Book Review Deadly Medicines and Organised Crime by Gøtzsche

• Conclusion
• 1. Summary
• 2. Book review
• • 2.1. Confessions from an insider
  • 2.2. Organised Crime, the Business Model of Big Pharma
  • 2.3. Very few patients benefit from the drugs they take
  • 2.4. Clinical trials, a broken social contract with patients
  • 2.5. Conflicts of interest at medical journals
  • 2.6. The corruptive influence of easy money
  • 2.7. What do thousands of doctors on industry payroll do?
  • 2.9. Impotent drug regulation
  • 2.10. Public access to data at drug agencies
  • 2.11. "Neuront..", an epilepsy drug for everything
  • 2.12. Merck, where the patients die first
  • 2.13. Fraudulent "celecox.." trial and other lies
  • 2.14. Switching cheap drugs to expensive ones in the same patients
  • 2.15. Blood glucose was fine but the patients died
  • 2.16. Psychiatry, the drug industry’s paradis
  • 2.17. Pushing children into suicide with happy pills
  • 2.18. Intimidation, threats and violence to protect sales
  • 2.19. Busting the industry myths
  • 2.20. General system failure calls for a revolution
  • 2.21. Having the last laugh at big pharma
• 3. About the book

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.

© CC-by-sa 2.0, Ernst Erb, Foundation Diet Health Switzerland

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.

Dr. Gerd Gigerenzer, psychologist and director of the Max Planck Institute for Human Development, praised the book as being a true eye-opener.

Dr. Peter Sawicki, diabetologist, agrees with the author that:

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.

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.

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 (German only). "The substances with the highest physical addiction potential are heroin and nicotine."

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.

At the time, Astra had just introduced the drug Globacillin, a "p." that was supposedly more effective against acute sinusitis 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).

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.

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).

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 "terbutali.." 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.

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!

The most important drug for this company was naproxen ("Napros.."), 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.

The principal 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.

Other companies also used aggressive methods to try to sell their NSAR as the best on the market.

• Pfizer stated that "piroxic.." ("Felde..") 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 ("celecox..", "etoricox..", "rofecox..", "lumiracox..", and "parecox..") was accompanied by serious cardiac side effects (selective COX-2 inhibitors).

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, "morphi..", 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 the sale of the tranquilizers "Vali.." and "Libri..". 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).

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 "Zyvo." (active ingredient: "linezol.."), which caused a number of deaths because the company falsely claimed that it was more effective against serious infections than the standard drug "vancomyc..". They claimed this because "Zyvo." cost eight times more than "vancomyc..".

Novartis agreed to pay $423 million in 2010 for illegally marketing the epilepsy drug "Trilept.." ("oxcarbazep...") for unauthorized use (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).

Sanofi-Aventis knew about cases of fraud in a study on its antibiotic "Ket.." ("Telithromy..."), 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.

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 "Wellbutr.." ("Bupropi..") for weight loss and the diabetes drug "Avand.." ("rosiglitazo..") 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 "Seroqu.." ("quetiapi..") 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 "Tamif.." ("oselta....") 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 "Tamif.." in the amount of several billions of dollars to prevent an influenza epidemic.

An official at the Food and Drug Administration (FDA) had been assigned the application for "oselta....", but as a result of pressure from Roche, this was taken away from him.

Even though "Tamif.." 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 "Risperd.." ("risperido.."). 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 "Zypre.." ("olanzapi..") 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 "Depako.." (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 "Ket.." ("Telithromy..."), 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, "Zolad" ("Goserel.."), 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 ("citalopr..") as a way to delay the market entry of the drug.

The firm Purdue Pharma falsely claimed that its opioid "OxyCont.." ("oxycodo..) was less addictive than other opiates.

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.

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.

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 "thalidomi.." 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: "prasugr.." 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 "rosiglitazo.." in the RECORD trial for GlaxoSmithKline.

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).

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, "voriconazo.." was significantly inferior to the comparator drug, liposomal "amphoteri..." B, according to the prespecified analysis plan, which staff at the FDA pointed out in a subsequent letter, but the paper concluded that "voriconazo.." was a suitable alternative. More patients died in the "voriconazo.." group and a claimed significant reduction in ‘breakthrough’ fungal infections in favour of "voriconazo.." disappeared when we included infections that had arbitrarily been excluded from analysis. The abstract described manipulated results ... (p. 66).

The other trial used "amphoteri..." 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 "voriconazo..", 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 "voriconazo.." led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with "amphoteri..." 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 "fluticaso.." (cortisone or glucocorticoid), but the recommendation was made based on an inappropriate analysis.

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 $1'000 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.

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.

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.

Gøtzsche tells us about a number of the tricks used, giving relevant examples, and writes the following about one of the examples:

Why "olanzapi.." beats "risperido..", "risperido.." beats "quetiapi..", and "quetiapi.." beats "olanzapi..": 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).

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.

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 "ondansetr", 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.

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:

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.

The ALLHAT trial showed with a comparison of a number of drugs used to treat high blood pressure that "doxazos.." from Pfizer was less effective than the other drugs. The American College of Cardiology then recommended that doctors "discontinue use of "doxazos.." (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.

The commissioner who approved "Vio.." left the agency to work as a high senior official at Merck, the company that produced "Vio..". "Vio.." 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.

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.

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 "salmeter..", 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 "salmeter..". The author recommends taking "salmeter.." 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, "atropi..", and adrenalin (in the case of status asthmaticus, these can be quite dangerous for the heart), "theophylli..", antihistamines, parasympatholytics as "anticholinerg..." ("Ipratrop..." bromide — sounds good, but it is usually only effective in combination with beta-antagonists), and "monteluka.." 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?

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 "rosiglitazo..", 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.

Drugs with known harms are approved without adequate safety data

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 "Alim.." and "Propuls.."). 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.

2.10. 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.

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.

2.11. "Neuront..", an epilepsy drug for everything

In 2004, Pfizer paid a $27 million penalty for selling its epilepsy drug "Neuro...." (active ingredient: "gabapent..") for off-label uses. This was a trivial matter for a company that has an annual turnover of $2.7 billion.

Preceptorship: the practice of planting representatives in doctors’ offices

Warner-Lambert, the patent owner for "gabapent.." 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).

2.12. Merck, where the patients die first

Even before the market launch, Merck knew that "Vio.." — 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 "Vio.." reduced urinary metabolites of prostacyclin in healthy volunteers by about half, which indicates that "Vio.." 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).

"Vio.." caused about 120'000 deaths before it was finally removed from the market

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 "Vio..", 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, "Vio.." caused about 120,000 deaths before it was finally removed from the market.

EE: See also information about "rofecox..". 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."

2.13. Fraudulent "celecox.." trial and other lies

This chapter tells a similar story, but this time it is about "celecox.." (product: "Celebr.."), the COX-2 inhibitor produced by Pfizer. The company conducted two trials, comparing "Celebr.." with "Diclofen.." 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.

"Celebr.."

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 "Vio.." was taken off the market in 2004, Pfizer used the opportunity to claim they had analyzed the data from 400'000 patients and "celecox.." was not linked to an increased risk of heart attack.

Dr. LÖ: "Celebr.." 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 "Vio.." or "Celebr..". But the promise of NSAIDs without side effects for the stomach was indeed very enticing.

2.14. 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 "insul.." that in the case of "insul.." analogues actually only make sense for individuals who experience troublesome hypoglycaemia (p. 172).

How companies can continue to sell their expensive drugs even after the patent has expired

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.

2.15. Blood glucose was fine but the patients died

This chapter looks at "rosiglitazo.." ("Avand.."), 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 "pioglitazo..", 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 "rosiglitazo.." 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).

"Miracle cure"

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 "rosiglitazo.." 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 "rosiglitazo.." was higher than with "pioglitazo..".

This is no surprise since "Avand.." 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 ("pioglitazo.."), or causing liver failure as does troglitazone — which was why it was removed from the market.

Another diabetes drug available is "liragluti.." ("Victo.."), a glucagon-like peptide-1 (peptide hormones) produced by Novo Nordisk. Independent researchers determined that patients who take "Victo.." 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 "Victo.." 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.

The only drug that increases the life expectancy of diabetics who have diabetes type 2 is "metform..", 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.

2.16. Psychiatry, the drug industry’s paradis

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.

Premenstrual Dysphoric Disorder

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 "proz.." ("fluoxeti..", 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.

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.

Antidepressants, "Proz.." and "Paroxeti.."

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 "Proz.." ("Fluoxeti..") 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, "Proz.." was approved for them. The author also reports on the number of suicides among healthy women taking "duloxeti..", 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 C. Gøtzsche then writes about "paroxeti.." ("Pax.." or "Serox.."), 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.

2.17. Pushing children into suicide with happy pills

In 2001, GlaxoSmithKline published a trial in children and adolescents, study 329. This study reported that "Pax.." ("Serox..") 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.

Antipsychotic drugs

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 "Zypre.." (active ingredient: "olanzapi..") 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 "olanzapi.." trial was published 142 times (!), and "Zypre.." became the world’s best-selling antipsychotic although it didn’t have any advantages over "haloperid..". 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, "Zypre.." was recommended for use in children and older adults. After its patent for "Proz.." ran out, Eli Lilly even tried to market "Zypre.." as an effective drug to treat depression.

2.18. 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.

"Adams Affiar"

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.

"We may need to seek them out and destroy them where they live"

Merck also selectively targeted doctors who raised questions about "Vio.." ... 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 "Vio..", 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 "Vio..".

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.

2.19. 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).

2.20. 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".

© CC-by-sa 2.0, YouTube, Alltime10s

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.

Medications are the third most common cause of death

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).

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.

How extreme the situation is

"Eflornith.." (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).

2.21. 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.

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.

Health check

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).

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.

3. About the book

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.

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).