Ethical violation
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Roger Anis
In order for a drug to be approved in Switzerland, clinical trials must be undertaken. Once an active substance has been discovered, synthesised and studied in the laboratory, its efficacy and safety have to be tested on humans. Companies do this in three waves of trials, which serve as the basis for the authorisation of the drug. A fourth phase is sometimes undertaken for the purposes of complementary research.
Several million people take part in tens of thousands of clinical trials at any one time. In July 2018, Roche was sponsoring almost 3000 active clinical trials in 80 countries, and Novartis almost 2500 in more than 75 countries.
These stages are very costly. Between 60% and 70% of the R&D budget is allocated to them, or 80 to 90 billion dollars out of the 130 billion spent annually by the pharmaceutical industry worldwide. In 2017, the costs for Roche and Novartis amounted to 7 and 5.5 billion dollars respectively.
©
Roger Anis
The «globalisation» of clinical trials
More and more often, pharmaceutical giants like Roche or Novartis prefer to delocalise testing to developing – and especially emergent – countries. In China, Russia, Egypt, India or Argentina, taking part in drug testing programs is often the only option for poor individuals to get treatment. But this “globalisation of clinical trials” brings with it ethical violations, as shown by the investigations conducted by Public Eye in six countries on four continents, In Switzerland, the monitoring is insufficient: Swissmedic, the organisation responsible for the approval of drugs, is not taking the necessary steps to halt this scandal.
Although most clinical trials are conducted in the United States and Europe, over the last 20 years there has been a strong tendency towards offshoring to developing and emergent countries. The proportion of testing in emerging markets increased from 10% to 40%. This continued to increase between 2006 and 2010, while the proportion of clinical trials conducted in Western Europe and the United States fell from 55% to 38%. Between 2011 and end-2017, the number of active clinical trials conducted by the Swiss giants in developing and emergent countries continued to progress (+47% pour Novartis and +15% pour Roche).
The preferred destinations of industry for the delocalisation of clinical trials are Asia (Chine, India, Thailand), eastern Europe (Russia, Ukraine, Poland), Latin America (Argentina, Brazil, Colombia, Mexico) and Africa (South Africa, Egypt). These regions represent strong market potential for pharmaceutical multinationals.
Why delocalise?
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CHEAPER, and a high number of potential participants
Delocalising enables pharmas to reduce their costs. In poorer countries, most people have no access to basic medical care, and have to pay for medication themselves. Participation in a clinical trial therefore represents for many people the hope of receiving better care. Those people who qualify for participation are therefore more numerous and easier to convince. Labour costs, recruitment and follow-up of clinical trials are also cheaper there.
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FASTER, and therefore more profitable
Recruiting participants in developing countries enables a reduction of the total duration of a trial by six months on average, which prolongs the very profitable period of commercialisation of a patented drug. Each additional day of commercialisation of a drug with a monopoly (protected by a patent) can amount to more than a million dollars.
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SIMPLER, the checks in place often being inadequate
In developing or emergent countries, the regulations concerning clinical trials are often less strict, and the checks are limited. The risk of ethical violations is therefore high. The investigations led by Public Eye paint a disturbing picture of the clinical trials sector: problems in obtaining informed consent; deprivation of the best proven treatment (standard of care) for those participants in the control group; discontinuation of treatment at the end of the trial; and a lack of commitment to provide compensation where serious side-effects occur.
Ethical violations noted in the field
Public Eye investigated in six countries that represent preferred destinations for the pharmaceuticals industry for clinical trials. Our investigations performed in India, Argentina, Ukraine and Russia in 2013, in Poland since 2015, and in Egypt in 2016, paint a disturbing picture of this very opaque sector. The following ethical violations have regularly occurred:
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Absence of free and informed consent
The person taking part in a trial must give his/her “free and informed consent”. This requirement is often not met in contexts of socio-economic or health-related vulnerability, where there is a very high degree of trust in doctors. It is not unusual for a doctor to exert inappropriate influence over the person he or she wants to recruit (especially if they are in charge of the research), and for subjects to be incorrectly informed or to even be unaware that they are going to take part in an experiment. This means that the patients may not be aware of the risks involved.
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Patients deprived of the best proven treatment
The use of a placebo as medication for reasons of comparison makes it easier to obtain clear results. However, it constitutes an ethical violation if existing, efficacious medication exists, and if therefore the absence of treatment represents a risk to the patient. To retain the best tested treatments from a control group is also an ethical violation according to the Declaration of Helsinki.
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Insufficient or non-existent financial compensation in the case of serious adverse events
In case of harm or death related to the tested medication, financial compensation must be allowed for. Evidently, most people participating in a clinical trial are unwell and there is a risk that their health may deteriorate during the study. However, others may suffer or die after taking the tested drug. All too often, the evaluation of the link between the side-effect and the drug being tested is not conducted in an independent way, but rather by those responsible for the study. The patients do not have the means to defend their interests.
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No access to treatment at the end of the trial
A person who agrees to participate in a study should be guaranteed access to the treatment when the trial ends if the drug is found to be beneficial, or to any other treatment. In reality, the treatment is often stopped at the end of the trial, a problem which is all the more acute in countries where access to drugs is limited.
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Unavailable or too-expensive medication
Clinical trials should only be performed in those countries where authorisation to market the product will be requested if the tests prove positive. Roche and Novartis assert that they respect this ethical rule to the letter. However, our investigations have revealed that some drugs are not available in the countries where they are tested. When they are eventually commercialised, their price is so exorbitant that they are too expensive for most of the population.
An aggravating factor: sub-contracting
Pharmaceutical companies are increasingly entrusting the conduct of clinical trials to specialized companies known as contract research organisations (CROs). This sub-contracting multiplies the number of players involved and makes the traceability more difficult. It also raises the issue of dilution of responsibility in the case of ethical violations, as illustrated by the case of the clinical trial on the H5N1 conducted by Novartis in Poland. According to the international texts in force, it is the promoter or sponsor of the study who has ultimate responsibility for the proper conduct of clinical trials, even though sponsors sometimes attempt to shift this responsibility onto sub-contractors.