|Title||Deadly Medicines and Organised Crime|
|Subtitle||How Big Pharma Has Corrupted Healthcare.|
|Author||Professor Peter Christian Gøtzsche|
|Publ. date||2013 in English and Danish, 2015 in German|
|Comments||BMA Award winner in the category Basis of Medicine 2014 (BMA, British Medical Association).|
In a precise and in-depth manner, professor PETER CHRISTIAN GØTZSCHE describes the many manipulations (also intrigue) of the pharmaceutical industry. It is a story of deception, concealment of negative studies, bribery, intimidation, and threats directed at critics (criticism). The goal of the major players in this industry is to make their already huge profits even larger. The book does not contain a critique of capitalism.
It is easy to read and comes across a bit like a crime thriller. However, in our book review, we only have room to present the facts, which are somewhat drier to read. We were onlz able to include a few of the many examples from the book.
The author suggests a number of solutions, which he summarizes in Chapter 21. Keywords here are independent MEDICAL TESTING BODIES and regulatory authorities, rejection of money and benefits the industry provides to those who play a role in the healthcare industry including physicians, hospitals, universities, institutes, self-help groups, newspapers, journalists, and politics, and preventing conflicts of interests where experts are involved.
The book is definitely a must-read for all medical professionals who still believe that the pharmaceutical industry acts in the best interest of patients and not simply for their own benefit. It is a question whether or not this book should also be recommended to laypeople without prior knowledge. After reading this book or our book review, no one should simply stop taking their medications. Instead, they should consult their physician and give him or her this book review to read. You can just send them the link. There are many essential medications.
In contrast to the information in this book, you should know that we owe the successes we have had with achieving a higher life expectancy to the pharmaceutical industry. This scathing but objective critique doesn’t have the task of conveying this fact. This book review includes confirmation that GØTZSCHE is right on the mark. Click on the images with links to YouTube to hear more about ways the pharmaceutical industry engages in fraudulent behavior.
In the section about the author, we learn that GØTZSCHE is highly educated and holds several degrees and from the statements and forewords written by his colleagues, we see that he is highly regarded in the scientific community. You should read both of the forewords before you read this book review because the facts seem almost unbelievable and shocking — even for a physician — or maybe especially for a physician. The forewords are available on amazon. Simply click on the image of the book there to access them.
|EE: ZDF, a German public-service television broadcaster in Germany, is known for its reliable and unbiased reports. The YouTube channel DieAndereWahrheit (The other truth) includes a ZDF video of just over three minutes with the title Ein Pharma-Insider packt aus (A pharma-insider reveals the shocking truth). This is further evidence that the book discussed here depicts the situation as it is — without exaggerating.|
What is the subject of this book? It deals with the methods employed by pharmaceutical companies and their managers. Their goal is usually to increase their profits, no matter what the price. Using the tricks provided by the author, they could offer good, effective medications that have very few side effects and are reasonably priced. But if a company wants to be successful today, this can’t be their goal. Society would have to first change.
The book has 22 chapters. There is also an appendix that includes numerous literature references (pp. 443–502) for every chapter as well as a ten-page index (p. 503–512). In this book review, you will find links to some of the literature references. But this is still a work in progress. The quality of Dr. GØTZSCHE’s work can also be seen in the number of literature references (1,142) that for the most part are scientific articles that interested readers can obtain and review.
The author dedicated the book to the many honest people who work in the pharmaceutical industry who are as outraged as he is about the criminal dealings of their superiors and the consequences that these have on patients and the economy. To some extent, the companies in the food industry act similarly, as we saw in the book review of Salt Sugar Fat (book written by Michael Moss). Moss received a Pulitzer Prize for his book.
EE: Both books, Salt Sugar Fat and Deadly Medicines and Organised Crime actually only show how people act when money and/or prestige are at stake. In our schools, we are failing to teach ethics and the meaning of ethics. In-depth study, specifically applied ethics (see domains included), philosophy, and further education should be offered for young adults — as required subjects for both genders. Otherwise, society doesn’t have the chance to change, and it must change. There is no doubt about that. This is similar to when we take a country that doesn’t understand democracy and try to introduce just this or even a direct democratic system as we have in our Western countries.
See also the entry on business ethics on Wikipedia. On the German entry for the topic, we read “Central values here are humanitas, solidarity, and responsibility.” When we compare theory and practice with political entanglement, we can only come to the conclusion that the well-intentioned and good recommendations the author makes aren’t realistic as they aren’t far-reaching enough. The majority doesn’t have the will to change the situation. And they are far from being able to delve into this topic or see the problem and its implications in the long term.
As the table of contents is very detailed, here is a list of just the chapters (as clickable anchors):
- Confessions from an insider
- Organised crime, the business model of big pharma
- Very few patients benefit from the drugs they take
- Clinical trials, a broken social contract with patients
- Conflicts of interest at medical journals
- The corruptive influence of easy money
- What do thousands of doctors on industry payroll do?
- Hard sell
- Impotent drug regulation
- Public access to data at drug agencies
- Neurontin, an epilepsy drug for everything
- Merck, where the patients die first
- Fraudulent celecoxib trial and other lies
- Switching cheap drugs to expensive ones in the same patients
- Blood glucose was fine but the patients died
- Psychiatry, the drug industry’s paradise
- Pushing children into suicide with happy pills
- Intimidation, threats, and violence to protect sales
- Busting the industry myths
- General system failure calls for a revolution
- Having the last laugh at big pharma
See this Wikipedia entry on CONSORT (Consolidated Standards Of Reporting Trials). The CONSORT Group, based at The Ottawa Hospital Research Institute (OHRI) in Canada and at additional locations, is trying to introduce guidelines for publishing randomized treatment studies that could dramatically increase their reliability.
You can enlarge all of the images by clicking on them and in this case then read the text.
About the author
Professor PETER C. GØTZSCHE is a specialist for internal medicine. Before going to medical school, he earned a master’s degree (MS) in biology and chemistry. From 1975–1983, he led clinical studies for pharmaceutical companies and was involved in the approval of medicines and in 1984 he completed his medical degree. Since 2001 GØTZSCHE has served as a professor for clinical research design and analysis at Rigshospitalet in Copenhagen.
He cofounded the Cochrane Collaboration in 1993. This is an independent, nonprofit organization that carries out rigorous and systematic analyses of randomized controlled studies to provide clear information about the advantages and disadvantages of treatment options. GØTZSCHE is the coauthor of the CONSORT Statement for randomized controlled studies, the STROBE Statement for observational studies, the PRISMA Statement for systematic reviews and meta-analyses, and the SPIRIT Statement for recommendations for interventional trials.
He is an editor in the Cochrane Methodology Review Group, which has the slogan “Trusted evidence. Informed decisions. Better health.” (Cochrane). According to the back cover (German edition) of the book, GØTZSCHE has written more than 50 articles for the “big five” medical journals: BMJ, The Lancet, JAMA, Annals of Internal Medicine, and New England Journal of Medicine. His scientific works have been quoted by others more than 10,000 times (p. 21 and back cover).
He is also the author of Rational Diagnosis and Treatment: Evidence-Based Clinical Decision-Making (Wiley, 2006) and Mammography Screening: Truth, Lies and Controversy (Radcliffe 2012). GØTZSCHE received the Annual Book Award of the British Medical Association in 2014 in the category Basis of Medicine.
On the ZDF’s heute-show (satirical television program) on May 14, 2010, Martin Sonneborn interviews a spokesperson for the lobby association ProGenerika. In this YouTube video (German only, 3:42 min) uploaded by QVCinsider, you can hear more about how cheap medications from China or India really have the same quality as medications produced in Europe.
|It’s quite funny, the point being that the pharmaceutical industry wants us to buy their more expensive medications, but it doesn’t add anything that isn’t already included in this book.|
Forewords and statements
Dr. Peter Sawicki, diabetologist, agrees with the author that the pharmaceutical industry is endangering our health with the ways that they strive to make profits, regulatory authorities that work inefficiently, and legislative bodies that fail to pass effective laws to protect the people. Dr. Sawicki is the former head of the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wissenschaftlichkeit im Gesundheitswesen, IQWIG). Politicians released him from service in 2010.
Dr. Wolfgang Becker-Brüser, also a Pharm. D. and editor of Arznei-Telegramm (German medical journal) doesn’t see the provocative title to be an exaggeration. The sponsor of Arnzei-Telegramm, an ad-free journal, is A.T.I. Arzneimittelinformation Berlin GmbH.
Best-seller author Dr. Frank Wittig considers GØTZSCHE to be the most high-profile pursuer of the pharma mafia in the world. Dr. Wittig is also an author and wrote the books Die Weisse Mafia (The white mafia, Feb. 2013), which was a Spiegel (influential German magazine) best seller, and Krank durch Früherkennung (Sick by early detection, Sept. 2015). See the interview with him conducted by Thieme Verlag with the title Mafiöse Machenschaften (Mafia-style manipulations, in German only) and an interview conducted by SWR1 (German radio station) about his latest book published by Riva Verlag on senseless early detection methods for breast and prostate cancer.
In his foreword, Dr. Richard Smith praises the way GØTZSCHE systematically uncovers the methods used by pharma companies and their warehouses. These include, bribery, deception, concealment of study results, use of medications that don’t meet the requirements of regulatory authorities, threats, and the pursuit of informants. Dr. Smith worked for the British Medical Journal (BMJ) for a total of 25 years and was the editor for 13.
Wikipedia on Dr. Smith: “He sits on the Board of Directors of the Public Library of Science, an open access publisher of scientific and medical research. He was editor in chief of the open-access Cases Journal, which aimed to create a database of medical case reports.” And he was also head of UnitedHealth Europe, a division of UnitedHealth.
See also The Constant Gardener by John le Carré (2001) and the film adaption with the same name by Fernando Meirelles (2005).
Smith quotes the former vice-president of Pfitzer as saying: “It is scary how many similarities there are between this industry and the mob. The mob makes obscene amounts of money, as does this industry. The side effects of organized crime are killings and deaths, and the side effects are the same in this industry. The mob bribes politicians and others, and so does the drug industry” (p. 13).
In a second foreword, Dr. Drummond Rennie, a former editor for the Journal of the American Medical Association, affirms the author’s unparalleled position that are result of “his unique scientific abilities, research, integrity, truthfulness, and courage” (p. x). As Rennie has also had decades of experience with the pharmaceutical industry and knows Dr. GØTZSCHE well, he trusts him to “have his facts right” (p. x). The title of his forward is “Evidence-based outrage.”
Several of the chapters are broken into sections with subtitles, one of which has 11 in total. The table of contents above does not include these subtitles as it would then be too long for our purposes, but in the text below, these three-digit decimal numbers are easy to find. If you click on the titles of the chapters in the table of contents above, you will be brought directly to the relevant chapter (anchor).
Professor PETER CHRISTIAN GØTZSCHE writes that the major epidemics are under control in the majority of the countries in the world — and he criticizes the fact that many poor people still die of AIDS or malaria because they can’t afford the expensive medications. Instead we have two new epidemics: tobacco and medications.
Quote from the author: “In the United States and Europe drugs are the third leading cause of death after heart disease and cancer” (p. 1).
He compares the tobacco industry with the pharmaceutical industry. Although there have long been studies about the addictive nature and the harm that both active and passive smoking cause, these were not published and their existence was kept confidential. The tobacco firm Philip Morris even conducted some of the studies itself. When reputable researchers prove that a product is dangerous, a number of studies appear out of nowhere that show the opposite and make people feel insecure. And this allows the industry to buy themselves time — both the tobacco — and the pharmaceutical industries. “This is corruption” (p. 2).
There are various types of addiction including substance dependence, which is a group of psychological and behavioral disorders (syndrome) caused by repeated consumption of psychoactive drugs. This can include strong, periodic, or lasting desire for a certain substance, a progressive neglect of responsibilities or activities, loss of control, and compulsive consumption of the substance. In medical terms, this is called addiction.
Society often tolerates certain types of addiction such as nicotine dependence, video game addictions, gambling addictions, caffeine dependence (coffee addictions), and alcohol dependence (alcoholism). See also information about the dangers of passive smoking
Very few people know that caffeine can have toxic effects when more than 1 g per day is consumed. 1 g of caffeine is found in 10 liters of standard soft drinks or about 11 cans (250 mL each) of energy drinks. Wikipedia shows the addiction potential of a number of substances here (German only). “The substances with the highest physical addiction potential are heroin and nicotine.”
In the United States, TV commercials urge viewers to take pills, tablets, or capsules as a way to get their life back under control. “The characters in Aldous Huxley’s novel from 1932 Brave New World can take Soma tablets every day ... ” (p. 2). According to the author, the people in Denmark take so many drugs that it equals an average of 1.4 daily adult doses per person. Why do people do this? The author believes that the main reason is that the pharmaceutical companies aren’t selling drugs to people, but instead lies about drugs.
This book is not about the successes the pharmaceutical industry has had against infections, some types of cancer, and hormone deficiencies such as Type 1 diabetes; instead it is about the failures of the system and the reasons for this. The author writes, “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 are paid to remain anonymous, and the articles are then published under the names of well-known professors even though they often contribute nothing to the text (p. 3).
Confessions from an insider
The author begins by reporting on his first experiences with preventative medicines. When he was eight years old, he remembers his mom telling him that he should take two vitamins every day. In the 1950s, people still believed in the great benefits of taking multivitamins. It was not until 2008 that a study found that taking some types of vitamins increases overall mortality. See Bjelakovic G, Nikolova G. et al.: Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev.
His second experience was with Enterovioform (Clioquinol), which his grandfather gave them to take in case they got diarrhea while on vacation in Italy. This was quite senseless as the drug is only effective against diarrhea caused by protozoans (amoebae and Giardia) or Shigella bacteria (Shigella), but these were definitely not a problem in Italy. However, when used for a longer period of time, this drug can cause everything from nerve damage to paralysis of the legs and serious eye disorders. The company Ciba (a division of Novartis) knew this for some time. Even though 10,000 people in Japan had developed SMON by 1970 and the company paid 490 million dollars in damages to them, it didn’t take the drug off the market until 1985. SMON is the acronym for subacute myelo-optic neuropathy.
In the 1960s, corticosteroids were introduced to the market as the new miracle cure for Rheumatoid arthritis. It wasn’t until later that the serious adverse effects (e.g., bone fractures) of corticosteroids were discovered.
Upon completing a degree in chemistry and biology, the author applied for a position as a drug representative at Astra (today AstraZeneca). There he learned how to persuade physicians to use the company’s product rather than the products of its competitors. At the time, Astra had just introduced the drug Globacillin, a penecillin which was supposedly more effective against acute sinusitus than other drugs on the market. However, the supposed proof for this provided to him by the company was incorrect. The position wasn’t good for the author’s self-esteem, especially after he read the book Death of a Salesman (1949) by Arthur Miller (1915–2005).
After eight months, he became a product manager. In this position, he was responsible for the sales of the asthma spray Bricanyl (terbutaline and inhalers). The goal was to get doctors to prescribe their patients constant treatment with the spray. And asthma death rates increased accordingly.
The epidemiologist Dr. Neil Pearce from New Zealand (London School of Hygiene & Tropical Medicine (LSHTM) and previously president of the International Epidemiological Association (IEA)) wrote “a most disturbing account of the powers of the drug industry and its paid allies among doctors in relation to asthma” (p. 11).
Pearce N. Adverse Reactions: The Fenoterol Story. Auckland University Press. 2007. Why wasn’t this book published earlier? Because the author wasn’t able to find a medical journal that would print it in spite of threats from Boehringer Ingelheim! Link to a video titled Top 10 Lies That Advertising Has Sold You (7:13 min.).
Image: YouTube video about marketing persuasion techniques, with some photoshop corrections
Today, doctors no longer recommend the regular inhalation of short-acting beta-antagonists (Beta2-adrenergic agonist). And the asthma death rate has decreased accordingly.
The drug industry also tried to get doctors to prescribe terbutaline for chronic bronchitis. However, it wasn’t approved for this as no relevant studies had been conducted. And they also wanted to sell it as a cough medicine — but it was not approved for this purpose either.
Zinc lozenges were another “miracle drug” introduced at the time. They were approved for the treatment of venous and ischaemic leg ulcers. Although the studies conducted by the company were supposedly very impressive, a Cochrane review later showed the lozenges to have no beneficial effect.
During his time at Astra-Syntex, where he was responsible for clinical studies and registration applications for new drugs and indications, the author studied medicine. The most important drug for this company was naproxen (Naprosyn), a nonsteroidal anti-inflammatory drug (NSAID) used to relieve pain and inflammations without cortisone and prescribed, for example, for “joint wear.”
NSARs are a dime a dozen. A new drug should actually be better than the previous, cheaper versions, but the company wasn’t interested in a comparative study. Those responsible already knew that their drug wasn’t better, only more expensive. In a study conducted in cooperation with orthopedic surgeons, PETER C. GØTZSCHE determined that naproxen did not have an anti-inflammatory effect, as the company had claimed.
The principle investigator divided the patients with ankle distortions into two groups. One group received crutches and the other did not (mobilization). The swelling (edema) disappeared more quickly in the patients who were mobilized. Naproxen had no impact. As NSARs have been shown to have a number of side effects on the stomach, heart, and kidneys, in many cases they could be replaced by less dangerous and perhaps cheaper pain relievers.
The company advised physicians to prescribe a double dose instead of the standard dose, but failed to mention that the effects did not improve and the harm, in the form of side effects, doubled.
In his doctoral thesis Bias in Double-Blind Trials, PETER C. GØTZSCHE showed that many studies are designed to come out in favor of the sponsoring company’s drug and against the control drug (sponsors).
Other companies also used aggressive methods to try to sell their NSAR as the best on the market. Pfizer stated that piroxicam (Feldene) was more effective than aspirin, even though it was shown to be dangerous for older people in particular as the slower excretion causes it to accumulate in the body and to cause an increased incidence of stomach bleeding. Eli Lilly even went so far as to falsely claim that its drug benoxaprofen (Opren, Oraflex) was capable of preventing the advance of joint damage. It did not inform the authorities that the drug caused severe liver defects.
The supposedly good gastrointestinal tolerance of the coxibs (celecoxib, etoricoxib, rofecoxib, lumiracoxib, and parecoxib) was accompanied by serious cardiac side effects (selective COX-2 inhibitors).
Organised Crime, the Business Model of Big Pharma
The pharmaceutical industry doesn’t speak about the advantages and disadvantages of its drugs, but instead of their efficacy and safety. When doctors prescribe medications and patients take them, both parties are convinced that the pharmaceutical industry has done thorough testing and the drug regulatory authorities have “carefully scrutinised” them (p. 53). Pharmaceutical companies try to create the impression that they do so, but not even the majority of the employees believe their bosses are honest.
Examples of settlements
In 2012 Pfizer paid $60 million to stop a US federal investigation into bribery in Europe and Asia. Pfifzer was accused of hiding money paid out as costs for training, freight, and other regular expenses.
From the 1970s up to the end of the 1990s, a cartel of vitamin producers (Vitamin Inc.) led by Hoffmann-La Roche worked together to artificially keep the prices of vitamins high. After the conspiracy was uncovered, some managers were imprisoned for a short period of time, and some companies paid fines in amounts up to $500 million and £523 million. But that is only a small percentage of the profits that the companies made with their price manipulations.
Between the two world wars, Roche and other drug companies supplied the black market in the United States with opium, morphine, and heroin. For more information, see Corporate Crime in the Pharmaceutical Industry by John Braithwaite, publisher Routledge & Kegan Paul, London, 1984.
At the beginning of the 1970s, Roche was ordered to pay fines for obstructing sale of the tranquilizers Valium and Librium. After reports were published which clearly showed that tranquilizers are addictive, it took 27 years before drug regulators acknowledged this fact.
Quote from the author: “I believe that the fact that some drugs affecting the brain are legal and others are illegal is irrelevant from an ethical perspective, if we try to understand what the drug industry is doing to the population” (p. 25).
|This video (44:17 min.) is from the program ZDF Frontal 21 (political show on the German television channel ZDF). The video titled Das Pharma-Kartell - Wie Patienten betrogen werden (The pharma cartel—how patients are deceived) clearly explains how the pharmaceutical industry uses certain steps and strategies to achieve its goals. Uploaded by DieAndereWahrheit.|
The Hall of Shame for Big Pharma
Although the British Medical Journal (BMJ) and the New York Times publish articles almost weekly about the misconduct of drug companies, the companies dismiss these by stating that they are isolated cases. In order to determine if this was indeed the case, in 2012 the author searched the Web (Google search combining the names of the top 10 drug companies with the word “fraud.” He then chose the most prominent case to describe in more detail:
- Pfizer agreed to pay $2.3 billion in 2009 because it was found that the company had marketed four drugs illegally. The company signed a Corporate Integrity Agreement, committing to good behavior for the next five years. Most likely it paid as little attention to this agreement as it had to the previous three similar agreements. One of these drugs was the antibiotic Zyvox (active ingredient: linezolid), which caused a number of deaths because the company falsely claimed that it was more effective against serious infections than the standard drug vancomycin. They claimed this because Zyvox cost eight times more than vancomycin.
- Novartis agreed to pay $423 million in 2010 for illegally marketing the epilepsy drug Trileptal (oxcarbazepine) for unauthorized used (pain and psychiatric issues). However, the company did the same with five other drugs.
- Sanofi-Aventis agreed to pay $95 million in 2009 for fraud. “The firm deliberately misquoted the prices, underpaying rebates to Medicaid and overcharging some public health agencies for the medications” (p. 27).
- GlaxoSmithKline (GSK) paid $3 billion as part of the largest healthcare fraud settlement in the US for illegally marketing drugs for off-label uses. This included marketing the antidepressant Wellbutrin (bupropion) for weight loss and the diabetes drug Avandia (rosiglitazone) for its supposedly positive effect on the circulatory system. The drug was later taken off the market because it was shown to have caused heart failure.
- AstraZeneca agreed to pay $520 million for fraud. The firm had recommended its antipsychotic drug Seroquel (quetiapine) to children, the elderly, and others for off-label uses. These included aggression, anxiety, dementia, Alzheimer’s disease, attention-deficit hyperactivity disorder (ADHD), depression, and sleep disorders.
- Roche was not even brought to court for what was the “biggest theft in history” (p. 28). Based on independent studies, the firm claimed that Tamiflu (oseltamvir) significantly descreased hospital admissions caused by influenza and secondary complications. In 2009, Roche managed to convince the governments in the United States and many European countries to purchase Tamiflu in the amount of several billions of dollars to prevent an influenza epidemic. Neither Tamiflu nor Relenza (zanamivir), the drug from rival company GlaxoSmithKline, are more effective than a placebo. An official at the Food and Drug Administration (FDA) had been assigned the application for oseltavamir, but as a result of pressure from Roche, this was taken away from him. Even though Tamiflu wasn’t effective, it did have some unpleasant side effects: hallucinations and weird accidents.
- Johnson & Johnson paid a fine of $1.1 billion in 2012 because it had downplayed the risks of the antipsychotic drug Risperdal (risperidone). J&J and its subsidiary Janssen had claimed that it had fewer side effects than other drugs in the same group and it was then prescribed to children and the elderly.
- Merck, the largest pharmaceutical company, paid $670 million over Medicaid fraud in 2007 because it “failed to pay the appropriate rebates to Medicaid and other government healthcare programmes” (p. 31).
- Eli Lilly paid $1.4 billion for illegal marketing in 2009 because it sold its antipsychotic drug Zyprexa (olanzapine) for several off-label uses (including dementia, Alzheimer’s disease, and depression, particular in children and the elderly) and minimized the side effects (e.g., heart failure, pneumonia, considerable weight gain, and diabetes. See the film Der Diabetesmythos (The diabetes myth).
- Abbott paid $1.5 billion for fraud in 2012 because it sold its epilepsy drug Depakote (Valproate) for uses not approved by the FDA.
We could naturally continue to list out many more cases:
Sanofi-Aventis knew about cases of fraud in a study on its antibiotic Ketek (Telithromycin), but the drug was still approved by the FDA. However, it wasn’t very long thereafter that the first death as a result of liver failure occurred. The drug is still sold in the United States, but there is a warning on the package and also a 26-page information brochure included.
And AstraZeneca , for example, paid millions as a payoff “after pleading guilty to charges that it encouraged physicians to illegally request Medicare reimbursements for its drug against prostate cancer, Zoladex (goserelin), and bribed doctors to buy it” (p. 33). Johnson & Johnson bribed hospital administrators and physicians in a number of countries so that they would use its products. ...
It is illegal to push generic drugs out of the market when the patent runs out (p. 34). Glaxo filed law suits without cause against its generics competitor as a way to keep a certain generic drug off the market. In the United States, a company can legally do this to keep a competitor’s product off the market for 30 months.
For decades, Bristol-Myers Squibb blocked the market entry of cheap cancer drugs by paying a generic manufacturer (generic drug) and providing false information. Lundbeck paid large sums of money to generic producers of Cipramil (citalopram) as a way to delay the market entry of the drug.
The firm Purdue Pharma falsely claimed that its opioid OxyContin (oxycodone) was less addictive than other opiates.
“In 2004–05, the Health Committee in the British House of Commons examined the drug industry in detail and found that its influence was enormous and out of control. They found an industry that buys influence over doctors, charities, patient groups, journalists and politicians, and whose regulation is sometimes weak or ambiguous” (p. 37).
The report showed that it would be good to limit the industry’s influence, also good for the industry because then they could again concentrate on developing new drugs instead of spending money on corrupt deals. But the British government did nothing; after all, the pharmaceutical industry is the third most profitable industry in the country (p. 37).
As proof that the pharma industry falls into the category of “organised crime,” the author describes the Racketeer Influenced and Corrupt Organizations Act (RICO, act against racketeering), which was created to fight against the mafia and similar organizations. “The list of offences that constitute racketeering include extortion, fraud, federal drug offences, bribery, embezzlement, obstruction of justice, obstruction of law enforcement, tampering with witnesses, and political corruption” (p. 38).
In the United States, the pharmaceutical companies violate the law three times more than other industries. The number of settlements and fines for misconduct has increased dramatically over the last few years and decades. The pharmaceutical industry’s claims that these accusations are old and that it has changed its practices radically are therefore simply not true.
Very few patients benefit from the drugs they take
In this chapter, the authors explains the importance of double-blind trials. With this type of study, neither the patients nor the doctors know who receives the medication and who receives the placebo. The assessment of the effectiveness changes depending on who and what percent of the investigators and test subjects aren’t “blind.” The author also explains that the patients who receive the placebo often know this because they don’t experience any side effects. For a while, “active” placebos were used. These produce side effects similar to that of the active drug, for example, dryness in the mouth. However, active placebos are no longer used because they are not in the best interest of the pharmaceutical industry. This is because they show a smaller difference between the effectiveness of the drug and placebo. But with clever mathematical calculations and repeat studies, the results can be inflated. Because there is certainly a study out there that will yield the right results.
The Number Needed to Treat (NNT) is a practical method used to determine how many people will be helped by a certain treatment. Using the example of statins, the author explains that an NNT is not provided for healthy patients with high cholesterol because they do not benefit from the treatment. However, they do experience a diminished quality of life because of muscle pain and weakness.
Clinical trials, a broken social contract with patients
As the pharmaceutical industry has had a monopoly on clinical trials conducted on its own products and only published the information that is to its benefit, this social contract has been broken over and over again. The industry doesn’t only hide negative studies, it also intimidates people who have discovered harmful effects of its medications. It covers up study aims if the desired result is not achieved and it designs studies so that the results can hardly be refuted.
Our governments have not succeeded in regulating the powerful pharmaceutical companies or in protecting “scientific objectivity and academic curiousity” (p. 52) against commercial interests.
In the first half of the twentieth century, drugs were hardly tested before they were put on the market. However, this did change to some extent after the thalidomide disaster in 1961–62. The drug was recommended by the manufacturer Grünenthal GmbH for several indications including pregnancy-induced nausea. After this disaster, extensive animal experiments and efficacy trials were finally introduced. However, a large number of drugs that had not been tested remained on the market.
It is particularly problematic that the only requirement for the approval of a drug is that the pharmaceutical industry can show it has a statistically significant effect in two placebo-controlled trials. “However, there are numerous ways in which a drug company can manipulate its clinical trials to ensure that the results become useful for its salespeople, no matter what an honest approach to science would have shown. The manipulations are so common and serious that one of my colleagues said that we should see published reports of industry trials as nothing else than advertisements for its drugs. To which I dryly remarked that industry trials do not even live up to EU requirements for advertising” (p. 53)
In the case of three major cardiovascular trials conducted by independent researchers, it was shown that the results were misleading and in each case in favor of the sponsor’s drug. The names of the drugs, trials, and sponsors were as follows: prasugrel in the TRITON trial for Daiichi Sanyko and Eli Lilly; ticagrelor in the PLATO trial for AstraZenca, whereby for these two the number of heart attacks for the comparator was doubled, and rosiglitazone in the RECORD trial for GlaxoSmithKline. In the RECORD trial, the number of heart attacks supposedly decreased from 24 to 8. However, to achieve this result the pharmaceutical company had to slightly change the definition of a heart attack.
If the main trial doesn’t yield any positive results, researchers always have the option of focusing on subgroup analyses. The practice of going through data until something is found randomly is referred to as data massage or fishing expeditions. One of these fishing expeditions led to the recommendation that patients with spinal cord injury be prescribed high-dose steroids. Fourteen years and thousands of deaths later, it was discovered that in the trial with 31 patients one of the patients who had been treated with cortisone instead of the placebo had died.
As long as studies are designed by firms and the data can only be published with their approval, we shouldn’t wonder that our drugs are getting more expensive but not better. The Fortune 500 (500 companies with the most revenue) report for 2012 found that the profits of the ten pharmaceutical companies with the most revenue exceeded the sum profits of 490 other companies.
The extensive CRASH trial published in The Lancet on the effects of steroids on 10,000 people with serious brain injuries showed that steroids are very dangerous. “For every 31 patients treated with steroids rather than placebo, there was one additional death. Thousands of patients with spinal cord or brain injuries have died because they were given steroids and the fishing expedition in the New England Journal of Medicine is to blame for many of these deaths” (p. 61). Another interesting link: Why we can’t trust clinical guidelines.
Conflicts of interest at medical journals
Medical journals are finding it increasingly difficult to find authors who are independent from the pharmaceutical industry. They also have difficulties rejecting “pro-industry” articles because they then lose out on the profits for lucrative reprints and advertisements paid for by the industry. This fact was also confirmed by the former editor of the British Medical Journal. According to GØTZSCHE, the New England Journal of Medicine (NEJM) is the pharmaceutical industry’s preferred journal and the journal with the highest impact factor. As an example of why he is not a fan of this journal, he describes an article about a drug from Pfizer for treating invasive fungal infections. Two trials were conducted:
“In one of the trials, voriconazole was significantly inferior to the comparator drug, liposomal amphotericin B, according to the prespecified analysis plan, which staff at the FDA pointed out in a subsequent letter, but the paper concluded that voriconazole was a suitable alternative. More patients died in the voriconazole group and a claimed significant reduction in ‘breakthrough’ fungal infections in favour of voriconazole disappeared when we included infections that had arbitrarily been excluded from analysis. The abstract described manipulated results ... ” (p. 66).
“The other trial used amphotericin B deoxycholate as a comparator, but handicapped the drug by not requiring pre-medication to reduce infusion-related toxicity or substitution with electrolytes and fluid to reduce nephrotoxicity, although the planned duration of treatment was 84 days.” The new drug voriconazole, which was under investigation was given as treatment for serious fungal infections (mycosis) for an average of 77 days, whereas the comparator drug was only given for an average of 10 days.
This “precludes a meaningful comparison. The last sentence in the abstract was: ‘In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.’ A trial that is seriously flawed by design doesn’t allow any such a conclusion” (p. 66).
“By publishing such terribly flawed trial reports the New England Journal of Medicine not only earns a lot of money from selling reprints, the editors also boost the journal’s impact factor, especially because companies usually orchestrate a large number of ghostwritten, secondary publications that cite the trial reports” (p. 66).
The author shows how a number of various types of studies have resulted in misleading results and describes one study in particular that was published in the NEJM. This study recommended that all patients with smoker’s lung be prescribed fluticasone (cortisone or glucocorticoid), but the recommendation was made based on an inappropriate analysis. According to the author, the British Medical Journal (BMJ) is a journal that is very dependent on pharmaceutical companies.
The corruptive influence of easy money
Speaking from his own experience, the author explains how corruption can begin. About 20 years ago, he took part in a planning meeting with clinical investigators and a certain company. In the evening, the head of the division for clinical trials gave him an envelope that contained cash. “If you don’t send the money back, you have signalled that you might be willing to think you are even more valuable for the company the next time” (p. 70). At the beginning, the amount of money you receive could be considered commensurate to the service you provide. But with time the amount increases and at some point the person receiving the money doesn’t even notice how disproportionately high the payments have become. They are, of course, beholden to the company and have to sometimes recommend drugs that are more expensive or less effective or use these in their practice even if a cheaper generic version becomes available.
Comment from EE: On page 70 of the book, you can find this statement about the envelope. “The envelope contained a letter thanking me for my contribution to the one-day meeting and a $1000 bill.”
I believe that this must be a translation error because the last time that one thousand dollar bills were printed was in 1945, and the distribution of these was stopped in 1969. However, they were still a legal means of payment after this. On the German version of Wikipedia, it says, “Banknotes with a value of $100 or more are no longer distributed, but they are still considered to be a legal means of payment; however, their collector’s value exceeds their face value by far. The majority of these banknotes that are still in circulation are owned by collectors and museums.”
The pharmaceutical companies naturally also have influential friends in politics and law. “When a person from the Pennsylvania Office of the Inspector General had uncovered payments into an off-the-books account from Pfizer and Janssen, he was appointed lead investigator. After his findings had revealed that these payments went to state employees who developed guidelines recommending expensive new drugs over older, cheaper drugs, he was escorted out of his workplace and told not to come back after being told by a manager that ’drug companies write cheques to politicians on both sides of the aisle’ ” (p. 71).
Comment from Dr. LÖ: The following quote was taken from the article The Drug Pushers, which appeared in The Atlantic: “A particular gift may have no influence, but it might make a doctor more apt to think that he or she would not be influenced by larger gifts in the future. A pizza and a penlight are like inoculations, tiny injections of self-confidence that make a doctor think, I will never be corrupted by money.” I think this idea that a pizza or penlight would do so much for the self-confidence of doctors that they could be bribed in this way is an insult to “small doctors” who really give their all when working with patients. Our self-confidence is really not so low, and we are not worth so little that we would prescribe something we weren’t confident of.
What do thousands of doctors on industry payroll do?
A small percentage of doctors serve in valuable research positions, for example, as investigators in relevant trials. However, most doctors work to help companies market their products. This is necessary because there are only rarely truly new and better drugs. In 2009, Prescribe (journal in France) analyzed 109 new drugs or indications: 3 were considered a minor therapeutic breakthrough, 76 added nothing new, while 19 were deemed to represent a possible public health risk” (p. 74). In order to sell the 106 products that weren’t really necessary, they needed a lot of assistants. These companies sponsor clinical trials whose only purpose is to provide the marketing department with sales arguments. The worst of these trials are called seeding trials. These studies are not of any scientific value and are conducted without a control group. Doctors are given a supply of the new drug and paid for every patient they have who uses the drug. Most of the doctors actually believe that in this way they are contributing to research.
Opinion leaders can be bought for a price. They receive a lot of money, and in return companies occasionally use their name for recommendations and these individuals refrain from writing negative articles about poor or overpriced medications.
Companies also need a lot of lecturers for industry-sponsored meetings. These lecturers explain why the sponsor’s drugs are better and whether or not there are off-label uses for these drugs. “A notorious example of off-label use of drugs that has harmed hundreds of thousands of healthy people is the so called hormone replacement therapy. The name legitimised the idea that the hormones should be taken not only around menopause but for the rest of the women’s lives” (p. 83). The hormones had been praised for their ability to help prevent coronary heart disease until a randomized trial showed that they in fact cause heart disease. See also the Million Women Study.
Wikipedia (German version): “In Great Britain, the use of HRT drugs in women between the ages of 50 and 64 led to an estimated 20,000 cases of breast cancer.”
YouTube video, 13 min, with Dr. David Healy called “Bad Medicine.”
Clinical trials conducted by pharmaceutical companies are often marketing in disguise. The author gives the example of trials conducted for new nonsteroidal anti-inflammatory drugs that were much too small to be statistically significant. A Cochrane review also concluded that in the majority of statin trials they analyzed, the sponsor’s drug had much better results as compared to the competitor’s product. GØTZSCHE tells us about a number of the tricks used, giving relevant examples, and writes the following about one of the examples:
“ ‘Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an explanatory analysis of head-to-head comparison studies of second-generation antipsychotics.’ In a mathematical sense, this shouldn’t be possible. If A is higher than B, and B is higher than C, then C cannot be higher than A” (p. 89).
As was already mentioned, the industry likes to have ghostwriters write its articles. These can then be quoted in other ghost-papers and in promotional materials, as if they had been written by another author. Of course, it is even better to find a renowned expert who is willing to put their name on the article without ever having contributed to the content of the article.
Dr. David Healy reported how open some companies are toward the doctors they work with. He once received the following: “We have had our ghostwriter produce a first draft based on your published work. I attach it here” (p. 91). When Dr. Healy stated that the drug didn’t deserve such a positive review and suggested changes, he received the answer that the company had overlooked some “commercially important” points. The company then published the article under the name of another researcher (p. 91).
However, literature is not necessarily needed for marketing to be successful. An aggressive advertising campaign can also do the trick as the author shows with the example of the gastric acid inhibitor Zantac (ranitidine). Up until 1977, stomach ulcers were frequently treated by operations, and people sometimes died of stomach bleeding. But in 1976, Cimetidine, a drug that reduces stomach acid, came on the market under the name Tagamet. This drug was developed by James Whyte Black from the company Smith Kline & French. Black received a Noble Prize for his work.
In 1983, GlaxoSmithKline introduced a very similar drug to the market called rantidine under the name Zantac. It wasn’t better, but the fact that the price was 50% higher than its predecessor suggested its superiority. The company also carried out an extensive promotional campaign, making this the number 1 choice for the treatment of heartburn
After just three years, Zantac had become the best-selling drug in the world. On Wikipedia (German entry), we read “Rantidine has about 10 times the activity of cimetidine, but it has significantly fewer side effects.” Today there are generic versions of rantidine called Junizac (D), Pylorisin (A), Ranic (A), Ranicux (D), Ranimed (CH), Raniprotect (D), Ranitic (D), Sostril (D), Ulcidin (CH), Ulsal (A), Zantac (A), and Zantic (D, CH) as well as numerous generic products.
It is much more lucrative for pharmaceutical companies to put their money into advertising, drug samples, sponsored meetings and training, and paid experts and pharmaceutical representatives than into serious research and trials. In any case, it will definitely pay off to invite the right experts to come on a promotional trip to the Caribbean. The author gives the example of one such trip on which the doctors learned about a new antibiotic and a new cardiovascular drug. Afterwards, the antibiotic was prescribed three times as often at the participants’ hospitals and the cardiovascular drug twice as often.
Using the example of ondansetron, a drug used against nausea and vomiting caused by chemotherapy, the author shows how the company used small trials to prove that this drug also worked against similar problems after surgery. When the patent ran out, it seemed that the effectiveness of this drug “evaporated overnight” (p. 96).
Previous editors of the NEJM and the BMJ have written books about the mostly undesirable interactions between the pharmaceutical industry and physicians, for example, The Truth About the Drug Companies, How They Deceive Us and What to Do about It by Marcia Angell, (MD, born 1939) New York 2004, Random House.
On the left is an image from this informative video, which is however quite long at 1 hour 17 minutes. If you search the name Dr. Marcia Angell, you will find other shorter viedeos, but these naturally include less information.
The book On The Take: How Medicine’s Complicity with Big Business Can Endanger Your Health by Jerome P. Kassirer, MD, Oxford University Press, 2005 contains the statement “Some physicians become known as whores.” This strong statement simple can’t be misinterpreted. Kassirer is a professor of medicine with a wealth of experience who writes very candidly. Because Kassirer was honest, he lost his position as chief editor as did his successor Marcia Angell, who also remained upstanding and honest.
The current and future trends in medical publishing, the ethics, and the influence the pharmaceutical industry and mass media have on medical journals are discussed in the book The Trouble with Medical Journals written by Richard Smith and published by Taylor & Francis Ltd (2006). An important related article also appeared in the Journal of the Royal Society of Medicine (JRSM). At the end of the article in the notes section, JRSM writes the following: “Richard Smith was editor of the BMJ and chief executive of the BMJ publishing Group for 13 years.”
With the example of biologic agents (biopharmaceutical) used to treat rheumatoid arthritis, PETER C. GØTZSCHE shows how an expert panel recommended these expensive medications even though two cheap medications had been shown to achieve the same results. After such recommendations are issued, it is very difficult to change them.
The author describes examples of expensive cancer drugs that, for example, only prolong life by 10 days and reduce the quality of life. In many cases, a cheap pain treatment would be better for patients.
The ALLHAT trial showed with a comparison of a number of drugs used to treat high blood pressure that doxazosin from Pfizer was less effective than the other drugs. The American College of Cardiology then recommended that doctors “ ’discontinue use of doxazosin’ ” (p. 99), but it changed its stance just a few hours later after Pfizer complained. After all, the company donated half a million dollars to the college each year.
|Wikipedia reflects on this trial as others have also done. When a damaging verdict is the result of a large-scale, double-blind trial, the industry answers with a number of studies that show the opposite — something the dairy industry also does — and consumers are left with the following statement: "The analysis of the study results remains controversial." After all of this, who should question the practices of large, established companies? Their helpers are often insiders at Wikipedia and block any and all corrections.|
As an example of an expert paid by the industry, PETER C. GØTZSCHE refers to the chairman of the Danish Society for Hypertension, an individual who always recommends the newest and most expensive drugs of his sponsor company.
Many patient organizations, for example, support groups, funded by the pharmaceutical industry play quite the inglorious role. And the members often don’t know that they are being used by the company to introduce and pay for expensive and often ineffective drugs.
Impotent drug regulation
There are federal drug agencies, but since the companies conduct trials themselves or have them conducted on their behalf or at least monitor them and then only have to submit reports about them, a number of tricks are possible to cover up harmful effects. Drug agencies can, for example, hide information about serious side effects in their “mountains of documentation” (p. 107).
Some officials virtually work part-time as advisors for companies that they should actually be monitoring or they might even own shares in these companies. If they have to leave a regulatory agency after a particularly large scandal, lucrative positions in the pharmaceutical industry are waiting for them.
The commissioner who approved Vioxx left the agency to work as a high senior official at Merck, the company that produced Vioxx. Vioxx is a arthritis drug that later had to be taken off the market because it increased the risk of heart attacks.
When unexpected serious side effects occur with drugs that are already approved, it often takes a long time until they are taken off the market because those involved don’t want to harm the company and, on the other hand, they don’t want to lose face because they approved a drug that had been poorly tested. The well-being of the patients is at best a very distant third.
Former employees of the Food and Drug Administration (FDA) report widespread corruption, including the intimidation or transfer of honest officials. In one case, the FDA even installed spyware on the computers of some of its scientists, and a manager threatened one of the employee’s children (pp. 111–112).
For example, “In 2006, the FDA introduced new labelling regulations, but after the 5-year period of comments had expired, the agency quietly added a new section that would make it virtually impossible for patients to file liability claims against the companies when the patients had been harmed by their drugs. ... This immunity would apply even if a company failed to warn prescribers or patients adequately about a known risk, unless a patient could prove that the company intentionally committed fraud” (p. 111).
In 1993, a bribery scandal was uncovered in Italy in which the minister of health, the general manager of the pharmaceutical department, and a number of academics were involved. These individuals were responsible for the approval of many drugs that were either dangerous or sold at exorbitant prices; they caused the state damages in the amount of $3 billion.
The unbearable lightness of politicians (p. 114)
In the United States, the pharmaceutical industry is a very generous donor to election and political campaigns. And there is more than one lobbyist from the pharmaceutical industry for every member of Congress. The Republicans receive the majority of the money. And in return they take measures to help the industry; for example, in 1994 the Republicans attempted to get rid of the FDA altogether and let the pharmaceutical industry approve drugs on its own and regulate itself.
“The lobbying has been so successful that FDA executives now see the industry, and not the American people, as their clients and they even negotiate with the industry about performance goals” (p. 114). In 2002, the nomination of a new FDA commissioner was withdrawn because it was felt that he placed too much importance on drug safety.
The industry has benefited from the shorter turnaround times for drugs because drugs can then be approved after only superficial testing. These expedited procedures were intended for the approval of urgently needed lifesaving drugs. Whether or not the umpteenth drug for Diabetes type 2, pain, or obesity falls into this category is questionable — all three of these types of drugs had to later be taken off the market because of serious side effects.
Good lobbying caused the European Commission to make the absurd recommendation that the following clause be deleted: “marketing authorisation for a drug shall be refused if its therapeutic efficacy is insufficiently substantiated by the applicant!” (p. 117). The consumer organization Health Action International (HAI) Europe has protested this and many other dangerous proposals. You would think that this would be the responsibility of politicians.
There have also been some small signs of progress. For example, the European Medicines Agency (EMA), which you could say is the European FDA, was until recently under the Directorate General for Enterprise and Industry in the EU, but is now part of the Directorate General for Health & Consumers. And the extreme privacy rules for drug regulation were relaxed in 2010.
Drug Regulation Builds on Trust
In this section, the author begins with a quote from Dr. Alan Maynard, a well-known British health economist: “Economic theory predicts that firms will invest in corruption of the evidence base wherever its benefits exceeds its costs. If detection is costly for regulators, corruption of the evidence base can be expected to be extensive” (p. 119).
The industry claims again and again that the drug regulatory system builds on trust. But why should we believe that a drug doesn’t cause cancer based on information that rats in toxicology studies didn’t develop cancer? Perhaps they died from side effects before they had a chance to develop drug-induced cancers (EE: We live a lot longer than rats, which only live to be 2 to 3 years old).
The author describes the SMART study conducted by GlaxoSmithKline on salmeterol, long-acting beta-agonists for treatment of asthma. In this case, GlaxoSmithKline supplied the FDA with manipulated data. The trial period lasted 28 weeks, but if the researchers had wanted to, they could have reported serious adverse events that occurred over the next six months as well.
The company included the follow-up data in the study as well and admitted when asked that only part of the data had come from a randomized, double-blind trial. The study showed an increase in asthma-related deaths for patients treated with salmeterol. The author recommends taking salmeterol off the market and the FDA that it only be used when other asthma drugs are not effective.
Dr. LÖ: What other drugs? As an older doctor, I experienced the time when the following drugs were common: high dosage cortisone, atropine, and adrenalin (in the case of status asthmaticus, these can be quite dangerous for the heart), theophylline, antihistamines, parasympatholytics as anticholinergics (Ipratropium bromide — sounds good, but it is usually only effective in combination with beta-antagonists), and Montelukast which only rarely helps, but is very expensive.
Since the long-acting beta-2 antagonists were introduced, we have hardly seen serious asthma attacks, which are not good for the heart, and the hospital stays of our asthmatics have decreased dramatically. And strangely enough, they are also getting older. The difference between Europe and the United States seems to be very clear here. In the case of the short-acting beta-antagonists, I agree with the author — these really do kill asthma patients.
Inadequate Testing of New Drugs
Two placebo-controlled trials that show an effect are simply not enough. Companies can repeat trials as often as they want until they get two trials that show an effect. A drug cannot be approved if it is less effective than the products currently on the market. But how can this be determined if only tests comparing the drug to placebos are required?
There are a number of over-the-counter cough medicines on the market that simply don’t work. And they do indeed have side effects (e.g., hallucinations and cardiac arrhythmias), but still their sale continues to be permitted.
The Declaration of Helsinki requires that results of human trials be published and medical research involving human subjects be based on thorough knowledge of scientific literature.
In 2008, the FDA decided that products could be approved in the United States that were based on trials conducted abroad and that these trials no longer had to follow the guidelines set out in the Declaration of Helsinki. The author writes, “Pardon me, but have they gone completely mad at the FDA? Has the FDA leadership never heard about the Nürnberg processes? ... Or about the Tuskegee affair where researchers in Alabama followed 399 black men infected with syphilis without treating them for 40 years to study the natural course of the disease ...?” (p. 124).
The industry likes to use people who live in poor countries as guinea pigs because there isn’t any danger that they would sue the companies for injury. The most well-known example is when oral contraceptives were initially tested in Puerto Rico, Haiti, and Mexico, and then later on poor women in the United States. The US Court of Appeals ruled that the Declaration of Helsiniki was indeed binding in this case.
Pfizer had to pay compensation to the Nigerian families whose children died of meningitis or were injured. The children had participated in a study with one of Pfizer’s drugs without their parents knowing; however, there was a better drug at the time that was freely available (p. 124).
“An effect on a surrogate outcome is not enough” (p. 125). This includes, for example, laboratory values such as blood glucose and cholesterol. When these are lowered, this alone does not mean that a patient will live longer or have fewer complications. An example of this is the diabetes drug Rosiglitazone, which does indeed lower blood glucose, but increases cardiovascular complications and resulting deaths.
Another example the author gives are anti-arrhythmic drugs (cardiac arrhythmia) used in the late 1980s. They did have a positive effect on ECGs, but they caused 50,000 deaths each year. And a final example are cancer treatments that reduce the size of the cancer, but at the same time increase mortality.
“It’s a gross failure in drug regulation when drugs with known harms are approved without adequate safety data. The COX-2 inhibitors are a perfect example, as their mechanism of action predicted an increased risk of cardiovascular mortality” (p. 126).
Sometimes post-marketing studies after approval are requested, but these are often not performed because the fines for not complying are so low. What is $10 million to a pharmaceutical company? And the list of warnings on the package insert is so long that very few people are aware of these or even read through them.
The author describes an advertisement for a statin (lipid-altering agents) to show that the drug can indeed reduce lipids, but that it doesn’t decrease the risk of having or dying of cardiovascular complications. And the drug can cause rhabdomyolysis (breakdown of muscle tissue), liver failure, liver damage, and increases in blood glucose levels.
It happens again and again that dangerous drugs are approved, and we don’t even know if these are effective. Here an example: cisapride (sold, for example, under the brands Alimix and Propulsid). This drug was intended to help with gastric emptying, but it caused fatal cardiac arrhythmias. This information was nowhere to be found on the package insert. After the drug was removed from the market, company representatives admitted they had never determined whether or not this drug was actually effective.
Polypharmacy (multipharmacy): most patients, in particular, older patients are treated with multiple drugs. However, as the author writes, “We know very little about what happens when patients take many drugs, but we know enough to act. Every one of them may affect many bodily functions apart from the intended one and they may interact in unpredictable ways” (p. 132). Sometimes it helps to take patients off of medications and, in some cases, “dementia,” confusion, and dizziness simply disappear. PETER C. GØTZSCHE takes his patients off unnecessary medications when they are admitted to the hospital.
|Dr. LÖ: When patients are discharged from the hospital, they are taken off medications — for example, lipid-lowering agents for 80 year olds who had previously been healthy, antihypertensive drugs to achieve “youthful” values, but that cause dizziness, and sleeping pills. The next time they are admitted to the hospital or see a specialist for internal medicine they get all of these again.|
Public access to data at drug agencies
The pharmaceutical industry claims that trials and the data obtained in these trials are its trade secret. The FDA contends they aren’t allowed to correct false statements made by pharmaceutical companies – after all, “they have no mandate to inform the public” (p. 138). On average, half of all trials are never published, but trials with favorable results are often published multiple times, as if they were different trials.
In reality, all trials (including and especially the negative ones) conducted with patients or healthy volunteers should be made available to the public, and anyone who is interested should be able to access them.
In 2007, GØTZSCHE and Jørgensen asked the European Medicines Agency (EMA) for access to all of the data on anti-obesity drugs. Their request was denied with the reason that it was not in the commercial interest of the companies. They then appealed to the European ombudsman Nikoforos Diamandouros, who decided that the documents did not contain any trade secrets and it would be in the public’s best interest to release them.
When three years later the EMA was still not prepared to release the documents for inspection, the ombudsman decided to take additional action and in a press release, he accused the EMA of maladministration. The EMA then responded by trying to create the impression that they had been in favor of releasing the data all along. “In November 2010, the EMA declared that it would widen public access to documents, including trial reports and protocols” (p. 141). The EMA’s executive director left the organization and established his own consulting firm for the pharmaceutical industry.
The new head Guido Rasi announced that the conversation would no longer be about whether or not clinical-trial data would be released, but only how. See also European Medicines Agency: Access to Clinical-Trial Data and Transparency. Workshop report from 2012.
The access to data at other regulatory agencies is also difficult, albeit to varying degrees. Great Britain destroys files after 15 years. The FDA accepts only specific inquiries, and this is difficult when you don’t know what type of information is available. And it has been known to delete certain pages.
The author describes the history of slimming pills (anorectic) to show how companies fight with all means they have available in order to bring and keep dangerous drugs on the market that are hardly effective but bring in a profit. The majority of slimming pills are similar to amphetamines (Aufputschmittel, Upper). In one study, weight loss while on Redux, a common slimming pill, was about 3% more than those on the placebo; however, when compared to the baseline weight, it was only about 1.5%. And these pills can cause pulmonary hypertension, a condition that can be lethal.
Rat trials also showed that the pills caused the additional adverse effect of valve disease, but Redux (manufactured by Wyeth) was still approved. The company bribed officials at the drug agency and bought experts – the same old tune.
Neurontin, an epilepsy drug for everything
In 2004, Pfizer paid a $27 million penalty for selling its epilepsy drug Neurotin (active ingredient: gabapentin) for off-label uses. This was a trivial matter for a company that has an annual turnover of $2.7 billion. Warner-Lambert, the patent owner for gabapentin and company that later acquired Pfizer, paid doctors to allow pharmaceutical representatives to be present during patient visits and recommend Neurotin for a wide range of health problems. This included, for example, bipolar disorder (manic depression), pain, migraine, attention deficit disorder, restless legs syndrome, and drug and alcohol withdrawal. The practice of planting representatives in doctors’ offices is called ’preceptorship’ and seems to be quite common in the United States.
|Dr. LÖ: In my work, I have never experienced anything like that which Dr. GØTZSCHE describes here. However, important individuals such as department heads from universities, clinical programs or divisions were invited to go on luxus trips and they received honoraria for giving lectures about Neurotin. Others were paid for their name so that articles published could appear in their name.|
Pfizer’s openness: “In relation to the illegal marketing, the company had a publication strategy. The results, if positive, will be published.” But in spite of partial bleeding (and sometimes a Blindstudie) during the planning phase of the trial for other uses of Neurotin, there was very little or no effect, but they did have side effects. “Pfizer never told doctors or patients that its studies had shown that Neurotin was no more effective than a placebo for some of its off-label uses” (p. 154).
Merck, where the patients die first
Even before the market launch, Merck knew that Vioxx — just like the other COX-2 inhibitors — increases the risk of thrombosis and therefore also the risk of heart attack. They knew this because scientists had found that “Vioxx reduced urinary metabolites of prostacyclin in healthy volunteers by about half, which indicates that Vioxx causes thrombosis. However, Merck convinced the authors to change what they had written into a meaningless sentence: ‘Cox-2 may play a role in the systemic biosynthesis of prostacyclin’ ” (p. 155).
Individuals with a risk of cardiovascular problems were then not accepted to take part in the VIGOR trial. This was a comparative study with older NSAIDs (nonsteroidal anti-inflammatory drug, antiphlogistics). And although there were more heart attacks in this trial, which didn’t include any risk patients, this observation was not made public.
Trials that show an increased risk of cardiovascular problems are not published until the drug is no longer on the market. The flawed VIGOR trial was published in the NEJM. Although scientists pointed to errors made, the NEJM did not publish any type of correction.
Even though the risk of thrombosis is still increased in the year following the discontinuation of Vioxx, the company ignored all of the results that were gathered more than two weeks after patients stopped taking the drug. Based on the author’s estimates, Vioxx caused about 120,000 deaths before it was finally removed from the market.
|EE: See also information about rofecoxib. Wikipedia (German entry): “In 2009 it became known that before market withdrawal Merck had drawn up an internal list of experts critical of the drug who needed to be silenced.”|
Fraudulent celecoxib trial and other lies
This chapter tells a similar story, but this time it is about celecoxib (product: Celebrex), the COX-2 inhibitor produced by Pfizer. The company conducted two trials, comparing Celebrex with Diclofenac in one and with Ibuprofen in the other. Pfizer used different test plans but summarized the favorable data to make it appear as if it were one trial.
The company only published information about the supposedly better stomach tolerance and avoided the topic of cardiac side effects altogether. When the number of deaths caused by heart attack (approx. 100,000) increased and Pfizer was no longer able to hide this information, the FDA demanded that there be a warning on the package insert.
It was then changed to “Clinical studies suggest that the group of selective COX-2 inhibitors may be associated with a risk of thromboembolic events” (p. 165). When Vioxx was taken off the market in 2004, Pfizer used the opportunity to claim they had analyzed the data from 400,000 patients and celecoxib was not linked to an increased risk of heart attack.
|Dr. LÖ: Celebrex is still on the market today, but fortunately many of the national health systems no longer pay for it. So at least fewer patients are getting this drug. Without such shameless and aggressive advertising, we would have never had the idea to prescribe Vioxx or Celebrex. But the promise of NSAIDs without side effects for the stomach was indeed very enticing.|
Switching cheap drugs to expensive ones in the same patients
The author first gives the example of diabetics who were switched to new more expensive insulin that in the case of insulin analogues actually only make sense for individuals who “experience troublesome hypoglycaemia" (p. 172).
The trick with stereoisomers, which is also called evergreening and me-again, is an example of how companies can continue to sell their expensive drugs even after the patent has expired.
There are drugs which have two halves that are mirror images of each other. When a patent runs out, the company patents the most active part and then starts an intensive promotional campaign in which they claim that the new drug is even more effective, a fact that isn’t true but which causes many doctors to refrain from prescribing the cheaper generic drugs.
The author provides an example of a drug used to treat stomach ulcers. When the patent for the proton-pump inhibitor omeprazole (Losec, Prilosec) ran out, AstraZeneca brought the other half under the name esomeparazole (Nexium) onto the market. And they also published flawed trials. For example, 40 mg Nexium against 20 mg Losec was used to prove that one substance was better than the next (p. 172–73). The ratio should have actually been the other way around. After all, Nexium was 30 times more expensive.
|Dr. LÖ: I’m relieved to hear this. I have never been so impressed with Nexium and have only given follow-up prescriptions for it when patients had received the initial prescription from a specialist and were insistent about continuing to take it.|
AstraZeneca spent $500 million marketing Nexium in the first year alone.
Blood glucose was fine but the patients died
This chapter looks at rosiglitazone (Avandia), a drug produced by GlaxoSmithKline that reduces glucose. Although comparator trials conducted by the company before approval showed an increased risk of heart attack as compared to pioglitazone, the company decided only to stop conducting comparator studies and keep the data from the initial trials secret.
“ ... although there were more thrombotic heart events than with placebo or active comparators” the FDA approved rosiglitazone in 1999. “However, as stated in the package insert, the drug increased LDL cholesterol by 19%, which explains its harmful effect on the heart” (p. 176).
In response to pressure from respected members of the diabetes community, the EMA intervened in Europa a year later and also approved the drug. The diabetes community didn’t want to miss out on this “miracle cure.” In 2004, the WHO sent a notification to the company about cardiac events caused by the drug, and the company then even informed the FDA and EMA. In 2006, a GlaxoSmithKline study confirmed this information. However, not one of these organizations published a warning because they were dealing with a company secret.
But not long later, independent researchers sent their meta-analysis of rosiglitazone to the New England Journal of Medicine. The journal then sent the article to the company, whereupon the company quickly published the interim results of an unblinded trial. A careful objective review of the individual case files in the RECORD trial showed that the cardiovascular risk with rosiglitazone was higher than with pioglitazone.
This is no surprise since Avandia increases cholesterol levels. In 2009, the company started a new study that should run until 2015. Fortunately, the drug was removed from the market in Europe. But it can still be purchased in the United States, albeit with a new package insert.
Thiazolidinediones, also known as glitazones, often have other undesirable characteristics, for example, promoting the occurrence of bladder cancer (pioglitazone), or causing liver failure as does troglitazone — which was why it was removed from the market.
The only drug that increases the life expectancy of diabetics who have diabetes type 2 is metformin, which is old and cheap. The only disadvantage is that patients who have a damaged liver — which is a common diabetes complication — cannot take this drug.
Another diabetes drug available is liraglutide (Victoza), a glucagon-like peptide-1 (peptide hormones) produced by Novo Nordisk. Independent researchers determined that patients who take Victoza have an increased risk for inflammation of the pancreas (pancreatitis) and pancreatic cancer, and they then published the results on the home page of the journal Gastroenterology. Novo Nordisk convinced the journal to retract the article.
There were already serious safety concerns at the time of the drug’s approval, but business interests prevailed.
|Dr. LÖ: Incidentally, the only female patient we had who was treated with Victoza actually did develop pancreatic carcinoma — and the drug didn’t even help her with the surrogate parameters (measured values) of weight and blood sugar levels.|
Psychiatry, the drug industry’s paradise
The author quotes Dr. Marcia Angell, MD and former editor of the New England Journal of Medicine as follows: “I have spent most of my professional life evaluating the quality of clinical research, and I believe it is especially poor in psychiatry. The industry-sponsored studies ... are selectively published, tend to be short-term, designed to favor the drug, and show benefits so small that they are unlikely to outweigh the long-term harms” (p. 191).“Psychiatry is the drug industry’s paradise as definitions of psychiatric disorders are vague and easy to manipulate” (p. 191). In the United States, the Diagnostic and Statistical Manual of Mental Disorders (DSM) of the American Psychiatric Association (APA) is quite notorious. In each new version, minor problems are transformed into new disorders. This is dangerous because new disorders are just asking to be treated. The DSM is not based on scientific findings, but is instead a consensus document that is voted on in this association.
An example is Premenstrual Dysphoric Disorder (dysphoria). Tests showed that women who weren’t menstruating and even men indicated that they had the same symptoms. In spite of these results, women were treated with prozac (fluoxetine, a selective serotonin reuptake inhibitor, SSRI) that had a new name and new look. And when women are in a bad mood, it is often blamed on PMS.
EE: We distinguish between premenstrual syndrome (PMS), which is quite common, and Premenstrual Dysphoric Disorder (PMDS), which is only diagnosed in 3–8% of patients based on the severity of their symptoms. However, the line between PMS and PMDS is quite blurry. For the psychiatrist, the latter is of particular “interest” ...
Researchers confirm that a certain combination of fatty acids can reduce symptoms and recommend women change their diet in the last few days before their period starts. On these days, they should avoid foods with a high salt content, alcohol, chocolate, and caffeine.
Another example is attention deficit hyperactivity disorder (ADHD) in children. According to the author, a very large number of school children in the United States now take drugs for ADHD. For example, in 2006 about a quarter of the children sent to summer camps in the U.S. were on medications for this. This number of children in schools on drugs for ADHD increased as school funding declined. ADHD have “amphetamine-like effects” (stimulants) and can cause hearing damage and bipolar disorder (mania-depression) (p. 194).
Depression can arise from mourning after the loss of a loved one, life crises such as losing your job or getting divorced, serious illnesses, and other difficult situations. It’s therefore no wonder that supposedly a fourth of American adults suffer from psychological disorders.
Bipolar II disorder has become the new “epidemic.” For this diagnosis, mania or psychotic features are no longer necessary. One episode of depression and at least one episode of hypomania that lasts four days is enough to make a diagnosis. Hypomania is characterized by a persistent elevated mood, which can also be caused by medications.
On page 196 the author quotes the UK general practitioner Des Spence from his paper Adult attention deficit/hyperactivity disorder, BMJ 2011, 343d7244. Dr. Des Spence describes how psychiatry has become so lucrative for the pharmaceutical industry:
“Psychiatry has ... become pharma’s goldmine, with a simple business plan. Seek a small group of specialists from a prestigious institution. Pharma becomes the professional kingmaker, funding research for these specialists. Research always reports underdiagnosis and undertreatment, never the opposite. Control all data and make the study duration short. Use the media, plant news stories, and bankroll patient support groups. Pay your specialists large advisory fees. Lobby government. Get your pharma sponsored specialists to advise the government.”
A corrupt psychiatrist at an American university found an easy solution. He wrote psychiatric evaluations for his critics and caused them to get fired. With this and other methods, he was able to get a vagal nerve-stimulating device for the treatment of depression on the market.
The author believes that screening for psychiatric disorders is harmful, particularly in the case of depression. Screening generally results in a great number of healthy people being classified as patients in need of treatment.
Dr. LÖ: I agree with the author that it is irresponsible to treat healthy individuals with antidepressants and I can also understand that doing so can lead to increased aggression and aggressive driving. We only treat severe depression — individuals who in many cases have already decided on the type of suicide they would prefer, are no longer able to work, no longer have social contacts, and have lain in bed worrying for weeks and still can’t sleep. This can be really difficult for the people around them.
These patients often see great improvement when they take antidepressants. I have seen a lot of suicides where the individuals weren’t treated (I can only cynically write that the dead person is certainly doing well), but very few where the individual had been taking SSRIs. The author claims that over half of patients stop taking SSRIs within two to three months. I haven’t experienced this in my practice. Instead, I have had patients who become depressed again after several months or years and need to reenter treatment.
The author also describes the steps the company Eli Lilly took to get Prozac (fluoxetine) approved. These included covering up side effects, suicide attempts, aggression, and hallucinations that healthy test subjects experienced during trials and also bribing several officials and experts.
In spite of the increased suicide rates in children, Prozac was approved for them. The author also reports on the number of suicides among healthy women taking duloxetine, a selective-norepinephrine reuptake inhibitor (SNRI) as part of a trial that was supposed to help get this drug for stress-related incontinence approved.
|Dr. LÖ: The author recommends that people who are depressed exercise instead of taking medications. In the case of mild cases of depression, I agree completely. But has he ever tried to convince someone who has severe depression and isn’t being treated with medications to go outside and take a short walk? I have — but it was usually without success.|
Dr. PETER CHRISTIAN GØTZSCHE then writes about paroxetine (Paxil or Seroxat), which is produced by GlaxoSmithKline. The company failed to disclose the fact that the medication caused withdrawal reactions in 30% of the patients and can lead to suicides.
Pushing children into suicide with happy pills
“In 2001, GlaxoSmithKline published a trial in children and adolescents, study 329. This study reported that Paxil (Seroxat) was effective with minimal side effects, and it was widely believed and cited, no less than 184 times by 2010, which is remarkable. However, the trial was fraudulent” (p. 217). The efficacy was achieved in a subgroup only by massaging the data, and the side effects (harms) were covered up. Some of the study participants were even made up and after a suicide another participant was assigned the same trial number as the suicidal person.
The department of one of the “experts” received huge amounts of money from the company. After several suicides, the use of the drug for children and adolescents was finally prohibited.
The author then tells the story of another old favorite: citalopram produced by H. Lundbeck A/S in Denmark. This drug is an isolated stereoisomer (isomer). After the patent for the racemate from citalopram ran out, the company patented the active half of under the name escitalopram (Cipralex or Lexapro). The “new” drug cost 19 times more than the generic versions of citalopram. And here the paid experts were also able to show that the drug was better than itself.
The author next focuses on antipsychotic drugs (antipsychotics).
Dr. LÖ: I agree with the author that the newer antipsychotics are not so much better and don’t have fewer side effects than the old ones. In comparative studies, too high of doses of the old drugs were used or the doses were increased too quickly so that better results could be achieved for the new drugs. Nobody would prescribe these (hopefully) for disorders that weren’t serious. But I don’t agree with the author that it would be better for patients if all psychotropic drugs were taken off the market.
I remember clearly that we had one patient who came to our practice shortly after it had opened to get a prescription for an antipsychotic. At first, she didn’t really want to say why she needed it. But then she confessed that she had been in two psychiatric institutions for a longer period of time. But since our predecessor had prescribed her this drug, she had been doing well.
Unfortunately, this drug was at some point taken off the market, and the woman didn’t want to try anything else. After a few weeks, she burned her daughter’s school supplies and threw the furniture out the window. She thought that the doctor who came to the scene was the devil and wanted to throw him and his doctor bag out the door. After a longer stay in yet another psychiatric institution and new medications, after 20 years she is finally doing fairly well again.
The antipsychotic Zyprexa (active ingredient: olanzapine) produced by Eli Lilly is an old substance, but the company claimed that it increased the cholesterol levels in dogs less than another drug that never came on the market. The largest olanzapine trial was published 142 times (!), and Zyprexa became the world’s best-selling antipsychotic although it didn’t have any advantages over haloperidol. The main difference was that it was seven times more expensive.
In spite of serious side effects, such as heart failure, pneumonia, substantial weight gain, and diabetes, Zyprexa was recommended for use in children and older adults. After its patent for Prozac ran out, Eli Lilly even tried to market Zyprexa as an effective drug to treat depression.
Intimidation, threats and violence to protect sales
It is difficult and dangerous to uncover criminal acts in the pharmaceutical industry. Stanley Adams, a former employee at the Basel pharmaceutical company Hoffmann-La Roche, informed the European Commission about Roche’s vitamin cartel; the company accused him of being a spy and he ended up in a Swiss jail. “Willi Schlieder, Director-General for Competition at the Commission, leaked Adams’ name to Roche ... and when Adams’ wife was told he could face 20 years in prison, she committed suicide” (p. 236).
|EE from Weltwoche (Swiss magazine): |
“As Gerber began his position in 1978 as a reformer, he knew that the residents of Basel particularly liked price fixing. And he was directly confronted with this problem. One of his first tasks as CEO consisted of cleaning up after the Adams Affair (German only). Starting in 1970, Roche had forced its bulk buyers to sign “loyalty contracts” so that the company could secure a large market share. Stanley Adams, an employee who was frustrated that he wasn’t being promoted, gave the European Commission documents that verified these illegal agreements. Roche had to pay a fine, and the lawsuit, which attracted a lot of public attention, ended in front of the European Court of Justice a year after Gerber’s started as CEO.
Gerber should have given warnings and built in appropriate controls because the competition regulators were by that time handing out draconian fines all around the world. He didn’t do this, and he also apparently didn’t notice that between 1989 and 1999 the top managers in his vitamin division were meeting on a monthly to quarterly basis with senior representatives of competing companies such as BASF und Rhône-Poulenc. They met to discuss billions in turnover, sales volumes, and prices on the global vitamin markets.
Under the watch of Henri B. Meier, one of the most respected finance experts in the country, economic theorems were quickly overridden as the prices in the fiercely competitive displacement markets didn’t have to be lowered, but could in fact be increased by up to 15 percent.”
The link Adams-Affäre (in German only) is to an article on Zeit Online titled Allein gegen den Multi (Alone against a multinational) by Wilfried Kratz (appeared January 27, 1984). See also pages two and three of the article.
In the United States, whistle-blowers may receive a large monetary reward. And they need this because they may never be able to find a job in the field again. If an employee dares to first inform the company, the employee is often intimidated, defamed, and threatened in an attempt to discourage them from making the information public.
Thalidomide (Contergan): The doctor, who first discovered this drug was the cause of several cases of extremely rare birth defects informed Grünenthal, the company that developed and sold the drug. For 10 years, this company harassed the doctor and threatened him with legal action. The case against the drug company Astra, which manufactured thalidomide in Sweden, proved to be very difficult because it was hard to find experts who would testify against Astra.
“In the United States, the company that had distributed thalidomide even though it wasn’t approved by the FDA had hired every expert there was on birth defects to prevent them from testifying for the victims.” In Germany, nobody was found guilty, and the settlement ended in “about $11,000 for each deformed baby.” And in the UK, everything was kept confidential. It took 16 years until an article with “incriminating evidence” was made available to the public — and this only happened thanks to pressure from the EU (p. 237).
“Merck also selectively targeted doctors who raised questions about Vioxx ... A few days after Eric Topol had testified for a federal jury that Merck’s former chair, Raymond Gilmartin, had called the chair of the clinic’s board of trustees to complain about Topol’s views on Vioxx, his (Topol) titles as provost and chief academic officer at the medical school in Cleveland were removed” (p. 238)
An internal email from Merck on the topic reads as follows: “We may need to seek them out and destroy them where they live” (p. 238). Dr. LÖ: “We are dealing with doctors here, not with rats.” The company recorded successful outcomes such as “NEUTRALIZED” and “DISCREDIT” (p. 238). The author includes other quotes from a secret meeting and compares these with the book 1984, a dystopian novel by George Orwell (actually Eric Arthur Blair. See also Animal Farm).
An FDA director also tried to discredit a subordinate because the subordinate wanted to publish a trial about side effects caused by Vioxx.
Companies can be especially malicious if someone finds out that they have covered up life-threatening side effects. “Such threats have included frightening telephone calls from the company warning that ‘very bad things could happen’, cars waiting near the researcher’s home through the night, a ghoulish funeral gift, or an anonymous letter containing a picture of the researcher’s young daughter leaving home to go to school” (p. 240). Companies have also been known to take legal action taken against these researchers, even though the researchers have legal permission to publish their work.
The Canadian Ministry of Health capitulated under threats made by AstraZeneca and withdrew its guidelines stating that all proton pump inhibitors were essentially the same, and the German Zeitschrift für Allgemeinmedizin (Journal of General Practice) didn’t want to risk publishing an article that contained the same basic statement. A researcher who spoke out against giving women hormones during menopause was threatened with legal action, and another researcher who showed that new contraception pills caused blood clots more frequently than the older pills was “fiercely attacked by colleagues on Bayer payroll” (p. 241).
One academic was sent a death threat because he was planning to present the cardiac side effects of an expensive GlaxoSmithKline drug at an international congress. The author provides many other similar examples. Even if a small organization or an individual wins a lawsuit, the legal fees are much more damaging to them than the penalty the pharmaceutical company has to pay.
Busting the industry myths
“The drug industry’s myths about their activities and motives have been repeated so often that they are widely believed by doctors, politicians and the general public. As they are an impediment for creating a rational healthcare system, devoid of corruption, I shall debunk the worst of them before suggesting reforms in the next chapter” (p. 249).
Myth 1: “Drugs are expensive because of the high discovery and development costs”
In reality, the price of medications is determined by “what society is willing to pay but also how good the companies are at keeping competition at bay” (p. 249) (e.g., price fixing). Two universities sponsored by the pharmaceutical company have claimed it costs $800 million to bring a new drug to market. However, the true costs are likely more around $100 million. Many drugs are developed at public institutions, and the most expensive thing is often the advertising campaign.
The author verifies this and other production expenses with examples such as “Schering bought a hormone from another company for use in women with menopausal symptoms and sold the drug with a mark-up of 7000%” (p. 250).
“If new drugs were as good as the industry wants us to believe they are, there wouldn’t be much need for pushing them and for bribing doctors into using them” (p. 251).
Myth 2 “If we don’t use expensive drugs, innovation will dry out.”
In 1993 in New Zealand, “it was decided to subsidise drugs in the same class (e.g., NSAIDs and SSRIs) that had similar effect with the same amount, whatever the price of the drug was (reference pricing). In addition, drug companies negotiate with the drug agency over price and other conditions for access. The policy had dramatic effects. Statins were provided at half the cost compared to Australia, and the price of generic drugs was less than a quarter of the price in Canada. ... Although there are only 4.4 million inhabitants in the country, the annual savings amounted to about €1 billion” (p. 252).
Since the 1980s, profits in the pharmaceutical industry have increased exponentially. But in the same time period, an ever decreasing number of innovative drugs have come on the market (p. 251).
Myth 3: “Savings are greater than costs for expensive drugs.”
Economists in the pharmaceutical industry claim that the savings a drug brings are higher than what the drug costs. However, depending on what economic model is used, any result and the converse result can be obtained. The director of the Danish National Board of Health said, “it was curious that no matter how expensive a new drug was, the company was always able to provide a pharmacoeconomic analysis (efficiency) that showed that the savings in terms of less sick-leave, premature retirement, and whatever else, were greater than the costs for the drug” (p. 252).
Myth 4: “Breakthroughs come from industry-funded research.”
“Virtually all the basic science that enables modern medicine to move forward takes place in the non-profit sector, at universities, research institutes and government laboratories” (p. 252). The three most important discoveries in the twentieth century (penicillin, insulin, and polio vaccine) were all made in publicly funded laboratories. For the five best-selling drugs in 1995, “16 of the key 17 scientific papers leading to the discovery and development of these drugs came from outside the industry” (p. 253). “More than four-fifths of all funds for basic research to discover new drugs and vaccines come from public sources” (p. 253).
Myth 5: “Drug companies compete in a free market.”
“There can be no free market for products that are heavily subsidised by taxpayers’ money and when fraud and crimes are widespread” (p. 254). In this section, Dr. GØTZSCHE tells about some of his experiences in this area of the pharmaceutical industry.
Myth 6: “Public-industry partnerships are beneficial for patients.”
Partnerships are sometimes beneficial for both sides, but these partnerships generally bring no advantages for patients. The idea that public health and the drug industry have shared goals is nothing other than a PR trick. The author spends almost two pages here on the topic, explaining certain practices and empty claims that come primarily from the book Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients by Ben Goldacre (London: Fourth Estate 2012, Harper Collins Publ., UK, available from August 29, 2013).
Myth 7: “Drug trials are done to improve the treatment of patients.”
“Either a study is designed to maximise sales or it is designed to determine the best way to prevent or treat a particular health problem.” Trials in the pharmaceutical industry are conducted for marketing purposes. Companies keep undesired results confidential or they distort the results before publishing them. Without access to the raw data, it is very difficult to prove this and even if it were proven, the fines are much too small and the damage to their reputation has very little effect.
Myth 8: “We need many drugs of the same type because patients vary in their response.”
Dr. GØTZSCHE writes: “I have heard this argument countless times from doctors who have listened to the pep talks of drug salespeople without reflecting much on whether it was true or not. In rare cases, it could be true, but I have not seen convincing data that confirm it” (p. 256).
Myth 9: “Don’t use generic drugs, as their potency varies.”
Drug agencies require generic manufacturers to provide comparative studies and “ensure that generic drugs are bioequivalent with the original drug” (p. 256). For these studies, they measure, for example, the levels of the active substance in the blood. “Many doctors believe in this nonsense, which has been consistently rejected whenever researchers without conflicts of interest did the bioavailability studies” (p. 256).
Myth 10: “The industry pays for continuing medical education because the public purse won’t.”
That would be very generous, but objective continuing education would not be in the interest of the pharmaceutical companies. They would then have to sometimes say that we should choose the product from the competition because it is cheaper and better than our product. When a company provides “educational” opportunities for doctors, it is usually to help their market share.
General system failure calls for a revolution
“If an improvement in human health was our primary aim, some of the billions currently invested in expensive drugs to lower cholesterol of the worried well might be far more efficiently spent on enhanced campaigns to reduce smoking, increase physical activity, and improve diet” – quote at the beginning of this section, Moynihan and Cassels, in Selling Sickness
|EE: On YouTube , there is a series of videos about common practices in marketing and production. This video shows some quite disgusting facts about the foods at McDonald's. Length: 7:08 min.|
|EE: Selling Sickness: How the World’s Biggest Pharmaceutical Companies are Turning us All into Patients by Ray Moynihan and Alan Cassels. Nation Books; annotated edition (June 24, 2005). Alan Cassels also wrote Seeking Sickness: Medical Screening and the Misguided Hunt for Disease, Greystone Books; edition: 1 (July 24, 2012).|
The author explains that medications are the third most common cause of death after coronary diseases and cancer: “Good data are available, and what I have made out of the various studies is that around 100 000 people die each year in the United States because of the drugs they take even though they take them correctly. Another 100 000 die because of errors, such as too high dose or use of a drug despite contraindications.
A carefully done Norwegian study found that 9% of those who died in hospital died directly because of the drugs they were given, and another 9% indirectly. ... The European Commission has estimated that adverse reactions kill about 200 000 EU citizens annually (at a cost of €79 billion)” (p. 259).
|Dr. LÖ: If these people hadn’t been taking drugs for their illnesses, then wouldn’t they have died anyway because they weren’t taking any medications? I naturally agree with the author that we need fewer and better medications and that many things can and should be left untreated. Compared to European countries, the United States spends about twice as much on health care and 2.7 times more on medications. But their healthy life expectancy is lower. One study showed that total mortality decreases by 6% when the number of general practitioners increases by 20% — and here (in Switzerland) the number of general practitioners is actually decreasing.|
How much medicine do we really need and at what cost?
“The use of inferior drugs had caused heart failure in 40 000 patients in the United States at the same time as they had to pay 20 times more for the inferior drugs” (p. 100). Some of these medications are unnecessary, and there are cheaper alternatives for others. “ ... the data support the finding that drugs are a major killer:
- At the peak of their use, anti-arrhythmic drugs were likely causing about 50 000 deaths every year in the United States (p. 126).
- By 2004, rofecoxib had likely caused about 120 000 deaths worldwide because of thrombosis (p. 161).
- By 2004, celecoxib had likely caused about 75 000 deaths worldwide because of thrombosis (p. 167).
- NSAIDs likely causes about 20 000 deaths every year in the United States because of ulcer complications (p. 169).
- By 2007, olanzapine had likely killed about 200 000 people worldwide (p. 232).
In addition to all the deaths, millions of people experience serious, disabling drug injuries every year” (p. 260).
For-profit is the wrong model
When a CEO in an American pharmaceutical company earns 531 times more than an employee at the same company, the difference is “staggering” (p. 264). A purely profit-oriented industry that puts much more emphasis on their stock profits than on producing effective and cost-effective medications will not be able to save our health care system.
Eflornithin (α-difluoromethylornithine or DFMO) is an example of a drug that came on the market because it would bring in a profit and not because it was urgently needed. The drug was developed by Aventis (later Sanofi-Aventis and then Sanofi) to treat cancer. It was shown to be ineffective against cancer, but proved to be a very effective treatment for sleeping sickness (African trypanosomiasis). However, as most of the potential patients were poor, Aventis stopped producing the drug. It later turned out to be an effective depilatory (chemical depilatory) and was put back on the market (p. 264, EE: see also Pharma-Kritik (Independent, non-profit journal with information on a large number of drugs), volume 30, number 12, PK239, in German only).
Dr. GØTZSCHE shows us how extreme the situation is: “Healthcare and pharmaceutical executives were four of the top 10 best-paid executives in the United States in 2010. The top earner, John Hammergren, was chief executive of the drug distributor McKesson Corp., with total remuneration of $145 million. If the poor guy were to be fired, he would receive $469 million in severance pay ... ” (p. 264).
It is not a good thing that drugs can be patented if this allows them to become so expensive that we can no longer afford them (EE: particularly when we as taxpayers fund this process). The author suggest some innovative alternatives.
One possibility would be a state-owned industry or another would be as follows: “As long as we continue to endure the for-profit model, we could introduce an award system, where drug companies, instead of patent monopoly, would receive a financial award when they have obtained marketing authorisation, the size of which could be related to the degree to which the invention represented a breakthrough” (p. 265).
Clinical trials (p. 265)
The current system does not look to change any time soon even if some countries are introducing initial initiatives (Italy and Spain). By now, only studies that are supported by a strict systematic analysis of previous studies on similar medications should be approved. The drug regulatory agencies should decide which clinics test drugs, not the companies. The pharmaceutical industry should be required to make placebos (at the manufacturing cost) and the pure form of the drug available for independent research. Since we can’t trust trials conducted by the industry, we need independent trials. The simplest solution would be if all of the pharmaceutical companies would contribute money to a fund which could then be used to pay for independent researchers to conduct the necessary trials.
Drug regulatory agencies (p. 268)
Drug regulatory agencies should reject many more dangerous drugs (and not just put them on the market with a long list of warnings and precautions), and they should also require far more data to be submitted regarding the safety of drugs.
Surrogate outcomes should not be accepted (p. 269)
With cancer drugs, often only surrogate outcomes — decreases in the size of the tumor — are provided, but no information about life expectancy is given.
Relevant patient populations, comparators and outcomes (p. 269)
Patients 65 or over are most likely to take medications, but this age group is routinely excluded from trials sponsored by the industry.
Most patients also take multiple medications, but the pharmaceutical industry frequently requires that test subjects only take the test drug. “A survey showed that common medical conditions formed the basis for exclusion in 81% of the trials, and patients receiving commonly prescribed medicines were excluded in 54% of the trials” (p. 270)
“According to the Helsiniki Declaration, a new drug must be tested against those of the best current proven intervention, and placebo should only be used when no such intervention exists, or where there are compelling and scientifically sound methodological reasons for the use of a placebo” (p. 270).
Safety (p. 270)
Many drugs are approved based on short-term trials with only a smaller number of patients (500–3,000) even though they are intended for long-term use. Drug regulatory agencies must demand that trials be conducted over several years and involve a large number of patients. For the few drugs that are urgently required (by the patients, not the company), exceptions could be made.
All clinical data must be publicly available (p. 271)
If patients are involved, the data must be made available to the public. People don’t participate in studies to increase a company’s profits; they do so to contribute to the development of better treatments. The simple solution would be for drug regulatory agencies to reject medications for which the data was not available to the public. The public should also have access to drugs that were not approved because similar drugs may have similar harmful effects, which people could then be informed of. Companies should also be required to disclose everything that they know about a drug.
Conflicts of interest (p. 272)
“Drug agencies should be publicly funded, as user fees create competition between the agencies about becoming the fastest and therefore also the least critical agency” (p. 272). And at drug agencies, the division for approval should be separated from the division for side effects. It is harder to take a drug from the market that your own division approved.
Labelling of drugs (p. 272)
Patients should be given clear information about a drug’s effects. And this information should include the basic numbers about benefits and side effects. Researchers at Dartmouth College have shown that patients are then much better at being able to choose the better drug.
Drug formulary and guideline committees (p. 273)
“Doctors with financial ties to drug companies should not serve on drug or guideline committees ... ” (p. 273). Even if they disclose their connections to the pharmaceutical industry, this doesn’t change the fact that they have a conflict of interests.
We need skilled methodologists who are knowledgeable about the specialty areas in question. These individuals are capable and willing to find flaws in scientific documentation. Doctors with connections to the pharmaceutical industry should not serve on drug formulary or guideline committees.
Drug marketing (p. 275)
“There is no need for drug marketing, as the products should speak for themselves” (p. 275). Advertising and promotional events for drugs should be prohibited as should seeding trials and studies conducted purely for marketing purposes. Fines for illegal marketing should be so high that they have a “preventive effect” — that they could cause a company to go bankrupt. Pharmaceutical companies must not be able to avoid conviction by “settling accusations of crimes” ( p. 276). Top executives need to be held accountable for such crimes. And those in the pharmaceutical industry who are found responsible for a patient’s death should have to serve a prison sentence. Just as they would have to if they were in any other sector.
Doctors and their organisations (p. 277)
“Physicians’ organisations should declare that it’s against the patients’ interests that physicians participate in meetings or educational events sponsored by the industry, accept visits from drug salespeople, or accept donations from industry, including free travel and free samples of drugs (the delivery of which should be prohibited by law), as this has clear negative consequences for patients” (p. 277).
For example, in 2001 the American Medical Association (AMA) started a campaign intended to convince physicians to stop accepting gifts from pharmaceutical companies. However, the association itself continued the practice of accepting gifts from the industry.
“A study of 105 residents at a university-based internal medicine residency programme showed that 61% believed that contact with industry didn’t influence their own prescribing, while only 16% believed that other physicians were similarly unaffected” (p. 277).
“A US survey found that a staggering 94% of a broad range of physicians had interacted with the drug industry within the last year” (p. 278).
Restricted uneducational grants
When a company provides discretionary funds for continuing education and the like, it expects that its drugs will be used and not the cheap generics. Doctors should refuse to participate in continuing education and conventions where the contents are determined by the industry. And the author writes, “Ghostwritten articles should be seen as scientific fraud, and the honorary authors should be treated like students who sign their names to papers they buy on the internet” (p. 279).
Patients and their organisations (p. 280)
The industry sponsors many patient organisations. Many were even founded by the pharmaceutical industry and support (often without knowing it) the marketing goals of the companies. They are sent forward “when national bodies have decided a drug is too expensive to be used compared to what it has to offer, whereas I have never heard any patient organisation complain that the price was too high and that the drug company should lower it” (p. 280). Patient organizations should warn their members about “information” that comes from the pharmaceutical companies and their websites.
On page 282, the author makes some suggestions as to what individuals can do:
- Withdraw your membership if your patient organisation accepts industry favours.
- Ask your doctor whether he or she receives money or other benefits from the industry, has shares in a company or is visited by drug salespeople, and if so, find yourself another doctor.
- Avoid taking drugs unless they are absolutely necessary, which they rarely are. Ask if there are other options and whether you’ll be better also without treatment; remember that very few patients benefit from the drugs they take (see Chapter 4).
- Ask if there are cheaper drugs than the one your doctor suggests.
- Avoid taking new drugs the first 7 years they are on the market because, unless it is one of those very rare ‘breakthrough’ drugs that offers you a documented therapeutic advantage over older drugs, most drugs that are withdrawn for safety reasons get withdrawn within the first 7 years.
- Remind yourself constantly that we cannot believe a word of what drug companies tell us, neither in their research nor in their marketing or information to patients.
Medical journals should stop publishing advertisements. Many would not be able to survive without ads but right now there really are far too many journals.
They should check articles about drugs and medical devices with particular care to ensure they aren’t endorsing ghost authorship or illegal marketing. “Finally, journals should not accept editors that have conflicts of interest in relation to drug and device companies” (p. 283).
Journalists (p. 283)
Companies offer journalists awards for writing articles that may increase sales. Patient organizations sponsored by the industry also set up interviews with patients who have been helped by a “miracle drug.” These “anecdotes of treatment success” don’t have any scientific value and do not help readers to assess the effectiveness of a drug (p. 284).
“Journalism educators should not accept funding from the healthcare and drug industries, journalist should not accept gifts, awards or any financial support from the industries they cover, and journalists should routinely disclose their own conflicts of interest and those of their sources” (p. 284).
Having the last laugh at big pharma
PETER C. GØTZSCHE was invited to speak at an industry-sponsored meeting for the Danish Medical Association for Rheumatology. He listed out the “sins” of the sponsors focusing on each company individually: drug trafficking, refusing access to and concealing trial data, lies about dangerous side effects and threatening doctors who asked uncomfortable questions. The conference had the theme Collaboration with the drug industry. Is it THAT harmful? — after the conference, the association continued to be sponsored by the industry.
At other conferences, he had more success and the organizations came to see that it wasn’t that much more expensive to conduct conventions without money from the industry.
Money doesn’t smell (p. 293)
In this section, the author describes a drug to treat urge incontinence, a disorder that was renamed overactive bladder (urinary incontinence) by the industry. Giving diseases a more catchy name is something that pharmaceutical companies have been known to do on more than one occasion. In an advertising circular, the company claimed that 6% of the entire population (including children) suffer from overactive bladder, but that their drug provided a solution to this problem (“The number of leakage episodes per 24 hours was 3.2 on drug and 3.3 on placebo ... ” (p. 293)). However, the drug can have serious side effects including dry mouth, blurred vision, constipation, and confusion.
Creating diseases (p. 295)
Lobbyists of the pharmaceutical industry like to convince politicians that regular health checks are beneficial. They are, but for the pharmaceutical industry. “Health checks lead to more diagnoses of diseases or risk factors, which lead to more drug use and more harms” (p. 295). However, these checks and associated treatments don’t have any impact on total mortality.
EE: However, the word health check is really too broad. It can be used to refer to any of the following: early detection of diseases (e.g., screening), incl. the Gesundheitsuntersuchung zur Früherkennung von Krankheiten, (Health check for early detection of diseases: a program in Germany offering physicals every two years to individuals over 35, link in German only), check-ups for children, prenatal care, early-detection measures such as early detection of occupational diseases, dental check-ups and examinations, preventive healthcare, vaccinations, medical hygiene, sunscreens, sex education, and other programs. Health and social policy are also involved in this area; for example, they offer substance abuse prevention, protection for nonsmokers, and violence protection programs.
The author provides various examples to show this and then concludes his book with Stephen Whitehead’s (chair of the Association of the British Pharmaceutical Industry) response to an article written by Dr. Margaret McCartney that was critical of the drug industry. His response was published in the BMJ in October 2012 and can indeed provide you with a “final laugh” if you are even only somewhat familiar with the misconduct of this industry.
Here an important quote from this section:
“In 2011, our new government had regular health checks on the menu, but I asked for a meeting with the minister of health where I told her that the Cochrane review we had just completed, and which includes 16 trials, almost 250 000 participants and almost 12 000 deaths, found no effect of health checks on total mortality, cancer deaths or cardiovascular deaths. One of my colleagues told her about a large Danish trial he had just finished that also failed to find an effect. Health checks lead to more diagnoses of diseases or risk factors, which lead to more drug use and more harms” (p. 295).
The definition of osteoporosis has been a true gold mine for the pharmaceutical industry (p. 296). Since almost all of our health parameters deteriorate as we age, this is naturally also the case for bone mineral density. Websites sponsored by the industry claim their drugs are effective in preventing bone fractures and that they should also be used to treat osteopenia (bone mineral density slightly below normal). However, independent institutions have a different view here. If you treat one hundred women, you may be able to prevent one hip fracture, but only maybe. And many healthy people will exercise less when they hear that they have osteoporosis as they are afraid of bone fractures. But exercise is something that strengthens our bones.
The conditions of prehypertension (precursor to high blood pressure) and prediabetes (precursor to high increased blood sugar levels) are also treated by many practitioners with medications.
On YouTube, you can watch hoax videos like the one Australian artist Justine Cooper created for a make-believe drug in 2007. “It looks like a TV commercial and advertises Havidol (have it all), with the chemical name avafynetyme HCl (have a fine time plus hydrochloric acid)” (p. 297).
|EE: Here is the link to the Wikipedia entry on Havidol, and there are also several Havidol videos on YouTube. In addition, there are videos about other “drugs” such as Fukitol. Having the last laugh at big pharma summarizes a number of parodies on the state of the pharmaceutical community. The article from 2007 appears on NCBI, a NIH website. At that point, INDOBELANT had not yet been developed.|
Literature references from pages 299–300
At a later point, we will list the most important literature references with links to the abstracts for scientific articles or to the book texts, where possible. In total, there are over 1,142 literature references, 140 of which are related to “General system failure calls for a revolution” and 120 related to “Impotent drug regulation.” There are also 104 entries on the topic of psychotropic drugs, a topic discussed in the chapter “Psychiatry, the drug industry’s paradise.”