The framework of clinical trials as an increasingly important element of the decision relating to drug safety at the EMA
The European Medicines Agency (EMA) is responsible for the approval of new drugs authorized in Europe. On its website, the EMA promises to work "independently, openly and transparently and to adhere to the highest standards in scientific recommendations“. This should in fact be a matter of course and is not only of highest importance for every new drug – but a question of survival for many patients. But what if the studies that the EMA relies on and refers to are not compatible with the countries for which the drugs are approved? In technical jargon this means “distortion due to the design”.
Huseyin Naci from the London School of Economics and Political Science, in the BMJ, now looked into this and other questions and found out: Numerous high-priced drugs intended for oncology are shown better in studies than they are. Also when used in clinics, it can be seen that the cancer drugs have less effect and more side effects.
Falsified results in every second registration trial
Between 2012 and 2016, half of the new drugs were approved by the EMA, which could only be examined in a single approval-related study * Between 2014 and 2016, the EMA approved 32 new cancer drugs based on 54 pivotal studies – for Europe. The studies included 41 randomized controlled trials and 13 non-randomized trials or one arm studies. (A randomized controlled trial is the proven best study design in medical research in order to get a clear answer to a clear question and to prove the causality.) In his current work, Huseyin Naci uncovered weaknesses in every second registration study.
But does the pharmaceutical industry actually re-designs studies to fit their high-priced ontological medications – and not the other way around, as can be expected from an objectively active approval body? Serious clinical studies use various parameters to assess the effectiveness of a substance to be tested. An important statistical measure is progression-free survival. Huseyin Naci rated 19 (almost half) of the randomized controlled trials as highly distorted. Missing data on results and weaknesses in the measurements he blamed to be responsible.
One example: Studies carried out on American patients cannot be used seriously as the basis for medication for German patients. Important parameters such as DNA, disease and living conditions are too different. However, this is the basis of work at EMA which should give us food for thought.
More and more and more and more expensive drugs are entering the market
What should be done in everyday practice if suddenly – contrary to the study statement – strong side effects occur? Or the disease takes a completely different course than the studies predict? The weaknesses uncovered by Huseyin Naci are only considered by experts to be the beginning of an worsening situation. More and more and more and more expensive drugs enter the market. Therapy, and in general medicine, is becoming more and more personalized, so studies are getting smaller and less meaningful.
The main design techniques to avoid bias in clinical trials are blinding and randomization. Even if personalized medicine is forward-looking, the maximum profit should not be the defining factor for research. Rather: what value does this drug have for the patient. Also: this product is really better than others that are already on the market?
If studies are falsified and adapted to the desired results, this can have the effect that patients take medicine that is counterproductive for their cancer, or in the worst case, life-shortening.
*Department of Global Health and Social Medicine, King’s College London, London, UK
**Design characteristics, risk of bias, and reporting of randomised controlled trials supporting approvals of cancer drugs by European Medicines Agency, 2014-16: cross sectional analysis
BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l5221 (Published 18 September 2019) Cite this as: BMJ 2019
Read more: FDA-whistleblower Ronald Kavanagh reports on his work at the American drug agency, which has directed scientists to accept pharmaceutical companies' claims without verifying the data.
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