Crimes and Abuses of the Pharmaceutical Industry

CRIMES AND ABUSES OF THE PHARMACEUTICAL INDUSTRY

Teresa Forcades i Vila, MD OSB

1. THE CASE OF “FEMALE SEXUAL DYSFUNCTION” ...... 3 2. THE CASE OF DRUGS USED TO COMBAT AIDS IN AFRICA ...... 6 3. WEALTH AND POWER AGAINST THE POOR ...... 9 3.1. Current wealth and political power of large pharmaceutical companies ...... 9 3.2. Ways in which the wealth and power of large pharmaceutical companies is being used? ...... 10 4. AN INTERNAL CRISIS: INNOVATIONS IN TREATMENT REPLACED BY ADVERTISING ...... 22 4.1. Current Crisis of Pharmaceutical Companies ...... 22 4.2. A Decrease in Innovation and a Rise of Marketing ...... 24 5. AN OPPORTUNITY TO DISMANTLE THE SYSTEM ...... 26 In the brief period from 2000 to 2003, almost all the large pharmaceutical companies went before state tribunals in the USA, accused of fraudulent practices. Eight of these firms were fined over 2.2 billion dollars. Four of these eight companies — TAP Pharmaceuticals, Abbott, AstraZeneca and Bayer- admitted criminal responsibility for activities that put the lives and health of thousands of people at risk1. What were these activities? And who bore the price? What causes pharmaceutical companies to behave in such a way? What actions have been taken in response to these abuses, and what actions still need to be taken? This booklet will examine the current strategies used by the pharmaceutical industry and the direct impact these strategies have on the way health and illness are defined and on which types of resources are available today to promote health and to prevent or cure disease.

Teresa Forcades i Vila is benedictine nun. Medicine doctor, she prepares a docto- rate in theology. She belonged to the first group of young people of Cristianisme i Justícia.

Translation: Gerarda Walsh and Cheryl Waschenko • Printed on ecological paper and recycled cardboard • Editors: CRISTIANISME I JUSTÍCIA • R. de Llúria 13 - 08010 Barcelona (Spain) • Tel. 93 317 23 38 Fax: 93 317 10 94 • [email protected] • www.fespinal.com • Printed by: Estilo Estugraf Impresores, S.L. • ISBN: 84-9730-152-8 • Legal Deposit: M-46906-06 • December 2006 1. THE CASE OF “FEMALE SEXUAL DYSFUNCTION”

In 1998, Pfizer, the largest and most profitable American pharmaceutical company, introduced a drug known as “Viagra” for the treatment of male sexual dysfunction (defined as erectile dysfunction). By 2001, Viagra had become a “blockbuster” drug with 17 million prescriptions written and a billion and a half dollars in sales2. (“Blockbuster” is the term used by the industry to describe a drug with annual sales exceeding the billion dollars mark.) With its stock price soaring, the management of Pfizer turned its attention to women, hoping to identify some sort of female sexual dysfunction for which another lucrative “blockbuster” could be developed. The main obstacle was that while there were seemingly clear and objective criteria to define male sexual dysfunction (erectile problems), female sexual dysfunction was much more difficult to define and, most importantly, much more difficult to quantify and objectively evaluate.

In 1997, only a few months after maceutical industry3. A year and a half lat- Viagra had appeared on the market, nine er, in October 1998, the first international pharmaceutical companies planned, or- conference to develop a clinical consensus ganized and financed a meeting of medi- on female sexual dysfunction took place in cal specialists in Cape Cod Boston4, fully financed by eight pharma- (Massachusetts). Plainly stated, their goal ceutical companies. Eighteen out of the ni- was to create a new pathology (namely, neteen authors of the new internationally “female sexual dysfunction”) in order to agreed upon definition had direct econo- suit the economical interests of the phar- mic ties with the companies that financed

3 the event or with other pharmaceutical of the same year, a third meeting on the companies. One year later, in 1999, an ar- issue took place, organized by the ticle entitled “Sexual Dysfunction in the Medical School of Boston University, but USA: Prevalence and Predictors” appea- promoted and financed by sixteen phar- red in the Journal of American Medical maceutical companies. 50% of those Association (JAMA)5. The authors of the present admitted having direct economic article asserted, with seeming scientific links with the pharmaceutical industry6. objectivity, that 43% of the American fe- From this meeting came the Forum on male population was suffering from this Female Sexual Function, which held two “new illness,” an illness in fact created and more conferences in Boston in 2000 and defined to suit the economic interests of 2001 thanks to the generous financial the pharmaceutical industry. contributions of twenty pharmaceutical Three steps were used to identify the companies led by Pfizer7. “affected population.” (1) A list of seven In 2003, Ray Moynihan denounced “symptoms” was developed, each of this manipulation of medical criteria to them considered significant enough to serve commercial interests in the presti- justify a diagnosis of the new condition if gious British Medical Journal (BMJ)8. a woman were to present it for two Over six weeks, the editors of the maga- months or more in the previous year, (2) zine received a total of seventy responses A questionnaire about these seven to Moynihan's article. Two-thirds of the symptoms was answered by a total of responses were in support of the article 1,500 women, (3) Results were evaluated and confirmed the growing indignation of in such a way that a single “Yes” response medical professionals in the face of this would be seen as sufficient grounds for manipulation although, as one of the re- diagnosing the condition. One of the se- plies made very clear, without the help of ven “symptoms” was the lack of sexual the same medical professionals, this si- desire. In other words, women who re- tuation would not have arisen in the first ported a lack of sexual desire for two suc- place9. If we doctors did not take part in cessive months or more over the previous the exploitative abuse carried out by phar- year —not taking into account whether maceutical companies, such situations they had been mourning the death of a lo- would not arise. ved one, stressed with too much work, In December of 2004, the U.S. regu- trapped in an unhappy relationship, enjo- latory agency (the Food and Drug ying a period of solitary creativity etc.— Administration (FDA)) prevented the were automatically labeled as “sexually commercialization of the first drug that dysfunctional,” thus increasing the per- was developed to treat “female sexual centage of potential candidates for the dysfunction,” a testosterone patch offered treatment that the pharmaceutical in- by Proctor and Gamble10. The principal dustry hoped to develop in the near futu- investigators of the clinical trials —all di- re. Two out of the three authors of this ar- rectly financed and supervised by Proctor ticle had economic links with and Gamble— had presented their results pharmaceutical laboratories. In October in such a biased manner, that the doubtful

4 benefits and the likely dangerous side-ef- ceutical companies exerts on the practice fects (breast cancer and cardiac disease) of medicine11. were instead advertised as clear benefits There is no doubt that female sexual and negligible risks. problems exist, but they (like any other me- No other drug has yet been developed dical condition) need to be studied in rela- to treat female sexual dysfunction, largely tion to the medical needs and the personal because of a growing awareness of all tho- concerns of the women affected, and not in se involved of the detrimental effects that relation to the economic interests of some the excessive influence of the pharma- of the richest companies in the world.

5 2. THE CASE OF DRUGS USED TO COMBAT AIDS IN AFRICA

On March 23rd 2005, the Indian Parliament was obliged to modify its patent law in accordance with the stipulations of an international agency (the World Trade Organization, WTO), which had been created in 1994 to defend the interests of wealthy countries confronting the challenges of glo- balization. The new patent law required the commercialization of drugs in India be made subject to the international patenting system stipulated by the WTO. Under increasing international pressure, the Indian Parliament had to repeal its own 1970 legislation that had included safeguards to protect against the abusive power of patent holders. For example, if a company imposed prices that were too high for the Indian population, India could, within its own boundaries, legalize the production of generic versions of medicines still protected by patents in other countries.

Under the 1970 law, Indian companies Let us examine the effect that such a were also permitted to commercialize the- change in patent law has upon those suf- se (much cheaper) generic medicines in fering from HIV in Africa. In 2003 more other poor countries. The new internatio- than 30 million people infected with HIV nal patenting system imposed by the (out of a total 40 million worldwide) we- WTO has no mechanism to protect re living in sub-Saharan Africa. In against unaffordable pricing nor does it Botswana, for example, 40% of women allow for the commercialization of Indian are infected with the HIV virus, and in generics in poor countries. It should also Lesotho a third of the total population are be noted that the generic pharmaceutical infected13. Due to the lack of affordable industry is a major employer in India. In antiretroviral drugs, three million Africans 2003, this industry provided work for die from AIDS every year. Until 2005, the 500,000 people in over 20,000 companies Indian pharmaceutical companies that that were themselves able to provide work produced generic drugs had been able to to another 2.5 million people through sub- grant access to essential drugs to an extre- sidiary contracts12. mely low (less than 1%) but steadily gro- 6 wing percentage of the population of poor refused requests will need to be reasses- countries. Due to the free market compe- sed and it will be virtually impossible to tition allowed in India under the 1970 le- legally refuse them again. More than gislation, the price of the standard antire- 7,000 of these requests come from large troviral treatment had been reduced (in foreign multinationals, including the 2004) from 1,500 dollars to 150 dollars per pharmaceutical giant Pfizer. Today, Pfizer person per year14. In addition, the bypas- is the largest pharmaceutical company in sing of the patents allowed the generic ma- the world and a key player in the US eco- nufacturers to combine the different drugs nomy. A potent example of Pfizer's power into one single tablet. The astonishing re- can be seen in the way it prevailed over duction in price together with the simpli- the French government in 2002. After the fication in the treatment protocol were al- French government opposed its abusive ready starting to show dramatic effects in prices, Pfizer threatened to withdraw its the possibility of successfully treating the products from the French market. The worldwide AIDS epidemic. French government, after many failed ne- On a global scale, some 350,000 peo- gotiations, ended up yielding to the pres- ple undergoing antiretroviral treatment sure15. If a prominent member of the are dependent on the production of gene- European Union had to yield in the face ric drugs in India. This figure represents of Pfizer's economic threats, then what half of all those currently undergoing an- political power could developing coun- tiretroviral treatment in developing countries possibly hope to use to oppose unfa- tries. That is to say, less than 2.5% of pe- vorable agreements? ople who are HIV positive in developing The direct link between the introduc- countries are currently receiving treat- tion of patenting laws and the mortality of ment. Millions of people die every year the population can be seen in the case of because of this. With the move to streng- Brazil. Since laws were passed that prohi- then international patenting laws, all bited the patenting of drugs that had appe- drugs developed between 1995 and 2005, ared on the Brazilian market before 1997, as well as all those developed after 2005, Brazil was able to locally produce the ge- are now protected by patent laws and the- neric equivalent of eight out of the ten an- refore cannot enter into free competition, tiretroviral drugs currently available meaning that their price is soon likely to worldwide, with an average reduction in increase (at least) tenfold. This applies to price of 79%. In 2003 it became clear that drugs that are essential to treat the HIV vi- the Brazilian AIDS epidemic had been sta- rus as well as other very prevalent and po- bilized and the mortality rate reduced by tentially fatal diseases such as malaria, tu- half16. With the new international legisla- berculosis, and cancer. tion, however, the production of generic Between 1995 and 2005, 8,926 new medicines in Brazil will also be blocked. patent applications were made to the Due to its relevant content, we will Indian regulatory agency. Many of these now reproduce some extracts of the letter were refused as abusive but now, due to which Karim Laouabdia, spokesperson the new law imposed by the WTO, all the for Médecins Sans Frontières (Doctors

7 Without Borders), addressed to Pascal capacity to produce them generically such Lamy on September 20th 2005, on the oc- as India, Brazil and Thailand. (...) In ad- casion of Lamy's election as Director dition, the impact of patents is not limited General of the World Trade Organization to antiretroviral drugs, but will increa- (WTO). singly be felt across all diseases with all “The HIV/AIDS crisis has shown the medicines brought to market from now on. urgent need to ensure that essential medi- (...) The patent system is intended as a sti- cines are available at affordable prices. mulus for innovation, but there is no Today approximately half of the one mi- mechanism for directing that innovation, llion people in the developing world who and as a result many diseases are comple- receive antiretroviral drugs rely on gene- tely ignored. We face the consequences on ric production. The fixed-dose combina- a daily basis in our projects, for example tions, produced in India, greatly simplify to diagnose TB [tuberculosis] in HIV pa- the administration of antiretroviral the- tients and in children; to treat tropical di- rapy and have been critical to scaling up seases like leishmaniasis, which affects 12 treatment in resource-poor settings. The million people; to monitor HIV patient 2001 WTO Doha Declaration on TRIPS progress, and to treat HIV in children”18. and Public Health17 was a vital step in in- Less than three months after submit- creasing access to medicines. It provides ting this letter, Médecins Sans Frontières unambiguous support to any government exposed a new offense: some well-known that needs to protect the health of their pharmaceutical companies, after having people [because these governments are prohibited the production of generic drugs allowed] to use the TRIPS flexibilities to in poor countries, were refusing to com- overcome the barriers posed by patents, mercialize in these same countries the and helps the least developed countries by drugs that, despite being needed by the extending the transition period for enfor- population, were not lucrative enough for cing and granting pharmaceutical product the producing company19. The example patents until at least 2016. Since then, ho- used was that of the antiretroviral drug wever, there has been a systematic dis- Kaletra, marketed by Abbott. Abbott has mantling of the Doha Declaration through introduced a version of Kaletra that does bilateral trade agreements in which much not need to be refrigerated. In spite of the higher levels of intellectual property pro- enormous advantages that such a product tection are demanded than [those] requi- would represent to African patients (due red by the WTO. The impact of patent pro- to the high temperatures and the frequent tection on HIV programs will become very interruptions in electrical supply which apparent in the coming years when large occur in the African territory), Abbot re- numbers of patients currently on treatment fuses to market this medicine in Africa. will need to switch to newer, second-line Abbot is not alone. Gilead, the pharma- medicines. These drugs are at least 4-10 ceutical company that owns the patent of times as expensive as first-line treatments, tenofovir, another antiretroviral medicine and almost all are patented or are likely to recommended by the WHO, has also re- be patented in those countries that have fused to commercialize it in Africa.

8 3. WEALTH AND POWER AGAINST THE POOR

The extraordinary growth in political and economic power of the large American pharmaceutical companies began in 1984 with the law on the extension of patents (Hatch-Waxman Law) approved by the Republican- dominated Congress of the Reagan years. This power was then consolidated in 1994 with the World Trade Organization (WTO), whose creation was intended to prevent the rapidly expanding global economy from hindering the economic interests of the world's wealthiest companies20.

3.1. CURRENT WEALTH AND POWER OF LARGE PHARMACEUTICAL COMPANIES

The gross profit margins of the phar- 16.2% versus the 27.3% average rate im- maceutical industry range from 70 to 90% posed on other large industries22. Such a and its net income rate is the highest of all tax break is shocking when one considers industries. (According to Fortune maga- that annual prescription drug price in- zine, in the year 2000 the net income rate creases routinely outpace the level of in- of the pharmaceutical industry stood at flation (from 6% to 20% each year)23. 18.6% versus the 15.8% rate of commer- In 2000, the main pharmaceutical cial banks). In 2004, Pfizer, the largest lobby in the USA (PhRMA) counted 297 pharmaceutical company, had a net inco- professional lobbyists, that is, one for me rate of 22% of its total sales, which each two members of Congress24. This amounted to 53 billion dollars21. In spite number —already vastly exceeding the of these extraordinary profits, the tax rate number of any other lobby— has tripled imposed on pharmaceutical companies is in recent years. In 2002, PhRMA financed remarkably below average, standing at the work of 675 lobbyists, which means 9 that in Washington that year there were To highlight the current absence of more people working to promote the in- freedom and fair play and the need to bet- terests of pharmaceutical companies than ter regulate this market, Marcia Angell, members of Congress25. This unrelenting chief editor of the renowned medical re- pressure and influence on the legislative view The New England Journal of process has allowed the industry to obtain Medicine for almost twenty years, suc- the advantageous conditions (see section cinctly affirms: “The colossus that is the 3.2) that have permitted it to progressively pharmaceutical industry is today like a dominate the global market: today 60% of five-hundred pound gorilla: it can do all drug patents are owned by USA-based what it wants”28. And Philippe Pignarre, companies versus 20% owned by the EU. director for seventeen years of a large The USA controls the market of the 50 pharmaceutical company and currently best-selling drugs, all of them blockbus- Professor at the University of Paris-VIII, ters26. In 2002, the total earnings of the insists that the market is not and has ne- ten largest pharmaceutical companies ex- ver been a natural reality, but is always ceeded the combined earnings of the other a cultural or a social one. That is to say, 490 companies listed in Fortune’s top 500 the concept of market necessarily im- most profitable companies: the ten largest plies norms and agreements whose goal pharmaceuticals together made a total is not to regulate some sort of pre-exist- profit of 35.9 billion dollars and the other ing ‘natural entity’, but instead to create 490 companies together made a total pro- the reality we call market. The norms are fit of 33.7 billion dollars27. The dispro- constitutive of the market. The so-called portionate privileges that the pharmaceu- ‘free market’ (an unregulated market) tical industry is enjoying in the form of tax cannot exist; instead, what can and — breaks and advantageous laws and agree- most certainly— do exist are the ‘brutal ments, show clearly that the industry’s market,’ that is, a market regulated ac- current power and wealth are not the re- cording to the interests of the five hun- sult of a “free market” but rather of a de- dred pound gorilla, and the ‘less brutal liberate policy designed to protect an in- market,’ that is, a market whose norms dustry that is as politically strategic to the attempt to temper the avidity of the USA as the petroleum industry. weightier29.

3.2. WAYS IN WHICH THE WEALTH AND POWER OF LARGE PHARMACEUTICAL COMPANIES IS BEING USED

Today large pharmaceutical compa- cases even the lives of others. That is why nies use their extraordinary wealth and they are accused of criminal behavior. power to defend their own interests at the According to the report issued last ye- cost of the well-being, health and in some ar (2005) by a committee of experts of the

10 British House of Commons, it is obvious nating their research into illnesses that pri- that the interests of the pharmaceutical in- marily affect the poor so they can focus dustry and those of the general public do their resources on profitable markets and not coincide. This committee concluded problems that affect populations with a that it is therefore (1) “essential to set up high degree of purchasing power, even an effective regulatory regime to ensure when that research does not involve actual that the industry works in the public in- diseases (for example, the proliferation of terest,” (2) “the present regulatory system anti-aging “medicines”), (4) forcing na- is failing to provide this” and (3) “as a tional and international laws and agree- consequence of lax oversight the indus- ments even if it is at the expense of mi- try’s influence has expanded and a num- llions of lives. ber of practices have developed which act against the public interest”30. The authors of the report also pointed 3.2.1. Marketing of useless out “that the aim of new drugs should be medicines that might prove to provide a real therapeutic benefit for harmful or even fatal 31 patients” . What does this mean? If they Statistics from the FDA show that bet- are not working towards producing real ween 1998 and 2002, eight suicides were therapeutic benefits now, then what are reported in the USA among sufferers of pharmaceutical companies spending their epilepsy that were taking the drug gaba- time doing? As the third most profitable pentin made by Pfizer (its commercial na- industry in the country (after tourism and me is Neurontin®)33. During the first six banking), this very same report called the months of 2003, the number of reported pharmaceutical industry “a jewel in the suicides was 17. A private law firm made 32 English crown” . Whence come the ex- these facts public and opened their own traordinary profits of this industry if not investigation of the incidents. During the from producing useful medicines? 12 months from September 2003 to The main strategies employed today August 2004 they documented 2,700 sui- by the pharmaceutical industry to create cide attempts among patients that were ta- their wealth include: (1) orchestrating ag- king gabapentin, 200 of which ended with gressive and often misleading advertising the death of the patient. In November campaigns and emphasizing propaganda 2004 the British Medical Journal (BMJ) in relation to the drugs they develop, whe- reported that since this issue had come to ther or not they are useful, and in spite of light, neither Pfizer nor the FDA had ta- the fact that some may be harmful or even ken any action not even by indicating on fatal, (2) seeking to monopolize the mar- the leaflet the increased risk of suicide34. kets by exploiting their medicines (inclu- As of the writing of this booklet, the risk ding the essential ones) in increasingly of increased suicide caused by abusive conditions that do not take into Neurontin® is noted on Pfizer’s webpa- account the objective needs of patients nor ge35. their purchasing power, (3) greatly redu- As for the anti-depressant sertraline cing or in some cases completely elimi- (Zoloft®), also produced by Pfizer, the sa- 11 me issue of the BMJ reported that the (made by Merck), and Bextra® and company had hidden information on pos- Celebrex® (made by Pfizer). These drugs sible side effects that included suicide at- had shown no therapeutic benefits in the tempts and aggressive behavior36. The ca- clinical trials that compared them to other se of Christopher Pittman (a 12 year-old anti-inflammatory drugs already on the boy who began to display highly aggres- market39. In 1998 and 1999, the manu- sive behavior within a few weeks of ta- facturers were nevertheless given the go king sertraline and who, two days after ahead by regulatory agencies because it having his dosage doubled, murdered his was hoped that these drugs would produ- grandparents and set fire to their house), ce milder side effects than the older anti- together with an accumulation of less dra- inflammatories. In September 2004, matic evidence along the same lines, was Vioxx® (Merck) was taken off the market enough to convince the European regula- after it became clear that its side effects tory agency for medicines to prohibit its were not only not milder but potentially prescription to patients under 18 years fatal (stroke and heart attack). The FDA old37. reported that Vioxx® was likely to be res- Unnecessary medicines are known in ponsible for 27,785 deaths from heart at- pharmaceutical slang as “me-too drugs.” tack between 1999 and 200340. In April These drugs are designed and marketed 2005 Bextra® and Celebrex® (Pfizer) with the aim of substituting a previous were also taken off the market following drug whose patent is about to expire. The a long and difficult struggle between the therapeutic qualities of me-too drugs are FDA and Pfizer. That such a prolonged essentially the same as those of the pre- struggle ensued for a drug that had shown vious drug, but because they are introdu- little or no potential benefit but rather gre- ced as new drugs into the market, phar- at risk, highlights just how much political maceutical companies have the right to power this giant of the pharmaceutical in- obtain a new patent. The success of such dustry really wields41. unnecessary medicines can only be ex- Whenever a new drug is developed, plained through the power of advertising there is always a risk of unwanted side ef- to doctors and patients (see section 4.2). fects that could not be detected at the re- One example of this type of drug is ceri- search phase. This cannot be avoided. But vastatin made by Bayer (its commercial if every medicine has a risk of causing se- names are Baycol®, Lipobay®, rious side effects and in some cases death, Cholstat® and Staltor®). Cerivastatin is why are new medicines developed that of- an anti-cholesterol medication that had to fer no real therapeutic advantage over tho- be taken off the market in 2001 after ha- se already on the market? Why do phar- ving been shown to cause 1,100 cases of maceutical laboratories produce them? severe rhabdomyolysis (a muscular was- Why do regulatory agencies approve ting condition that can be irreversible) as them? Why do doctors prescribe them? well as one hundred deaths38. On the topic of unnecessary medica- Another more recent example is that tions, we shall mention the drugs that are of the anti-inflammatory drugs Vioxx® designed to cure illnesses —such as fe-

12 male sexual dysfunction as defined abo- categorizing more and more individuals ve— that the pharmaceutical industry la- as ‘abnormal’ or in need of drug treat- bels as such according to their own inter- ment”45. ests. Some examples of non-pathological According to the French network of human conditions that are labeled as ill- regional centers of drug-vigilance, every ness so that drugs can be sold to cure them year 1.3 million French citizens are hos- include: menopause (allegedly cured with pitalized due to side effects of medicines hormone replacement therapies that have they are taking. This figure represents recently shown unacceptable side-ef- 10% of all hospitalizations per year. A fects), appropriate sadness (labeled as de- third of this total figure (ca. 400,000) is pression and allegedly cured by anti-de- admitted in a serious condition and 18,000 pressants that we have already seen are of them end up dying. This means that, in capable of causing suicide or even mur- France, the mortality rate per year due to der42), and memory loss among the eld- side effects of medicines is double that of erly (labeled as “incipient cognitive defi- road accidents46. cit” and treated with anti-dementia medicines; it is to note that on learning that they might have incipient dementia, 3.2.2. Exploitation of essential the elderly often feel sad and become sui- drugs in abusive conditions table candidates for anti-depressant the- In the discussion on the marketing of rapy). antiretroviral drugs in Africa, we saw the There is a popular English expression brutal effect that the new international pa- used to denounce this abusive intrusion of tent law is having on access to essential the medical model (and the medical busi- drugs in poor countries. According to ness) into non-medical aspects of human Pignarre, in the face of direct accusations life: “a pill for every ill.43” The 2005 re- from humanitarian organizations, the big port by the committee of experts of the pharmaceutical companies defend them- House of Commons notes that in 2003, selves in this way: 650 million prescription drugs were sold The pharmaceutical industry explains in England. This number (to which we that any move against the right to uphold should add the blossoming business of the patents in the Third World, and particu- over the counter sales of drugs) reflects an larly in Africa in relation to drugs used to increase of 40% in relation to the amount combat AIDS, would signify the end of the of prescription drugs sold in the ten years research into such drugs, for nobody will prior to 2003 and means that each English be willing to fund research into drugs that citizen takes an average of 13.1 prescrip- will not be able to be protected by patents. tion medicines each year44. The same re- (...) This reasoning implies that port remarks that “while the pharmaceu- tomorrow’s theoretical progress can only tical industry cannot be blamed for be pursued at the cost of sacrificing mi- creating unhealthy reliance on, and over- llions of today’s lives… it implies a choice use of, medicines, it has certainly exacer- in favor of improving the quality of life of bated it. There has been a trend towards the privileged populations of the North at

13 the cost of immediately cutting short, by nazol, a drug used by AIDS patients, ha- several decades, the life expectancy in the ve a market price that ranges from $18 to South. It is equivalent to condemning to 32 in the countries where Pfizer has main- death 90% of those who need essential tained its monopoly, and a price of only medicines, in order to maintain the high $1 in countries where a generic equivalent prices that only the privileged 10% are exists? Why does the Indian company able to pay. This obscene dialectic —into Cipla that makes generic drugs offer which the pharmaceutical industry of ri- Médecins Sans Frontières (MSF) an an- cher countries unanimously wants to trap nual charge of $450 per patient for anti- us— is the beginning of a reign of terror47. AIDS treatment in contrast to the $13,300 During the international controversy demanded by western laboratories? that followed the obligation imposed on 3. The actual patent system favors the poor countries to respect —at the expense interests of private companies at the ex- of the lives of their citizens— the abusive pense of the common good. It is clear that patents on essential antiretroviral drugs, there is a conflict of interests between the the UN World Intellectual Property pharmaceutical companies and the com- Organization (WIPO) developed a propa- mon good and it is as well clear that the ganda document in favor of the pharma- market in general —and very particularly ceutical companies, in which the six main the drug market— is not “free”, but rather accusations leveled against the patent subject to legislation in every country. At system by humanitarian organizations the present time, this legislation is aimed from all over the world were labeled as at favoring private interests. “myths” and were refuted with false ar- 4. The actual patent system prevents guments. real competition. Nobody claims this. The Here is a summarized version of the actual patents system does allow compe- six accusations that the WIPO discarded tition, but its rules are not aimed at favo- as myths (underlined), followed by some ring the common good.. critical comments by Philippe Pignarre48. 5. The actual patent system is particu- 1. The difficulties of access to health larly unfair for developing countries that care and the restricted availability of es- are facing very complex social and eco- sential drugs are a consequence of the ac- nomic situations, and so should therefore tual patent system. If this is a myth, why be made exempt from such obligations as have countries that up until now have not are linked to the international intellectual respected the patent system (like India) property, particularly in relation to cer- been able to combat the AIDS epidemic tain drugs. Not only is this not a myth, but much more successfully than countries a growing large-scale health emergency. that were forced to accept these regula- An international forum —with no right to tions from the beginning? veto allowed to the US nor to any other 2. The high market price of drugs is country— should be immediately set up mainly caused by a patent system that to deal with this question. allows the industry to fix artificially high 6. Actual international treaties on the prices. If this is a myth, why does fluco- protection of patents prevent the exercise 14 of the fundamental human right to have wealth in our world is well known: 20% access to available drugs that can save of the global population enjoys and was- one’s life. As we have seen, this is indeed tes 80% of the planet’s wealth, while 80% the case today. We need a new, more just, of the global population struggle and die international patents system. with the remaining 20% of global resour- The abuse of the current patents ces. One could imagine that with regard to system does not solely affect Third World essential medicines, this imbalance could countries. In richer countries, increasing at least be partially ameliorated because numbers of patients are facing difficulties this is a sensible topic that moves many to in paying for the treatments they are pres- compassion and because of the many in- cribed. In order to reduce expenses, some ternational agencies involved. However patients take their daily medications every the opposite is true; the imbalance betwe- other day or share them with other mem- en rich and poor in our world is made bers of the family. In the USA the cost of much worse by the inequities involved in taking one drug can reach as high as the allocation of resources and the availa- $1500 per year. On average, elderly US bility of essential medicines: 90% of all citizens take regularly six different drugs. health resources are committed to resear- This represents a total average annual ex- ching diseases that affect 10% of patients pense for prescription drugs of roughly (those living in the developed world), and $900049. 10% of all health resources are committed to researching diseases that affect 90% of patients (those living in the developing 3.2.3. Research driven exclusively world). This is known as the “10/90 gap”50. by economic profit Tropical diseases belong to the cate- In 2001, the group set up by Médecins gory of neglected diseases. Out of a total Sans Frontières (MSF) to study neglected of 1,393 drugs that were marketed betwe- illnesses published a report called “Fatal en 1975 and 1999, only 13 (1%) were de- Imbalance”. The report concluded that, in veloped for the treatment of a tropical di- spite of the fact that certain illnesses af- sease. The forgotten illnesses include: fect millions of people in a significant way malaria, tuberculosis, sleeping sickness and in spite of the fact that they can po- (African Trypanosomiasis), Chagas disea- tentially be cured: a) hardly any research se (South American Trypanosomiasis), is done into illnesses that primarily affect Buruli ulcer disease, Dengue fever, leish- the poor, and b) illnesses that only affect maniasis, leprosy, filariasis and schistoso- the poor are not investigated at all. miasis. Apart from the first two, the illnesses in this list almost exclusively affect The name of the report, “Fatal the poor. Of particular note is Chagas di- Imbalance,” refers to the fact that only sease, currently affecting 16-18 million pe- 10% of the world’s health research pro- ople, with some 100 million (25% of the jects (including all those undertaken by Latin American population) at risk of ac- governments and universities) is dedicated quiring it51 and 50,000 people dying an- to illnesses that affect 90% of patients nually from it52. worldwide. The scandalous imbalance of 15 The authors of the MSF report, in co- maining 30% of the work was carried out llaboration with the Harvard School of by academic institutions outside of the Public Health, sent a questionnaire to the USA almost entirely financed with public twenty largest pharmaceutical companies money54. of the world requesting information on The MSF report makes clear that res- their research programs. Only eleven ponsibility for the fatal imbalance lies not companies replied, including six out of only with the pharmaceutical industry but the ten largest companies. Out of the ele- also with all the public and private insti- ven companies that responded, none we- tutions that participate in a system see- re researching sleeping sickness and only mingly driven exclusively by profit with three had invested some money into little or no regard for the suffering of pa- Chagas disease and leishmaniasis. tients55. According to the same MSF re- One could argue that private compa- port, in 2001 the majority of financial and nies have the right to invest their money intellectual resources invested in health as they please, but the remarkable point research throughout the world were com- here is the fact that the money that funds mitted to investigating impotency/erectile the health research carried on by the phar- dysfunction, obesity and insomnia56. maceutical industry comes largely from In addition to not being taken into ac- the public: six out of the eleven compa- count when deciding the priorities of nies studied by MSF had financed their pharmaceutical research, the patients of studies primarily through agreements poor countries —particularly those in with public health organizations. A study Africa— are often used as experimental by The Boston Globe on the 50 most wi- subjects in unethical clinical trials. In dely sold drugs between 1992 and 1997 Kenya, for example, towards the end of concluded that 45 of these had received the 1990’s and under the responsibility of public funding53. The public pays first to the University of Washington, clinical fund the research and then again to buy trials were carried out to observe the na- the product. It is no surprise then that the tural progression of AIDS. What that me- earnings of the industry be so spectacular. ans is that, with the excuse that these pa- Of the 17 final clinical trials that led to the tients would have died anyway, hundreds approval of the five most widely sold of Africans were submitted to comple- drugs in 1995 (Zantac®, Zovirax®, mentary tests in order to document and Capoten®, Vasotec® and Prozac®), only study how they deteriorated until their de- one was financed entirely by the pharma- ath. As the infection advanced they were ceutical industry. Of all the research in- never offered any of the treatments that volved in the development of these five could have stopped it57. In his 2000 report drugs, only 15% was financed by the “The Shame of Medical Research,” David pharmaceutical industry; 55% of the rese- Rothman exposed the fact that in 15 of 16 arch work was carried out by the National clinical trials that were being carried out Institute of Health (the public govern- in developing countries to study the most mental institution of the USA that is fi- cost-effective way to prevent the trans- nanced through tax revenues), and the re- mission of the AIDS virus during preg-

16 nancy, the women enrolled in the control ests. As we have seen, these interests are group received a placebo drug (a sugar contrary to the common good. pill) instead of the AZT treatment that has In addition to attempting to directly in- been shown to reduce the maternal-fetal fluence the highest levels of the govern- transmission of the virus. According to the ment, pharmaceutical companies in the Helsinki Convention on ethical protocols US have begun to develop a parallel stra- for medical research, a new treatment tegy meant to manipulate public opinion. should always be compared with the most They promote organizations that appear to effective treatment available on the mar- be spontaneous initiatives and are in rea- ket. The study of the Harvard School of lity supported and run by citizens that Public Health in Thailand was the only work for the pharmaceutical companies ones who honored the Helsinki and are paid to promote their interests “on Convention. The other 15 studies enrolled the ground” as it were, without being no- a total of 17,000 women and allowed half ticed60. These associations are especially of these women (those in the control useful when pressure is being exerted to groups) to go through multiple blood ex- remove a new drug from the market be- tractions and through the additional tests cause of its harmful side effects. As the required by their study protocol, while gi- pressure begins to build, these “spontane- ving them daily a useless sugar pill and ously” formed organizations recruit peo- documenting how their health deteriora- ple to loudly and publicly complain and to ted and how the virus infected the child bombard the media with an avalanche of they were carrying58. glowing patient testimonials about the wonderful improvements they have expe- rienced on the new drug. 3.2.4. Manipulation of legislation in Today, neither the FDA, nor any other their own countries and with regulatory agency in the world, requires regard to international agreements that in order to approve a new drug for sa- In 2002, 26 of the 675 pharmaceutical le, proof that this new drug is better than lobbyists on payroll were former members the drugs already available on the market of Congress, and 342 of them were former be demonstrated. Taking into account that employees of Congress (20 of whom had —as we have seen— there is always a pos- held management roles)59. Each lawma- sibility that hitherto unknown side effects ker has assigned to her/him one or more of a new drug prove fatal, this demand lobbyists who have the time and financial seems only too logical and reasonable. All backing to study their psychological pro- over the world, however, all that is neces- file, personal and employment history, and sary for a new drug to be approved for sa- their weaknesses. This information is used le is that it be shown to be better than ta- to exert as much pressure as possible upon king nothing at all. each lawmaker so as to garner support for The fact that patenting a new medicine legislation favorable to the interests of the does not require proof that this drug re- pharmaceutical industry and to curtail any presents an improvement over similar measures that would inhibit these inter- drugs already on the market explains the

17 proliferation of the so-called “me-too wer is yes. And did they succeed in doing drugs”, drugs that, as well as being unne- so? Again the answer is largely yes, at le- cessary, are capable of causing death or ast with regard to the USA. Let us exami- other serious or irreversible illnesses. For ne how this occurred. a pharmaceutical company it is much mo- In 1992, the US Congress approved a re profitable to minimally modify an old law allowing pharmaceutical companies drug and sell it with a new patent when the to accelerate the process of obtaining new patent of the first is about to expire, than patents in exchange for economic com- to pour money into researching a new drug pensation62. The pharmaceutical company from scratch. Between 2000 and 2004, 314 wanting to patent a new drug can —if it so new drugs were approved in the USA of wishes— pay a considerable sum to the which only 32 could actually be conside- FDA so that they hire more workers and in red “new”61. As we shall see, this possibi- this way decide more speedily whether a lity of making the industry profitable by new drug should be approved. Of course producing drugs that are simply copies of this is not supposed to be a matter of buy- others already in existence is the key facing governmental approval, but rather a tor of the crisis that this industry is cur- question of economically contributing to rently facing (see section 4.1). the improved functioning of the regulatory The demand that new drugs prove their agency. In practice, however, what occurs worth before being allowed to enter the is that the very salary of some of the FDA market is reasonable enough, but more employees responsible for evaluating a reasonable still would be for drugs to be new drug comes ultimately from the phar- evaluated by independent organizations maceutical company interested in obtai- rather than by the same companies that ning its patent63. Under these conditions, will be economically benefiting from it is not surprising that since this law was them. Today, none of the democratic go- passed, there has been a marked increase vernments of the world requires that an in- not only in the total number of patents ap- dependent body assess the effectiveness proved (a logical consequence after ha- and safety of drugs. The existing regula- ving increased the number of workers), but tory agencies evaluate the data provided also in the percentage of patents approved by pharmaceutical companies, but do not (i.e., other things being equal, if 10 wor- carry out any research of their own. kers reject 5 patents and approve 5, 100 Pharmaceutical companies make the workers should reject 50, and approve 50, drugs, validate them, and sell them. The not more than 50; the total number of ap- only task left out of their direct control is proved patents should increase, the per- the approval necessary for the sale of the centage should remain stable). product. This is the responsibility of the re- This irregular situation that compro- gulatory agencies. The question is: have mises the neutrality of the FDA, would not pharmaceutical companies used their im- have been allowed to arise had the phar- mense power and clout to influence and maceutical industry not controlled the no- manipulate the regulatory agencies meant mination of the director of the FDA. In to ensure the safety of the public? The ans- 2002, the candidacy of the respected pro-

18 fessor of pharmacology Alastair Wood Thomson Corporation, a company which was blocked in favor of Mark McClellan, offers courses and training to physicians) who, besides being the brother of the press serves their interests in the following way: secretary of the White House, had as his (1) a pharmaceutical company wants to in- greater asset the fact of being unreservedly crease the list of conditions that can be in favor of the politics of the pharmaceu- treated by one of their drugs (drug X), (2) tical lobby PhRMA and its fraudulent it contacts Drugdex to request that certain practices. McClellan held the highest po- conditions be included in their official list sition in the FDA between the years 2002 of indications for drug X, (3) Drugdex in- and 200464. cludes them without too strictly assessing There are more irregularities. In 1997, the information submitted by the pharma- Congress passed a law allowing a com- ceutical company, (4) in return, the phar- pany known as “Drugdex” to develop and maceutical company finances a conti- distribute an official list of recommended nuous education course offered by the uses for medicines much broader than that professionals from Thomson Corporation approved by the FDA. One might wonder to which Drugdex belongs, and (5) the whether it is ever possible to prescribe a subject of the course offered is, naturally medicine to treat a condition for which it enough, “New indications of drug X.” As has not been approved by the regulatory the course is being offered in more and agency. The answer is yes, because physi- more medical centers, Thomson cians are entitled to make use of medicines Corporation benefits because it is offering in the way and at the doses they deem ap- a course and is being paid for it, and the propriate for they patient, always under pharmaceutical company benefits because their direct responsibility and understan- the physicians trained by Thomson start ding that they can be sued if their use of prescribing drug X to treat the new set of the medicine proves wrong. “Wrong use” ailments, thus increasing its sales and its is not the same as “use not sanctioned by profits. Another convenient consequence the regulatory agency”. Physicians need to of this cooperation is that physicians who have leeway in prescribing and this is ack- prescribe drugs for the additional ailments nowledged and respected by all. However, listed by Drugdex are legally covered, it is one thing to allow a physician to use should any complications arise. And, last her/his clinical judgment as she/he sees fit, but not least, Medicare, the public program and it is another —very different— thing in the USA that helps the elderly pay for to create, with the support of government, medical care and prescriptions, is obliged a second much longer list of official uses by law to at least partially reimburse pres- of a medication parallel to the list given by criptions if the conditions for which they the regulatory agency. are written are listed in Drugdex65. This The benefit to the pharmaceutical in- abuse of the Medicare system translates industry is clear: the more conditions a drug to a substantial and direct transfer of pu- can treat, the greater its potential market. blic money to pharmaceutical companies. Not being directly part of the pharmaceu- The dangers of such an indiscriminate tical industry, Drugdex (a subsidiary of broadening of the medical indications of a

19 drug cannot be underestimated. The drug imposition of the TRIPS (both took pla- Neurontin®, for instance, in addition to ce in 1995), the majority of countries in being used to treat epilepsy, which is the the world did not even acknowledge the official condition recognized by its patent, patenting of medicines, given that they can also —according to Drugdex’s list— were not considered commercial pro- be appropriately prescribed to treat 48 ducts but rather items of “first necessity” other conditions. Its additional indications that should be made available to all pa- include conditions as common as hiccups, tients, regardless of their economic sta- migraines, and smoking cessation. In sec- tus. tion 3.2.1, we have seen that Neurontin is The WTO regulations regarding gene- a “me-too drug” with a potential risk for ric drugs were approved in 1995, but poo- inducing suicide66. How is it possible that rer countries were given until 2005 to pre- a drug with such a profile be officially ap- pare for these new laws. The South African proved in the US to treat 48 different me- government, realizing that the introduc- dical conditions including hiccups? tion of the new legislation would make it To avoid such abuses, the committee impossible to treat their population due to of experts of the English Parliament re- a lack of funds, and that this in turn would commended that their public health bring about an increase in the AIDS epi- system be funded to carry out independent demic, announced at the end of the nine- studies on drugs and also be given the ne- ties that they would begin producing ge- cessary authority to compel pharmaceuti- neric antiretroviral drugs in their own cal companies filing for patents to carry laboratories. In response, the pharmaceu- out clinical trials comparing their new tical industry pressured the American go- drug with the drugs already on the mar- vernment, and the Clinton administration ket67. threatened South Africa with crippling With regard to international politics, commercial sanctions if they dared to pro- the influence of the large pharmaceutical duce their own drugs in order to fight the companies is mediated in two ways: (1) AIDS epidemic. through the pressure the US government Where is the free market in all this? exerts on other countries by threatening On February 17th 2006, the English them with economic sanctions if they newspaper The Independent published an don’t accept devastating bilateral agree- article which further illustrates the extent ments contrary to their national interests to which the actions of pharmaceutical and favorable to the American pharma- companies are abusive towards poorer ceutical industry, (2) through the countries, and in particular towards WTO68, one of whose first agreements Africa70. The article denounced the fact was the TRIPS69, which, apart from im- that pharmaceutical companies are pros- posing an abusive patent system to all pecting the African continent to obtain countries —including developing coun- natural resources that could be used to be- tries— lengthened the validity of phar- nefit their own industry, with a complete maceutical patents from 17 to 20 years. disregard for the UN convention on bio- Before the creation of the WTO and the diversity that establishes the inviolable

20 sovereignty of a country over its own nat- a bacterial strain found in Lake Ruiru in ural resources71. The pharmaceutical Kenya, from which it was able to create company SRPharma used a micro-bacte- a drug used to treat diabetes (Precose® or ria discovered in Uganda in the seventies Glucobay®). This drug generated more in order to develop a drug that would tre- than 380 million dollars in sales. The at chronic viral illnesses, including Bayer group flouted the same internatio- HIV/AIDS. The Managing Director of nal conventions as SRPharma and did not SRPharma acknowledged that his com- offer Kenya anything in return for this pany had offered no economic compen- discovery. Bayer acknowledged this, but sation to Uganda in return for this disco- defended itself by saying that in spite of very. SRPharma did not respect the fact that the origin of the drug lay in international law and did not compensa- the bacterial strain found in Kenya, its te Uganda for using the country’s natural biotechnological development meant that resources for their own benefit. Neither the end product was completely different, did they allow Uganda to use the drug that concluding that “we patented the end pro- was made from this discovery to treat duct, and not the bacterial strain.” Ugandan patients. In the same article, the However, the investigators responsible Managing Director of SRPharma com- for studying the violations to the con- plained that the drug had not brought vention on biodiversity in Africa72 rea- about the anticipated benefits, and yet re- ched a very different conclusion: “We mained silent about the 20 million dollars find ourselves facing a new form of co- that had been received to finance its de- lonialism”. International agreements are velopment. For its part, the Bayer forced upon the poor and are flouted by Company benefited from the discovery of the wealthy.

21 4. AN INTERNAL CRISIS INNOVATIONS IN TREATMENT REPLACED BY ADVERTISING

Between 1994-96, the large pharmaceutical companies were willing to pay up to 59 million dollars to smaller companies for a new molecule that had successfully completed pre-clinical trials, so that they could then carry on the required clinical trials and hopefully end up reaping the benefits of patenting a new medicine and introducing it into the market. Between 2000- 02, the figure that these same companies were willing to pay had risen to 148 million dollars73.

4.1. CURRENT CRISIS OF PHARMACEUTICAL COMPANIES

The information above brings to to an average 4-5% in the following five sharp light the hidden cause of the cur- years, 1998-2003”75. rent crisis of the pharmaceutical in- Another significant fact is the growing dustry: its innovatory capacity has prac- frequency and volume of mergers taking tically disappeared. And without place between larger pharmaceutical com- capacity for innovation the industry has panies in recent years. In 2002, Pfizer be- no future. The alarm was first sounded by came the largest pharmaceutical company The Wall Street Journal in 2003 when after merging with Warner-Lambert and consultants at IBM studied the twenty Pharmacia (not long after Pharmacia had largest pharmaceutical companies and bought Upjohn and Monsanto). Following revealed a dramatic decline in sharehol- this merger, Pfizer controlled 11% of the der return74: “The return that the twenty global market. Five years earlier, Merck largest pharmaceutical companies were had been the No. 1 pharmaceutical com- able to offer to their shareholders, which pany, but theirs was only a 5% share of the had averaged 28% from 1993-1998, fell global market76. 22 This extraordinary concentration of ced new effects (effects different from capital creates gigantic corporations that those of the drugs already available on the are very difficult to manage and more im- market). The yearly distribution of these portantly, breaks up consolidated research 58 genuinely new drugs was as follows: groups and places their leading-scientists 16 were developed in 1998; 19 in 1999; under non-scientific administrators that only 9 in year 2000, and only 7 each in interfere with their research projects. 2001 and 2002. This is the real producti- Jürgen Drews, an ex-researcher with vity of the —up to now— most profitable Hoffmann LaRoche, states: All in all, the industry in the US. Such meager produc- pharmaceutical industry is replacing its tivity is particularly shocking considering old investigative structure with a techni- the money invested during this period cal apparatus that is still able to carry on (around 30 billion dollars), and the size of analysis, animal research, and chemical the 35 companies involved (in 2003 Pfizer synthesis of molecules, but that is proving alone owned more than 60 laboratories in utterly unable to develop new ideas. The 32 different countries)79. research departments of the large labora- The consequences of the industry’s tories are not any more autonomous and misguided politics are becoming evident the scientists working for them cannot ma- to all involved. The patent controversy nage their own affairs; their creativity is over antiretroviral drugs in Africa has being curtailed by lawyers, economists, drawn attention to the policies and privi- businessmen and top-ranking administra- leges enjoyed by pharmaceutical compa- tors unable to imagine the future other nies, and these are now being questioned than as a lineal development of what we at an international level. In the US, the two already have (...). The pharmaceutical in- most important factors that have raised the dustry has created conditions that destroy awareness on this issue have been: (1) the originality, creativity and freedom and fa- growing difference in prices between US vor consensus, imitation, submission and and Canada with regard to drugs that are repetitiveness77. protected by patents, and (2) the super- In 1990, an efficient researcher could fluous and potentially hazardous nature of test the reactive capacity of 2,000 mole- “me-too drugs.” Let’s have a look at the- cules per year. In 2000, a robot, like the se two factors in a little more detail. ones that are currently used in large rese- The price of a medicine protected by arch laboratories, could test 6,000 mole- a patent is in Europe or in Canada one half cules in a single day78. But this exciting or even one third the price of the same quantitative increase has not brought medicine in the US. Since1987, it is ille- about an increase in innovation; rather it gal in the US to import medicines from seems to have caused the opposite. In the Canada. Despite this prohibition, in 2002 five years between 1998 and 2002, a total over a million American citizens were re- of 415 new drugs were approved in the gularly buying their medication from USA. Out of these, only 133 (32%) were Canadian pharmacies. In several areas based on new molecules and of these 133, close to the border buses were even or- only 58 were new molecules that produ- ganized to transport them. By 2003, 7%

23 of American citizens were buying their panies and a growing number of states ha- medication from Canada over the Internet ve developed and approved formularies (the number of on-line Canadian pharma- that exclude them. These insurance com- cies rose between 1999-2003 from 10 to panies will not reimburse the prescription 140). The city of Springfield, Massa- expenses of their clients if they are pres- chusetts, in an open act of defiance meant cribed drugs that are not included in their to denounce the unfair price differential, list of useful medications. On their part, decided to lower its administrative costs some states have begun to pass legislation by purchasing all drugs for its public offi- ruling that their Medicare program (the cials through Canadian pharmacies. The program that partly covers the cost of me- city of Boston and governmental repre- dication for those over 65 years of age) sentatives from 12 other states followed will only cover the cost of those drugs in- the protest made by Springfield and are cluded in their state formulary, and not currently seeking alternative ways of buy- those that appear in the official Drugdex ing drugs at more reasonable prices80. list (ultimately controlled, as we have se- With regard to the growing awareness en, by the pharmaceutical companies of the unnecessary character and potential themselves). In 2001 only 2 states had en- dangers of the “me-too drugs,” it should acted this legislation; by 2003, half of all be noted that the largest insurance com- American states had81.

4.2. A DECREASE IN INNOVATION AND A RISE OF MARKETING

A study carried out by a committee of cost of drugs financed by pharmaceutical experts selected by the US Congress esti- companies alone. How is it possible? This mated that the cost of producing a new disparity arises because under production drug in 1993 stood at 802 million do- expenses, the pharmaceutical companies llars82. The center for the Study of routinely include the greatest proportion Responsible Legislation in Washington of their marketing expenses. In the case of released a counter-report calling this figu- orphan drugs, the companies are obliged re into question after assessing the cost of to make available and correctly differen- producing the so-called orphan drugs. tiate their production expenses from their Orphan drugs are drugs that —having a marketing expenses in order that the go- potential market too small to motivate the vernment can pay its share. That marke- investors — are co-financed by pharma- ting —and not research or production— ceutical companies and public funds. is the greatest investment of today’s phar- They represent 20% of the US drug mar- maceutical companies is not a fact openly ket. The total cost of production of co-fi- acknowledged because only the disguise nanced drugs is three times lower than the of marketing costs as research and pro- 24 duction costs, allows the pharmaceutical vision and sports figures that give moving companies to pass the enormous cost of (usually false) testimonies; (2) targeting advertising to the consumers in the form college and university students for massi- of higher drug prices. ve promotion campaigns of anti-depres- Pharmaceutical marketing is directed in sants. In return for large sums of money, the first place to physicians. In 2001, some educational centers have allowed American doctors were regularly visited by physicians paid by pharmaceutical com- a total of 88,000 representatives of the phar- panies to give conferences to their stu- maceutical industry. These drugs repre- dents with the goal of encouraging them sentatives distributed a total of 11 billion to ask their doctors for prescription anti- dollars worth of free samples of new medi- depressants that could cure sorrows and cations to doctors so that they could “test mood-swings common among normal he- them” on their patients. In addition, they of- althy adolescents and young people. fered personal gifts, all-expenses paid holi- By way of personal testimony, I re- days and other forms of remuneration. member the impact that one of these con- The advertising of prescription drugs ferences had on medical interns. It was is also increasingly being directed to the offered a few months after our arrival at patients themselves, in the hope that physi- Buffalo, New York, where we were to cians can and will be persuaded to write complete our three-year medical resi- prescriptions if pressured to do so by their dency. We were told that the suicide rate patients. The USAand New Zealand allow among first-year residents was very high, the direct advertising of prescription drugs and that we should look for treatment for to patients. All the other industrialized na- our depression as soon as possible (we tions —despite being pressured by the were all quite logically exhausted from pharmaceutical industry— still explicitly our long shifts). They also told us that a prohibit such advertising, recognizing the new treatment had just come out that se- vulnerability and susceptibility of patients emed to prevent depression. I was lucky looking for relief from serious condi- enough to have a medical tutor who war- tions83. ned me about the economical interests The following are two examples of hidden behind this “academic act.” I how a patient’s vulnerability can be ex- could have become ill or died from the si- ploited: (1) advertising directly to hospi- de effects of a drug that I did not need and talized patients through the patient chan- that had been: (1) produced solely with nel. The patient channel is a US TV the intention of making money, (2) tested channel only transmitted in hospitals. and approved too hastily, and (3) pro- Patients lying in their hospital bed, may- moted to me at a very vulnerable mo- be severely ill, are targeted for the deli- ment. I didn’t take the medicine and no- very of biased information on new drugs thing happened to me, but other people that promise them relief or even a cure. —thousands of other people— have not These ads are presented by famous tele- been so lucky.

25 5. AN OPPORTUNITY TO DISMANTLE THE SYSTEM

The sources consulted in preparing this booklet agree that the pharmaceutical industry is in urgent need of immediate and substantial reform. Such reform is possible and necessary above all in the interest of patients (be they in the first or third world countries), but also to ensure the future of the industry itself. Below is a summary of the conclusions of the main sources consulted.

MAIN CONCLUSIONS OF M. ANGELL, 2005*

1. Pharmaceutical companies are produ- 3. Pharmaceutical companies have too cing too many “me-too drugs” and too much control over the clinical tests that few drugs that are genuinely new. assess the effectiveness and safety of 2. The most influential regulatory agency their own products. in the world (the American FDA) is too 4. The current 20-year period of validity closely linked to the industry that it is of drug-patents is unjustified and its supposed to be regulating. present regulation is detrimental to the

* Marcia ANGELL. A The Truth about Drug Companies, Random House, 2004. For almost 20 years Marcia Angell has been editor-in-chief of the most influential medical review, the New England Journal of Medicine. 26 quality of clinical research. Drugs to- cal companies to block the arrival of day are patented before having com- generic drugs on the market for 30 pleted the clinical tests necessary to months following the expiry of their prove their effectiveness and safety. own patent. This means that the 20-years period of 5. Pharmaceutical companies have an un- validity of a drug-patent includes the due influence over medical schools years necessary for its clinical testing. curricula (2/3 of US university hospi- To avoid the pressure to shorten clini- tals have direct economical links to this cal studies, the law should be modified industry). so that the clock starts ticking once a 6. Important information on research, de- drug can be sold and not before. The velopment, marketing, and pricing of total length of the patent could then be drugs is kept secret from the public. reduced to 6 years. Legislation should 7. Drug prices are too high and too in- also be enacted to eliminate the current consistent. legal loopholes used by pharmaceuti-

MAIN CONCLUSIONS OF P. PIGNARRE*

In order to achieve the necessary re- 1. Setting up democratically agreed natio- form of the pharmaceutical industry nal and international priorities (highly (see below), citizens have to be invol- lucrative rewards / sales conditions ved in: could then be offered to those advan- cing research in those areas). 1. The establishment of priorities for research and for the allocation of re- 2. Highlighting the active principle of a sources. drug rather than its commercial name 2. The development of research (particu- (medical packaging should show the larly on the design of clinical trials) generic name of the drug clearly visi- and, ble and the commercial brand name in 3. the commercialization of drugs (patent smaller print, the reverse of the current rights and pricing policy) situation). Objectives of the reform of the pharma- 3. Rewarding the real worth of a drug ra- ceutical industry: ther than its promotional value (a 5%

* Philippe Pignarre worked as director of a large pharmaceutical company for seventeen years and is currently working as a Professor at the University of Paris-VIII. 27 increase in therapeutic effect does not cause this information is already avai- need to imply a 10, 15 or even 100 fold lable in specialized magazines. increase in price). 6. Taking decisions democratically. This 4. Reconsidering the length of patents; should be at the heart of all economic they could be extended in richer coun- practices, but is particularly feasible in tries in return for eliminating them in the case of drug development because poorer countries. no new drugs can be developed without clinical trials and no clinical trials can 5. Creating a research observatory to be carried on without the written con- maintain an independent registry of all sent of the patients. As the association the processes leading to the discovery “Act Up” has demonstrated in the case of each new drug in order to be able to of AIDS, the power to stop the current rationalize investment and avoid dis- abuses is in the hands of the citizens. honesty. This could be easily done be-

MAIN CONCLUSIONS OF THE MSF REPORT “FATAL IMBALANCE”, 2001

1. Diseases that mainly affect poor people be made accessible and economically are not researched because they are not available to all patients. profitable for the pharmaceutical in- 6. The capacity for drug-research and pro- dustry. duction in poor countries should be 2. The WHO should develop an effective fostered. plan to solve this problem. 7. An independent assessment of the long- 3. The governments of rich and poor term impact on global health of current countries should redress the unfairness patent policies should be urgently car- of the current global market. ried out. 4. A complete and independent analysis of 8. A new international body needs to be the real cost of producing a new drug created to address the problem of ne- should be carried out. glected diseases (MSF have already in- 5. In return for the investment of public itiated the process with the DND NfPI money poured into the research and (Drugs for Neglected Diseases Non- development of new drugs, they should for-Profit Initiative)).

28 MAIN CONCLUSIONS OF THE COMMITTEE OF EXPERTS SET UP BY THE BRITISH HOUSE OF COMMONS, 2005:

1. “Me-too drugs” are a real problem. 8. Advertising that is directed specifically 2. An independent center to carry out cli- at patients is inappropriate and unne- nical research should be set up, becau- cessary in the UK. This sort of adver- se the current system is too biased. tising has a highly emotional content. 3. The aggressive direct marketing cam- The laws that prohibit it should be rein- paigns that accompany the launch of a forced. new drug, the avalanche of information 9. Indirect advertising made through so- that is distributed, and the disguising of called educational campaigns is not this information as medical fact all sufficiently regulated. contribute to the fact that medicines are 10. Often, the remuneration offered by inappropriately prescribed. pharmaceutical companies to patients’ 4. The falsification of scientific reports groups is not revealed. This informa- and the hiding of unfavorable results tion should be made public. gained in clinical research by the in- 11. The monitoring of drugs already on dustry bring about the proliferation of the market is insufficient. these inappropriate prescriptions. 12. The government should finance the 5. The responsibility for inappropriate study of alternative forms of non-phar- prescriptions does not lie with the pharmacological treatment that are cur- maceutical industry alone, but also rently being ignored by the pharma- with doctors and other professionals ceutical industry because they are not who show too much willingness to ac- profitable. cept gifts from pharmaceutical compa- 13. Doctors and other professionals who nies and to take at face value the clini- can prescribe medication should ack- cal information they provide. nowledge their responsibility for the 6. The marketing strategy of the pharma- problems caused by the inappropriate ceutical industry is relentless and per- prescriptions of SSRI anti-depressants vasive and is not directed at professio- and COX-2 anti-inflammatories. nals alone, but also at patients and the These drugs have been prescribed in- general public. discriminately on a large scale. This 7. A leaflet for patients should be develo- was due in part to the huge promotion ped containing general and compre- they received, particularly at their hensive information clarifying the im- launch onto the market, but is also due portant but limited role drugs play in to the fact that important information the treatment of illnesses. Drugs are not was kept secret while the propaganda the only therapeutic alternative availa- of the pharmaceutical companies was ble and patients should know it. taken at face value without much hesi-

29 tation. Aggressive marketing cam- a drug, also be made responsible and gi- paigns have led too many health pro- ven due authority for restricting its uses. fessionals to prescribe inappropriately. 20. We recommend that an improved No effective mechanism exists to mo- system of registering the side effects of derate the explosion of prescriptions drugs be set up throughout the country, that follows the launch of a new pro- that all these cases should be duly in- duct. As well as being the most crucial vestigated and that this should be car- time to promote a product, it is also the ried out with transparency and without time at which the least is known about giving false assurances. the drug’s potential side effects. 21. We recommend that public procee- 14. We recommend that an independent dings should always take place when a body keep a record of all clinical trials drug is withdrawn from the market due and that the results of all trials related to its side effects. to a given drug —whether favorable or 22. Excessive marketing leads to inappro- not— be made public, as a precondition priate prescriptions. Current strategies to its being launched on the market. to provide unbiased information to the 15. The number of free samples received public are insufficient. We recommend by professionals should be reduced, that the regulatory agency should have particularly during the first six months the right to veto any promotional mate- of the appearance of the product on the rial belonging to a new medicine as well market. as limiting (by specialty for instance) 16. The decisions of the regulatory agency the right to prescribe new drugs during and the information and criteria used to their first two years on the market. reach conclusions should be made pu- 23. We recommend better coordination blic. Ordinary citizens should be in- and promptness in the area of investi- volved at the clinical research stage gating complaints on illegal advertis- and should be offered training and suf- ing. Illegal advertising is a criminal of- ficient support so that they can play an fense and the punishment should active role in the making of decisions. reflect this. In cases where it is neces- 17. Improved research into side effects of sary to correct false information, the medication should be carried out. The correction such receive as much publi- observations made in clinical trials prior city as the initial information. to launching a drug are insufficient. 24. The existing market of generic drugs 18. The regulatory agency should employ is useful and important. Large pharma- more people in the monitoring of new ceutical companies should be prevent- drugs during their first six months on ed from damaging this market by ma- the market. We recommend that all nipulating the legislation in order to new drugs be systematically and unduly lengthening patent rights. throughly re-assessed five years after 25. We recommend that medical students their original launch on the market. be better taught to critically evaluate 19. We recommend that the regulatory the results of clinical trials, to recogni- agency, besides authorizing the sale of ze the side effects of medications, and 30 to have an appropriate relationship the favors they receive from pharma- with the representatives of the pharmaceutical companies. ceutical companies. Obligatory post- 29. The incidence, cost and implications graduate courses should exist for all of illnesses caused by medication health professionals allowed to pres- should be investigated in a systematic cribe drugs so that they are always up way by the Department of Health along to date. The prescription practices of with the regulatory drug agency. these professionals should be more 30. The government should create a new strictly regulated. program that grants all patients access 26. We recommend that professional asso- to medication, and that adequately gua- ciations keep a public record of any gifts, rantees the safety and effectiveness of money, honors or other benefits that the- these medications as well as their ap- se associations and their members may propriate use. Comparative studies of have received from pharmaceutical pharmacological versus non-pharma- companies. Each member should be res- cological treatments should routinely ponsible for keeping this record up to da- be carried out. te. The professional associations should 31. The national health system should mo- clearly and publicly state the level of fa- dify their current legislation so that ef- vors that they consider acceptable for its fective non-pharmacological treatments members to receive. are considered in the same category as 27. The standards of health campaigns pharmacological treatments. promoted by laboratories should be 32. The responsibility of representing the toughened so that it is always required interests of the pharmaceutical in- to clearly state which company is fi- dustry should be transferred to the nancing these campaigns and which Department of Trade and Industry so are the medications commercialized by that the Department of Health can com- this company. mit itself exclusively, as is its obliga- 28. Patients’ groups should make public tion, to dealing with the regulation of their sources of funding as well as all drugs and the promotion of health.

* * * The study of the current crimes and abuses of the pharmaceutical industry should have helped us move beyond the fallacious discussion between those who favor the free-market and those who favor greater government regulations. It is clear that without the unduly favorable laws of the US Congress and without the unduly favorable agreements of the WTO, the pharmaceutical industry would not have thrived the way it has. The market is always necessarily regulated by policies. What is needed is that the policies that today regulate the pharmaceutical market be reassessed and brought into line with the above recommendations, so that the industry can survive its present crisis and, most importantly, so that the patients can be better served by it. 31 NOTES

1. Angell, Marcia. The Truth about the Drug 11. Many articles and books have been recently Companies: how they deceive us and what to published on this topic. Besides the excellent do about it. Is the Party Over? pp. 217-36. reviews by Pignarre and Angell frequently 2. Pfizer. Annual report 2001. www.pfizer.com quoted in this booklet, see also: The $800 quoted by Moynihan, R. “The making of a Million Pill by M Goozner; Powerful disease: female sexual dysfunction”. BMJ Medicines by J Avorn; Overdo$ed America by 2003; 326: 45-47. J Abramson or On the Take by J Kassirer. 3. Special Supplement. Int J Impotence Res 1998; 12. Pignarre, p. 124. 10 (supl 2): S 1-142 (The Cape Cod conferen- 13. Pignarre, Philippe. El gran secreto de la indus- ce: sexual function assessment in clinical tria farmacéutica. Barcelona: Gedisa, 2005 trials, 30-31 May, 1997. Hyannis, (original in French, 2003), p.117. Massachusetts, USA), quoted by Moynihan 14. Press release from the coordinators of the 2003. Médecins Sans Frontières (MSF) Campaign 4. Basson R, Berman J, Burnett A, Derogatis L, for Access to Essential Medicines. Prognosis: Ferguson D, Fourcroy J, et al. “Report of the short term relief, long-term pain. The future of international consensus development confe- generic medicines made in India. April 21 rence on female sexual dysfunction: defini- 2005. tions and classifications”. BMJ 2005; 330: 15. Pignarre, p.140. 192-94. 16. Pignarre, p.127. 5. Laumann E, Paik A, Rosen R. “Sexual dysfunc- 17. In response to stark international criticism, the tion in the United States: prevalence and pre- Doha's Declaration (Qatar, 2001) modified the dictors”. Urology 2000; 163: 888-93. scandalous 1994 WTO agreement on the rein- 6. Kaschak E, Tiefer L, eds. A new view of wome- forcement of patents (Trade-Related Aspects n's sexual problems. Binghamton, NY: of Intellectual Property Rights, TRIPS). Some Haworth Press 2001: 70, quoted by Moynihan of the most abusive clauses from TRIPS are: 2003. an obligation on the part of the laboratory wis- 7. Moynihan, 2003: 45. hing to produce generic drugs to buy not only 8. Moynihan, Ray. “The making of a disease: the patent right of that medication but also of female sexual dysfunction”. BMJ 2003; 326: any other products chosen by the patent owner 45-47. as "linked sales"; the right of the patent owner 9. Tonks, Alison associated editor BMJ. “Summary to determine the way in which the laboratory of electronic responses. The making of a dise- buying the product must produce the generic ase”. www.bmj.com 2003. drug; the obligation on the part of the buyer to 10. Moynihan, Ray. “The marketing of a disease: inform the patent owner of any improvements female sexual dysfunction”. BMJ 2005; 330: carried out on the product; the limitation or 192-194. prohibition of exporting the product (cf.

32 Lecourieux A. “Patents that Kill”. In Le 41. Angell, pp. 270-72. Monde Diplomatique. December 2005). 42. House of Commons, p. 8. It states that: a) 65% 18. www.essentialdrugs.org/edrug/archive/- of patients taking anti-depressants clearly do 200510/msg00001.php. Last accessed on not need them; b) 65% to 95% have a doubt- November 9, 2006. ful diagnosis; and c) only for the remaining 19. Lorenz J, Berman D. “Companies not selling 5% can the prescription of anti-depressants be new AIDS drugs in Africa”. MSF, December 8 medically justified. 2005. 43. House of Commons, p. 4, p. 10 and p. 102. 20. Pignarre, pp.13-14. 44. House of Commons, p. 7. 21. “The Fortune 500”, Fortune April 18 2005 45. House of Commons, p. 4. (F28). Quoted by Angell, p. xv. 46. Pignarre, p. 147. In England, hospitalizations 22. “The Fortune 500”, Fortune April 18 2005 due to side effects of medicines represent 5% (F28). Quoted by Angell, p. xv. of all hospitalizations (cf. House of 23. The price of the well-known anti-allergy medi- Commons, p. 8). cation Claritin (Schering-Plough) was allo- 47. Pignarre, p. 121. wed to rise 13 times in 5 years with a total 48. Pignarre, pp. 125-27. increase of 50% of its initial price. This repre- 49. Angell, pp. xxi-xxii. sents a four-fold increase above inflation (cf. 50. Fatal Imbalance MSF, p.10. Angell, p. xx). 51. WHO. Chagas. Last accessed 20 September 24. Pignarre, p. 19. 2006. 25. Angell, p. 198. 52. Carlier,Y. “Chagas Disease (American 26. A "blockbuster" is a drug with annual sales Trypanosomiasis)”. eMedicine (27 February exceeding the billion dollars mark. 2003). 27. Pignarre, p. 129. 53. Angell, p. 65. 28. Angell, p. 3. 54. Angell, p. 65. 29. Pignarre, p. 129. 55. MSF, p. 10. 30. House of Commons. The Influence of the 56. MSF, p. 12. Pharmaceutical Industry. March 22, 2005. 57. Pignarre, p. 150. p.5. 58. Rothman, David. “The shame of medical rese- 31. House of Commons, p.5. arch”. The New York Review of Books, 32. House of Commons, p.3. November 30, 2000. Quoted by Pignarre, p. 33. Food and Drug Administration (FDA). 150. 34. Eaton, Lynn. “More surveillance of drugs is 59. Angell, p. 198. needed to protect public”. BMJ, 2004; 60. Angell, p. 201. 329:1124. 61. Angell, p. 234. 35. www.pfizer.com/pfizer/download/uspi_neu- 62. Prescription Drug User Free Act, 1992. rontin.pdf. 63. Angell, pp. 208-11. 36. Lenzer, Jeanne. “Documents missing from a 10 64. Angell, pp. 211-14. year old murder case sent to the BMJ”. BMJ, 65. Angell, pp. 202-06. 2004; 329: 1365. 66. During the 12 months from September 2003 to 37. Eaton, Lynn. “Regulator restricts use of SSRIs August 2004 there were 2,700 suicide in children”. BMJ, 2005;330:984. attempts among patients that were taking 38. Pignarre, p. 37; Angell, p. 81; see also gabapentin, 200 of which ended with the death www.humanite.fr. of the patient (see section 3.2.1 of this boo- 39. Angell, p. 269; Pignarre, p. 143. klet). 40. A study by David Graham, Associate Director 67. House of Commons p. 116 (recommendations of Science at the Office of Drug Safety of the 18-20). See a summary of the 32 recommen- FDA. Quoted by www.consumeraffairs.com dations of the Experts Committee in section 5 and in the House of Commons report, p. 4. of this booklet.

33 68. World Trade Organization (WTO). J. “SkyePharma rebels lose vote to appoint 69. Trade-Related Aspects of Intellectual Property Thian on board”. The Independent March 10, Rights (TRIPS). 2006). 70. Buncombe, Andrew. “African bio-resources 75. Lorelle, Véronique. “Les industriels devront 'exploited by West'”. The Independent. accelérer le lancement de médicaments plus February 17, 2006. ciblés”. Le Monde, January 15, 2003., quoted 71. International Convention on Biodiversity. by Pignarre, p. 29. ONU, 1992. 76. Pignarre, p. 85. 72. Mariam Mayet from The African Center for 77. Drews, Jürgen. In Quest of Tomorrow's Biodiversity and Beth Burrows from Medicines. Springer: Nova York, 1998. p. 221, Edmonds Institute. quoted by Pignarre, p. 91. 73. Pignarre, p. 39. 78. Pignarre, p. 105. 74. At the time of writing this booklet, news has 79. Angell, p. 221. come out that the value of activities of the 80. Angell, pp. 220-21. pharmaceutical company SkyePharma has 81. Angell, p. 227. been reduced by half in the last 5 years, and 82. "OTA Study". Marketletter. January 13 1997, that last year the company could not find a pp.24-25, quoted by Pignarre, p. 24. financial partner that would promote its new 83. House of Commons, recommendation n.8. anti-asthmatic medicine Flutiform (Kollewe,