Questions and answers on the Clinical Trial Regulation and transparency.
Clinical research is enormously complex and today most doctors and patients do not receive enough information to know the real effect of the medicines they are prescribing and taking. Problems of bias and selective reporting by companies carrying out clinical trials have been abundantly documented in numerous scientific articles. Access to trial data is crucial because often a new scientific consensus is formed on a specific treatment changes due to the availability of new information. Many clinical trial results, whether they result in a marketing authorization or not, are never published, especially those with negative results. This is a great loss for the defence of public health and for the advance of medical science. Transparency means much more efficient and responsible science that can save thousands of lives and billions in research funding.
Why are Clinical Trial Summaries, as proposed by the European Commission proposal, not sufficient nor ethical?
Clinical Trial Summaries, the only required publicly accessible requirement by the European Commission Clinical Trial Regulation proposal, are of little scientific value and they are of little use for doctors and patients. Short summaries can often conceal more than they reveal and they can be misleading. There is no clear set of criteria nor definition of what a summary should cover. Moreover, summaries allow scant information for independent reviewers or other researchers who wish to check the reliability of the trials. Summaries do not create a science we can trust in.
Why are accessible clinical study reports (CSR) and anonymized individual patient data necessary for reliable and serious biomedical science?
Unlike summaries Clinical Study Reports are scientifically useful for independent researchers, doctors and patients. They must have clear definitions like this one:
“The report should provide a clear explanation of how the critical design features of the study were chosen and enough information on the plan, methods and conduct of the study so that there is no ambiguity in how the study was carried out. The report with its appendices should also provide enough individual patient data, including the demographic and baseline data, and details of analytical methods, to allow replication of the critical analyses when authorities wish to do so. It is also particularly important that all analyses, tables, and figures carry, in text or as part of the table, clear identification of the set of patients from which they were generated.”
The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), 1995.
Why should Clinical trial reports and anonymised individual patient raw data be accessible and available for all trials, whether they are for marketing authorization or not?
It is ethically wrong, according to the Helsinki Declaration signied by the EU, to conduct trials on human subjects, who are taking a personal risk for the benefit of scientific knowledge, and to then not to publish or to conceal or destroy the results. The value of clinical trial results should not only be decided by its sponsor, commercial or public. If there are a lot of unpublished trials, we are missing a large body of important evidence derived from trials on humans that can be critical for public health and the advance of science.
If comprehensive clinical data on children is already required by the EU to be submitted to EU data bases, then why not for all medicines?
ComprehensiveClinical trials results on children in Europe must be submitted toe the EudraCT database within 6 months. One reason given for this obligations is to “increase the availability of information on the use of medicinal products in the paediatric population and to avoid unnecessary repetition of studies.” http://ec.europa.eu/health/
Should not the same argument be used for all biomedical clinical trials.
Myths and Realities about clinical trial transparency
Accessible clinical study reports contain commercially sensitive data?.
There is nothing in clinical study reports that needs protection according to the European Ombudsman. The “overriding public intrest” of defending public health takes preference over commercial interests.
?More openness with clinical trial data threatens investments in clinical trials in the EU. ?
Where there has been much more openness with trial registers and accessible public portals there has been no evidence of reduced investments. Transparency does not threaten investments. If industry increased its trials outside the EU it could encounter serious problems in having their drugs approved in the EU as trial results in many countries are much less dependable.
?Industry already shares data in numerous partnerships with multi-stakeholders.
?These “partnerships” are not genuine because industry controls the data and doctors in multi-centre trials are not allowed access to individual patient data. As a consequence Industry controlled trials are often biased in their design and even more biased in the analysis of the data. There is an evident and very dangerous conflict of interest between industry control of data and public health.
?Information other than the summary of the the approved clinical trial protocol is commercially confidential information.
Industry does not own the data of clinical trials; society does. Non-disclosure of the data violates the Helsinki Declaration that protects the ethical practice of clinical trials. “Overriding public interest” will always take preference over commercial confidentiality as a default in EU law and according to a recent EU Ombudsman ruling. In any exception commercial interests must be specifically proven to be threatened by disclosure in each case. See BMJ, 2011;342:d2686.
Intellectual property rights are threatened by openness.
Patents are usually not affected because patents are almost always registered long before clinical trials take place. Protection of IPR has practically nothing to do with publishing clinical trial data. Nevertheless, If there is a specific problem concerning IPR protection, the burden or proof should be on the promotor of the trial to request special protection.
The Requirement of submitting a clinical trial report is a great administrative burden for academic and low-interventional researchers.
It is already done. Presently,academic researchers are required, as laid out by the Helsinki Declaration, to write a report of their study under any circumstances and to make them publicly available. Nevertheless, there are no requirements that academic publishers must produce a report with the same level as detail as industries applying for marketing authorization for a biomedical product.?
Administering penalties for not submitting a summary of results will be high and disproportionate compared to the benefits.?
Should there be no penalties levied on a drug company to reveal that they have found in a trial that their top-selling drug is killing the patients? There are so many examples in the last 10-15 years that drug companies have concealed lethal harms of their drugs, see, for example: Gotzsche PC. Trials 2011;12(1):249..
Maintaining an EU data base will be expensive.
This is not true. The EMA maintains a data base already and the Commission could have a common database with the existing structure of the EMA database in order to reduce costs. In any case, the cost is negligible in comparison with the massive public health and economic benefits from openness.