1 December 2013
Argentina is in third position in terms of the number of drug tests hosted in Latin American countries, behind Brazil and Mexico. This country presents a number of advantages for pharmaceuticals companies. The first of these is structural: well-trained health professionals; an ethnically diverse population, but genetically close to that of western Europe and the United States; a large network of hospitals; and relatively low costs in terms of other countries. In addition, it is easy to recruit patients for clinical trials, as the multi-tier health system put in place in the 1990s makes certain treatments inaccessible for a big part of the population. The doctors, highly respected in this country, therefore have no problem in convincing their patients that being part of a “protocol” is the best option for them.
While the framework for clinical trials in Argentina is judged to be “quite good” by those involved in medical research, it has some drawbacks: no national law; private ethical committees whose independence is doubtful; and a regulatory agency – ANMAT – that does not really ensure the respect of ethical standards.
Ethical committees: lack of transparency and conflicts of interest
In response to the regulatory vacuum and the gaps in ANMAT, two private institutions were set up as “independent ethical committees”, which are the only responsible organisations in Argentina for the protection of participants. These organs, which are more like protocol “rubber stamps”, are called into question by many health professionals, who accuse them of totally lacking in credibility and independence. With good reason, apparently: in an analysis of 36 clinical trial protocols dating from 2005 and 2006, a doctor identified almost 100 violations of current standards in 85% of protocols studied. Between the two of them, these committees approve 80% of clinical studies in Argentina. The FEFyM, directed by a certain Dr Zieher, reviews the protocols of 85% of clinical trials conducted by Roche and Novartis in Argentina. Two non-ethical trials by Roche and Merck, revealed by our investigation, were actually revised by the FEFyM.
Schizophrenic adolescents deprived of their treatment
While testing a drug against a placebo enables the obtention of clearer results, administering a “sugared pill” to patients who are in need of treatment is dangerous and inacceptable from an ethical point of view. This practice was however adopted by the American firm Merck in a study performed in 2010 in eastern and southern countries, including Argentina. It concerned the use of an antipsychotic drug – Saphris (Asenapine) – on adolescents suffering from schizophrenia.
Though approved by ANMAT, this trial put in danger the participants, whose existing treatments (antipsychotics, antidepressants, etc.) were stopped, while they took Asenapine or a placebo. Following an anonymous denunciation, the study was finally suspended by ANMAT. In spite of the seriousness of the facts, no legal proceedings were begun, and the story did not appear in the media. Public Eye is the first organisation to openly denounce this scandal.
A non-approved treatment as standard
In 2008, Roche tested the use of an immunosuppressor – ocrelizumab – to treat lupus nephritis, an auto-immune disease responsible for kidney problems. Conducted in several countries, including Argentina, the trial was eventually suspended because the drug caused serious side-effects. But the problem does not reside there. According to the consent form, the patients received – in addition to ocrelizumab or a placebo – a so-called “standard” treatment including CellCept, an immunosuppressor used to prevent rejection following transplantation.
Although doctors prescribe it informally for lupus, CellCept is not authorised to treat this illness. To present it as a “standard” treatment is therefore a falsehood and constitutes an ethical violation. This also means that, once the trial is completed, patients can no longer have access to CellCept, even if its efficacy is proven. This is what happened to Maria, a patient who agreed to relate her story to us.
GSK guilty of ethical violations
In Argentina, decisions of ethics committees are characterised by a total lack of transparency. Indeed, there is no national public register, not even for professionals. If a committee rejects a protocol, the pharmaceutical company can simply turn to another institution until one of them – less scrupulous – accepts it. This is what happened in the case of COMPAS, a vast study conducted by the British company GlaxoSmithKline (GSK) on Synflorix, a vaccine against pneumonia, otitis and meningitis.
Between 2007 and 2011, this drug was tested on 14,000 new-born children, in three provinces among the poorest in the country. The affair created a scandal in the media, as fourteen babies died during the study, which finally led to the opening of an official enquiry. Even though the link between the vaccine and the deaths was not proven, the work of journalists and the disclosures by health professionals revealed serious irregularities, confirmed by an in-depth investigation by ANMAT. For the first time, the Argentinian authorities imposed fines on a multinational for ethical violations.
Among the facts criticised were in particular the inclusion of babies having previously suffered from respiratory infections or infected with HIV. Irregularities in the obtention of informed consent were also denounced by several parents. The mother of one of the deceased children related to a journalist from the magazine El Guardian that the vaccine would soon become compulsory and would cost 300 pesos. They asked her: “Do you have the 300 pesos?” Not having this sum, she signed the form. Another mother was threatened by the medical staff that her child would be taken from her if she did not accept a second injection. Some parents registered their new-born baby to receive better medical support. The father of one baby explained the system thus to investigators: “You arrive here and they take you in charge. Otherwise, you have to come at four in the morning and you’re treated like a dog.”
The integrity of the doctors was also questioned, due to their interest in seeing the study “expand”, as GSK paid 350 dollars to them for each new-born recruited. This represented a significant sum for these doctors, whose monthly salary ranged between 1200 and 1400 dollars.
A worrying aspect: the principal coordinator of this study and a provincial responsible, both of them prosecuted for ethical violations, were involved in similar trials conducted in parallel by Novartis. When questioned on the subject, the representatives of the Basel-based giant did not see any problem. The medical director of their Argentinian subsidiary even related having subsequently re-hired one of these two persons.
This investigation has not (and probably will not) be followed up or updated. The results published on this web site are those obtained during our research in 2013.
Investigative Report by Public Eye: Clinical Drug Trials in Argentina - Pharmaceutical Companies Exploit Flaws in The Regulatory System (2013)