We often say in a "PC" way that a patient who refuses to take medicines as precribed by a doctor is "Pharmacologically Autonomous", but that does not get to the heart of the problem of restoring him/her to health. It is often stated that if patients were better educated about the nature of their (chronic) disease, or their treatment, then compliance would increase, and we would have a healthier society. Nothing that I have seen in over 35 years of practice substantiates that belief:
1) When I am attending and I poll the medical students and residents, fewer than 50% of them have consistently taken the full course of antibiotics (e.g. 10 days for a strep throat) that was prescribed for them. If patients who are in the medical system and presumably have the most complete understanding of their disease and treatment are not compliant, why should be expect that non-doctors would react any differently? (I won't even mention the large numbers of chest surgeons who operated on lung cancer patients and still smoked cigarettes.)
2) Most patients believe, either consciously or subconsciously, that the less medicine they take the less sick they are. That is precisely why although we know than penicillin will cure a strep throat in 7 days we prescribe a 10 day course of the antibiotic. Many patients will stop as soon as they feel better. In fact, a study done about 20 years ago at Columbia's Vanderbilt Clinic demonstrated, by having the mothers bring in the bottle of penicillin at the next clinic visit, that fewer than 80% of them completed the indicated course for their children.
3) Over the years I have told many diabetic patients that if they lose a certain # of pounds they can recover their normal insulin-glucose axis, and no longer be diabetic. The believe it, but even with support, going to a nutritionist, or going weekly to a diabetic clinic, none of them can achieve and sustain a weight loss. The only method demonstrated to cause sustained weight loss and thus reverse diabetes is stomach banding or stomach bypass surgery. This is at least 90% successful. And remember that stomach banding does not permanently change a patient's eating habits, but only the amount that can be consumed at a single sitting and within one hour's time. Occasionally, when stomach bypass surgery had to be reversed because of developing liver failure, the patient would put back on the 50 or 100 pounds that was lost.
4) The only patients who consistently lose weight (besides anorectics, bulemics and purgers) are some overweight men after their first heart attack. This makes instant believers of them of the health benefits of weight loss. Many of them eat so much fish that I have to check their blood mercury levels every six month.
5) It isn't that patients don't KNOW about healthier actions, they just don't act on their knowledge. Some of this may be wishful thinking, some may be people's refusal to acknowledge their own mortality (Freud stated that it is impossible for the ego to envision its own non-existence), and some is due to the fact that we evolved by reacting to immediate dangers, and not to those postulated to be off in the distant future. Many if not all smokers know that smoking is dangerous (when we were teen-agers we called them "coffin nails") but no one believes that the cigarette they are smoking at this present moment will kill them.
6) People know from experience how much better they feel after exercising, no matter how tired they thought they were, yet once they get out of the habit, it is very difficult for them to get back into the exercise rhythm. I woke up one day in my dorm room and said to myself "I'm not smoking any more cigarettes", and to this day I have no idea why I stopped. People know they should use seat belts when driving, but the knowledge alone was not sufficient----but when the state started giving out tickets for non-compliance the rate of seat-belting went up sharply.
7) Some overweight people decide one morning to go on a diet, start eating less, and lose weight. But none of them (usually) can tell you why they made the decision that particular A.M. rather than one week or one month or one year previously. The first time a man goes from a size 36 to size 38 belt, or a woman from a size 6 to a size 8 dress, it is obvious to each and every one of them that they have gained at least 10 pounds, but almost none of them decides immediately to lose the weight. We know from various experiments in big-city schools that if you offer students money to improve their grades, many of them will get higher grades. Perhaps the state should give every citizen $10 for each pound that is taken off and kept off for one year. I bet we would see a lot of weight loss!
8) And let us not forget individual health belief systems. Some people feel that vaccines are dangerous and unnecessary, some people refuse to get mammograms or colonoscopies, some people have unprotected sex,
some people don't believe in sleeping pills, some don't believe in anti-depressants, some believe a daily bowel movement is necessary for good health, and so on. Some patients may be covered by their spouse's drug plan, but need to be on a drug that the spouse does not "believe" in, so they purchase the prescription with their own money and hide the bottle. Some of my diabetic patients will only take pills for their elevated glucose and absolutely refuse to take insulin-----so long as they don't take insulin they can tell themselves that they are not truly diabetics, but only have a "sugar problem".
9) In summary, many people know what is "good" for them, so to speak, but refuse to act on their knowledge. Thus we have dead jaywalkers, drunken driving accidents, people who drown while swimming alone, campers who get mauled by a bear while trying to feed it, and people who get severely hung over more than once or twice. No one likes being told what to do, even if it is "for their own good". So all recommendations of prescriptions, actions and tests by a doctor to his/her patients is really a series of negotiations, because you first have to talk to the patient long enough to understand his/her model of disease and treatment, or else none of your recommendations will be followed.
Sunday, October 30, 2011
Sunday, October 16, 2011
Dietary Supplements (Vitamins and Minerals): Killers or Life Extenders?
This blog was triggered by an article in a medical journal and the subsequent media coverage. The article is "Dietary Supplements and Mortality Rate in Older Women, in Archives of Internal Medicine, Vol 171, (#18), Oct 10, 2011, pp 1625-1633. I also refer my readers to a blog I published in 2009 entitled "Nutrition".
Let us begin with some basic definitions. A vitamin is a molecule that is necessary/essential for human life, but which our body cannot synthesize. For instance, neither humans nor guinea pigs have the enzymes necessary to synthesize ascorbic acid, aka Vitamin C, but all other animals can synthesize it. So only we and the guinea pig can get scurvy. The vitamins we need are present in our food if we eat a "well-balanced" diet, by definition, This includes Vitamins A, the whole B complex (1,2,6,12), Vitamin C,D, E, and folic acid., There are also eight amino acids essential for the synthesis of human protein, three essential fatty acids, and a host of elements (iron, iodine, calcium, cobalt, magnesium,copper, zinc, selenium,...) that we must ingest. If we ingest too little of the vitamin we get ill (scurvy, night blindness, pernicious anemia, iron-deficiency anemia, ...). The question is if too much of a vitamin or a supplement is injurious to our health. Very few studies have addressed this question, and our beliefs are not a substitute for clinical studies. Also, it would not be ethical to deliberately overdose human subjects, so we are left with experiments of nature, or retrospective diet histories.
We do know that an excess of the fat-soluble vitamins (A,D, and E) is injurious to our health.Cod liver oil contains vitamin D and a daily spoonful is probably OK, but eating a polar bear's liver has given Eskimos vitamin D toxicity and even caused death. We also cannot generalize from animal studies: chromium and selenium can help control a lab rat's sugar level but there is no evidence than these elements can be used to treat or prevent diabetes in humans. We must always remember that ALL chemical substances are poisonous; it is only a matter of dose (digitalis, opium, water, salt, iodine, etc.).
Let me first remind my readers that only animal cells contain Vitamin B-12 (cyanocobalamin) because only animal DNA requires Vitamin B-12 as a cofactor (along with folic acid) for its enzymatic synthesis. Vegetable DNA does not require Vitamin B-12 for its synthesis, and therefore no vegetable cells contain this vitamin. In other words, if you ate only vegetables (and this excludes fish) you would die from Vitamin B-12 deficiency after first suffering irreversible brain and peripheral nervous system damage. Vegetarians must take B-12 supplements, which may be synthesized in a lab, since the human body's enzymes have no way of determining the source of the Vitamin B-12 that it needs and uses.
We also know from "experiments of nature", i.e. genetic/enzymatic defects that prevent the normal clearing of minerals, that an accumulation of certain elements can cause disease and death. For instance: excess iron (hemochromatosis), excess copper (Wilson's Disease), etc. The question that remains is whether an excessive intake of water-soluble vitamins, which are excreted unchanged in our urine, is beneficial or detrimental to human health. By excess, I mean a daily dose much greater than that needed to prevent vitamin-deficient disease. Based on the problems caused by too much iron or too much copper or too much iodine (affects the thyroid gland) it is probably true that an excess of any mineral element in the diet can be injurious (lead being the most notable, especially for the developing nervous system in children).
It is difficult to find any study that conclusively demonstrates than a dietary excess of any vitamin is either beneficial or injurious. We do know that it gives the user the most expensive urine in the world. The reason for the lack of good studies is that the human generation cycle is 25 years, and there are no good 25-year vitamin studies (not counting Framingham and beta-carotene) with a good control (i.e. no excess vitamin intake) group. But it seems to me that if you want to make a change in the human diet, it is up to the proposer of the change to demonstrate that no harm will come from adopting the change. Too often we assume that any intervention that is not obviously immediately dangerous will prove to be beneficial in the long run. In my opinion (and I emphasize opinion) everything we ingest is potentially poisonous, so we should probably never eat the same meal two days in a row (and certainly not eat tuna fish more than twice a week) so as to distribute and minimize the effect of any dietary poisons. And except for a daily aspirin in some people, and a daily glass of wine in everyone, it is probably incorrect to assume that any substantial change in our diet will prove to be beneficial and overcome the result of millions of years of evolutionary pressure on our body's chemistry.
And let's remember again that the theory that oxidative stress contributed to the shortening of life and the induction of cancers was tested by giving the anti-oxidants Vitamin E to many American heart disease patients and giving beta-carotene to male Finnish smokers (who have the highest rates of heart attacks and lung cancer in the world). The patients given daily high doses of Vitamin E had an increased rate of heart attacks. The Finnish smokers given beta carotene had a higher rate of lung cancer. And let's not forget taht the Japanese, with their "healthy" fish and vegetable diet have such a high rate of stomach cancer that just as we recommend colonoscopies at age 50 to screen for colon cancer, the Japanese start upper endoscopies at age 40 to look for stomach cancer.
Let us begin with some basic definitions. A vitamin is a molecule that is necessary/essential for human life, but which our body cannot synthesize. For instance, neither humans nor guinea pigs have the enzymes necessary to synthesize ascorbic acid, aka Vitamin C, but all other animals can synthesize it. So only we and the guinea pig can get scurvy. The vitamins we need are present in our food if we eat a "well-balanced" diet, by definition, This includes Vitamins A, the whole B complex (1,2,6,12), Vitamin C,D, E, and folic acid., There are also eight amino acids essential for the synthesis of human protein, three essential fatty acids, and a host of elements (iron, iodine, calcium, cobalt, magnesium,copper, zinc, selenium,...) that we must ingest. If we ingest too little of the vitamin we get ill (scurvy, night blindness, pernicious anemia, iron-deficiency anemia, ...). The question is if too much of a vitamin or a supplement is injurious to our health. Very few studies have addressed this question, and our beliefs are not a substitute for clinical studies. Also, it would not be ethical to deliberately overdose human subjects, so we are left with experiments of nature, or retrospective diet histories.
We do know that an excess of the fat-soluble vitamins (A,D, and E) is injurious to our health.Cod liver oil contains vitamin D and a daily spoonful is probably OK, but eating a polar bear's liver has given Eskimos vitamin D toxicity and even caused death. We also cannot generalize from animal studies: chromium and selenium can help control a lab rat's sugar level but there is no evidence than these elements can be used to treat or prevent diabetes in humans. We must always remember that ALL chemical substances are poisonous; it is only a matter of dose (digitalis, opium, water, salt, iodine, etc.).
Let me first remind my readers that only animal cells contain Vitamin B-12 (cyanocobalamin) because only animal DNA requires Vitamin B-12 as a cofactor (along with folic acid) for its enzymatic synthesis. Vegetable DNA does not require Vitamin B-12 for its synthesis, and therefore no vegetable cells contain this vitamin. In other words, if you ate only vegetables (and this excludes fish) you would die from Vitamin B-12 deficiency after first suffering irreversible brain and peripheral nervous system damage. Vegetarians must take B-12 supplements, which may be synthesized in a lab, since the human body's enzymes have no way of determining the source of the Vitamin B-12 that it needs and uses.
We also know from "experiments of nature", i.e. genetic/enzymatic defects that prevent the normal clearing of minerals, that an accumulation of certain elements can cause disease and death. For instance: excess iron (hemochromatosis), excess copper (Wilson's Disease), etc. The question that remains is whether an excessive intake of water-soluble vitamins, which are excreted unchanged in our urine, is beneficial or detrimental to human health. By excess, I mean a daily dose much greater than that needed to prevent vitamin-deficient disease. Based on the problems caused by too much iron or too much copper or too much iodine (affects the thyroid gland) it is probably true that an excess of any mineral element in the diet can be injurious (lead being the most notable, especially for the developing nervous system in children).
It is difficult to find any study that conclusively demonstrates than a dietary excess of any vitamin is either beneficial or injurious. We do know that it gives the user the most expensive urine in the world. The reason for the lack of good studies is that the human generation cycle is 25 years, and there are no good 25-year vitamin studies (not counting Framingham and beta-carotene) with a good control (i.e. no excess vitamin intake) group. But it seems to me that if you want to make a change in the human diet, it is up to the proposer of the change to demonstrate that no harm will come from adopting the change. Too often we assume that any intervention that is not obviously immediately dangerous will prove to be beneficial in the long run. In my opinion (and I emphasize opinion) everything we ingest is potentially poisonous, so we should probably never eat the same meal two days in a row (and certainly not eat tuna fish more than twice a week) so as to distribute and minimize the effect of any dietary poisons. And except for a daily aspirin in some people, and a daily glass of wine in everyone, it is probably incorrect to assume that any substantial change in our diet will prove to be beneficial and overcome the result of millions of years of evolutionary pressure on our body's chemistry.
And let's remember again that the theory that oxidative stress contributed to the shortening of life and the induction of cancers was tested by giving the anti-oxidants Vitamin E to many American heart disease patients and giving beta-carotene to male Finnish smokers (who have the highest rates of heart attacks and lung cancer in the world). The patients given daily high doses of Vitamin E had an increased rate of heart attacks. The Finnish smokers given beta carotene had a higher rate of lung cancer. And let's not forget taht the Japanese, with their "healthy" fish and vegetable diet have such a high rate of stomach cancer that just as we recommend colonoscopies at age 50 to screen for colon cancer, the Japanese start upper endoscopies at age 40 to look for stomach cancer.
Tuesday, October 11, 2011
To PSA or Not To PSA, That is the Question
In view of the recent hooraw over whether or not testing for and treating prostate cancer saves lives, I feel I should re-visit this subject, which I first discussed in my blog of May 15, 2009. I want to begin by emphasizing once again, speaking as a trained scientist, that in any given field what counts is what we can show to be true by experiment, and not what we can deduce or think should be true (with Einstein's Theory of General Relativity being a notable exception, but even that theory was based upon an experimental result, namely the equivalence of inertial and gravitational mess, as first shown by Galileo). It also doesn't matter what we would like to be true, because Mother Nature's rules are independent of our beliefs.
Some of the examples of medical facts and treatments that we thought should be true or benefit patients but were shown to be false or harmful or not proven when subjected to clinical testing are:
1) If a patient has calcium oxalate kidney stones then the proper treatment is toDEcrease the amount of calcium in the diet.
2) Beta-blockers should never be used in a patient who is in heart failure.
3) Everyone needs 8 glasses of water or fluid a day for good health.
4) Everyone needs at least one bowel movement a day.
5) If a patient is ill, bleeding with leeches will generally make him/her better.
6) An hour of sleep before midnight is worth two hours after.
7) If you go swimming right after eating you will develop an abdominal cramp and drown.
8) Vitamin E, because of its anti-oxidant properties, prevents heart attacks.
9) Beta-carotene, because of its anti-oxidant properties, protects smokers from lung cancer.
10) Mammograms taken between the ages of 40 and 50 saves lives.
11) The optimum time interval between complete physical exams is one year.
12) The optimum time interval between colonoscopies is 10 years.
13) The optimum time interval between mammograms is one year.
14) A drink of alcohol a day cannot possibly be good for you.
15) Daily doses of saw palmetto help treat an enlarged prostsate.
16) Daily doses of gingko balboa help prevent Alzheimer's Disease.
I could easily add another 10 to 20 pseudofacts to the above list. Now let us look at the question of PSA testing as well as the treatment of prostate cancer. Before asking whether or not measuring the PSA saves lives, we first have to determine if treating prostate cancer saves lives. As of today, there is absolutely no evidence that it does. It may seem counterintuitive that this is so, but the fact is that the majority of men die WITH prostate cancer, and not OF prostate cancer. Roughly speaking, the percentage of men who have prostate cancer at autopsy is equal to their age at death: 70% of men at age 70 have microfoci of prostate cancer, etc. Much as we would like to believe that detecting prostate cancer early and treating it will save lives, there is absolutely no evidence that this is so.
There have been many review articles coming to this conclusion, and you can check PubMed, the abstract archive of the National Institutes of Health for references. So why do people do the PSA, or take treatment if a prostate biopsy shows prostate cancer? The answers are many and varied, and all are ultimately the result of individual decisions by individual patients. Some of the reasons are:
1) Some people cannot tolerate the thought of having cancer within their bodies.
2) Some wives cannot tolerate the thought that their husband is walking around with cancer.
3) Some men believe that treatment of prostate cancer will save their lives.
Very few men are told that most prostate cancers detected on biopsy will not spread and kill them. Very few men are told of the possible lingering (6 months to 2 years) or permanent symptoms of radiation proctitis that can result (chronic bloody or non-bloody diarrhea). Many men don't fully understand the implications of the fact that 30% of treated men will develop urinary incontinence (and need to wear a diaper) or be unable to mount or maintain and erection (even with the help of Viagra), or both.
Since a physician's first duty to his/her patient is to "do no harm", I lay out all the above info to my patients, and if asked, I tell them that I never have taken a PSA test and would never treat prostate cancer in myself. However, if a patient decides on treatment, I urge him to consult with both a urologic surgeon and a radiation oncologist to listen to the pros and cons of each procedure, and then to consult with a medical oncologist for an overall view. I also suggest that he not discuss his decision with any friends who have been treated in order to avoid impassioned but not dispassionate arguments and lectures. And then I remind him that it is his body, that he is the patient and must make the final decision, and not to do any treatment or non-treatment that he does not fully agree with.
Some of the examples of medical facts and treatments that we thought should be true or benefit patients but were shown to be false or harmful or not proven when subjected to clinical testing are:
1) If a patient has calcium oxalate kidney stones then the proper treatment is toDEcrease the amount of calcium in the diet.
2) Beta-blockers should never be used in a patient who is in heart failure.
3) Everyone needs 8 glasses of water or fluid a day for good health.
4) Everyone needs at least one bowel movement a day.
5) If a patient is ill, bleeding with leeches will generally make him/her better.
6) An hour of sleep before midnight is worth two hours after.
7) If you go swimming right after eating you will develop an abdominal cramp and drown.
8) Vitamin E, because of its anti-oxidant properties, prevents heart attacks.
9) Beta-carotene, because of its anti-oxidant properties, protects smokers from lung cancer.
10) Mammograms taken between the ages of 40 and 50 saves lives.
11) The optimum time interval between complete physical exams is one year.
12) The optimum time interval between colonoscopies is 10 years.
13) The optimum time interval between mammograms is one year.
14) A drink of alcohol a day cannot possibly be good for you.
15) Daily doses of saw palmetto help treat an enlarged prostsate.
16) Daily doses of gingko balboa help prevent Alzheimer's Disease.
I could easily add another 10 to 20 pseudofacts to the above list. Now let us look at the question of PSA testing as well as the treatment of prostate cancer. Before asking whether or not measuring the PSA saves lives, we first have to determine if treating prostate cancer saves lives. As of today, there is absolutely no evidence that it does. It may seem counterintuitive that this is so, but the fact is that the majority of men die WITH prostate cancer, and not OF prostate cancer. Roughly speaking, the percentage of men who have prostate cancer at autopsy is equal to their age at death: 70% of men at age 70 have microfoci of prostate cancer, etc. Much as we would like to believe that detecting prostate cancer early and treating it will save lives, there is absolutely no evidence that this is so.
There have been many review articles coming to this conclusion, and you can check PubMed, the abstract archive of the National Institutes of Health for references. So why do people do the PSA, or take treatment if a prostate biopsy shows prostate cancer? The answers are many and varied, and all are ultimately the result of individual decisions by individual patients. Some of the reasons are:
1) Some people cannot tolerate the thought of having cancer within their bodies.
2) Some wives cannot tolerate the thought that their husband is walking around with cancer.
3) Some men believe that treatment of prostate cancer will save their lives.
Very few men are told that most prostate cancers detected on biopsy will not spread and kill them. Very few men are told of the possible lingering (6 months to 2 years) or permanent symptoms of radiation proctitis that can result (chronic bloody or non-bloody diarrhea). Many men don't fully understand the implications of the fact that 30% of treated men will develop urinary incontinence (and need to wear a diaper) or be unable to mount or maintain and erection (even with the help of Viagra), or both.
Since a physician's first duty to his/her patient is to "do no harm", I lay out all the above info to my patients, and if asked, I tell them that I never have taken a PSA test and would never treat prostate cancer in myself. However, if a patient decides on treatment, I urge him to consult with both a urologic surgeon and a radiation oncologist to listen to the pros and cons of each procedure, and then to consult with a medical oncologist for an overall view. I also suggest that he not discuss his decision with any friends who have been treated in order to avoid impassioned but not dispassionate arguments and lectures. And then I remind him that it is his body, that he is the patient and must make the final decision, and not to do any treatment or non-treatment that he does not fully agree with.
Sunday, October 9, 2011
Why You Can't Get The Medicines You Need, Especially Generics at a Reasonable Price
The capitalist profit system usually works, except in a few cases. The courts have held, for instance, that you cannot charge an outrageous price for a drink of water for a man dying of thirst or for a crust of bread for a starving man. Similarly, there are laws against ticket scalping, and no matter what the underlying economic theory (communist, capitalist, libertarian) there are always subsidies given to farmers to avoid a famine, which subsidies are NEVER provided for or explained in the original theory, but is rather based upon thousands of years of experience with farmers, food crops and famines. That is probably why there has never been a killing famine in a democracy---the voters would never stand for it.
When it comes to drug prices, however, the economic and politico-legal landscape becomes murkier. About 10 years ago, Lilly and Lederle got so tired of being sued by parents who claimed that their children were permanently damaged by the MMR (measles, mumps, rubella) vaccine, that Lilly threatened to institute the default position that only Lederle of Canada would manufacture the MMR vaccine, and it would never be sold in the USA so as to avoid tort claims of damage in the US courts. The US government, faced with this possibility, passed a law that the government would reimburse any parents who sued and could prove a case.
Similarly, the morning sickness of pregnancy with horrendous vomiting and secondary severe dehydration can prove fatal, as it did to the novelist Charlotte Bronte, sister of Emily. Merrill-Dow had a drug that treated and reduced the severity of morning sickness, called Bendectin. Now historically one out of 2500 children born has some sort of birth defect. One year, seven of the parents of such children sued Merrill-Dow, claiming that the Bendectin the pregnant mothers had taken had caused the birth defect. Merrill-Dow won all seven cases, but the legal fees far exceeded their profit from making Bendectin, so they ceased production. Their final words on the subject were: "If you are pregnant and suffer from morning sickness, call a malpractice lawyer".
Now we come to generic drugs. When a new drug is patented, there are virtually no limits on the price that the manufacturing pharmaceutical company can charge, and it is impossible to calculate what a "fair" price should be, after you try to amortize the years of studies needed to produce the drug as well as those drugs that were tested and never made it to market. It's somewhat similar to the fact that most movies never show a "net" profit, so a smart actor/producer takes a percentage of the gross, which is readily measured. If I am not mistaken, the film company that produced "The Producers" claimed that there was no net profit, and Mel Brooks had to sue them for his share of the net profits. (Caveat: if it was not "The Producers", it was a similarly successful film that generated huge grosses.) In order to encourage the production of a generic substitute, the US government will grant a six month exclusive license to the first generic company to bring a generic product to market when the patent on the brand name wears off.
Now what do the brand name drug manufacturers do when the patent for the parent, patented drug nears an end? The simplest practice was done by Roche, who put a hollow "v" in their brand name Valium, so patients could complain to their doctors that the generic valium tablet looked different, which it had to, by law. Similarly, the makers of Ativan converted the basic shape to a pentagon, again uniquely and memorably different in appearance from the generic lorazepam. Another solution is to take Prilosec, which is a mixture of right-handed and left-handed molecules (and there IS a difference in their chemical action) and start to make only (purple) Nexium, which is the isolated right-handed form of the basic patent and therefore is entitled to a new patent. Similarly Floxin is the brand name for ofloxacin, which is also a 50-50 mixture of right and left-handed molecules, and the company went on to patent and market only the L-form , called Levaquin, heavily and successfully. A final chemical "trick" was done with the anti-histamine Seldane, which was patented as the first non-sedating anti-histamine. This pro-drug was converted into its active form Allegra, in the liver. As Seldane neared the end of its patent life, the company merely stopped producing it and started to produce the newly patented and tested Allegra. None of these practices is illegal or dangerous to the patient. It just increases the cost of medicine to the patient and the profits of the drug company.
Now, however, things get a little murkier. Let us say that the generic maker "first on the scene" stands to make a profit of $200,000,000 in the first 6 months of sole production of the generic drug. The brand name producer makes $4,000,000,000 in the same six months, or 20 times the profit. The brand name company simply offers the generic company $400,000,000 free and clear,if the generic company does NOT make the generic drug, i.e. buys up their six-month rights, so the generic company makes double the profit without tying up their production lines, and the brand name company makes an additional $4B, and the consumers pay more. Just good old free enterprise in action. Or, the brand name company can (and this has happened) buy up all the basic chemical from which Xanax is made, so the generic manufacturers have to buy their base
product from them.
But the most egregious, albeit legal events have occurred in generic drugs that treat breast and other common cancers such as the drug adriamycin. Generic drugs yield the least profit, so few companies want to manufacture them or devote a lot of their production line to them, For this reason there has been a severe shortage of many cancer-treating drugs, and many patients have to wait to start their treatment. A few even had to halt their weekly treatment in the middle. A weekly bulletin of the drug shortages can be found at the FDA web site. There is at present absolutely no legal method whereby the federal government can compel any generic manufacturer to make any drug, whether the drug is used to treat cancer, heart failure, or warts, and there seem no solutions on the horizon.
When it comes to drug prices, however, the economic and politico-legal landscape becomes murkier. About 10 years ago, Lilly and Lederle got so tired of being sued by parents who claimed that their children were permanently damaged by the MMR (measles, mumps, rubella) vaccine, that Lilly threatened to institute the default position that only Lederle of Canada would manufacture the MMR vaccine, and it would never be sold in the USA so as to avoid tort claims of damage in the US courts. The US government, faced with this possibility, passed a law that the government would reimburse any parents who sued and could prove a case.
Similarly, the morning sickness of pregnancy with horrendous vomiting and secondary severe dehydration can prove fatal, as it did to the novelist Charlotte Bronte, sister of Emily. Merrill-Dow had a drug that treated and reduced the severity of morning sickness, called Bendectin. Now historically one out of 2500 children born has some sort of birth defect. One year, seven of the parents of such children sued Merrill-Dow, claiming that the Bendectin the pregnant mothers had taken had caused the birth defect. Merrill-Dow won all seven cases, but the legal fees far exceeded their profit from making Bendectin, so they ceased production. Their final words on the subject were: "If you are pregnant and suffer from morning sickness, call a malpractice lawyer".
Now we come to generic drugs. When a new drug is patented, there are virtually no limits on the price that the manufacturing pharmaceutical company can charge, and it is impossible to calculate what a "fair" price should be, after you try to amortize the years of studies needed to produce the drug as well as those drugs that were tested and never made it to market. It's somewhat similar to the fact that most movies never show a "net" profit, so a smart actor/producer takes a percentage of the gross, which is readily measured. If I am not mistaken, the film company that produced "The Producers" claimed that there was no net profit, and Mel Brooks had to sue them for his share of the net profits. (Caveat: if it was not "The Producers", it was a similarly successful film that generated huge grosses.) In order to encourage the production of a generic substitute, the US government will grant a six month exclusive license to the first generic company to bring a generic product to market when the patent on the brand name wears off.
Now what do the brand name drug manufacturers do when the patent for the parent, patented drug nears an end? The simplest practice was done by Roche, who put a hollow "v" in their brand name Valium, so patients could complain to their doctors that the generic valium tablet looked different, which it had to, by law. Similarly, the makers of Ativan converted the basic shape to a pentagon, again uniquely and memorably different in appearance from the generic lorazepam. Another solution is to take Prilosec, which is a mixture of right-handed and left-handed molecules (and there IS a difference in their chemical action) and start to make only (purple) Nexium, which is the isolated right-handed form of the basic patent and therefore is entitled to a new patent. Similarly Floxin is the brand name for ofloxacin, which is also a 50-50 mixture of right and left-handed molecules, and the company went on to patent and market only the L-form , called Levaquin, heavily and successfully. A final chemical "trick" was done with the anti-histamine Seldane, which was patented as the first non-sedating anti-histamine. This pro-drug was converted into its active form Allegra, in the liver. As Seldane neared the end of its patent life, the company merely stopped producing it and started to produce the newly patented and tested Allegra. None of these practices is illegal or dangerous to the patient. It just increases the cost of medicine to the patient and the profits of the drug company.
Now, however, things get a little murkier. Let us say that the generic maker "first on the scene" stands to make a profit of $200,000,000 in the first 6 months of sole production of the generic drug. The brand name producer makes $4,000,000,000 in the same six months, or 20 times the profit. The brand name company simply offers the generic company $400,000,000 free and clear,if the generic company does NOT make the generic drug, i.e. buys up their six-month rights, so the generic company makes double the profit without tying up their production lines, and the brand name company makes an additional $4B, and the consumers pay more. Just good old free enterprise in action. Or, the brand name company can (and this has happened) buy up all the basic chemical from which Xanax is made, so the generic manufacturers have to buy their base
product from them.
But the most egregious, albeit legal events have occurred in generic drugs that treat breast and other common cancers such as the drug adriamycin. Generic drugs yield the least profit, so few companies want to manufacture them or devote a lot of their production line to them, For this reason there has been a severe shortage of many cancer-treating drugs, and many patients have to wait to start their treatment. A few even had to halt their weekly treatment in the middle. A weekly bulletin of the drug shortages can be found at the FDA web site. There is at present absolutely no legal method whereby the federal government can compel any generic manufacturer to make any drug, whether the drug is used to treat cancer, heart failure, or warts, and there seem no solutions on the horizon.
Monday, October 3, 2011
New Medical Device = Guinea Pig Patient
By now almost all of my readers have probably read about the horrific results that have developed and will continue to develop in some patients whose artificial hip is the new one of metal-on-metal rather than the old one of metal-on-plastic.The old artificial hip used a metal rod with an attached metal ball to replace the upper half of the femur, and installed a plastic cup into the acetabulum, or that part of the pelvis with which the femoral head fitted and subsequently pivoted, rotated and articulated , just as in the old hip joint. The new artificial hip used a metal cup instead of plastic so there was constant grinding of metal-on-metal.
Unbeknownst to anyone, this constant grinding of metal on metal created thousands if not millions of tiny metal splinters and released them around the joint space. The white blood cells engulfed and tried to destroy them as if they were foreign invaders (which is why an unattended splinter in your finger turns red and the surrounding area gets tender). The subsequent release of inflammatory chemicals generated by the white blood cells apparently caused chronic pain and also damaged some of the leg muscles around the joint, necessitating the replacement of the new metal-on-metal joint with the older metal-on-plastic one.
I mention this not to criticize the inventor of the new artificial joint, but to illustrate the dangers inherent in replacing a " tried-and-true" device with a new one that has theoretical advantages. There is no experimental way to mimic the effect of inserting a medical device into a human being for five minutes, let alone five years. In my opinion unless a medical device immediately provides a tangible benefit that no previous device did, you should let someone else be the guinea pig and have it inserted in them for the first six months to five years of the release of the new device. BTW, did you know that the salesman for the new orthopedic device often accompanies the surgeon into the OR to verbally instruct in the insertion of the device? You certainly have the right to (a) ask the surgeon how many of these devices he/she has personally installed, and (b) ask that only doctors, nurses, etc. be allowed into the OR while they are operating on you, or that you be told who besides the surgeon will be present.
The FDA clearance of a device does not imply verification of its "duty cycle" This is an engineering term. A light switch has a (tested) duty cycle of, say 10,000, meaning that it can be turned on and off at least 10,000 times before it fails to work., A light bulb has a defined duty cycle based on how often it is turned on and off, and for how long it is kept lit each time. A soldier's rifle has a tested duty cycle, as does your car's ignition and your electric garage door opener. (For a wonderful movie about the vibration duty cycle of the tail of an airplane, I heartily recommend "No Island in the Sky", based on the novel of the same name by Nevil Shute, and starring James Stewart as the airplane designer and co-starring Marlene Dietrich and Glynis Johns.) But the duty cycle of any device inserted into a human being is NEVER tested under true operating conditions. Thus we have had some heart valves that shattered, or some that clotted in an unacceptable way. We have had new materials inserted into human bodies that were subsequently rejected by the body and had to be removed. If any doctor wants to insert a new material into you (and to me "new" means being on the market for less than 5 years), I would think carefully before agreeing. The same would apply, for different reasons, if a new drug has been out for less than six months, unless no other drug does what it does, e.g. oral Dabigatgran. And remember also that you may be able to tolerate a brand-name drug, but be allergic to the products that are use to constitute the tablet that contains the generic drug.
What this means is that any new product implanted in your body is a potential time bomb, similar to the cardiac (heart) permanent pacemaker wires that broke inside the body after months of use, or the use of Xrays to treat childhood acne which greatly increased their risk of developing thyroid cancer, or the rush of men to treat their prostate cancer with external beam radiation rather than surgery in the belief that this treatment lessened their chance of becoming impotent which has been shown not to be the case. When it comes to surgery, newer is not necessarily better, and we should not confuse the French work "neuf" with the French word "nouveau".Remember that the purpose of all advertising, including the advertising of medical services and products, is an effort to convince you to buy or insist on using the advertiser's product, just as in the 1920's tapeworm eggs were advertised and sold to women as a guaranteed method of weight loss.
Finally, remember that the government always has its own agenda, and you might not know what it is truly looking for. To mention some of the more egregious government-sanctioned medical "experiments" on unwitting human guinea pigs (and Wikipedia can give you further information on each indicent) we have had (1) The Tuskegee experiment where Negro men in the USA were infected with syphilis without being told what was being done, and with treatment then being withheld so the doctors could study the "natural" course of the disease, (2) The infecting of Guatemalan natives with gonorrhea, again without telling them what was being done to them, or offering any treatment (3) the testing of the efficacy of Birth Control Pills on females in Puerto Rico who were told that they were getting a free pill to prevent pregnancy, but 50% of the women received sugar placebos instead without being told of the substitution. I won't even mention the escape of nerve gas from the U.S.Army Proving Ground in Dugway, Utah that killed over 6,000 sheep, or the CIA putting LSD into the drinks of unsuspecting drinkers at bars in the 60's to study the effects of LSD on unsuspecting users.
And be very careful about announcing that the (government) agent is wearing no clothes. In 1947 or so, a noted atomic physicist, Lewis Branscomb, was appointed head of the National Bureau of Standards, In the course of his government-directed studies, he conclusively demonstrated that an advertised additive did not extend the useful life of a car battery. He was subsequently hounded and persecuted by the Senator from the state in which the additive was manufactured.
Unbeknownst to anyone, this constant grinding of metal on metal created thousands if not millions of tiny metal splinters and released them around the joint space. The white blood cells engulfed and tried to destroy them as if they were foreign invaders (which is why an unattended splinter in your finger turns red and the surrounding area gets tender). The subsequent release of inflammatory chemicals generated by the white blood cells apparently caused chronic pain and also damaged some of the leg muscles around the joint, necessitating the replacement of the new metal-on-metal joint with the older metal-on-plastic one.
I mention this not to criticize the inventor of the new artificial joint, but to illustrate the dangers inherent in replacing a " tried-and-true" device with a new one that has theoretical advantages. There is no experimental way to mimic the effect of inserting a medical device into a human being for five minutes, let alone five years. In my opinion unless a medical device immediately provides a tangible benefit that no previous device did, you should let someone else be the guinea pig and have it inserted in them for the first six months to five years of the release of the new device. BTW, did you know that the salesman for the new orthopedic device often accompanies the surgeon into the OR to verbally instruct in the insertion of the device? You certainly have the right to (a) ask the surgeon how many of these devices he/she has personally installed, and (b) ask that only doctors, nurses, etc. be allowed into the OR while they are operating on you, or that you be told who besides the surgeon will be present.
The FDA clearance of a device does not imply verification of its "duty cycle" This is an engineering term. A light switch has a (tested) duty cycle of, say 10,000, meaning that it can be turned on and off at least 10,000 times before it fails to work., A light bulb has a defined duty cycle based on how often it is turned on and off, and for how long it is kept lit each time. A soldier's rifle has a tested duty cycle, as does your car's ignition and your electric garage door opener. (For a wonderful movie about the vibration duty cycle of the tail of an airplane, I heartily recommend "No Island in the Sky", based on the novel of the same name by Nevil Shute, and starring James Stewart as the airplane designer and co-starring Marlene Dietrich and Glynis Johns.) But the duty cycle of any device inserted into a human being is NEVER tested under true operating conditions. Thus we have had some heart valves that shattered, or some that clotted in an unacceptable way. We have had new materials inserted into human bodies that were subsequently rejected by the body and had to be removed. If any doctor wants to insert a new material into you (and to me "new" means being on the market for less than 5 years), I would think carefully before agreeing. The same would apply, for different reasons, if a new drug has been out for less than six months, unless no other drug does what it does, e.g. oral Dabigatgran. And remember also that you may be able to tolerate a brand-name drug, but be allergic to the products that are use to constitute the tablet that contains the generic drug.
What this means is that any new product implanted in your body is a potential time bomb, similar to the cardiac (heart) permanent pacemaker wires that broke inside the body after months of use, or the use of Xrays to treat childhood acne which greatly increased their risk of developing thyroid cancer, or the rush of men to treat their prostate cancer with external beam radiation rather than surgery in the belief that this treatment lessened their chance of becoming impotent which has been shown not to be the case. When it comes to surgery, newer is not necessarily better, and we should not confuse the French work "neuf" with the French word "nouveau".Remember that the purpose of all advertising, including the advertising of medical services and products, is an effort to convince you to buy or insist on using the advertiser's product, just as in the 1920's tapeworm eggs were advertised and sold to women as a guaranteed method of weight loss.
Finally, remember that the government always has its own agenda, and you might not know what it is truly looking for. To mention some of the more egregious government-sanctioned medical "experiments" on unwitting human guinea pigs (and Wikipedia can give you further information on each indicent) we have had (1) The Tuskegee experiment where Negro men in the USA were infected with syphilis without being told what was being done, and with treatment then being withheld so the doctors could study the "natural" course of the disease, (2) The infecting of Guatemalan natives with gonorrhea, again without telling them what was being done to them, or offering any treatment (3) the testing of the efficacy of Birth Control Pills on females in Puerto Rico who were told that they were getting a free pill to prevent pregnancy, but 50% of the women received sugar placebos instead without being told of the substitution. I won't even mention the escape of nerve gas from the U.S.Army Proving Ground in Dugway, Utah that killed over 6,000 sheep, or the CIA putting LSD into the drinks of unsuspecting drinkers at bars in the 60's to study the effects of LSD on unsuspecting users.
And be very careful about announcing that the (government) agent is wearing no clothes. In 1947 or so, a noted atomic physicist, Lewis Branscomb, was appointed head of the National Bureau of Standards, In the course of his government-directed studies, he conclusively demonstrated that an advertised additive did not extend the useful life of a car battery. He was subsequently hounded and persecuted by the Senator from the state in which the additive was manufactured.
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