutes or whatever well if a woman who is age 70 can only run a mile in 13 minutes, does that make her diseased? And the answer is obviously not. She is older and her physical capacities have gone down as part of normal, healthy aging.
So when we do these bone density tests, we are not measuring fracture risk. Only about a sixth of fracture risk is captured in a bone density test. The real problem is from a physiological point of view is that in the areas of our body that are most vulnerable to serious fracture, like hip or vertebra or wrist, the real strength in the bone comes not from the outer cortical bone but from the trabecular lace-like internal structure like buckyballs of calcium of lacey boney material inside the bone so there is an internal structure, so what happens is much of the fracture resistance is due to that internal structure not the outer cortical bone.
When women go through menopause, and the ratio of bone rebsorption and bone laying down changes, so that more bone is rebsorbed what happens is the lacelike structure in the middle of the bone is more metabolically active because there is a greater surface area to mineral content ratio in that lace-like structure so it is more of an active mineral reservoir. When bone is rebsorbed, it gets rebsorbed preferentially from that internal structure and when it gets rebsorbed from that trabecular structure, the footprint is lost the internal structure is lost because it gets rebsorbed which means you cant lay more calcium down when the structure is resorbed and what happens is you end up laying down more calcium in the cortical bone the dense outer core of bone not the internal structure. So when increasing bone density and these drugs clearly do increase bone density, you may not be preventing fractures in proportion to the amount you are increasing bone density.
For example the company that makes Fosamax did a study on women with osteopenia not osteoporosis and they found that treating women with osteoporosis with Fosamax did change their risk of fracture. It increased the risk of hip fracture by 84% which didnt quite hit statistical significance and increased the risk of wrist fracture by 50% that probably did reach statistical significance.
So when we treat women who have osteopenia or pre-osteoporosis with these drugs, we do improve their bone density, but there is not good evidence we reduce their risk of fracture.
The first thing to remember about this whole issue about the risk of osteonecrosis of the jaw with Fosamax is, what are we really doing with these drugs? We are treating a surrogate endpoint that may not be as meaningful a clinical endpoint as we think.
A wonderful example weve all heard about this issue youve got to pay attention to relative risk and absolute risk. We hear that Fosamax reduces the risk of hip fracture by 56% in women in mid sixties who have osteoporosis. You say well 56% reduction in hip fracture thats fantastic; every woman with osteoporosis should certainly be taking Fosamax. But if you look at the absolute risk reduction, what the numbers show is that a woman with osteoporosis in her mid-sixties has a 99.5% chance of getting through the next year without fracturing her hip. And if she takes Fosamax her chance of not fracturing her hip goes up from 99.5 to 99.8% which is a miniscule improvement but a 56% improvement in relative risk.
A long answer to say we can prevent six times more hip fracture if we get women exercising than if we give them osteoporosis drugs.
So the way the osteoporosis drugs have been marketed is almost identical to the pattern we talked about in hormone replacement therapy that this market got broadened to include natural aging of the skeleton and now we find out there is a serious, non-intended consequence hopefully unusual but with women who have dental surgery or get into any bony manipulations of the jaw it turns into a major medical problem.
But it is an unintended consequence for a drug that, in my opinion, is being over sold beyond its clinical usefulness and it just highlights the importance of understanding why we are using drugs and which are really going to be beneficial and that when the drug companies are allowed to produce the knowledge, they are going to spin it in a way that will be advantageous to their goals maybe even more than American womens goals.
ANTI-PSYCHOTIC DRUGS
I spend all day every day sometimes 7 days a week unraveling the spin and Ive got to tell you there isnt a week that goes by when I dont say I cant believe that that happened, I cant believe it went that far."
For example, an issue that Ive been working on for the last couple of weeks in a legal case, is the new anti-psychotic drugs being promoted so heavily and now being use even for children off label although the FDA hasnt approved them for use in children or elderly- like Zyprexa, Rispirdol, Seroquel drugs. [http://www.lawyersandsettlements.com/articles/zyprexa_Off_Label.html]
Spending on anti-psychotic drugs before this new generation came out was Thorazine, Haldol and Meloril in 1994 we spent $1.4 billion on those drugs; last year, we spent over $10 billion on those drugs. There arent any more schizophrenic people, so the spending went up by a factor of like 600% and we were lead to believe that these new drugs were worth the extra money and they literally can cost a hundred times more than the older drugs because they were more effective at treating the symptoms of schizophrenia and they caused fewer side effects.
But it turns out in the largest review article on this looked at 120 studies. 80 of the studies compared the new drug to Haldol. Now the standard of therapy is when treating a patient with Haldol is to give them an anticholinergic drug as well so they dont get the muscle rigidity shakes and the symptoms that go along with those drugs. But out of 82 studies that compared these new drugs to Haldol, only 4 of them gave anticholinergic medication along with the Haldol.
And now weve got a series of studies that show that these new drugs are no better and actually may not be as good as the old drugs. Probably most listeners arent prescribing the antipsychotic drugs but I raise this point just to show that it takes a constant vigilance the nature of which in people who are seeing patients every day dont have the time or the skill to unravel this mess. And I do it full time and Im losing ground, so its really a problem.
And these drugs arent being just used for schizophrenia anymore. The FDA has approved the use of those drugs for schizophrenia and bipolar disorder but if you look on the American Psychiatric Association website, youll see that those drugs are suggested in many other illnesses off label.
So the name of the game - The Hormone Replacement Therapy saga is sort of the grandmother of all of these marketing ploys is to get your drug approved and then convince patients and doctors that a wider/broader market can benefit from them even when the science hasnt been approved by the FDA.
Revisiting the Focus:
Dr. Abramson says, It is very hard now to get unbiased information, which is why I left family practice to write Overdo$ed America because that information just wasnt accessible. Through the book, Ive tried to make information accessible in readable but disciplined language what the statistical arguments are about the corruption of our medical knowledge.
The real core problem when you go all the way upstream is that the medical knowledge that drives our system not the advertising, not the PR messages, not the drug reps coming to doctors but the medical knowledge that is in our most trusted journals has been turned into a commodity; it is produced for its commodity value not for its health value and until, we as a people, understand that the fundamental mission of the drug companies and the other medical industries is to return as much money to their shareholders as they can, and that 80-90% of our clinical research is privately funded by the drug industry and other industries, and the reason why the companies engage in that research is to maximize their return on investment so at best, our medical knowledge grows toward profits the way plants grow toward sunlight. Unfortunately, that typically means growing away from an epidemiologically balanced approach to healthcare. So what weve got is this ever-widening chasm between whats called evidence-based medicine which is really commercially knowledge-based medicine and truly epidemiologically-based medicine which would help people get better.
Expenditures for prescription drugs are increasing 7 times faster than the rate of inflation...(now possibly slowing down just a bit.) Whats driving it is not necessarily that they are better drugs its that the knowledge thats produced much of which wont stand the test of time but it convinces people that there are better drugs and that drives the profit ratio. Its the belief they are better drugs and in many instances it is just like printing counterfeit bills except they are printing counterfeit knowledge and making money off the knowledge.
They stimulate greater demand - go back all the way upstream ¾ of the clinical trials published in our best journals the three most trusted journals in the world NEJM, JAMA and Lancet, are commercially funded and the odds are 5.3 times greater that commercially funded trials will conclude that the sponsors drug is the treatment of choice compared to non-commercially funded studies of exactly the same drugs.
So the evidence thats being produced when doctors think they are practicing evidence-based medicine by reading their most trusted journals more often than not, they are practicing infomercial-based medicine instead. And Im not being critical of the doctors because you cant see it. Often times, there arent clues even the best-trained eye cant see it because the drug companies just dont put the data in that allows for an objective conclusion. And the reason why the data is not there often is not a failure of peer review because the authors arent even allowed to see their own data. Most of the authors of most of these articles that are commercially funded are only allowed to see the data that the drug company parcel out to them. And one would suspect that the drug companies parcel out data that makes their drugs look better. This is a serious problem.
Additionally, the advertisements are a problem and are brilliantly made; you just have to look at them in awe and realize the emotional power of these advertisements how good they are at what they are doing. Unfortunately, they are playing with peoples health.
Ref. p 249 passing of new drugs by FDA - where funding comes from
We would hope the FDA was overseeing the safety of our drugs but they are not able to do that. There are really two major problems. One is new drug approval and the other is overseeing drug safety after approval.
The problem is that the FDA was inadequately funded in the late 80s and in fact, in truth, there were AIDS drugs that were stuck in the FDAs pipeline when people with AIDS were dying. AIDS activists were extremely effective back in the days of Act Up, climbing flag poles, they did a great job of drawing attention to this crisis to the politicians attention. The drug companies took this lemon and made lemonade. They said, we can fix the pipeline we can open up the bottleneck in the FDA we will pay user fees and well help finance the FDA so it has enough money to hire enough officers to approve these new drugs on a shorter timeline. And thus was born the Prescription Drug User Fee Agreement PDUFA effective in 1992 with the drug companies paying user fees directly to the FDA.
Now more than half of the budget of division of the FDA that approves new drugs and oversees drug safety is paid for directly by the drug companies. So in many ways, the FDAs primary client is not the American people, but the drug industry, itself.
There is a structural problem with the safety issues and this is really serious. When drugs are approved, the companies that make the drugs do Phase III trials which are clinical trials of the drug where the company just has to prove the drug is better or significantly more effective than placebo. It doesnt have to be better than any existing drugs, or could be significantly worse, but just better than placebo. So what the companies do is design their pre-approval trials (Phase III) so they have enough people in them for long enough so the trial will show a statistically significant benefit against placebo or better with a 95% certainty thats the statistical threshold thats used.
So when the drug companies statisticians determine how many people need to be in these studies, and how long they need to go on, usually several thousand people, and usually the duration is only 6 12 weeks, so there is enough of a difference between the drug and placebo to be 95% certain that it is effective then the FDA says its effective.
The problem is, that when we look at safety problems in these small, short-term trials also have to hit a 95% certainty level before the FDA will call a drug unsafe. But these trials are not designed to have safety problems (if they exist) before reaching statistical significance. So its an enormously stacked deck against safety problems coming out and thats what we saw in Vioxx. There was a weak safety signal in the studies submitted to the FDA for approval with only thousands of people involved in those studies and then suddenly 20 million Americans are taking this drug and you see an enormous safety problem. So there is this structural issue that the FDA is not set up currently to be able to spot safety issues. Recent studies by the Government Accountability Office and by the Institute of Medicine two of our most trusted institutions in Government both of them identified very serious problem in the FDA about drug safety that needs to be fixed.
With reference to Vioxx from thousands of to millions of people what was the time lapse there with the difference in the studies for approval? The approval studies went on for around 12 weeks which is not a long time for people with chronic conditions and they will be using these drugs for pain forever like RA or osteoarthritis forever although they were only on the market for 5 years.
Concluding commentary
It is important to leave on a positive note We are in a similar position here as where the womens movement was in the early 60s before the egregious attitudes about women and womens sexuality came to the fore as a legitimate issue. What happened is that women developed a language to say we dont want to be treated as objects we are subjective; we are sanctioned human beings; dont treat us as objects that dont have minds and souls.
I think we are now in another cycle of this objectification of human beings so that we are now all objects of marketing of this medicine. There are two sides to it. The critical side is like our defense department; weve got to know whats going on and how they do it so they dont get into our heads but there is also a very liberating side of this because we are not objects and the truth is that about 70% of our health is determined by how we live our lives and the environment in which we live.
So the final message that I want to leave people with is a message not of defeatism by these corporate influences but a message of empowerment that we can take back responsibility for our own health and we can help our patients and clients take back responsibility empowered autonomy for their own health and well being; so that instead of depression being framed as a biochemical disorder that needs the right drug, we can see most depressions as a symptom that is a consequence of a disordered way of being in the world and we can use it as a teacher to help people to learn how to realign their relationship whether it is with family, job, family origin or memories or trauma or whatever it is but to use the symptoms and the desire to be well in a positive way and empowering way.
I do think we have to talk about these critical and negative issues in order to step above them into true autonomy.
[End of Interview with John Abramson, MD ]
For more information, refer to the book, Overdo$ed America and go to www.overdosedamerica.com You can view the various articles published in newspapers across the country. Interviews arranged by Designs for Health.
FURTHER CONFIRMATION OF THIS TYPE INFORMATION
From the book by Carolyn Dean, MD, physician and author, Death by Medicine comes the following information reported in a book review by Russell Blaylock, MD. (The Blaylock Wellness Report January 2007) Note the mortality figures reported were collected after Overdo$ed America published.
Side effects from drugs are one of the leading dangers to patients. These hazardous side effects do not include allergic reactions or medication dosing errors, but rather the effects of the drugs themselves. Out of the 2.2 million cases of serious adverse reactions to drugs each year, authorities have pinpointed four classes of drugs as being the worst offenders:
Antibiotics: 17 %
Cardiovascular drugs: 17 %
Chemotherapy drugs: 15 %
Analgesics/anti-inflammatory drugs: 15 %
When a drug is presented to the FDA for approval, the drug company submits a series of studies, often performed by the drug companies themselves or farmed out to scientific consultants who are paid by the drug companies. They include human studies on a limited number of volunteers who take the drug to see if it works as expected and if there are side effects. What we have learned over the years and have frequently seen in newspaper headlines is that after a drug is approved and is being taken by millions of people, new problems associated with the drug suddenly appear.
The General Accounting Office (GAO) found that of 198 drugs approved by the FDA from 1976 through 1985, over 50 percent had serious post-approval reactions. Dr. Blaylock reports when he was practicing neurosurgery, he received a drug recall information letter from the FDA at least once a month warning that a new drug was found to have serious complications not previously discovered.
Increasingly, we are seeing that these serious reactions were discovered during clinical trials and were covered up by pharmaceutical manufacturers in order to get FDA approval. In many cases, the pharmaceutical company scientists were the ones presenting the data on the drug in public hearings attended by the unsuspecting public.
Shockingly, FDA scientists were often told by their supervisors not to release the uncovering of serious reactions to the media or public. Why would they do that? Because influential politicians and bureaucrats who receive support from the pharmaceutical companies apply enormous amounts of pressure on scientists within the FDA to play ball, letting them know that their jobs and promotions are at stake.
On the Vioxx Scandal, Dr. Dean reports that whistleblower, Dr. David Graham, an FDA scientist, reported in January 2005 that over 139,000 Americans died or were seriously injured by this drug not 28,000 as officially released by the FDA. The drug was pulled off the market on Sept. 30, 2004. [http://www.mercola.com/2004/dec/18/vioxx.htm]
The real shocker was that memos from Merck indicated that they knew of the connection to heart attack and stroke deaths but covered it up before they submitted the data for approval.
Because Vioxx was critical to their financial success, Merck is still trying to get the drug back in the market. The new push touts the idea that Cox-2 blocking drugs can inhibit cancer growth. While this is true, most cancers are dependent on more than just Cox-2. For that matter, a number of nutrients are more efficient at suppressing the enzymes associated with cancer growth.
Scientists for hire have become such a scandal that some journals require a disclosure of all financial interests to be printed with an article. Not many journals have this policy, which in any case relies solely on the honesty of the authors of the paper. And publication can be extremely important, with ramifications extending far beyond mere academic interest the pharmaceutical companies quickly realized that having an article in a prestigious medical journal was worth its weight in gold. Once a favorable article was published, they would buy reprints and use them to convince the unsuspecting physician that the drug they were promoting was supported by hard scientific evidence.
A former editor of the prestigious New England Journal of Medicine, Dr. Marcia Angell, published an article called Is Academic Medicine for Sale? that concluded that the lines between academic medicine and industry have become blurred. Dr. Richard Horton, editor of the prestigious British medical journal Lancet, appeared before the House of Commons and described the relationship between medical journals and the drug industry as being somewhere between symbiotic and parasitic.
In many cases, scientific papers are in reality ghostwritten by pharmaceutical company scientists for publication in reputable journals. In one instance, a doctor reported that a pharmaceutical company sent him a paper they had written, and asked him to attach his name to the paper. He refused and was later shocked to discover the very same paper in a well-known medical journal with another doctors name on it. This happens often.
Carolyn Dean, MD, a physician and author who helped to uncover the findings said, "I was completely shocked, amazed, and dismayed when I first added up all the statistics on medical death and saw how much allopathic medicine has betrayed us."
Her book, Death by Modern Medicine" and goes far beyond the statistics of deaths due to drugs. It shows how the allopathic medical monopoly has created a Health Care system that fails to encourage good health, especially by prevention. "Death by
Caveat lector: let the reader beware.
So often we reference clinical studies published in respected medical journals to support or refute a finding on a health issue, a drug, a supplement, procedure or medical device. Today, this is a risky practice.
The focus of this report is to alert readers as to why we should view studies with a critical eye (perhaps skeptical) and to create awareness about the bias or spin now permeating our most respected medical journal publications as well as the commercialization of clinical trial material to create demand for pharmaceuticals or medical innovations.
A number of years ago, some of the forward-thinking physicians who expanded their knowledge to include expertise in functional and nutritional medicine issued a caveat about studies. They said, Follow the money trail to examine the bias. This is especially true today. More and more criticism is coming forth from mainstream medicine about the bias of studies and the failure to separate out vested interests.
One such person is a physician who became so alarmed about this data manipulation that he left his practice to write a book to get the word out. This report centers mainly around two hour-long teleconference interviews in mid- and late- 2006 along with book contents with author, John Abramson, MD. This is not new news, but its important to understand that reliance on published studies can offer a false sense of security, correctness, accuracy, safety or honesty.
Most of the conventional medical community is unaware of the bias nor has the time to sort through the data to learn the true facts. Because they rely on pharmaceutical companies for continuing education, they are fed misinformation and biased data that places patient safety in jeopardy.
Dr. Abramson points out that three quarters of published study data in our most trusted and respected medical journals the New England Journal of Medicine, Journal of the American Medical Association and Lancet, are commercially funded; and, says that studies show that when drug trials are commercially funded, the odds are 5.3 times greater that commercially funded studies will conclude that the sponsor drug is the treatment of choice compared to studies of exactly the same drugs that are not commercially sponsored.
ABOUT THE AUTHOR:
The book, Overdo$ed America The Broken Promise of American Medicine (Harper Collins Sept 2004) was written by John Abramson, MD, a Family Practice physician who left his practice to go public to create awareness among healthcare consumers and his own medical profession that the drug companies are funding and manipulating data so that the truth about clinical trials or study results is often obscure and the safety of the public is in jeopardy. What he reveals about his findings is appalling and irrefutable because its right there if one has access and digs deeply enough.
Dr. Abramson is quick to point out full disclosure. After his book published, he has since become a medical advisor to plaintiffs attorneys and often spends every day, all day, six days a week pouring through clinical studies and published FDA reports. The research for the book was done long before his association with plaintiffs attorneys.
Dr. Abramson has expertise in statistical analysis and comments that studies these days are made so intentionally obscure; it is wise to leave interpretations to the experts. He also points out that the abbreviated studies most people can access are inaccurate and highly shortened versions of the original study. Even the articles published in journals are mere fractions in length compared to the original document. He says the Internet is a double-edged sword when it comes to research as sometimes it lets the commercial messages get out further looking as if it is unbiased information.
He worked for two years in Public Health Service as a family doctor in Appalachia and for 20 years in private practice in a small town North of Boston (Hamilton, Mass). Dr. Abramson was a Robert Wood Johnson fellow and is currently a clinical instructor at Harvard Medical School where he teaches primary care to medical students. He served for seven years as Chairman of the Department of Family Practice at the very well known Leahey clinic, twice voted best doctor in his area by readers of the local newspapers and three times, selected by his peers as one of a handful of best family practitioners in Massachusetts.
About his Harvard teaching experience, Dr. Abramson says he thinks it is important to continue to work with medical students who are smart and keep us on our toes and its important to try to communicate to students that the biomedical model of medicine they are learning is necessary to be a good doctor but no way sufficient to be a good doctor. That there is an illusion that all things that are valuable for a doctor to know are scientific and can be observed from a third-person perspective, can be measured so-called objectively and reproducibly, and those are the kinds of things that science can investigated. What happens is the interpersonal or subjective or soulful, or spiritual side of the doctor-patient relationship gets discounted.
The fact is that about 70% of our health has to do with how we live our lives and if doctors and healthcare professionals really want to help patients and clients they have got to have the kind of interpersonal subjective encounter that will allow people to grow beyond the boundaries that are keeping them from achieving better health and thats not a scientific matter, thats an interpersonal matter.
He says, in fact the book I love to teach in a course at Harvard Medical School called Healing & Spirituality and in that the book I use I and Thou by Martin Buber is where the subjectivity of one meets the subjectivity of another person and is the space in which a lot of healing gets done. I would say the majority of healing that good doctors do is in that space. But you also need in your black bag all the science and medications that are available and to know how to use them wisely but its that combination and thats why its so important for me to stay in touch with students.
Right after his book published, Vioxx was withdrawn from the market and he was in demand for public appearances. He has appeared over 60 times on national television including two appearances on the Today Show and is often quoted in the NY and LA times. He lectures frequently to both medical and non-medical audiences discussing the core problems of American medicine and the opportunities to reclaim responsibility for our health. The topic of one of his recent lectures at Harvard Medical School was Healing the Critically Ill Healthcare System.
He is a doctor with integrity; believes in patients first, science first, and believes in truth.
To learn more, I urge reading Overdo$ed America as I can scarcely do the contents justice without reproducing it again right here. Nothing is irrelevant; all is eye-opening, discouraging and disappointing but very enlightening. Once again the trust, safety and well-being of the public the healthcare consumer (and most in the medical profession) -- is slighted in favor of marketing ploys strategized to improve the bottom line of already wealthy corporations.
When asked about why he decided to write the book, Dr. Abramson said he really began to write a book about healing relationships but our medical system is so screwed up that he couldnt quite get to that writing because Rome is burning and weve got other things weve got to talk about that are more important.
He says, Really what turned me from the book about healing relationships to Overdo$ed America which is a critical exploration of how the drug companies and other medical industries is the distorted science that doctors are trained to believe so doctors do things to the patients that are often not effective and sometimes harmful and virtually always expensive.
And what really turned me from the other book was finding the data on the FDA website that the manufacturer of Vioxx and the manufacturer of Celebrex submitted to the FDA the results of the big studies that were published in the New England Journal and JAMA, both studies showing that Vioxx and Celebrex were safer that the older anti-inflammatory drugs.
When I found data on the FDA website that said that was not true and in fact that Vioxx was significantly more dangerous than Aleve and no more effective and cost 15 times as much and the NEJM had published an article that left good doctors reading and believing the article perfectly left them believing that Vioxx was a safer drug and I couldnt convince my colleagues that they were being misled by their trusted journals, I realized I had to write this book. I started to get more and more of a sense of the bias thats in the literature that we docs have been trained to accept as fact, isnt always trustworthy. That let me do the research that led me to Overdo$ed America.
The magnitude of this problem is hard to believe but the best estimates are that between 40 and 60,000 people died from taking Vioxx - thats as many Americans as died in the Vietnam war and as many Japanese as died from the Nagasaki A-bomb. This is an enormous problem. This is one drug. Its an enormous problem there are 24,000 law suits and the score right now is 7 for Merck and 6 for the plaintiffs. It is unclear how this is going to play out whether the cost/benefit ratio for drug companies to cover up and spin the unfavorable results so that doctors are led to believe that drugs are more effective and safer than they really are. The jury is literally out now as to whether this debacle is going to end in a way that the message to drug companies is that it is good business to hide to hide your bad results.
More examples of the turning point that motivated Dr. Abramson to write Overdo$ed America:
EXAMPLES OF OBSCURITY IN STUDIES (quotes and paraphrasing)
As the 90s wore on, you could feel the commercial pressure coming in the journals and it was actually one event that opened my eyes. All of you in clinical practice know how draining it is to focus on your patients and clients needs so I would make a habit of sequestering myself in my office for about 15 minutes at lunch reading the journals and just relaxing.
One day in August 2000, I was reading the NEJM and happened to see an article called Pravastatin and the Risk of Stroke (Pravachol) and the article claimed taking Pravachol lowered the risk of stroke but when I looked a little more deeply, I could see that when the results were adjusted for other risk factors for stroke like diabetes, hypertension and smoking, that the correlation was no longer statistically significant. And when I looked a little further, and saw that the average age in the study was 58 and 5/6th of the people in the study were men, and realized that the average age of a stroke patient is 76 and most stroke patients are women the study was done on the wrong population and for the women in the study who took the Pravachol, they actually had 26% more strokes than the women taking the sugar pills.
For the people over 70 who took Pravachol, they actually had 21% more strokes than the placebo people, so it looked like the article was really upside down. It was in the NE Journal and it was sponsored by a drug company but Id never seen anything that was quite so commercially distorted, so I went to a research expert at one of the Boston Universities and said , look, I was a Robert Johnson Fellow 20 years ago, maybe my skills are rusty and maybe Im missing something and making more of this than should be made of it, do you see anything wrong with my analysis -- that this article seems to be touting the use of a drug when there really isnt any evidence that it will help our patients. He looked and said I dont see anything wrong with your analysis and I suggested writing a paper together we could go a long way in helping to immunize practicing physicians from this growing commercial bias in our research. And he said to me, well, Id rather not get involved; I do a little research for the drug companies and Id rather stay out of this.
And I realized at that moment in 2000 that we trust that the universities are going to be the ultimate backstop to insure the integrity of our knowledge in this case medical knowledge, and whats happening is so much drug money and commercial industry money that the universities are now dependent on both the universities and the researchers within the universities that the universities can no longer play that role so that the researchers are somewhat neutralized in the critical position by the drug company ties, and the universities are and the medical journals are and it became clear that in order to fulfill the mission that brings us all together which is to help people to achieve healthier and happier lives, that the right thing for me to do was start to look at what really was going on with our medical knowledge from the best sources, the most trusted journals and to do the research and to tell the story about how our most trusted sources of information are now being so heavily biased by commercial influence.
Which brings up the question about media manipulation.... I think there is no question that the amount of money coming into the media through drug advertising and other avenues of producing and influencing shows, there is no question that the media is not able to maintain an unbiased point of view. Look at the evening news being so laden with drug ads. At first you may think it is the demographics of the evening news because older people listen at that time and they are thinking more about drugs, but youve got to assume that the amount of time that the drug companies are buying in advertising is giving them some influence over the editorial policy.
Since the book came out (Sept 21, 2004), its been a real trip for me Its a pretty hard-hitting book about the drug industry and it didnt get much press from mainstream press in large part because of the issues just mentioned but a week after the book came out, Vioxx was withdrawn and my publicist at Harper Collins called and said the limousine will be there in 50 minutes and youll do 4 national TV shows out of Boston and then go to the Today Show in NYC. Since then, Ive learned a lot about the media. Fox news will give me a pretty long leash but NPR, not so long and the media issues are more complex than they appear to be.
Question: In the past the FDA has had strict standards for releasing drugs but strong lobbying is continual to reduce the strict standards because of research costs. For now, what type of profits are the pharmaceutical companies enjoying?
Answer: Good question, because we hear it costs $800 million to develop a new pill and there is some argument about the math in that but the bottom line is when all is said and done, all the R& D is paid for, the marketing and other costs are paid, the drug companies are earning 17 or 18% profit on their sales. The average Fortune 500 company earns somewhere around 4-4.5% profit. So net of all the expense including all the research, the drug companies are 3 4 times more profitable than the average other industries in the Fortune 500 group and thats very important to remember because 60% of the drug companies profits come from the United States. The drug companies argue they need to charge the high prices in the US to fund the ongoing investment in research which seems to be a bit exaggerated because they are making 3 4 times the profit of other companies and even with just twice the profit margin of the other Fortune 500 group, I doubt they would cease their research activities and in fact might even increase them.
In the US, price is clearly a problem. We have the highest cost for prescription drugs, and we all know the stories of going to Canada. When writing the book, I asked the spokesperson from Health Canada which is like the FDA if she knew of any instance ever of a counterfeit drug from a Canadian pharmacy imported into the United States and she said she was not aware that it had ever happened. It seems to be a fiction made up by the drug industry to dissuade Americans from importing drugs but more importantly, the importing of price control because the truth is that the biggest importer of drugs is the drug industry itself. They manufacture drugs off shore, import to the US and then send them out to other countries.
So one issue is cost with the drug industry, but the real issue or problem that we all need to focus in on is the quality of the knowledge from the best journals because three quarters of the clinical trials that are published in our best journals the Lancet, NEJM and JAMA are now commercially funded. And the studies show that when drug trials are commercially funded, the odds are 5.3 times greater that commercially funded studies will conclude that the sponsor drug is the treatment of choice compared to studies of exactly the same drugs that are not commercially sponsored.
So, when doctors are reading their best journals, that are the source of their scientific evidence more often than not they are getting infomercial-based medicine, not science-based medicine and I think thats the core problem in American medicine is that medical knowledge, itself, has been transformed from a public good into a commodity.
THE VIOXX/CELEBREX STORY
Another turning point for me was when I found the data on the FDA website that the manufacturers of Celebrex and Vioxx had turned over to the FDA (in Feb 01) (I found it in Aug 01) when I went over this study- Mercks own study the penultimate study of this drug the biggest study and the most authoritative, Mercks own data shows ..
.. that Vioxx is no more effective at relieving arthritis symptoms or pain than Naproxen or Aleve sold OTC. The reason Merck was touting for doctors to prescribe Vioxx was that it is safer on the stomach when in fact what Mercks own data shows is that Vioxx causes more cardiovascular complications heart attacks, blood clots and stroke, than it prevents stomach complications and the real bottom line of Mercks own big study is that if I as a family doctor gave Vioxx instead of Naproxen to 100 patients in a row, over the following year, there would be two and a half serious medical complications because I gave them Vioxx instead of Naproxen when the only reason to give Vioxx was that it was supposedly safer.
So doctors had read the NEJM article which was written by 13 authors all of whom had financial ties to Merck and they came away with the belief that Vioxx was a safer drug because it was gentler on the stomach when in fact the real data that Merck had turned over to the FDA showed that Vioxx was a significantly more dangerous drug than naproxen. The tragedy of this story is that after Merck and the FDA knew that Vioxx was significantly more dangerous than Naproxen, American doctors prescribed $7 billion worth of Vioxx that caused approximately 100,000 heart attacks and deaths after Merck and the FDA knew it was significantly more dangerous than Naproxen.
When I found this on the web and realized the truth about Vioxx was 180 degrees different from what doctors were reading in their best journals it became like an emergency for me to tell the story. So as not to be selective and pick on just Vioxx, let me just talk about Celebrex for a second. First a cost question - It is about a factor of 10 more to use Vioxx rather than Naproxen.
More important than the cost different is the fact that Vioxx was a significantly more dangerous drug and Merck knew it. Merck claimed because the bigger study looked at Vioxx vs. Naproxen and didnt look at Vioxx vs. placebo Merck claimed it wasnt Vioxx that wasnt more dangerous but rather it was Naproxen that prevented heart attacks the way aspirin does except that it would have to be 2.5 times more effective than aspirin to accomplish that a little detail that never got worked out. But Mercks claim was that the evidence did not show that Vioxx was dangerous but that Naproxen was beneficial.
Well, there are two problems with that. One is there was no scientific evidence that that was true and it turns out not to be true and the FDA told them that. The second problem is that the real structure of the study was a head-to-head study with people who had rheumatoid arthritis and the question isnt whether Vioxx is more dangerous than placebo because no doctor would ever give a patient with RA a placebo you are going to give them some medicine. So giving them Naproxen which was at the time, the most widely used anti-inflammatory drug was a good test a so called head-to-head test and Vioxx failed the test. And then Merck tried to do heads I win, tails you lose and they got away with it for a while. Hopefully justice will be served in a way that drug companies will be dissuaded from trying to cover up important science that shows dangers of their drugs in the future well see.
Celebrex is a similar story and Pfizer got lucky because Celebrex is just a useless drug for most people its not a dangerous drug and the article that appeared in the JAMA that led doctors to prescribe billions of dollars of Celebrex concluded that Celebrex used for six months causes fewer stomach complications but the fact of the matter was it was a 12-month study and the whole 12 months showed that Celebrex was no gentler on the stomach and Pfizer (it was Pharmacia at the time) just didnt turn over half of their data to the Journal of the American Medical Association. When the editors found out about this they said things like we are flabbergasted; we were operating on a basis of trust that perhaps wasnt there because the editors of the journals didnt know that it was a 12-month study. They were hoodwinked into thinking it was just a 6-month study and the doctors who were reading a trusted journal were misinformed about the truth of Celebrex.
The problem is that most of the information that is available about drugs and medical devices is coming from research that the companies themselves are sponsoring and the reason why they sponsor that research is to maximize their return on investment to their shareholders. So we have a system where research has been privatized and we dont have the mechanisms to oversee the integrity of that research because more than half the budget of the FDA that oversees drug safety is now paid for directly by the drug companies, and the universities are dependent on the drug companies and the medical journals are dependent on the drug companies. So its like playing a professional football game and having one side bring their own referees. It just doesnt work.
So the question comes up to what extent should the American public and the medical profession be trusting what comes out of agencies like the NIH and the FDA? The GAO accountability office just did a report on the FDA and found the FDA as currently structured is not able to oversee the drug safety of the drugs that Americans are taking.
We have a very serious problem. 20 million people took Vioxx and most took Vioxx after the information was in that it was dangerous so with the drug companies funding more than half of the division of the FDA that oversees drug safety, they are not able to provide an independent, critical oversight of the safety of our drugs. This is a real crisis. It is unclear yet whether legislators will rise to the occasion or whether they too are so addicted to drug money that they are not able to move on this.
Weve got a situation where the information we are getting is produced to serve these ends so the American people . The American doctors are being gullible. We doctors are taught to trust the journals, were taught that whats in the bottom line of the abstract is the evidenced-base medicine that we should be practicing so whats happening is like a perfect symphony its just that the people are being hoodwinked, its not just that there are two lobbyists for every legislator in Washington and they are being inundated with the drug companies version of the truth, and its not just that the doctors when they go to continuing education 70% of their continuing education is funded by the drug companies or that the medical journals are too influenced by the drug companies, its like a symphony so that all works in concert and the problem is that we havent figured out as a society how to create a representation of the public interest.
What is most concerning, even after these drug recalls and deaths from drugs, is that the American public still trusts everything they see and hear from the drug companies on television and the media and the FDA allows this to happen.
[My comment: Just recently (January 31,07), press releases indicate the FDA plans to address concerns over how it handles drug safety including issuing a regular online newsletter summarizing findings about drugs already on the market. We should watch closely how these safety reforms will be supervised and by whom. January 12,07- a press release reported on the FDAs deal with Big Pharma about revisions in user fees that drug companies pay the agency to review their products which will probably raise prices paid for these drug reviews.]
CHOLESTEROL & STATINS
Another key motivating factor to write the book concerns cholesterol and the fact that the National Cholesterol Guidelines keep increasing in strictness.
To set the stage about this situation: In year 2000, Americans were twice as likely to be taking a statin a cholesterol lowering drug as people of equal risk in Europe and of the 25 million people world-wide who were taking a statin, 13 million were in the US. So we were taking twice our share of statins and Americans were getting three times the number of cardiac procedures angioplasty and bypass procedures as were the citizens of the other industrialized countries. So twice as many statins; three times as many procedures. You might say thats evidence of high-quality medicine but the problem is that the death rate for heart disease in the United States ranked 19th among the industrialized countries and we were losing ground to most of them we were not getting better, we were getting worse.
In response to that, instead of saying wait a minute, time out, maybe were approaching heart disease prevention the wrong way and maybe we ought to be looking at the scientific evidence that shows that lifestyle and nutrition are the key factors in heart disease prevention not cholesterol and giving drugs. But instead of going in that direction, we went in exactly the opposite so that in 2001, the third iteration of the Cholesterol Guidelines recommended taking the number of Americans on statins from 13 million to 36 million almost tripling the number of Americans on statins in one fell swoop.
And the problem is that most of the people for whom statins were recommended --23 million people- most of those people did not yet have heart disease because we already understood that statins are beneficial for people who do have heart disease (that came out in the 1993 Guideline) so those 13 million people already had statins recommended for them. So the 23 million people for whom statins became recommended in 2001, didnt have heart disease.
This is such an outrage the guidelines say recent clinical studies show that statins reduce the risk of heart disease in women who dont yet have heart disease and they cite 7 studies. But not a single one of those 7 studies shows evidence to substantiate that statement but there is no way any practicing clinician would ever know that. I found that out because I was doing research for Overdo$ed America and I went through all the footnotes and checked them but the good ole boys just werent telling the truth. And in fact thats section 2 anyone can get them if you just want to Google NCEP or National Cholesterol Education Program youll get this 284 page guideline. Section 2, they make this misrepresentation about the studies that show these drugs are beneficial for women. In section 8 which is the very back of the guidelines they say Special Considerations for Women and say Clinical studies to show that statins are beneficial are generally lacking for women. So they admit they werent telling the truth. And then they go on and say These recommendations for women are based on extrapolation of data from men. Womens blood should be boiling about this issue.
That was 2001. In 1998, we had the HERS study published in JAMA and that showed that women taking combined hormone replacement therapy their bad cholesterol goes down, the good cholesterol goes up and if anything they had more heart disease not less. It is very clear there is a different relationship between cholesterol and heart disease in women than men and the folks who are writing these guidelines knew it.
And the same story for people over 65. They say that recent studies show that aggressive LDL lowering is effective and cite 9 studies to justify that statement and not one of the 9 actually shows it.
(Ref. p 246 of the book) The PROSPER study came out after the 2001 guidelines and is a well-designed study. Its a drug-company sponsored and it is designed fairly. It looks at the effect of lowering cholesterol with a statin drug in people from age 70 to 82. Its a fair mix of men and women and a fair mix of people who did and did not have heart disease. What the PROSPER study found is that people age 70 and over who did not already have heart disease, got no benefit from taking a statin.
There was no significant reduction in the risk of heart disease or mortality compared to the people who took a placebo. But they did have a statistically significant higher incidence of cancer. So that in this study of people ages 70 82, who took a statin short study 3.4 years, in that 4th year of the study, for every 70 people taking a statin drug, there was one extra case of cancer.
So youve got the majority of people who are taking statins, dont have heart disease, there is no evidence they are beneficial for people over 70 for people who dont have heart disease, and there is statistically significant evidence they increase by 25% the risk of cancer.
When there is no randomized control study that shows benefit and we have a drug-company sponsored trial that shows the risk of cancer goes up in an older population, this makes no sense. To be on a national campaign to get people to take more statins in this category, I find sinful. Just plain sinful. Significant evidence of harm and not evidence of benefit.
If you look at the entire mix of these people age 70-82 , it gets even more striking - half already have heart disease and looking at the whole study, there is no reduction in mortality, when these people are treated with a statin. And yet we know from another study done in Europe, if we look at older people who do four healthy habits exercise routinely, eat a healthy, Mediterranean style diet, dont smoke and drink in moderation - the people over 65 who do those four things have a 60% lower death rate than the people who dont do those things. Yet we are spending our time putting them on statins which increases the risk of cancer.
Statin drugs are the most heavily prescribed drugs hands down no matter what age but especially for seniors. [Statins are #1 in prescription drugs]
Is there science to support how and why these are prescribed especially for seniors? Answer there is some science and its really important to look at this. This is an especially important topic. Statins are the biggest drugs used and its enormously important example of whats going on in the United States. We have this huge campaign to lower cholesterol and what has happened is just like a master magician. We have our eye on cholesterol when the real goal is to reduce the risk of heart disease and stroke. Whats happening is that the statin drugs reduce cholesterol very nicely no question but there is not a single randomized controlled trial that shows that these drugs are beneficial for women who dont have heart disease or people over 65. Not a single trial and ¾ of the people who take these drugs dont have heart disease
Now, there are three groups of people men under 65, women under 65 and people over 65. For men, there are shades of gray. Very high risk men get some benefit from statins not as much as they would get from, exercise, nutrition, quitting smoking and controlling stress but there is some benefit. But for women, there is not a single randomized controlled study on file that shows that women who do not have heart disease or diabetes benefit from taking a cholesterol lowering drug. Not a one. And yet millions of American women are on these drugs.
Similarly, for people over 65, there is not a single randomized, controlled trial that shows that people over 65 who dont have heart disease or diabetes would benefit from taking a statin drug. In fact, the one study that does address older people the PROSPER study, published in Lancet in 2002, looked at people over age 70 an equal mix of men and women and equal mix of primary and secondary prevention meaning people who did not yet have heart disease and those who already had heart disease and for the primary prevention patients (who dont have heart disease), statins were not beneficial they did not reduce the incidence of cardiovascular disease or death but statins did increase the risk of cancer by 25% in an older population. So to be recommending statins and weve all heard the phrase, statins should be put in the water they are so good for people over 65 who do not have heart disease when we dont have a randomized control study that shows its beneficial and we have a drug-company-sponsored trial that shows that the risk of cancer goes up by 25% in an older population, it makes no sense.
This reminds me of the situation we were in back in 1989 when hormone replacement therapy (HRT) was being recommended for all post menopausal women and then the study came out showing a 26% increase in the risk of breast cancer in 1989 but this was just dismissed by the authorities by the experts who said were so sure that hormone replacement therapy is beneficial that we are willing to except this small increase in the risk of breast cancer. Well, that small risk of breast cancer led to 200-300,000 unnecessary breast cancers in American women.
At some point, we have got to catch on that when drugs are marketed that dont have a clear benefit and have a clear harm, we have got to take notice of that and stop falling for the hype. In the case of heart disease it is particularly important because we know how to prevent most heart disease; we know that exercising routinely, eating a healthy diet, not smoking, controlling weight, and controlling stress in your life we know that each of those things independently is more important than cholesterol or lowering cholesterol with drugs. So the headline here ought to be We can reduce 83% of the heart disease in women by doing those 5 things. But instead, the headlines are all about cholesterol guidelines and statins as miracle drugs.
We keep working down in the acceptable numbers for cholesterol levels.
HORMONE REPLACEMENT THERAPY
An article had just come out in JAMA in 00 or 01 that showed for women taking combined hormone replacement therapy, the risk of breast cancer went up by 8% for every year they were taking the combined therapy. A woman who had been diagnosed with breast cancer consulted with me and who was on HRT for 12 years so her risk increased 96%. She showed me the article and asked why doctors ignored this clear and present danger. It is an example of how we get into a mindset and we just assume that certain things are beneficial and we dont listen to evidence to the contrary. The hormone replacement story is mostly gone now and if menopausal symptoms dont respond to natural products, Im not opposed to very short term therapy with hormones, but not long-term therapy.
The Hormone story itself tells about or sets the pattern of what we see over and over again and I think it is worth looking at how the marketing evolved in HRT because it is the same with anti-depressants- the same with the cholesterol drugs, and the osteoporosis drugs and wherever you look, its the same game.
Estrogen was approved by the FDA in 1942- brand name Premarin called that because it is made from pregnant mares urine. It was a very effective drug for treating severe menopausal symptoms, hot flashes, etc that were upsetting womens quality of life. In the early 60s, the drug company that owned the patent on Premarin realized the market was limited on women with severe menopausal symptoms and they could sell a lot more drugs if they could convince doctors and female patients that menopause is not a natural process in fact that menopause is essentially an endocrine deficiency. Like diabetes being an deficiency disease of the pancreas not producing enough insulin, menopause was a disease of the ovaries not producing enough estrogen.
Robert Wilson was a gynecologist in NYC who wrote a book called Feminine Forever that was a best seller in the mid-60s that explained this theory to women that menopause was an estrogen-deficiency disease and they could maintain their youth and not suffer the ravages of this disease if they took hormone replacement therapy. Well, it turned out that Dr. Robert Wilson, as you may suspect, was receiving financial support from the drug companies and what they had done was re-frame a normal biological stage of a healthy womans life to a pathological process.
We found out in the 70s that Premarin given to women who had not had a hysterectomy and still had a uterus, increased the risk of uterine cancer, so sales fell off for a little bit but then the drug companies found that adding progesterone to the estrogen would prevent the uterine cancer problem. Sales picked up; we had national guidelines from the American College of Physicians which is the professional society of all the Internal Medicine doctors in 1991 recommending all post-menopausal women who dont have a contraindication should be put on HRT.
Well, it turns out in retrospect, that yes, adding progesterone to HRT did decrease the risk of uterine cancer, but it more than offset that by increasing the risk of breast cancer and the experts never looked to see if the total cancer burden caused by HRT by giving combined hormones would be better or worse and, in fact, was worse.
And, we didnt even learn that until the Million Woman study was published out of the UK. So the pattern we see of getting a drug that was effective, short term, for limited use for symptoms, getting marketed as good for everyone and then realizing there were unintended consequences that were very severe for many women and then coming to the truth of having HRT put into perspective but unfortunately, then we immediately get on the osteoporosis drugs and the statins, the anti-depressants and the cycle starts to repeat itself with different kinds of drugs.
NATURAL PRODUCT STUDIES
What about natural or nutraceuticals products and reliable studies?
There is good news: Unbiased natural product research comes out of Germany and studies on US nutraceuticals is fairly unbiased and are still fairly accurate in medical journals.
Take the Glucosamine study, for instance partially funded by NIH. They looked at Glucosamine for people with mild/moderate and severe knee pain. The result that got all the press was if you looked at the population as a whole, Glucosamine was not effective and Celebrex was but if you looked at the subpopulation of people with moderate or severe knee pain from arthritis, they did much better with the Glucosamine than the Celebrex. that wasnt reported because the study wasnt designed to look at the people with more knee pain.
Results can be biased in favor of the products of the sponsors which is typical with a company researching its own products; it can be biased against the product if it is a competitor or straight medicine looking at alternative medicine and the lines between those is getting blurred more and more as there are hybrid studies that have some public and some private funding and sometimes you only hear about the public side of the funding.
I dont have a black and white answer to say this is a good source of information but we have to a type of connoisseur and develop your own critical faculties as you examine the research.
I would suggest Pubmed to see what type of straight research is out there with the understanding that if it drug-company-sponsored research, they may have a bias against natural products but check the whole range of research but in the end you have to make your own decision.
OSTEOPOROSIS/OSTEOPENIA/OSTEONECROSIS
Remember we dont want to become duped on focusing on a surrogate endpoint. So its not really bone density that were treating what we are trying to do is prevent women from having clinically relevant fractures. When we got involved in bone density alone as the outcome measure, thats when we started to get into trouble.
I spoke to the Association of Healthcare Journalists Annual Meeting in Chicago and shared the podium with a Pulitzer Prize winning journalist and I started to tell the story about osteoporosis, and told the definition of osteoporosis bone density testing came out of a meeting that was organized by the world health organization in 1993 and that is when this thing about T-score of minus 2.5 being osteoporosis and minus 1 being osteopenia was developed and that there were three drug companies involved in funding that conference that came up with the definition that led to so many women having bone density tests and being put on these drugs. She corrected me, she said that had actually gotten these people who wrote the definitions to talk and she said it wasnt at that conference but that it happened in a bar on the back of a napkin that these guys developed this definition.
So whats happened is this: T score is the number of standard deviations that a womans bone density is below the peak skeletal density that a women achieves somewhere around age 28 or 29. So now whats happened is that normal skeletal aging has been reframed as a bone disease so that instead of doing bone density tests, lets say we measured how long it took a woman to run a mile and we found the average woman at age 29 could run a mile in 6 minutes or whatever well if a woman who is age 70 can only run a mile in 13 minutes, does that make her diseased? And the answer is obviously not. She is older and her physical capacities have gone down as part of normal, healthy aging.
So when we do these bone density tests, we are not measuring fracture risk. Only about a sixth of fracture risk is captured in a bone density test. The real problem is from a physiological point of view is that in the areas of our body that are most vulnerable to serious fracture, like hip or vertebra or wrist, the real strength in the bone comes not from the outer cortical bone but from the trabecular lace-like internal structure like buckyballs of calcium of lacey boney material inside the bone so there is an internal structure, so what happens is much of the fracture resistance is due to that internal structure not the outer cortical bone.
When women go through menopause, and the ratio of bone rebsorption and bone laying down changes, so that more bone is rebsorbed what happens is the lacelike structure in the middle of the bone is more metabolically active because there is a greater surface area to mineral content ratio in that lace-like structure so it is more of an active mineral reservoir. When bone is rebsorbed, it gets rebsorbed preferentially from that internal structure and when it gets rebsorbed from that trabecular structure, the footprint is lost the internal structure is lost because it gets rebsorbed which means you cant lay more calcium down when the structure is resorbed and what happens is you end up laying down more calcium in the cortical bone the dense outer core of bone not the internal structure. So when increasing bone density and these drugs clearly do increase bone density, you may not be preventing fractures in proportion to the amount you are increasing bone density.
For example the company that makes Fosamax did a study on women with osteopenia not osteoporosis and they found that treating women with osteoporosis with Fosamax did change their risk of fracture. It increased the risk of hip fracture by 84% which didnt quite hit statistical significance and increased the risk of wrist fracture by 50% that probably did reach statistical significance.
So when we treat women who have osteopenia or pre-osteoporosis with these drugs, we do improve their bone density, but there is not good evidence we reduce their risk of fracture.
The first thing to remember about this whole issue about the risk of osteonecrosis of the jaw with Fosamax is, what are we really doing with these drugs? We are treating a surrogate endpoint that may not be as meaningful a clinical endpoint as we think.
A wonderful example weve all heard about this issue youve got to pay attention to relative risk and absolute risk. We hear that Fosamax reduces the risk of hip fracture by 56% in women in mid sixties who have osteoporosis. You say well 56% reduction in hip fracture thats fantastic; every woman with osteoporosis should certainly be taking Fosamax. But if you look at the absolute risk reduction, what the numbers show is that a woman with osteoporosis in her mid-sixties has a 99.5% chance of getting through the next year without fracturing her hip. And if she takes Fosamax her chance of not fracturing her hip goes up from 99.5 to 99.8% which is a miniscule improvement but a 56% improvement in relative risk.
A long answer to say we can prevent six times more hip fracture if we get women exercising than if we give them osteoporosis drugs.
So the way the osteoporosis drugs have been marketed is almost identical to the pattern we talked about in hormone replacement therapy that this market got broadened to include natural aging of the skeleton and now we find out there is a serious, non-intended consequence hopefully unusual but with women who have dental surgery or get into any bony manipulations of the jaw it turns into a major medical problem.
But it is an unintended consequence for a drug that, in my opinion, is being over sold beyond its clinical usefulness and it just highlights the importance of understanding why we are using drugs and which are really going to be beneficial and that when the drug companies are allowed to produce the knowledge, they are going to spin it in a way that will be advantageous to their goals maybe even more than American womens goals.
ANTI-PSYCHOTIC DRUGS
I spend all day every day sometimes 7 days a week unraveling the spin and Ive got to tell you there isnt a week that goes by when I dont say I cant believe that that happened, I cant believe it went that far."
For example, an issue that Ive been working on for the last couple of weeks in a legal case, is the new anti-psychotic drugs being promoted so heavily and now being use even for children off label although the FDA hasnt approved them for use in children or elderly- like Zyprexa, Rispirdol, Seroquel drugs. [http://www.lawyersandsettlements.com/articles/zyprexa_Off_Label.html]
Spending on anti-psychotic drugs before this new generation came out was Thorazine, Haldol and Meloril in 1994 we spent $1.4 billion on those drugs; last year, we spent over $10 billion on those drugs. There arent any more schizophrenic people, so the spending went up by a factor of like 600% and we were lead to believe that these new drugs were worth the extra money and they literally can cost a hundred times more than the older drugs because they were more effective at treating the symptoms of schizophrenia and they caused fewer side effects.
But it turns out in the largest review article on this looked at 120 studies. 80 of the studies compared the new drug to Haldol. Now the standard of therapy is when treating a patient with Haldol is to give them an anticholinergic drug as well so they dont get the muscle rigidity shakes and the symptoms that go along with those drugs. But out of 82 studies that compared these new drugs to Haldol, only 4 of them gave anticholinergic medication along with the Haldol.
And now weve got a series of studies that show that these new drugs are no better and actually may not be as good as the old drugs. Probably most listeners arent prescribing the antipsychotic drugs but I raise this point just to show that it takes a constant vigilance the nature of which in people who are seeing patients every day dont have the time or the skill to unravel this mess. And I do it full time and Im losing ground, so its really a problem.
And these drugs arent being just used for schizophrenia anymore. The FDA has approved the use of those drugs for schizophrenia and bipolar disorder but if you look on the American Psychiatric Association website, youll see that those drugs are suggested in many other illnesses off label.
So the name of the game - The Hormone Replacement Therapy saga is sort of the grandmother of all of these marketing ploys is to get your drug approved and then convince patients and doctors that a wider/broader market can benefit from them even when the science hasnt been approved by the FDA.
Revisiting the Focus:
Dr. Abramson says, It is very hard now to get unbiased information, which is why I left family practice to write Overdo$ed America because that information just wasnt accessible. Through the book, Ive tried to make information accessible in readable but disciplined language what the statistical arguments are about the corruption of our medical knowledge.
The real core problem when you go all the way upstream is that the medical knowledge that drives our system not the advertising, not the PR messages, not the drug reps coming to doctors but the medical knowledge that is in our most trusted journals has been turned into a commodity; it is produced for its commodity value not for its health value and until, we as a people, understand that the fundamental mission of the drug companies and the other medical industries is to return as much money to their shareholders as they can, and that 80-90% of our clinical research is privately funded by the drug industry and other industries, and the reason why the companies engage in that research is to maximize their return on investment so at best, our medical knowledge grows toward profits the way plants grow toward sunlight. Unfortunately, that typically means growing away from an epidemiologically balanced approach to healthcare. So what weve got is this ever-widening chasm between whats called evidence-based medicine which is really commercially knowledge-based medicine and truly epidemiologically-based medicine which would help people get better.
Expenditures for prescription drugs are increasing 7 times faster than the rate of inflation...(now possibly slowing down just a bit.) Whats driving it is not necessarily that they are better drugs its that the knowledge thats produced much of which wont stand the test of time but it convinces people that there are better drugs and that drives the profit ratio. Its the belief they are better drugs and in many instances it is just like printing counterfeit bills except they are printing counterfeit knowledge and making money off the knowledge.
They stimulate greater demand - go back all the way upstream ¾ of the clinical trials published in our best journals the three most trusted journals in the world NEJM, JAMA and Lancet, are commercially funded and the odds are 5.3 times greater that commercially funded trials will conclude that the sponsors drug is the treatment of choice compared to non-commercially funded studies of exactly the same drugs.
So the evidence thats being produced when doctors think they are practicing evidence-based medicine by reading their most trusted journals more often than not, they are practicing infomercial-based medicine instead. And Im not being critical of the doctors because you cant see it. Often times, there arent clues even the best-trained eye cant see it because the drug companies just dont put the data in that allows for an objective conclusion. And the reason why the data is not there often is not a failure of peer review because the authors arent even allowed to see their own data. Most of the authors of most of these articles that are commercially funded are only allowed to see the data that the drug company parcel out to them. And one would suspect that the drug companies parcel out data that makes their drugs look better. This is a serious problem.
Additionally, the advertisements are a problem and are brilliantly made; you just have to look at them in awe and realize the emotional power of these advertisements how good they are at what they are doing. Unfortunately, they are playing with peoples health.
Ref. p 249 passing of new drugs by FDA - where funding comes from
We would hope the FDA was overseeing the safety of our drugs but they are not able to do that. There are really two major problems. One is new drug approval and the other is overseeing drug safety after approval.
The problem is that the FDA was inadequately funded in the late 80s and in fact, in truth, there were AIDS drugs that were stuck in the FDAs pipeline when people with AIDS were dying. AIDS activists were extremely effective back in the days of Act Up, climbing flag poles, they did a great job of drawing attention to this crisis to the politicians attention. The drug companies took this lemon and made lemonade. They said, we can fix the pipeline we can open up the bottleneck in the FDA we will pay user fees and well help finance the FDA so it has enough money to hire enough officers to approve these new drugs on a shorter timeline. And thus was born the Prescription Drug User Fee Agreement PDUFA effective in 1992 with the drug companies paying user fees directly to the FDA.
Now more than half of the budget of division of the FDA that approves new drugs and oversees drug safety is paid for directly by the drug companies. So in many ways, the FDAs primary client is not the American people, but the drug industry, itself.
There is a structural problem with the safety issues and this is really serious. When drugs are approved, the companies that make the drugs do Phase III trials which are clinical trials of the drug where the company just has to prove the drug is better or significantly more effective than placebo. It doesnt have to be better than any existing drugs, or could be significantly worse, but just better than placebo. So what the companies do is design their pre-approval trials (Phase III) so they have enough people in them for long enough so the trial will show a statistically significant benefit against placebo or better with a 95% certainty thats the statistical threshold thats used.
So when the drug companies statisticians determine how many people need to be in these studies, and how long they need to go on, usually several thousand people, and usually the duration is only 6 12 weeks, so there is enough of a difference between the drug and placebo to be 95% certain that it is effective then the FDA says its effective.
The problem is, that when we look at safety problems in these small, short-term trials also have to hit a 95% certainty level before the FDA will call a drug unsafe. But these trials are not designed to have safety problems (if they exist) before reaching statistical significance. So its an enormously stacked deck against safety problems coming out and thats what we saw in Vioxx. There was a weak safety signal in the studies submitted to the FDA for approval with only thousands of people involved in those studies and then suddenly 20 million Americans are taking this drug and you see an enormous safety problem. So there is this structural issue that the FDA is not set up currently to be able to spot safety issues. Recent studies by the Government Accountability Office and by the Institute of Medicine two of our most trusted institutions in Government both of them identified very serious problem in the FDA about drug safety that needs to be fixed.
With reference to Vioxx from thousands of to millions of people what was the time lapse there with the difference in the studies for approval? The approval studies went on for around 12 weeks which is not a long time for people with chronic conditions and they will be using these drugs for pain forever like RA or osteoarthritis forever although they were only on the market for 5 years.
Concluding commentary
It is important to leave on a positive note We are in a similar position here as where the womens movement was in the early 60s before the egregious attitudes about women and womens sexuality came to the fore as a legitimate issue. What happened is that women developed a language to say we dont want to be treated as objects we are subjective; we are sanctioned human beings; dont treat us as objects that dont have minds and souls.
I think we are now in another cycle of this objectification of human beings so that we are now all objects of marketing of this medicine. There are two sides to it. The critical side is like our defense department; weve got to know whats going on and how they do it so they dont get into our heads but there is also a very liberating side of this because we are not objects and the truth is that about 70% of our health is determined by how we live our lives and the environment in which we live.
So the final message that I want to leave people with is a message not of defeatism by these corporate influences but a message of empowerment that we can take back responsibility for our own health and we can help our patients and clients take back responsibility empowered autonomy for their own health and well being; so that instead of depression being framed as a biochemical disorder that needs the right drug, we can see most depressions as a symptom that is a consequence of a disordered way of being in the world and we can use it as a teacher to help people to learn how to realign their relationship whether it is with family, job, family origin or memories or trauma or whatever it is but to use the symptoms and the desire to be well in a positive way and empowering way.
I do think we have to talk about these critical and negative issues in order to step above them into true autonomy.
[End of Interview with John Abramson, MD ]
For more information, refer to the book, Overdo$ed America and go to www.overdosedamerica.com You can view the various articles published in newspapers across the country. Interviews arranged by Designs for Health.
FURTHER CONFIRMATION OF THIS TYPE INFORMATION
From the book by Carolyn Dean, MD, physician and author, Death by Medicine comes the following information reported in a book review by Russell Blaylock, MD. (The Blaylock Wellness Report January 2007) Note the mortality figures reported were collected after Overdo$ed America published.
Side effects from drugs are one of the leading dangers to patients. These hazardous side effects do not include allergic reactions or medication dosing errors, but rather the effects of the drugs themselves. Out of the 2.2 million cases of serious adverse reactions to drugs each year, authorities have pinpointed four classes of drugs as being the worst offenders:
Antibiotics: 17 %
Cardiovascular drugs: 17 %
Chemotherapy drugs: 15 %
Analgesics/anti-inflammatory drugs: 15 %
When a drug is presented to the FDA for approval, the drug company submits a series of studies, often performed by the drug companies themselves or farmed out to scientific consultants who are paid by the drug companies. They include human studies on a limited number of volunteers who take the drug to see if it works as expected and if there are side effects. What we have learned over the years and have frequently seen in newspaper headlines is that after a drug is approved and is being taken by millions of people, new problems associated with the drug suddenly appear.
The General Accounting Office (GAO) found that of 198 drugs approved by the FDA from 1976 through 1985, over 50 percent had serious post-approval reactions. Dr. Blaylock reports when he was practicing neurosurgery, he received a drug recall information letter from the FDA at least once a month warning that a new drug was found to have serious complications not previously discovered.
Increasingly, we are seeing that these serious reactions were discovered during clinical trials and were covered up by pharmaceutical manufacturers in order to get FDA approval. In many cases, the pharmaceutical company scientists were the ones presenting the data on the drug in public hearings attended by the unsuspecting public.
Shockingly, FDA scientists were often told by their supervisors not to release the uncovering of serious reactions to the media or public. Why would they do that? Because influential politicians and bureaucrats who receive support from the pharmaceutical companies apply enormous amounts of pressure on scientists within the FDA to play ball, letting them know that their jobs and promotions are at stake.
On the Vioxx Scandal, Dr. Dean reports that whistleblower, Dr. David Graham, an FDA scientist, reported in January 2005 that over 139,000 Americans died or were seriously injured by this drug not 28,000 as officially released by the FDA. The drug was pulled off the market on Sept. 30, 2004. [http://www.mercola.com/2004/dec/18/vioxx.htm]
The real shocker was that memos from Merck indicated that they knew of the connection to heart attack and stroke deaths but covered it up before they submitted the data for approval.
Because Vioxx was critical to their financial success, Merck is still trying to get the drug back in the market. The new push touts the idea that Cox-2 blocking drugs can inhibit cancer growth. While this is true, most cancers are dependent on more than just Cox-2. For that matter, a number of nutrients are more efficient at suppressing the enzymes associated with cancer growth.
Scientists for hire have become such a scandal that some journals require a disclosure of all financial interests to be printed with an article. Not many journals have this policy, which in any case relies solely on the honesty of the authors of the paper. And publication can be extremely important, with ramifications extending far beyond mere academic interest the pharmaceutical companies quickly realized that having an article in a prestigious medical journal was worth its weight in gold. Once a favorable article was published, they would buy reprints and use them to convince the unsuspecting physician that the drug they were promoting was supported by hard scientific evidence.
A former editor of the prestigious New England Journal of Medicine, Dr. Marcia Angell, published an article called Is Academic Medicine for Sale? that concluded that the lines between academic medicine and industry have become blurred. Dr. Richard Horton, editor of the prestigious British medical journal Lancet, appeared before the House of Commons and described the relationship between medical journals and the drug industry as being somewhere between symbiotic and parasitic.
In many cases, scientific papers are in reality ghostwritten by pharmaceutical company scientists for publication in reputable journals. In one instance, a doctor reported that a pharmaceutical company sent him a paper they had written, and asked him to attach his name to the paper. He refused and was later shocked to discover the very same paper in a well-known medical journal with another doctors name on it. This happens often.
Carolyn Dean, MD, a physician and author who helped to uncover the findings said, "I was completely shocked, amazed, and dismayed when I first added up all the statistics on medical death and saw how much allopathic medicine has betrayed us."
Her book, Death by Modern Medicine" and goes far beyond the statistics of deaths due to drugs. It shows how the allopathic medical monopoly has created a Health Care system that fails to encourage good health, especially by prevention. "Death by
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Laura
Re: Caveat lector: Reliance on Published Studies is Risky February 05, 2007 12:42PM |
Jackie,
Thanks so much for the time and effort you put into this. Good information, and it makes me realize that I need to do more than subscribe to "Best Pills, Worst Pills" to stay educated. I see that Amazon is offering Dr. Abramson's book along with Marcia Angell's book about "Drug Companies and the Way They Deceive Us"--think those will be my next purchase.
Thanks so much.
Laura
Thanks so much for the time and effort you put into this. Good information, and it makes me realize that I need to do more than subscribe to "Best Pills, Worst Pills" to stay educated. I see that Amazon is offering Dr. Abramson's book along with Marcia Angell's book about "Drug Companies and the Way They Deceive Us"--think those will be my next purchase.
Thanks so much.
Laura
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SharonB
Re: Caveat lector: Reliance on Published Studies is Risky February 05, 2007 12:42PM |
Jackie,
Excellent interview! The information provided by you and Dr. John Abramson may very well be life saving. I plan to buy his book and may even get extras as gifts for family and friends. I also read the reviews Dr. Abramson's book received on Amazon...impressive! It's important to have someone like the good doctor on our side. Thank you, Jackie.
SharonB
Excellent interview! The information provided by you and Dr. John Abramson may very well be life saving. I plan to buy his book and may even get extras as gifts for family and friends. I also read the reviews Dr. Abramson's book received on Amazon...impressive! It's important to have someone like the good doctor on our side. Thank you, Jackie.
SharonB
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