Sunday, March 31, 2013

Drug Reps and Doctors

     Several non-physician readers have asked me questions about the relationship between drug reps and doctors, and between drug companies and doctors, so I thought I would set the record straight.

     Firstly, the major cost decision is when the doctor decides that the patient needs a new drug, e.g. a statin to lower cholesterol. The variation in price between two brands (or two generics) is generally less than 10%. The major cost comes from the doctor's deciding to prescribe the drug, and the drug rep has little or no control over that. Whether the doctor prescribes Lipitor, or Crestor, or simvastatin depends on many facts, mostly upon what the doctor has read. If he/she feels there is no difference among the statins on the market, then the decision is almost a random one. The point here is that the best a drug rep can hope for is to get the doctor to prescribe a particular brand of a statin, and the price difference between brand A and brand B is as I have said, not large. Again, let me emphasize that the medical decision that the patient needs a certain class of drugs is the major decision influencing the cost to the patient. For instance, if the patient has atrial fibrillation, then anticoagulation to reduce the risk of a stroke is usually mandatory.

     The drug reps are strictly limited by the FDA as to what information can be told to or given to the doctors. The rules are so strict that if a drug rep has highlighted a sentence in a journal article, then he/she can only hold the article up for me to read. It is forbidden to give me the article with highlighting because the FDA fears that drawing my attention to the highlighted sentence might unduly influence me. Another rule is that the drug company can only give as a  gift an an article that a non-doctor has no use for. They can give me reflex hammers or tuning forks or pocket eye charts, but no coffee cups or ballpoint pens(!). And if I have a question about the side effects, etc. of a drug, every company has a doctor's hotline whereby I can request information from the company directly. Alternatively, I can file a request for more information with the drug rep.

     The drug reps can invite the doctors to a dinner where another doctor is lecturing on the drug rep's drug. The slides are supplied by the drug company and the company's lawyers restrict the words the doctor can use. The doctor who gives the talk is paid for his/her speech but the other doctors are paid nothing, but the dinner is free.And doctors can no longer bring along their wives to the dinner, unless the wife also works in the office as an office manager, etc.

     There is a service that sells to the drug companies a list of all the doctors in a given area along with the number of prescriptions of the company's product a doctor prescribes in one or three months. The speakers at the dinner are chosen from doctors who are the heaviest prescribers of the medicine on which they are asked to speak, so paying them for the talk is  a post hoc decision, and does not induce the doctor to prescribe a drug that he/she  already heavily prescribes. The drug company only hopes the lecture will influence other doctors to prescribe more of the drug. After the talk, the doctors are free to ask questions to the speaker.

     Doctors who write published articles must post a disclaimer at the end of the article, listing all the drug companies for which they have given speeches, or been a consultant for, or received any remuneration from, so that readers are immediately made aware of any possible conflict of interest.

Monday, March 18, 2013

Calcium Supplements, Good or Bad?

     There have been several articles recently published in medical journals (JAMA, New England Journal of Medicine, British Medical Journal) about the possible risks associated with taking calcium supplements. The study groups are respected researchers, and include our own National Institute of Health. The studies addressed only  the question of calcium supplements, and not the impact on health of  a diet that was high in calcium.

     I must state in advance that one problem with the results of the studies, besides their contradictory results, is that we have no good explanation for their results. While this does not mean the results are not valid and true, this lack of reasoning as to cause and effect makes it more difficult to believe in the result. It is also puzzling why the two main studies found different effects in men and women, and the results of one contradicted the results of the other.

      The amount of calcium in your blood is very closely controlled by the body, and it is the ionized calcium, Ca++, a divalent cation that is the active form. Calcium exists in your blood both free as a cation and bound to serum proteins, and the aforementioned studies did not measure calcium levels. Because magnesium also exists as a divalent cation it often precipitates out in laboratory processes  along with calcium, which led to the belief that the use of a supplement that contained magnesium as well as calcium was beneficial; no such result has ever been shown to be valid. However, since calcium is mildly constipating and magnesium is a mild laxative, combining the two elements into one pill makes theoretical clinical sense. Strontium is also a divalent cation, and unfortunately can be taken up by your bones along with calcium, which explains  some of the bone marrow cancers induced by the radioactive strontium fallout from an atomic explosion.

     The calcium levels are controlled by parathyroid hormone, which also activates Vitamin D into its useful form and thereby promotes the uptake of calcium by your bones both directly and indirectly. As a rule, the amount of calcium in your diet does not affect the level of calcium in your bloodstream. It is generally agreed that the calcium in your diet should contain between 600mg to 1200mg of calcium daily, along with 400 Units of Vitamin D, in order to maintain bone strength and prevent osteoporosis because activated Vitamin D promotes the absorption of calcium from your gut. We also know that ingesting too much calcium if you have chronic kidney disease can promote calcification of the arteries in your body, probably because kidney failure induces a state of secondary hyperparathyroidism, but a further discussion of this condition is beyond the scope of this article. Parathyroid hormone also increases the absorption of phosphate from your intestine which makes clinical sense since the largest mineral constituent of your bones is hydroxylapatite, which contains both calcium and phosphorous.

     Now as to the studies. The question asked was whether or not taking calcium supplements (1000 mg or more in men and 1400 mg or more in women) had a benefit on the patient's health. One study showed an increase in overall mortality, and cardiovascular mortality as well as in heart attacks,  but not in stroke. This increase in mortality was shown to exist in men, but not in women. Another study, published at about the same time, showed a similar increase in overall and cardiovascular mortality in women, but not in men(!).In each study the control group was same-sex patients who did not take calcium supplements.

     So what are we to believe? There even are no clear-cut studies showing that calcium supplements prevent osteoporotic fracture; in fact some studies show an opposite result. (But taking extra Vitamin D at a dose of 800 mg/day does seem to prevent such fractures.) It is difficult to recommend calcium supplements in view of the above quoted data. It would be useful to have  a study that measured calcium levels in people having heart attacks were it not for the fact that no one knows whether or not a MI acutely affects calcium levels. And it would seem heartless to tell the patients to read all three studies and to make up their own minds. I think that because no study showed by clear-cut evidence that taking calcium supplements was beneficial for one's health, then the recommendation of the doctor should come down on not recommending calcium supplements, thereby combining two tenets of medicine: "first, do no harm" and "less is more".

Sunday, March 10, 2013

How Well Does the Flu Vaccine Work?

     I belong to the International Society for Infectious Diseases, or ISID, whose home page is It is a consortium of physicians and public health workers who are interested in aspects of public health that are related to possible epidemics, among other things. Any worker can post a finding thru their ProMed-mail post, located at In fact, it was a Dutch physician who had been working in China when the SARS pneumonia broke out who first announced it to the world when he returned to the Netherlands using this e-mail posting system. (Up to that point the Chinese government was minimizing the severity of the problem, in a replay of Ibsen's "Enemy of the People".)

     There are discussions now posted in ProMED mail  about the effectiveness of the present 3-strain flu vaccine in 2010-2011, with estimates of effectiveness ranging from 30% to 70%, and I refer you to their web site for further information.

     These results should not be that surprising. There have already been two (U.S.) government studies showing that the efficacy of the current vaccine falls below protective levels after about 4 to 6 months. It therefore follows that the best protection would be to get a flu vaccine every six months, even though no insurance company or HMO or MCR will pay for it. There was an even more recent study demonstrating that a vaccine of four times the standard dose will provide satisfactory protection for one year.

     I leave it to my readers to discuss these results with their primary care physicians. I myself plan to get a second flu shot six months after my last one, and pay for it of course. One caveat: we do not manufacture sufficient amounts of flu vaccine to give everyone in the U.S. two flu shots per year, and it is not clear what the government's response will be to requests for a second dose of flu vaccine.


Sunday, March 3, 2013

The Mediterranean Diet

     The cardiovascular benefits of the Mediterranean Diet (or MD)  have been in the news lately. The newspaper stories  were based on an article published in The New England Journal of Medicine (issue of February 25, 2013, by R. Estruch But since even the New York Times did not give a fully accurate description of the MD or the study and its results, I thought I would do so here.

     To quote from the article: "The MD  is characterized by a high intake of olive oil, fruit, nuts, vegetables and cereals; a moderate intake of fish and poultry; a low intake of dairy products, red meats, processed meats;  and sweets and wine consumed in moderation with meals". Over 7,000 male and female adults in Spain were admitted to the study, and all were given periodic instruction and review by nutritionists about the MD. The adults, who ranged in age from 55 to 80, were split into three groups: one group was given extra olive oil (1 liter per week), one group was given extra nuts (30 grams of mixed walnuts, hazelnuts and almonds per week), and the third group was given periodic reinforcements about the design and benefits of a low fat diet.

     There were no restrictions placed on the total caloric intake, and no advice about increasing physical activity. In addition, although none of the study patients had any evidence of cardiovascular disease, all were at risk for developing this problem: they either had adult-onset diabetes, or they had three or more of the following risk factors: smoking, hypertension,elevated LDL cholesterol, low HDL cholesterol, overweight or obesity, or a family history of premature heart disease. The primary endpoint was heart attack, stroke or death from cardiovascular disease.

     The two MD groups increased their fish consumption by 0.3 servings/week, increased their legume consumption by 0.4 servings per week,  and they increased their consumption of olive oil to 50 or 32 grams per day. No change in physical activity was observed. In the 5 year follow, there were 288 events noted: 96 with extra olive oil, 83 with extra nuts, and 109 in the control group who were encouraged about a low fat diet. Only the reduction in stroke risk reached statistical significance, and the calculated benefit was 3 major cardiovascular events per 1000 person-years.

     I think  it would be fair to say that any intervention in a group at elevated risk for cardiovascular disease would be beneficial, but it is scientifically difficult to extrapolate the above results to normal, healthy individuals with no health risks, especially if they live in a country with a low mortality rate, such as Japan.

     Added note: The hard copy was just published in The New England Journal of Medicine, vol. 368, pp 1279-1290, April 4, 2013, by R. Estruch et. al.