Ethical violations in clinical trials
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Roger Anis
Pharmaceutical companies such as Roche and Novartis outsource clinical trials to poorer countries. In lower-income countries, participation in a clinical trial is often the only chance for people to receive treatment. Investigations carried out by Public Eye in six countries on four continents confirm that this “globalization of clinical trials” is often accompanied by ethical standards being violated. In Switzerland, the controls applied are inadequate as Swissmedic, the body responsible for the authorization of medicines, is not taking the necessary measures to end this scandal.
Why are trials outsourced?
1. CHEAPER and lots of potential study participants
Relocating trials to lower-income countries allows pharmaceutical companies to reduce their costs. In many countries, the majority of the population does not have access to health care. For many patients, participation in a clinical trial is the only way to gain access to (better) medical care. This means that the bar is low in terms of getting subjects to participate in trials. So there are more people who are willing to participate in trials, making them easier to persuade. Another factor is that labour costs, as well as the recruitment and supervision costs for clinical trials are cheaper in these countries.
2. FASTER and therefore more lucrative
Outsourcing to a lower-income country also allows the contracting companies to shorten the total duration of a trial by an average of about six months. It’s worth it because every additional day a drug with patent protection is sold, giving it therefore a monopoly position, can generate additional revenues of over one million dollars.
3. EASIER as local controls are often inadequate
Regulation of clinical trials in lower-income countries is often less stringent and controls are limited. This poses a correspondingly high risk of human rights being violated. Problems in obtaining the participants’ consent; lack of compensation in the event of serious side effects; lack of medical care following the trial; participants in control groups who are deprived of the best possible standard treatment are some of the numerous ethical violations highlighted by the investigations carried out by Public Eye in relation to clinical studies.
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GMB Akash/Panos
Our investigations show that ethical violations are the rule rather than the exception
Public Eye has conducted investigations in six countries that are among the pharmaceutical industry’s top destinations for clinical trials. Our investigations carried out in India, Argentina, Ukraine and Russia in 2013, in Egypt in 2016 and a case in Poland investigated between 2015 and 2017 painted a bleak picture of this very opaque sector.
More infos
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Our studies: Problems with outsourcing clinical trials
Public Eye has been conducting investigations with partner organizations and journalists in Russia, Ukraine, Argentina, India and Egypt. Due to the lack of transparency in implementing drug trials, it proved to be difficult to carry out the investigations. Hardly any information is published as the research teams are bound by confidentiality and are afraid of being prosecuted if they were to say anything. Identifying trial subjects or approaching them is also very difficult. After interviewing key figures, studying confidential documents and a great deal of fact-checking, it emerged that serious ethical violations had been committed in each of these countries. After the investigations conducted in Egypt were published, Roche tried to intimidate Public Eye with a super-provisional injunction. However, the lawsuit was completely dismissed. Finally, Public Eye has investigated a case in Poland. However, the person concerned had to drop his lawsuit against Novartis because the evidence was deemed inadmissible by the Swiss court.
No free, informed consent granted by trial participants
Every person participating in a clinical trial must give consent based on their free will and appropriate information. In view of the lack of health care and precarious social circumstances, these conditions are difficult to guarantee. Doctors, frequently commissioned to carry out the study themselves, are often held in high esteem thanks to their social status. As a result, they can exert undue influence on the patients they want to recruit for a clinical trial. Trial subjects are often insufficiently informed in advance. They sometimes don’t even know that they are participating in a trial and are therefore unaware of the risks that may be associated with treatment in its experimental phase.
Withholding the best possible standard treatment
The use of placebos for comparison purposes in the control group of a clinical trial makes it easier to obtain clearer trial results. However, it is ethically unacceptable to expose trial participants to a health risk by administering a placebo if there are drugs that are already approved on the market and proven to be effective. Refusing to provide the best proven treatment to the participants in the control group is also a violation of ethical standards under the Declaration of Helsinki.
No financial compensation in the event of consequential harm
In the event of any injury or death relating to the drugs being tested, financial compensation must be given. The majority of people participating in clinical trials are already sick. Their participation raises the risk of their health deteriorating further over the course of the trial. Other subjects, in turn, suffer from the consequences of the trials and die due to the drug being tested. All too often, the link between the injury suffered and the drug tested is not investigated by independent experts, but described and trivialized by the trial managers themselves. Those affected do not have the necessary means to defend their interests.
Discontinuation of treatment at the end of the trial
Anyone who agrees to participate in a trial must be given the guarantee that they will continue to have access to treatment after the end of the trial if the drug being tested or another treatment method proves to be effective (standard of care). In reality, however, treatment is often discontinued at the end of the trial – a serious problem for those affected in countries where access to medicines is already limited.
No access to tested medicines
Roche and Novartis claim that they follow international ethical guidelines and only conduct clinical trials in countries where they later seek authorization for the drug being tested (if it proves effective). In actual fact, progress has been made in terms of approval rates, but still not all drugs are coming onto the market in the countries where they were tested. And those that are authorized are often inaccessible to the local population because of their inflated prices. Access to these drugs often resembles a lottery due to the irresponsible pricing policy of the pharmaceutical companies, as Public Eye’s investigations on “post-trial access” show.
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Our study: No access to tested medicines
Medicines that have been tested in lower-income countries must be authorized in the respective market in accordance with international ethical guidelines. A pharmaceutical company can apply for marketing authorization if all stages of the clinical trials have been successfully completed. Each country has its own authorization authority that reviews such applications, while the Member States of the EU also have a common one.
In Egypt in 2016, Public Eye worked with its Egyptian partner organisations EIPR and Shamseya to investigate how many of the medicines tested in the country were authorized there. Of 24 drugs, all marketed in the United States and the EU, only 15 were also marketed in Egypt. This gives a rate of only 62.5%.
A study from India found an authorization rate for India of 66.5% in the same period. Another comparable study from 2014 concluded that in South Africa only about 40% of all drugs successfully tested in the country were also marketed there.
The Public Eye follow-up study “Post-Trial Access to Swiss Medicines in Five Low and Middle-Income Countries” (2019) in Colombia, Mexico, Thailand, Ukraine and South Africa showed that the authorization rate has noticeably improved.
Authorization alone is not enough
However, even if a drug is authorized, it is its price that determines whether it will be available or not. And it’s only when a drug is available that patients can benefit from it. For this reason, Public Eye has queried the prices of the drugs tested in all countries. At first glance, we noticed that prices were in the same ballpark as prices in Switzerland or the United States.
If we then take a closer look at the minimum wages and healthcare provision in the individual countries, the true conditions become apparent. Public Eye has done this for five countries, including Mexico and Ukraine. Both countries are in a particularly difficult position due to their proximity to the economic powers of the United States and the EU.
Mexico and Ukraine are in the backyard of the United States and EU respectively, the two regions with the highest medicine prices in the world. In addition, both Mexico and Ukraine have signed free trade agreements with their high-income neighbours that limit their political room for manoeuvre, including with regard to the regulation and pricing of medicines.
Mexico: Unacceptably high prices
A worker who earned the minimum wage in Mexico would theoretically have had to work for 20 to 50 years at the time of the study to be able to pay for cancer treatment with one of the products tested for just one year. Even with the price negotiated by the Mexican health insurance companies, the costs would still have been enormous, for example for the cancer drugs Afinitor (Novartis) and Avastin (Roche): one year of treatment would have been equivalent to working 14 years on a minimum wage.
20 to 50 years of work for a year of cancer treatment
Avastin was covered by health insurance for children and adults with a very severe disease progression. Herceptin (Roche) was also reimbursed for certain forms of breast cancer – provided that the product was available at the point of treatment. Previous studies have shown that this is often not the case for new cancer drugs in Mexico.
Ukraine: Illness as a risk of poverty
Even with the very patchy health insurance available in Ukraine, patients often had to pay for their medication themselves. On paper, the Ukrainian healthcare system offered unrestricted access to health care in public medical facilities, but in reality, Ukrainians had been suffering for years from the outrageous expenses resulting from falling ill, which put them at risk of poverty.
Ukraine also had schemes for dispensing some medicines for free. However, none of the medicines we investigated were on the Ministry of Health’s reimbursement list. As in Mexico, the prices for cancer drugs in Ukraine must be described as unacceptably high – even though the country provided trial subjects for their development.
Roche’s Tarceva cost a Ukrainian lung cancer patient more than $47,000 per year
This figure is roughly twenty times the country’s gross per capita national income, which was $2,390 in 2017. Cancer drugs are renowned for their high prices. However, Ilaris, a drug used to treat rheumatoid arthritis, also turned out to be surprisingly expensive. Annual treatment with Ilaris would have cost a person earning a minimum wage the equivalent of 25 years’ income.
A complete lottery
Our investigation delivered the following results. Pharmaceutical companies often do only the bare minimum to benefit the communities in which they have previously conducted clinical research. The various cancer treatments we studied were officially offered at prices that usually exceeded gross national per capita income. Many of the newer cancer drugs were not covered by basic insurance, and if they were, patients had to be lucky enough to have them available at the time. With a few exceptions, access to these drugs was like a lottery.
Neither Novartis nor Roche can therefore claim that they meet their ethical obligations in terms of post-trial access (i.e. the availability of drugs after a clinical trial). The irresponsible pricing policy pursued by the companies is the reason for this. Although patients in economically disadvantaged countries are the preferred subjects for pharmaceutical companies’ clinical trials, they can hardly benefit from therapeutic progress made. Far too often, they have to resort to older, less effective treatments.
Subcontracting: lack of transparency and accountability
Pharmaceutical multinationals often don’t carry out their clinical trials themselves, but outsource this task to specialized companies, known as “Contract Research Organizations” (CROs). This form of subcontracting is problematic because it makes traceability difficult. It is also difficult to clarify who will be held responsible in the event of an ethical violation when awarding contracts to CROs. The case of the clinical trial carried out by Novartis in Poland illustrates this problem. According to internationally applicable laws, the contracting company is responsible for conducting a clinical trial. In practice, however, pharmaceutical companies like to hide behind their subcontractors.