Workshop on Effectiveness of Medicines and Therapies, Brussels, 18 September 2013 Presentation by Lidija Gajski, page 1

Workshop on "Effectiveness of Medicines and Therapies" 18 September 2013, European Parliament, Brussels

Useful, superfluous, unnecessary and dangerous drugs Presentation by Lidija Gajski

Dear ladies and gentlemen, Thank you for inviting me to participate in the workshop. I was asked to talk about drugs, which will inevitably lead to drug science, drug policy etc. Let me start with one simple classification of the medication curative drugs eliminate the disease; they are clearly beneficial. There is also no doubt about the need and efficiency of numerous groups of symptomatic drugs; I pointed out substitution pharmacotherapy which literally saves lives insulin in type I diabetes, for example. What is less clear is the need for and effectiveness of preventive drugs ones that are given to the people with no symptoms of disease. Lets start with those that consume the most of the money. Clinical trials of 3-5 years duration show that in people with cardiovascular disease or high cardiovascular risk, antihypertensives, hypolipidemics and aspirin reduce the rate of cardiovascular events from approximately 4.5% to 2.5 3% per year, i.e. about 80 patients must be treated to prevent one heart attack or stroke. In healthy population with low cardiovascular risk, reduction of unwanted events is from about 0.8% to 0.5%, or it takes a few hundred people to treat, in order to prevent one unwanted event. There is no evidence whatsoever that these drugs prolong life in the latter population, i.e. when given for primary prevention. As for antidiabetics, strict pharmacological regulation of blood sugar saves one complication of diabetes (mostly minor eye operation) in 200 patients treated, per year. The effect of drugs for osteoporosis on the only really relevant bone fracture the hip fracture, in clinical trials was below statistical significance. Hormone replacement therapy is a symptomatic therapy; there are no benefits in prevention of future disease. Obesity drugs have minimal effect on weight loss; capacity to prevent disease unknown; well, it is known for some agents which have been found harmful. Antidepressants prevent neither suicide, nor new episodes of depression; even as a symptomatic therapy, except for severe depression, they are equivalent to placebo. Chemotherapy works for some relatively rare types of tumours, notably hematologic; the most common cancers are resistant to cytotoxic agents. Antiviral drugs very limited effects. Whether vaccines actually prevent infectious diseases is not known, because proper studies have never been performed. Data regarding efficacy which I have presented derive from the scientific research (it was impossible to cite all the literature), mostly clinical trials; efficiency in real life is even smaller

Workshop on Effectiveness of Medicines and Therapies, Brussels, 18 September 2013 Presentation by Lidija Gajski, page 2

for many reasons limitations of the clinical trial itself in the first place. What deserves special attention in this context is funding numerous evidence and scandals show that industry manipulates the results of drug trials to make their products look better than they really are. Studies which have analysed the relationship between outcomes of the studies and their sponsorship found that those financed by pharmaceutical companies are four to five times more likely to produce results in favour of the sponsor, compared to studies paid from other sources. And the drug industry finances about 70% of the clinical trials published in major journals. By taking over the scientific research pharmaceutical industry not only overestimates the drug benefits, but broadens the drug indications as well. Special populations and special outcomes are created in which the effect of the substance is demonstrated. Antidepressants, formerly given for severe forms of depression only, now have twelve indications including milder anxiety disorders. Statins have evolved from cholesterol lowering drugs in patients with coronary heart disease, into universally beneficial anti-atherosclerotic medication. Industry sponsored epidemiological studies exaggerate disease prognosis and prevalence flu has become a life threatening disease; one twelfth of mankind is infected with hepatitis virus. Next expanding disease definition clinical trials simply found that drugs are effective in milder forms of disease like asthma and depression and in physiological or borderline conditions, or temporary disorders; these conditions are then pronounced illnesses. Thanks to the observational studies which have shown benefit of blood pressure lowering, the number of hypertensive people has increased from 20% to 44%. Finally, inventing new diseases 30 years ago anyone hardly knew of cholesterol, which was right since it is more or less unimportant biological parameter; thanks to manipulated scientific studies and a concept of cardiovascular risk, it has become the main topic in the doctor's office. Next concept, applied in the case of osteoporosis youth equals health, old age equals disease. Menopause normal period of life turned into disease; Helicobacter pylori majority of people have it; the abundance of newly created psychiatric entities; example social anxiety disorder, formerly known as shyness. And here we are, talking about healthy people, people whose manifestations of normal life have been medicalized. This is where the drugs don't belong. Methodologically rigorous and correctly interpreted trials show no effect of drugs in either of these conditions. Same goes for prevention. We are witnessing a medical paradigm shift from traditionally curative to preventive. There is nothing wrong with the prevention of disease, of course, but we are talking about pharmacological prevention here, and it is in the primary prevention setting far from cost-effective. Pharmacological prevention is the concept of drug industry, which has in the last few decades consumed the really ill and discovered an endless market and enormous profit prospects in the healthy population. It is a distortion and abuse of the very term of prevention and preventive approach. And it causes harm medical, economic, social and cultural.

Workshop on Effectiveness of Medicines and Therapies, Brussels, 18 September 2013 Presentation by Lidija Gajski, page 3

Ivan Illich, a brilliant critic of modern society, of Croatian origin I must say, anticipated almost 40 years ago what has now become obvious to many insiders and outsiders of medicine. Talking about the harm that medication causes, let me focus on the direct, medical harm only. Studies show that every fourth prescription drug user experiences an adverse event. Among the side effects recorded in hospitals, around 1% was fatal, 12% were life-threatening and 30% serious. A meta-analysis showed that the incidence of serious side effects occurring while in hospital plus those causing admission to hospital is 6.7%; 0.32% were lethal. Authors estimated that it equals 106 000 of deaths in USA every year, making drugs between the fourth and sixth leading cause of death. A similar study demonstrated 6.5% adverse drug reactions in UK hospitals, of which 0.15% were fatal. It is very important to stress that these numbers differ very much from the official statistics, which substantially underestimates pharmacotherapy-induced harm. How come the substances intended for cure are so harmful? First, their use is increasing, with the growing possibility of unpredictable interactions and errors on the part of both the doctor and the patient. Second, insufficient testing adverse drug events are not sufficiently explored, they get underreported in the studies and interpreted in the way that minimizes their significance no wonder, knowing who pays for the studies. Many think that the drug approval process is too lax. Regulatory agencies licence drugs on the basis of the relatively small number of studies, often of short duration, sometimes including only surrogate outcome measures, and, most importantly, with the possibility of coming exclusively from the industry (I wouldn't know that firsthand, I'm citing other people). This is, again, the result of the influence pharmaceutical companies have in the regulatory bodies, by financing them through paying for licencing procedure and by having their lobbyists among the staff. Insufficiently tested pharmaceuticals come into use and later are recalled because of toxicity. Thanks to postmarketing surveillance, which is, however, also inadequate. Only 5% to 20% of side effects are reported. Why? There are no sanctions for non-reporting, physicians are insufficiently educated and sensitized, and fear of liability; companies are not interested for obvious reasons and state agencies are understaffed and underpaid. How to achieve a rational drug policy? By dealing with the conflict of interest. The prime duty of the industry is earning money and it is perfectly legitimate. The ones who have failed are the civil servants paid by the public money who have exchanged their primary for the secondary interest. Solution is not in the actual non-productive conflict of interest-regulation approach, but in its elimination, meaning exclusion or strong reduction of the corporate influence, i.e. private money from the scientific research, professional education, public opinion creation and the drug regulation.