Deadly Medicines and Organised Crime

by Peter Gotzsche

  In a lecture I gave to an audience of judges I noted that clinical researchers and the legal profession used the same word, ‘trial’, for two sorts of process, one legal and the other scientific. Speaking for my own profession, I had to acknowledge that legal ‘trials’ were set up in a way that was generally fairer, and based on a sounder ethical footing than clinical trials. (Gøtzsche quotes this here.)

  Gøtzsche has proposals and calls for revolution. To me nothing will help unless we disconnect completely the performance and assessment of trials from the funding of trials. We base our treatments on the results of clinical trials, so the results are a matter of life and death. Patients who allow themselves to be entered into trials expect their sacrifice to benefit humanity. What they do not expect is that their results will be held, and manipulated, as trade secrets. These results are a public good and they should be financed by the government using taxes paid by the industry, and available to all. As it is, we have the ironic situation in the US where the drug companies pay the agency, the FDA, to assess their projects. Is it any surprise that the agency has been captured by the industry it is supposed to regulate?

  Revolution? Gøtzsche is right. We landed in our present mess because of innumerable mistakes in the past, and he describes many of these in his detailed inventory. They include failure of clinical scientists, their institutions and the editors of the journals publishing their science to understand how thoroughly they were being caught up by the marketers who paid them. I believe it will take a revolution to sweep away decades of self-dealing by industry.

  I hope you will read this book and reach your own conclusions. Mine? If Gøtzsche is angry at the behavior of academia and industry, he has a right to be. What’s needed is more of Gøtzsche’s evidence-based outrage.

  Drummond Rennie, MD

  June 2013

  About the author

  Professor Peter C Gøtzsche graduated as a Master of Science in biology and chemistry in 1974 and as a physician in 1984. He is a specialist in internal medicine; he worked with clinical trials and regulatory affairs in the drug industry 1975–83, and at hospitals in Copenhagen 1984–95. He co-founded The Cochrane Collaboration in 1993 and established The Nordic Cochrane Centre the same year. He became professor of Clinical Research Design and Analysis in 2010 at the University of Copenhagen.

  Peter Gøtzsche has published more than 50 papers in ‘the big five’ (BMJ, Lancet, JAMA, Annals of Internal Medicine and New England Journal of Medicine) and his scientific works have been cited over 10 000 times.

  Peter Gøtzsche has an interest in statistics and research methodology. He is a member of several groups publishing guidelines for good reporting of research and has co-authored CONSORT for randomised trials (www.consort-statement.org), STROBE for observational studies (www.strobe-statement.org), PRISMA for systematic reviews and meta-analyses (www.prisma-statement.org), and SPIRIT for trial protocols (www.spirit-statement.org). Peter Gøtzsche is an editor in the Cochrane Methodology Review Group.

  Books by Peter Gøtzsche

  Gøtzsche PC. Mammography Screening: truth, lies and controversy. London: Radcliffe Publishing; 2012.

  Gøtzsche PC. Rational Diagnosis and Treatment: evidence-based clinical decision-making. 4th ed. Chichester: Wiley; 2007.

  Gøtzsche PC. [On safari in Kenya] [Danish]. Copenhagen: Samlerens Forlag; 1985.

  Wulff HR, Gøtzsche PC. Rationel klinik. Evidensbaserede diagnostiske og terapeutiske beslutninger. [Rational clinical practice. Evidence-based diagnostic and therapeutic decisions] 5th ed. Copenhagen: Munksgaard Danmark; 2006.

  1

  Introduction

  The big epidemics of infectious and parasitic diseases that previously took many lives are now under control in most countries. We have learned how to prevent and treat AIDS, cholera, malaria, measles, plague and tuberculosis, and we have eradicated smallpox. The death tolls of AIDS and malaria are still very high, but that’s not because we don’t know how to deal with them. It has more to do with income inequalities and the excessive costs of life-saving drugs for people in low-income countries.

  Unfortunately, we now suffer from two man-made epidemics, tobacco and prescription drugs, both of which are hugely lethal. In the United States and Europe,

  drugs are the third leading cause of death after heart disease and cancer.

  I shall explain in this book why this is so and what we can do about it. If drug deaths had been an infectious disease, or a heart disease or a cancer caused by environmental pollution, there would have been countless patient advocacy groups raising money to combat it and far-ranging political initiatives. I have difficulty understanding that – since it is drugs, people do nothing.

  The tobacco and the drug industries have much in common. The morally repugnant disregard for human lives is the norm. The tobacco companies are proud that they have increased sales in vulnerable low-income and middle-income countries, and without a trace of irony or shame, Imperial Tobacco’s management team reported to investors in 2011 that the UK-based company won a Gold Award rating in a corporate responsibility index.1 The tobacco companies see ‘many opportunities … to develop our business’, which the Lancet described as ‘selling, addicting, and killing, surely the most cruel and corrupt business model human beings could have invented’.1

  Tobacco executives know they are peddling death and so do drug company executives. It is no longer possible to hide the fact that tobacco is a major killer, but the drug industry has done surprisingly well in hiding that its drugs are also a major killer. I shall describe in this book how drug companies have deliberately hidden lethal harms of their drugs by fraudulent behaviour, both in research and marketing, and by firm denials when confronted with the facts. Just like the chief tobacco executives each testified at a US Congressional hearing in 1994 that nicotine wasn’t addictive, although they had known for decades that this was a lie.2 Philip Morris, the US tobacco giant, set up a research company that documented the dangers of sidestream smoke, but even though more than 800 scientific reports were produced none were published.2

  Both industries use hired guns. When robust research has shown that a product is dangerous, numerous substandard studies are produced saying the opposite, which confuse the public because – as journalists will tell you – ‘researchers disagree’. This doubt industry is very effective at distracting people into ignoring the harms; the industry buys time while people continue to die.

  This is corruption. Corruption has many meanings and what I generally understand by it is how it is defined in my own dictionary, which is moral decay. Another meaning is bribery, which may mean a secret payment, usually in cash, for a service that would otherwise not be rendered, or at least not so quickly. However, as we shall see, corruption in healthcare has many faces, including payment for a seemingly noble activity, which might be nothing else than a pretence for handing over money to a substantial part of the medical profession.

  The characters in Aldous Huxley’s novel from 1932, Brave New World, can take Soma pills every day to give them control over their lives and keep troubling thoughts away. In the United States, TV commercials urge the public to do exactly the same. They depict unhappy characters that regain control and look happy as soon as they have taken a pill.3 We have already superseded Huxley’s wildest imaginations and drug use is still increasing. In Denmark, for example, we use so many drugs that every citizen, whether sick or healthy, can be in treatment with 1.4 adult daily doses of a drug every day, from cradle to grave. Although many drugs are life-saving, one might suspect that it is harmful to medicate our societies to such an extent, and I shall document that this is indeed the case.

  The main reason we take so many drugs is that drug companies don’t sell drugs, they sell lies about drugs. Blatant lies that – in all the cases I have studied – have continued after the statements were proven wrong. This is what makes drugs so different from anything else in life. If we wish to buy a car or a house, we may judge for ourselves whethe
r it’s a good or a bad buy, but if we are offered a drug, we have no such possibility. Virtually everything we know about drugs is what the companies have chosen to tell us and our doctors. Perhaps I should explain what I mean by a lie. A lie is a statement that isn’t true, but a person who tells a lie is not necessarily a liar. Drug salespeople tell many lies, but they have often been deceived by their superiors in the company who deliberately withhold the truth from them (and are therefore liars, as I see it). In his nice little book On Bullshit, moral philosopher Harry Frankfurt says that one of the salient features of our culture is that there is so much bullshit, which he considers short of lying.

  My book is not about the well-known benefits of drugs such as our great successes with treating infections, heart diseases, some cancers, and hormone deficiencies like type 1 diabetes. The book addresses a general system failure caused by widespread crime, corruption and impotent drug regulation in need of radical reforms. Some readers will find my book one-sided and polemic, but there is little point in describing what goes well in a system that is out of social control. If a criminologist undertakes a study of muggers, no one expects a ‘balanced’ account mentioning that many muggers are good family men.4

  If you don’t think the system is out of control, please email me and explain why drugs are the third leading cause of death in the part of the world that uses most drugs. If such a hugely lethal epidemic had been caused by a new bacterium or a virus, or even one-hundredth of it, we would have done everything we could to get it under control. The tragedy is that we could easily get our drug epidemic under control, but our politicians who hold the power to make changes do virtually nothing. When they act, they usually make matters worse because they have been so heavily lobbied by the industry that they have come to believe all its luring myths, which I shall debunk in every chapter of the book.

  The main problem with our healthcare system is that the financial incentives that drive it seriously impede the rational, economical and safe use of drugs. The drug industry prospers on this and exerts tight information control. The research literature on drugs is systematically distorted through trials with flawed designs and analyses, selective publication of trials and data, suppression of unwelcome results, and ghostwritten papers. Ghostwriters write manuscripts for hire without revealing their identity in the papers, which have influential doctors as ‘authors’, although they have contributed little or nothing to the manuscript. This scientific misconduct sells drugs.

  Compared to other industries, the pharmaceutical industry is the biggest defrauder of the US federal government under the False Claims Act.5 The general public seems to know what the drug industry stands for. In an opinion poll that asked 5000 Danes to rank 51 industries in terms of the confidence they had in them, the drug industry came second to the bottom, only superseded by automobile repair companies.6 A US poll also ranked the drug industry at the bottom, together with tobacco and oil companies.7 In another survey, 79% of US citizens said the drug industry was doing a good job in 1997, which fell to 21% in 2005,8 an extraordinarily rapid decline in public trust.

  On this background, it seems somewhat contradictory that patients have great confidence in the medicines their doctors prescribe for them. But I am sure the reason patients trust their medicine is that they extrapolate the trust they have in their doctors into the medicines they prescribe. The patients don’t realise that, although their doctors may know a lot about diseases and human physiology and psychology, they know very, very little about drugs that hasn’t been carefully concocted and dressed up by the drug industry. Furthermore, they don’t know that their doctors may have self-serving motives for choosing certain drugs for them, or that many of the crimes committed by the drug industry wouldn’t be possible if doctors didn’t contribute to them.

  It is difficult to change systems and it is not surprising that people who have to live with a faulty system try to make the most out of it, even though it often results in well-intentioned people doing bad things. However, many people at senior levels in the drug industry cannot be excused in this way, as they have deliberately told lies to doctors, patients, regulators and judges.

  I dedicate this book to the many honest people working in the drug industry who are equally appalled as I am about the repetitive criminal actions of their superiors and their harmful consequences for the patients and our national economies. Some of these insiders have told me they would wish their top bosses were sent to jail, as the threat of this is the only thing that might deter them from continuing committing crimes.

  References

  1 Tobacco companies expand their epidemic of death. Lancet. 2011; 377: 528.

  2 Diethelm PA, Rielle JC, McKee M. The whole truth and nothing but the truth? The research that Philip Morris did not want you to see. Lancet. 2005; 366: 86–92.

  3 Tanne JH. Drug advertisements in US paint a ‘black and white scenario’. BMJ. 2007; 334: 279.

  4 Braithwaite J. Corporate Crime in the Pharmaceutical Industry. London: Routledge & Kegan Paul; 1984.

  5 Almashat S, Preston C, Waterman T, et al. Rapidly increasing criminal and civil monetary penalties against the pharmaceutical industry: 1991 to 2010. Public Citizen. 2010 Dec 16.

  6 Straarup B. [Good treatment – then hotels are no. 1]. Berlingske Tidende. 2005 Nov 25.

  7 Harris G. Drug makers seek to mend their fractured image. New York Times. 2004; July 8.

  8 Brody H. Hooked: ethics, the medical profession, and the pharmaceutical industry. Lanham: Rowman & Littlefield; 2008.

  2

  Confessions from an insider

  ‘You should take two vitamin pills every day, a green and a red one,’ my mother said. I was only about eight years old but asked,

  ‘Why?’

  ‘Because they are good for you.’

  ‘How do you know?’

  ‘Because grandfather says so.’

  End of argument. Grandfather had a lot of authority. He was a general practitioner and he was bright and therefore right. When I studied medicine, I once asked him whether he had spared some textbooks I could compare with my own to see how much progress there had been in 50 years. His reply stunned me. He had donated all his books to younger students shortly after he qualified. He felt he didn’t need them because he knew what they contained!

  I had great respect for my grandfather and his superb memory, but I have scepticism in my genes. How could he be so sure the pills were good for me? In addition, the pills tasted and smelled bad despite being sugar-coated; opening the bottles felt like entering a pharmacy.

  I dropped the pills and my mother undoubtedly found out why they lasted for so long but didn’t try to force me into eating them.

  It all looked so simple back then, in the late 1950s. As vitamins are essential for our survival, it must be good to eat vitamin pills to ensure we get enough of what we need to thrive. But biology is rarely simple. Human beings have developed over millions of years into the current species, which is very well adapted to its environment. Thus, if we eat a varied diet, we can expect to get adequate amounts of vitamins and other micronutrients. If some of our ancestors had gotten too little of an essential vitamin, they would have had less chance of reproducing their genes than people who needed less of the vitamin or absorbed it better.

  We also need essential minerals, e.g. zinc and copper, to make our enzymes work. But if we ingest too much, we get intoxicated. Thus, given what we know about the human body, we cannot assume that vitamin pills must be healthy. It is the earliest memory I have of a medical prophylactic intervention, and it took about 50 years before it became known whether vitamins are beneficial or harmful. A 2008 review of the placebo-controlled trials of antioxidants (beta-carotene, vitamin A and vitamin E) showed that they increase overall mortality.1

  Another childhood memory illustrates how harmful and deceitful the marketing of drugs is. Because of our generally bad weather in Denmark, my parents, who were teachers with long vacations, migrated south every summer.
In the beginning only to Germany and Switzerland, but after some heavy bouts of bad weather with pouring rain even there, which isn’t great fun when you live in a tent, northern Italy became the destination. My grandfather gave us Enterovioform (clioquinol) to be used if we got diarrhoea. This drug was launched in 1934 and had been very poorly studied.2 What my grandfather didn’t know and hadn’t been told by the salesman from the Swiss company Ciba was that the drug only had a possible effect on diarrhoea caused by protozoans (amoebae and Giardia) and Shigella bacteria, and that even that effect could be disputed, as no randomised trials had compared the drug with placebo. Furthermore, it wasn’t likely we would get exposed to such organisms in Italy. Traveller’s diarrhoea is almost always caused by bacteria other than Shigella or by viruses.

  Like so many other general practitioners, even nowadays, my grandfather appreciated visits by drug salespeople, but he had been the victim of shady marketing, which had caused the drug to be very commonly used.3 Ciba started marketing clioquinol to fight amoebic dysentery,2 but by the time the company entered the lucrative Japanese market in 1953, it was pushing clioquinol worldwide for all forms of dysentery. The drug is neurotoxic and caused a disaster in Japan where 10 000 people had developed subacute myelo-optic neuropathy (SMON) by 1970.2 SMON victims suffered a tingling in the feet that eventually turned into total loss of sensation and then paralysis of the feet and legs. Others suffered from blindness and other serious eye disorders.

  Ciba, which later became Ciba-Geigy and Novartis, knew about the harms but concealed them for many years.4 When the catastrophe in Japan became known, the company released statements defending the drug, saying that clioquinol couldn’t be the cause of SMON because it was essentially insoluble and couldn’t be absorbed into the body.2 However, attorneys preparing a lawsuit against the company found disturbing evidence that the drug could indeed be absorbed, which the company also knew. Already in 1944, clioquinol’s inventors advised in light of animal studies that the administration of the drug be strictly controlled and that treatment should not exceed 2 weeks.