I find this to be good reading material from an “Anti-Pharma lobby” which is very healthy indeed as there needs to be some form of counterweight, i.e. need for checks and balances.
This article also supports our premise about being very cautious about introducing clinical trials in a developing country such as Pakistan.
Dumping Old or Unsuitable Drugs to Underdeveloped Countries as Aid and Charity
While pharmaceutical companies have no doubt created life-saving drugs that have saved millions of lives, they have also participated in practices around the world that have come under a growing amount of criticism. John Madeley is worth quoting at length:
[NGOs] allege that the corporations:
sell products in developing countries that are withdrawn in the West;
sell their products by persuasive and misleading advertising and promotion;
cause the poor to divert money away from essential items, such as foodstuffs, to paying for expensive, patented medicines, thereby adding to problems of malnutrition;
sell products such as appetite stimulants which are totally inappropriate;
promote antibiotics for relatively trivial illnesses;
charge more for products in developing countries than they do in the West;
fail to give instructions on packets in local languages;
resist measures that would help governments of developing countries to promote generic drugs at low cost;
use their influence to try to prevent national drug policies;
give donations of drugs in emergencies which benefit the company rather than the needy;
use their home government to support their operation with threats if necessary, such as withdrawing aid, if a host government does anything to threaten their interests.
… The methods used by the corporations are highly controversial. Making use of advertising that is inexpensive in comparison to what they pay in industrialized countries, the drug TNCs use the most persuasive, not to say unethical, methods to persuade the poor to buy their wares. Extravagant claims are made that would be outlawed in the Western countries. A survey, in the Annals of Internal Medicine found that 62 per cent of the pharmaceutical advertisements in medical journals “were either grossly misleading or downright inaccurate”.
— John Madeley, Big Business Poor Peoples; The Impact of Transnational Corporations on the World’s Poor, (Zed Books, 1999) pp. 145-146, 147
Madeley goes on to provide an example (amongst many others) where US-based drug company Eli Lilly made the largest one-time pharmaceutical donation at that time, to provide an antibiotic to Rwanda during their refugee crisis in 1994. They donated enough for 1.3 million people. However, the World Health Organization didn’t list this drug on their list of essential drugs for treating refugees. He also pointed out that “Médicins sans Frontiéres (Doctors without Borders) … said ‘it would never prescribe such medicines in the camps’.”
Many of the pills were past their expiry date, which added additional resource burdens to a country already suffering from the aftermath of a civil conflict. Madeley also shows some additional reasons to this apparent generosity that:
[w]hile Eli Lilly conceded that the tablets donated were excess stock nearing expiry date, they “felt it was the right thing to do.” … although drug donations may seem pure altruism, they can sometimes harm rather than help the victims of emergencies. However, they nearly always help a company’s balance sheet. European and USA-based TNCs receive substantial tax benefits when they give donations. For gifts to the needy, US tax regulations allow a write-off for tax purposes of up to twice the production costs.
— John Madeley, Big Business Poor Peoples; The Impact of Transnational Corporations on the World’s Poor, (Zed Books, 1999) p. 153
Madeley wrote the above in 1999. A decade later, Elizabeth Sukkar notes a similar pattern in the British Medical Journal, “International Aid; The cost of donated drugs”, October 10, 2009 (p. 832):
One example: the 4000 tonnes of medicines donated to people in the Aceh region of Indonesia after the December 2004 Tsunami; 600 tonnes were out of date or about to expire and cost an estimated $2.4m (£1.5m; €1.6m) to destroy.
To help prepare [for new and updated guidelines on drug donations], WHO [World Health Organization] did a systematic review of drug donations during 1998 to 2008. It found that only 56% of donations were appropriate given the characteristics of the event and what the recipient needed, and only 12.5% of drugs requested by recipient countries were received.
Of the inappropriate donations, 57% had improper labels … and 40% had expiry dates of less than one year. Up to 80% of appropriate donations were surplus to requirement. “The ensuing cost of drug destruction, where documented, was significant,” says Dr Moller, one of the authors of the review.
— Elizabeth Sukkar, International Aid; The cost of donated drugs, British Medical Journal, October 10, p. 832
Sukkar adds that the current WHO guidelines were written for emergencies, but the new ones are to include other scenarios such as protracted emergencies, donations targeting specific diseases, and other forms of donations.
Noting that drug companies are one of the key donors for long term programs, she lists why they are so:
- Tax incentives
- Good public relations
- Cost saving (it is cheaper to donate a drug than destroy it)
- Surpluses in the market, and
- A genuine desire to help
- She also notes that the industry has improved over the past 2 decades, suggesting it may partly be because there is more scrutiny over what drug companies do, these days.
More fundamentally, however, UNICEF and others feel that after the acute phase of an emergency is over, cash donations may be better than drug donations as that can be better targeted as needed. (Many humanitarian organizations find that in emergencies they sometimes receive many items in excess, where cash donations may be better for it can help mobilize local resources as needed). Of course, the problem of cash donations is corruption and misuse of such funds as well. These and more are discussed in more depth on this site’s section on foreign aid.
Testing Drugs On The Poor
In March 2005, India’s new patent law was passed that would bring it into line with the WTO rules that requires more protection of produced drugs, and restricted scenarios in which generic drugs (which are cheaper) can be produced. Oxfam has criticized this as saying the WTO rules will restrict access to life-saving drugs worldwide, not just in India, because India’s generics industry was popular around the world for its ability to produce more affordable medicines.
And as Wired News reported at the end of 2005, those new laws, somewhat ironically, now enable pharmaceutical companies to test drugs on India’s poor by using India’s cheaper, but highly skilled workforce to conduct drugs trials there, rather than in industrialized countries, thus saving significantly on the costs. However, as Wired also noted, this introduces a number of issues, such as:
That although administrations in the industrialized countries, such as the Food and Drug Administration of the US, require that testing shows safety of the products, it is largely up to the country that hosts the trials and tests to ensure that procedures used have been sound and ethical. A developing country such as India does not have the ability to do this as effectively.
Furthermore, many drugs are being developed for markets in industrialized countries. Yet, using incentives such as $100 for participation (even though patients may not be fully aware of all the issues, which poses other ethical issues) in effect, poor people in other countries are being used for testing drugs on, while the potential benefits would be for people elsewhere. Wired News cited an assistant professor of medical history and bioethics, Srirupa Prasad, who said, “Third World lives are worth much less than the European lives. That is what colonialism was all about.”
Power And Influence In Drug Testing
On April 27, 2003, Britain’s Channel 4 aired a documentary titled Dying for Drugs, raising many of the hard issues discussed here, that drugs bring billions to those companies, and hopes to people. Yet, how far would drugs companies go to get their drugs approved and the prices they want? As the documentary said in their introduction, the implications are alarming and if their “power remains unchecked, many more people will soon will be dying for drugs.”
In Africa the documentary showed how one of the world’s biggest drug companies experimented on children without their parents’ knowledge or consent. In Canada it revealed how a drug company attempted to silence a leading academic who had doubts about their drug. In South Korea it followed the attempts of desperately ill patients to make a leading drug company sell them the drugs they need to save their lives at an affordable price. And in Honduras they showed the brutal consequences of drug companies’ pricing policies. This documentary therefore covered four basic areas:
Testing on humans without permission
Voluntary human trials but where doctors are pressured not to reveal problems
Successful human trials, but drugs priced beyond the reach of many patients
Prices that kill, and resorting to breaking the law to save lives by smuggling medicines from other countries.
Testing On Humans Without Permission
Increasingly, the documentary highlighted, human trials without permission are taking place in the developing world, far away from scrutiny of European or American authorities.
The documentary focused in on a case in 1996 in a northern Nigerian town of Kano, already suffering from severe cholera and measles outbreaks. At that time, a third problem occurred: meningitis, where some 150,000 people were affected, and some 15,000 dies, many of which were children.
While this was mostly unreported in the West, it was noticed by the world’s biggest and richest drug company, Pfizer. They moved fast and flew to Nigeria with a new drug, a “potential life-saver and a potential billion dollar money spinner”, Trovan.
Trovan had never been tested on children before, and Médicins Sans Frontiéres (Doctors Without Borders, or MSF) had been at the hospital that Pfizer came to, and had for a number of weeks been offering free life-saving treatments, successfully treating thousands of people.
Yet it turned out that Pfizer were doing human testing or experiments without the voluntary consent of patients, a violation of basic human rights:
From standards set at Nuremberg trials after WWII, there are strict rules on the conduct of experiments on humans.
The first rule (and sentence of the Nuremberg Code) is that voluntary consent of the human subject is absolutely essential.
This basic right was ignored, the documentary pointed out.
Consent and risk explanation is normally recorded.
Yet Pfizer had “never produced a single consent form from the 200 odd children treated in the … experiment.” Pfizer claimed this was because parents were illiterate, so was explained verbally.
But interviews with some 100 sets of parents highlight that they too were not asked for consent, and that many could read and write.
A lawyer trying to sue Pfizer on behalf of some of the parents says that if they were told that this was experiment and there was option for actual alternative treatment (which groups like MSF were offering) then they would have gone with them.
But there was also apparent outright lying as well. Not telling your test subjects what you are doing is a fundamental breach of medical ethics, but that was not the only charge.
Trials like this must be approved in advance by an ethics committee.
Pfizer claimed an ethics committee approved Pfizer’s actions.
Their ethics committee approval letter was shown to be a backdated later, because when dated, the committee didn’t exist at the time.
A Pfizer doctor later admitted to doing this.
Unfortunately, as the documentary also noted, this is “sadly far from unique. Several leading drug companies have also conducted questionable trials. Increasingly, in the poorer countries of the world.”
One explanation given by James Love (also mentioned above on this page), Health Economist with the Consumer Project on Technology was due to lack of accountability. “This is a problem,” he said, “because you are operating in an environment where there is really very few people around to protect the patient.”
The United States had refused to license Trovan for use on children because of known side effects it caused.
Some children in Nigeria died when on this treatment.
It is not known if they could have been saved had they been on the other more standard treatment that organizations like MSF were already helping with, but it is standard practice to change treatment if a patient is not responding to one treatment when their life is on the line. Pfizer doctors did not do this.
A doctor in the Nigerian hospital said that “I think they [Pfizer] played with that baby”, referring to a baby that died when under such treatment and had not been switched to an alternative.
One of the most damning pieces of evidence was a letter sent to the Pfizer chairman, by the company’s own childhood disease specialist, Dr Walterspiel, protesting in the strongest possible terms about the trial.
The letter detailed 8 major objections, including that the drug was not tested against this particular form of meningitis.
The letter also referred to the lack of consent forms.
As a result of this letter, the company sacked him.
As well as the issue of human experimenting without permission, the actions of Pfizer highlighted the various ways power could be exercised to deal with the controversy. For example:
Sacking the doctor sent a message about the challenges to research scientists.
Lawyers in New York took this case, but Pfizer succeeded in getting the NY courts to agree that this trial should be held in Nigeria, which as the documentary pointed out, was rated the second most corrupt nation according to Transparency International, implying that Pfizer would be able to take advantage of that.
But even where trials were going well but doctors had concerns about side-effects, pharmaceutical companies have used their power to try and stifle concerns and criticisms.
Voluntary Human Trials Where Doctors Are Pressured Not To Reveal Problems
The documentary moved on to talk about a situation in part of the wealthy world, Toronto, Canada, where even where trials were voluntary, doctors may have been pressured not to reveal concerns to their patients.
This was a case at a hospital where children were suffering from a blood disease, thalassemia, (where the body doesn’t make red blood cells), requiring blood transfusion, regularly, to prevent certain side-effects, requiring lots of injections, which can be painful for children. Dr. Nancy Olivieri, one of world’s leading experts on thalassemia had been searching for alternatives to painful nightly infusions for many years and the inconvenience of the process that could affect compliance in patients to adhere to the things they needed to do.
She came across a pill, L1, by a drug company called Apotex offered this alternative. They agreed to fund international trials, which went very well. Dr. Olivieri was chair of these worldwide trials. But she began to detect worrying effects.
She wanted to simply inform patients to help in decision-making
Therefore she wanted to adapt the trial to help work out why these problems were occurring
The reaction from Apotex was shocking because, as the documentary said, she was questioning Apotex’s potential multimillion dollar drug.
She was basically reminded of confidentiality clauses in the trials and threatened to keep quiet. In addition Apotex immediately ended the trials and indicated that the product was going to market. This threat came from Mike Spino, Apotex Vice President.
She was fired as chair of worldwide trials and gagged from telling her patients or anyone else about her concerns about the drugs.
Professor, Sir David Weatherall, of the Weatherall Institute for Molecular Medicine at Oxford University, raised the issue of threats to “academic freedom” with this situation.
Also commenting on Dr. Olivieri’s situation, Dr. Drummond Rennie of the Journal of the American Medical Association added that, Apotex “may disagree with her medical opinion, but they cannot disagree with her right and duty to tell her patients….they can’t interfere with that. They cannot. And so what they did was outrageous. People have to grasp that.”
As well as patients suffering, Dr. Olivieri was showing signs of strain and this was an example of the threat to doctors as well as impact on patients.
As Dr. Rennie also added, “I was … writing … an editorial bringing attention to the strong-arm tactics on the part of drugs companies when they didn’t like the results of a good trial. She was extremely frightened, extremely intimidated. [and they threaten to] just have her professional life destroyed.”
All the while, concern about the effects of L1 were increasing. A panel of experts agreed with Dr. Olivieri’s concerns and findings, so despite legal threats, she advised patients to go back to the needles instead of using this drug, which she felt was unsafe.
After a year of silence, she confided with a senior colleague who, with other colleagues lobbied the university for support in the battle against Apotex. What they didn’t know was that the then president was negotiating a multi-million dollar donation from Apotex to fund a new building (some $20 million).
“Who’s pulling the strings?”, asked Dr. Rennie, “Because money tends to become the strings. THAT is the problem.… if you’ve got tons and tons and tons of cash, lo and behold, how do you use it? You use it to smooth the way; to get your product out there; to influence people, to influence institutions, research institutions and specific scientists.”
One of the first colleagues Dr Olivieri had confided in had received “poison pen” letters, with various threats.
But they managed to find out who sent those letters from DNA tests.
It was a colleague, the man who first involved Apotex in the trials and who was still receiving substantial research funding from the company, associate director of research, Dr. Gidian Corran.
He strenuously denied the allegation, initially. But after months of denial, with DNA proof, he finally admitted to sending the hate mail.
As the doctor receiving the threat commented, “It horrifies me that an individual in a position of trust, who is not only caring for children, is in the position of leadership and power in one of the largest pediatric institutions in the world would lie and lie and lie continuously.”
Under apparent pressure, the hospital fired Dr. Olivieri. But, intervention by a few key people led to her being reinstated. Apotex decided to move elsewhere. In 1999 Europe became the first territory to license L1 under the brand name Ferriprox.
The issue raised was not if doctor was right or wrong, but really the premature licensing of a drug without proven safety. The safety of this L1 drug had not been fully determined, and so this would not have been the time to release the drug. Apotex alleged that the trials Dr. Olivieri conducted were flawed, but this was proven wrong by independent verification. This whole process also took months away from Dr. Olivieri’s important work by having to defending these claims. The documentary highlighted that many other doctors had suffered similar problems in many situations, and their professional lives had been destroyed.
As Dr. Rennie also added, Dr. Olivieri “had a choice, and she took a courageous choice.… but what a huge hole she’s left in the field by taken herself out and not doing any research worth anything very much during those years.” Dr. Weatherall described her as a foremost person in this field that would be hard to replace. But as he also concluded, “nobody seems to want to discuss these issues: there is so much money involved … [universities that are short of funds] don’t want to rock the boat.”
But there are also other situations, where even if all these trial processes were going well, the issue of pricing beyond the ability of many patients had also been causing concern.
Successful Human Trials, But Drugs Priced Beyond The Reach Of Many Patients
In the next example, the documentary highlighted how after successful trials, high pricing of drugs meant they were sometimes beyond the means of the very same patients in the trials who depended on those drugs. The case in question involved an innovative drug for a form of Leukemia, developed by Novartis, trialled successfully in South Korea, but the issue highlighted deeper political and economic problems.
Even though the trials were very successful (the drug was approved in record time, for example), the eventual price of the drug was out of the reach for many, who ended up protesting on the streets.
This drug was going to be priced by Novartis at around $55K a year, 19 dollars a tablet, 8 a day. Yet, even with the Korean government helping with costs, many patients said they could not afford the drug.
As Jamie Love commented, “Products are priced according to what it is worth someone to get access to the drug. If it saves your life, it is worth quite a bit. It is certainly worth everything you have. What the companies want to do is they want to say is ‘this is how much a human life is worth and this is what our company wants to keep that life on.’”
Commenting on why this was more than merely economic issues, Dr Drummond Rennie pointed out, “Pharmaceuticals, they are a commodity. But they are not just a commodity. There is an ethical side to this, because they are a commodity that you may be forced to take to save your life. And that gives them altogether a deeper significance. But they [the pharmaceutical companies] have to realize that they’re not just pushing pills, they’re pushing life or death. And I believe that they don’t always remember that. Indeed I believe that they often forget it completely.”
But high pricing for drugs are often controversial. As the documentary noted, “Big pharma generally defends high prices for new drugs saying they have to cover costs for researching and developing new drugs. But in fact, most new drugs launched are just slight variations of existing medicines. So called Me Too.”
Commenting on this Nathan Ford, of Médicins Sans Frontiéres said, “At the moment we are getting more and more drugs of less and less use. Me Too drugs; the tenth headache pills; the 15th Viagra. There are currently eight drugs in development at the moment for erectile dysfunction. Do we need 8 more drugs for erectile dysfunction? I don’t think we do. Meanwhile diseases like Malaria, TB that kill 6 million people every a year, are neglected—no new medicines are coming out and we are left treating people with old drugs that increasingly don’t work.”
Ben Goldacre, in his book, Bad Science, (Harper Perennial, 2009), also adds that “the number of ‘me-too’ drugs has risen, making up to half of all new drugs.” And yet, “for all the hard work they involve, they don’t generally represent a significant breakthrough in human health. They are merely a breakthrough in making money.” (p.202, emphasis added)
As noted earlier on this page, this is related to how markets for pharmaceutical companies are not just about finding people to target, but people with money. Dr. Jonathan Quick of the World Health Organization (WHO) added that the majority of the market for some of the tropical diseases is in developing countries but, “it’s a market in terms of numbers of people but the purchasing power is not there. And if the purchasing power is not there then the normal dynamics of the research and development industry just don’t address those problems.”
The drug’s price from Novartis was justified due to the research and development costs, yet, as Jamie Love pointed out, the price was still too high:
A lot of important development was paid for by U.S. government.
The speed to approval and get to market was quick.
Short, small trials and short development period implies a relatively inexpensive product to bring to market.
All this touched deeper issues of intellectual property rights and international institutions such as the World Trade Organization (WTO).
WTO patent rules allow 20 years of exclusive rights to make the drugs.
Hence, the price is set by the company, leaving governments and patients little room to negotiate, unless a government threatens to overturn the patent with a “compulsory license.”
Such mechanism authorizes a producer other than the patent holder to produce the product though the patent-holder does get some royalty to recognize their contribution.
This is a very effective tool to get the price down. For example, the drug in question here had been offered in Brazil at 8 dollars per pill by Novartis themselves because of the threat of generic versions that would threaten competition.
In June, 2001, in Korea, leukemia patients turned to a lawyer who delivered a compulsory license application to the Korean authorities.
As the documentary detailed, the Korean government got a swift response
But it was from the U.S. Secretary of Commerce, warning Korea’s Minister of Health and Welfare not to meddle with the price of drugs. “We are concerned about the discriminatory effect the proposed changes to the pharmaceutical pricing system would have upon our products,” the Secretary said in a letter to the minister, “If not addressed properly, this issue is likely to develop into a serious trade dispute.”
Despite these threats, the Korean minister went on to campaign for lower drug prices.
He was sacked.
He went on to speak out about what he believed was behind the sacking—the power and influence of the pharmaceutical industry.
Also commenting on this, Jamie Love touched upon the pervasive concentrated power, “How is it that companies can terrify the governments of an Asian country so they won’t import cheap medicines? It’s because they not only can threaten not to make medicines available, but they can credibly threaten that the U.S. and Europe will impose trade sanctions on those countries and the financial markets will punish them for overriding the patent protection and hurt the rest of the economy. They can actually make the credible threat that if they don’t pay their price for their medicine you won’t be able to sell your products. You won’t be able to have jobs in the manufacturing sector. Your whole economy will suffer.”
In another example of how this power was used, in 1990, the Thai government was making a number of generic drugs. They also wanted to make a generic AIDS drug. But the U.S. Trade Representative threatened them with export tariffs on wood and jewelry exports, which made up some 30% of Thailand’s total exports. The Thai trade representative was very frightened and they stopped making the generic drugs.
Yet, these were not isolated cases. As also mentioned above on this page, and mentioned in the documentary, hard fought changes to WTO rules that would have allowed poorer nations easier access to generic drugs was agreed to by virtually every country in the world, but was resisted by the U.S. Their veto killed the agreement.
A major source of cheaper generic drugs in Asia is India, which has a strong, established generics sector. Under Indian patent law, big pharmaceuticals have only been able to patent the production process, not the final product. That is, only the way the product is made. This allows other companies to produce generic versions of the same product, using different processes. One such company is CIPLA, also mentioned above. CIPLA has been famous for offering AID drugs for a dollar a day, when the bigger ones were offering nearer to 30 dollars per day. Because CIPLA has been competing with other generic manufacturing companies this has also contributed to keeping prices down.
At the request of some Korean patients, CIPLA said they were able to make generic version of Novartis’ drug, at some 80 cents to 1 dollar per capsule they said. This was less than one twentieth the Novartis price. But the compulsory license on which the deal depended to have these generic drugs available in Korea, was thrown out by the Korean authorities. Novartis still insisting on that 19 dollar price.
Big pharmaceutical companies consider the generics companies as pirates, because of the threat to profits, and because they create the same end product without the amount of research and development effort that the big pharmaceuticals supposedly invest. Yet, as detailed above, often, a lot of initial research and development has come from the public sector, and so some have considered the big pharmaceuticals to also be guilty of the accusations that they levy against generics companies.
Under pressure from the large pharmaceutical companies, the WTO has decided that from end of next year, India must bring in full patent protection. India is one of the world’s main sources of cheap drugs, and this is now under threat. By destroying such competition, big pharmaceuticals, Dr. Rennie adds, will be able to charge anything. After 30 years of having drug prices undercut by India, they will once again have total control of supply. Just a handful of manufacturers will have a lot of control. “What worries me is the monolithic, overuse of power to push pills. That’s terribly worrying to me. That is not a future we should encourage. It is the worst possible future.”
The documentary then moved on to show how these prices directly caused the death of a child in Honduras, suffering from AIDS, while activists resorted to breaking the law and attempted to smuggle cheaper drugs from across the border, where generic ones were being sold