|
This
is a contribution from a member of THINCS, Book Review by
Joel M. Kauffman, PhD, Professor of Chemistry Emeritus, University of the
Sciences in Philadelphia Jerry Avorn. Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs, New York, NY: Alfred A. Knopf, 2004. viii + 448 pp ISBN 0-375-41483-5 $27.50 Easy to read and follow, wide-ranging in scope, dripping with insight from a real medical insider, and very humorous besides, this book is a tour-de-force in many aspects. Problems with HMOs, the FDA, Big Pharma, and out-of-control drug advertising are all addressed. The benefits of drugs are addressed by giving examples of the launching of some that were later risky enough to be banned. The most detailed illustration of the benefits and limitations of the randomized clinical trial (RCT) I have ever read are in this book. Dr. Avorn also gave the best illustration of the advantages of the observational study on large numbers of subjects as a better way to find the risks of drugs. The risks of drugs have many causes besides their inherent toxicity. Dr. Avorn shows how the subjects in an RCT may be healthier or younger or too male compared with the likely drug target group, how dosages may be too high for children or the elderly, how adverse effects are hard to predict and under-reported and that RCTs are not run for enough time. He notes how too many drugs are approved by the FDA based on handy measurements such as blood pressure or cholesterol levels, not real clinical endpoints, like death. The costs of drugs are noted to be whatever the markets will bear, even when the key discoveries are made in government or academic labs, as is usually the case. He writes about the drug information overload for physicians from ads or “detail women” from Big Pharma, and of “education” courses put on by Big Pharma, all biased of course. Dr. Avorn has, for >25 years, been involved in studies on how to use computerized data on filled prescriptions and later medical histories of each patient to correlate drug use with well-being. Some of the results have been put into practice with improved patient well-being and lower costs for drugs. He also introduced “academic detailing” to teach physicians how to prescribe better and cheaper drugs. For these efforts alone he should have a Nobel Prize in Medicine, in my opinion. He makes a number of practical suggestions on improving health care in the USA, all with understanding that pluralism, competition and choice are key features of any success in the USA. Prescribing via computer could alert the MD to cheaper drug alternatives, dosage for each age group, and potential interactions. The pharmacy would have accurate input and alerts to prescriptions being filled at other pharmacies. Of larger scope is Dr. Avorn’s idea of creating non-profit health-care provider organizations that are also the insurers. They would be audited annually and evaluated for effectiveness annually with all results being made public. Other suggestions are that drug approval by the FDA no longer be “yes and good luck” or “no”, but that there be conditional approvals to be reviewed. Some other federal agency would evaluate risks, not the same people in the FDA who approved the drugs. There is great detail and subtlety
overall. The index is adequate. Referencing by page number was sparse. Anticancer drugs usually do not prolong life (Moss, 2000). There is no evidence that the wide use of BP drugs provides major benefits, even Dr. Avorn’s preferred beta-blockers and diuretics. In RCTs combined in a meta-analysis, the use of beta-blockers reduced mortality by only 0.1% annually (Psaty, 1997). The ALLHAT RCT cited by Dr. Avorn had no placebo arm, and the results for the diuretic, which was not a thiazide type, were a bit worse than for the other drug types (Kauffman, 2004). Only when BP is very high, as in the Swedish Trial in Old Patients (STOP), (Dahlöf, 1991), is the result barely worthwhile. The 1627 subjects of both sexes were 70-84 years old and had mean BP = 195/102 at baseline and were followed for 4 years at 116 health centers in Sweden. The drugs were a diuretic, or the same combined with a beta-blocker. After 4 years 89% of the drug-treated group were alive vs. 85% on placebo, for a drop of just 1% per year in mortality. Stroke rate dropped just 1.5% per year. In the ASCOT trial of atorvastatin (Lipitor), the chance of not dying was improved by just 0.15% per year (Sever, 2003) at a cost of $1,000,000 to prevent 1 death for one year! And this was a trial that Pfizer chose to publish! In the few RCTs in which mortality for women on statin drugs was published, it was higher in all cases (Criqui, 2004), as it is also for aspirin use (Kauffman, 2002). The slight benefits of statin drugs on heart attack and mortality rates have nothing to do with lowering cholesterol or LDL levels, but are related to the presence of cytomegalovirus or inflammation in mostly male patients with severely blocked coronary arteries (Horne, 2003). Dr. Avorn does not admit that the low compliance rates with these two types of drugs is caused by their severe side-effects such that half drop them in a year and up to 3/4 after 2 years (Pahor, 2000; Jackevicius, 2002). Dr. Avorn was extremely negative on the use of supplements, and on the 1994 law that declared them foods, not drugs, unaware of the previous FDA bias in evaluating them. He wrote that none have had valid trial results. This is untrue for selenium (Bjelakovic et al., 2004), a few herbals (Vickers, 1999), ginkgo (Kleijnen, 1992), vitamin C (Hickey, 2004), magnesium (Paolissi, 1989) and some others. Stopping useless drugs altogether rather than substituting cheaper ones, and using certain supplements will save far more than prescribing generics! Willful perversions of RCTs is better covered in Overdo$ed America by John Abramson, MD. Complete references available. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (2004). Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 364:1219-1228. Criqui MH, Golomb BA (2004). Low and lowered total cholesterol and total mortality. J Am Coll Cardiology 1 Sep:1009-1010. Dahlöf B, Lindholm LH, Hansson L, et al. (1991). Morbidity and mortality in the Swedish Trial in Old Patients (STOP-hypertension). Lancet, 338:1281-1285. Hickey S, Hilary Roberts H. Ascorbate: The Science of Vitamin C, Napa, CA: Lulu Press, 2004. Horne BD, Muhlstein JB, Carlquist JF, et al. (2003). Statin Therapy Interacts With Cytomegalovirus Seropositivity and High C-Reactive Protein in Reducing Mortality Among Patients With Angiographically Significant Cornary Disease. Circulation, 107:1-6. Jackevicius CA, Mamdani M, Tu JV. Adherence With Statin Therapy in Elderly Patients With and Without Acute Coronary Syndromes. J Am Med Assoc 2002;288:462-467. Kauffman JM, “Aspirin Study Flawed”, Letter to Editor, J. Scientific Exploration 16(2), 247-249 (2002). Kauffman JM, Bias in Recent Papers on Diets and Drugs in Peer-Reviewed Medical Journals, J. Am. Physicians & Surgeons, 9(1), 11-14 (2004). Kleijnen J, Knipschild P (1992). Gingko biloba. Lancet 340:1136-1139. Moss RW (2000). Questioning Chemotherapy, Brooklyn, NY: Equinox Press. Pahor M, Psaty BM, Alderman MH et al. (2000). Health outcomes associated with calcium antagonists compared with other first-line antihypertensive therapies: a meta-analysis of randomised controlled trials. Lancet, 356(9246):1949-1954. Paolisso G, Sgambato S, Pizza G et al. (1989). Improved Insulin Response and Action by Chronic Magnesium Administration in Aged NIDDM Subjects. Diabetes Care 12(4):265-269. Psaty BM, Smith NL, Siscovick DS et al., Health outcomes associated with antihypertensive therapies used as first-line agents. JAMA 1997;277:739-745. Sever PS, Dahlof B, Poulter NR et al. Prevention of coronary and stroke events with atorvastatin in hypertenisve patients who have average or lower-than-average cholesterol concentrations, inthe Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003;361:1149-1158. Vickers A, Zollman C (1999). ABC of complementary medicine. Herbal Medicine. British Med J 319:1050-1053.
|
