A lack of transparency
When drugs are tested on voluntary subjects, the results should logically be made available to society. However, the pharmaceutical companies consider that the data gathered belongs to them. As a result, half of all clinical trials conducted in the world are never published, and unfavourable data is concealed or minimised. This leads to drugs that could prove to be more dangerous than useful being marketed or remaining on the market, such as Tamiflu and Vioxx.
The case of Vioxx
In September 2004, Merck announced the withdrawal from the market of its anti-osteoarthritis drug Vioxx due to a risk of cardiovascular complications. As long ago as 2001, the US drugs agency, the FDA, had found that Vioxx caused five times more infarcts than a rival anti-inflammatory product, although it did not suspend its marketing authorisation. Several clinical trial reports, some of which were not published immediately, confirmed this risk. In response, Merck stepped up its lobbying of doctors to counter the impact of these findings. The result was more than 100,000 cardiac arrests, leading to some 10,000 deaths in the United States alone. These could have been avoided if the results had been made public earlier.
Tamiflu – or the virus of profit
The decision taken by governments worldwide, including Switzerland, to stockpile the antiviral drug Tamiflu, made by Roche, as a precaution against flu pandemics, was based on a number of individual studies, eight out of ten of which have never been published. The pharma giant has also kept the lid on the results of other clinical trials. It took four years of insistance and a public campaign orchestrated by the British Medical Journal to enable independent scientists from the Cochrane network to get access, in 2013, to the complete set of data relating to clinical trials performed by Roche on Tamiflu.
For the first time, these scientists were therefore able to evaluate the efficacy and the precise toxicity of the anti-flu drug from the Basel-based pharmaceuticals giant on the basis of exhaustive documentation. The results of this evaluation, published in April 2014, are clear: contrary to statements from Roche, the prescription of Tamiflu neither reduces the number of hospitalisations nor the risk of serious complications in influenza sufferers. At best, patients experienced a diminution of ’flu symptoms within a few hours. Neither does Tamiflu stop the transmission of the virus.
The claims for Tamiflu were precisely those that had persuaded the WHO to recommend to states and large companies that they purchase high volumes of the drug during the alerts for the avian ’flu H5N1 (from 2004) and the pandemic linked to H1N1 in 2009. These false promesses brought in massive amounts of cash to the Basel company: since the launch of Tamiflu in 1999, Roche has earned 18 billion francs, most of it from the taxpayer.
Commercial confidentiality or public good?
Reports on clinical trials must make it possible to judge the efficacy and safety of the product being tested. Contrary to the arguments put forward by the pharmaceutical laboratories, no information is divulged on either the composition of the drug or on any aspect of its production. When questioned about this as far back as 2010, the European Ombudsman confirmed that these reports contain nothing pertaining to commercial confidentiality. They should therefore be considered public property, as the dissemination of anonymous reports normally makes it impossible to identify participants.
The EU shows the way
Faced with this phenomenon of selective publication, the regulatory authorities are both complicit and powerless, as they are financially dependent on the pharmaceutical industry. However, some of them have decided to react. The European Medicines Agency (EMA) intends to publish all the reports on clinical trials in its possession, and this is a step in the right direction.
The EMA has thus proceeded since 2015 with the pro-active publication of reports of clinical trials as a basis for approval decisions, and/or having been the object of a specific request for publication by groups of scientists. The only drawbacks are that this measure does not apply retroactively to drugs already in circulation, and that information judged to be confidential (trade secrets) is omitted at the request of the pharmaceutical company concerned.
This increase in transparency, to which Swissmedic could aspire, is a step in the right direction, even though its implementation still faces challenges from the strong lobbying of the pharmaceuticals industry with regard to this initiative.
The European Union has also taken concrete measures at a political level. In 2014, it adopted a new ruling requiring the publication of all the reports of clinical trials used as a basis for approval of medication, whether the decision is positive or negative. The European ruling has moreover confirmed that the principles of “industrial secret” and the confidentiality of participants – arguments dear to pharmaceuticals companies – may not be invoked to prevent the publication of these reports. The new ruling will come into force as soon as the database is operational.
Switzerland is lagging behind in terms of transparency of clinical data, but it has taken an initial step within the framework of the revision of the law on medicinal products and medical devices (TPA), which is scheduled to come into force in 2019. This law includes a new article on the publication of drug results testing used as a basis for the granting of authorisation of the marketing of the drug in Switzerland (art. 67b). Even if the extent and the method of publication must still be determined within the framework of the revision of the prescriptions, such an article constitutes an initial legal basis to combat the selective publication that exists in this sector. Apart from the possibility of an independent, scientific counter-expertise, the complete publication of reports of clinical trials would enable doctors to acquire a more solid and reliable basis for comparison when prescribing a treatment to their patients.
Registering of clinical trials
There is a multitude of clinical trials databases. The most complete of these are in the United States (ClinicalTrials.gov) and in Europe (Clinicaltrialsregister.eu) as well as at the WHO (apps.who.int/trialsearch), but none is exhaustive, since there is no obligation to register clinical trials at an international level. The decision taken in 2004 – by the most prestigious medical journals – to require the recording of studies before any publication has drastically increased the number of entries, but there are ways of getting around this. Moreover, these registers only include a summary of the clinical trials, which is insufficient for analysing the ethical and scientific aspects of the study.
With the coming into force of the Federal Act on Research involving Human Beings (HRA) in 2014, Switzerland also put in place its own public register (www.kofam.ch), but this only includes clinical trials conducted in Switzerland, and only contains minimal information.
According to the WHO, the recording of all clinical trials is a scientific, ethical and moral responsibility. In a position statement of April 2015, the WHO requires that all results be made public and accessible in the 12 months following the end of a clinical trial, whether they be positive or negative.