We have been talking about transparency and ethics of clinical trials for years. However, it is undeniable that the COVID-19 pandemic has the “merit” of having spread the term “transparency” coupled with the term “clinical research” very and very quickly. Sputnik, the much-criticized Russian vaccine, is just one example.
Not only the scientific community argues about the transparency and ethics of clinical trials. In fact, even people not involved in the sector talk about it. Everyone creates their own opinion and – as unfortunately too often happens when medical and scientific issues are touched – there is great chaos. Michele De Luca, director of the “Stefano Ferrari” Center for Regenerative Medicine of the University of Modena and Reggio Emilia and Gilberto Corbellini, epistemiologist, commented on the topic in an article entitled “Vaccini e trasparenza: una questione malposta” (Vaccines and transparency: a badly posed question). Their invitation, in summary, is to go back to believing in the work of the agencies that evaluate the data produced by clinical studies and submitted for the marketing authorization request.
The vaccine quality control system, set up over the years, has now become hypersensitive to risks and stating, for example, that you will not get vaccinated until the data on the vaccine are published means making at least two mistakes. A first mistake is to think that informations appearing in peer-reviewed scientific publications are more reliable than informations checked and analyzed by the scientists and technicians of the agencies that approve drugs and therefore also vaccines. The second mistake is a form of self-deception for which those who express reservations believe they are able to appreciate and judge very complex informations and situations, in which they are not competent and that are usually evaluated by a team of highly specialized experts.
According to a joint report published in 2019 by TranspariMED, BUKO Pharma-Kampagne, Test Aankoop and Health Action International, 83% of clinical studies (778) conducted by the top 30 European medical research universities violate European standards on transparency. In fact, it seems that, although European universities have had to publish the results of all their clinical trials since 2014 in order to safeguard the interests of patients and taxpayers, the reporting rates reported in the report are only 7%.
The investigators promoted only a few universities: the University of Oxford, University College London, and King’s College London. These universities have actually published over 80% of the results. For the others, however, the data are much less encouraging. The investigated French, Norwegian, Swedish and Italian universities published only one study. The remaining 13 also showed reporting rates of between 2% and 33%.
Greater transparency of clinical trials has indisputable advantages. It improves patient outcomes, allows a better allocation of the limited resources destined for biomedical research and healthcare, and accelerates the development of new therapies.
The bias in clinical studies
In the field of scientific publications there are two important phenomena that lead to overestimating the benefits and minimizing the risks: reporting bias and distortion of evidence.
The report bias
A common trend, although there has been much discussion on the subject, is to publish positive data and omit the negative ones. This phenomenon, known as reporting bias, results from the common interests of industry, publishers, and researchers.
Distortion of evidence
There are many forms of distortion, including:
- spin (alteration of truth)
- statistical manipulation
- the selective publication of partial results
- complete data manipulation.
The five pillars of ethics of clinical trials
For GIMBE foundation, the lack of transparency in clinical trials can increase the risk of undue influence, data manipulation and evidence bias. In addition, regulatory authorities have a very limited role in the reporting and publication process. And this phenomenon hampers the advances of medicine and the goals of public health system. In the most serious cases it can open the doors to fraudulent conduct and corruption. GIMBE proposes a model to improve the transparency of clinical trials based on five pillars:
- Registration: all clinical trials must be registered on a trial registry approved by the WHO, before the enrollment of the first participant. Prospective trial registration has been a universal ethical obligation in clinical research since 2008. However, a 2017 study of 860 clinical trials found that 556 had not been registered and another 157 had only been registered retrospectively. Less than 19% of the trials evaluated were prospectively registered.
- Key Findings Report: for all clinical trials, within 12 months of completion a key findings report must be published in the registries where they were initially recorded.
- Full report: all information relevant to interpreting trial results should be proactively disclosed and made available to the scientific community. This information includes the original trial protocol, the predefined statistical analysis plan, case report forms, and clinical study reports.
- Trial publication: the results of all clinical trials must be published in a scientific journal or made available free of charge in suitable trial registers or databases (preferably in both forms).
- Participants’ data sharing: legal frameworks, rules, policies and laws must be established in order to allow an effective and careful sharing of participants’ individual data.