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Animal research

05 - 02 - 2018

Pre-clinical trials: devastating BMJ investigation calls for more rigor and transparency

An investigation by the British Medical Journal revealed that for the development of a vaccine against tuberculosis, human clinical trials were conducted even though animal results were inconclusive. Explanations and implications.


Pre-clinical trials: devastating BMJ investigation calls for more rigor and transparency


This mid-January, a very dark affair shook the world of animal research, raised a lot of questions and led to a call for strict measures to further regulate animal experiments.



Unfavourable results ignored


An investigation, conducted by the British Medical Journal (BMJ), examined MVA85A, a vaccine candidate developed by a team from Oxford University (United Kingdom), which aims to strengthen the effectiveness of the BCG vaccine against tuberculosis.


According to the official publications, MVA85A is effective in four animal models (mice, guinea pigs, cattle and primates), but isn’t effective in the first clinical trials conducted in 2009 on South Africans infants.

In view of these contradictory findings, an independent BMJ review looked at the data from the preclinical studies.

Verdict: The scientists had publicly stated that the animal results were conclusive, when in reality the results are less straight forwards. Apparently, some of the animal studies were deliberately concealed and ignored because they did not meet the expected result. Only favourable results were publicly unveiled.


According to Dr. Deborah Cohen, associate editor of the BMJ, the disparities in the results between the animal and human studies have led the main funders of the work on tuberculosis to rethink their funding. This slows down the research in the field area, however capital it might be. In addition, Deborah Cohen recounts the difficulty experienced by the BMJ teams investigating the Oxford University work in obtaining research protocols and understanding the exact purpose of some animal studies. A sign of an important and disturbing lack of transparency.






An urgency to "reform" animal research


According to many researchers interviewed by the BMJ about this case, it unfortunately only illustrates the drifts of animal research: poor study design, lack of statistical methods understanding, lack of pre-specifications for the purpose of the animal studies, selective reporting of results driven by pressure to obtain funds and approval of ethics committees, ... The MVA85A case reveals the flaws of a system that lacks safeguards and controls. These deficiencies are all the more serious as these preclinical studies are used to validate the transition to clinical studies on humans. They are all the more regrettable in a time when public mistrust in regard to animal experimentation increases, due to a lack of clarity and explanations.


BMJ reviewers are calling for the implementation of concrete measures to put an end to this type of animal experimentation, far from exemplary. They believe that a systematic and thorough review of all animal studies should be conducted prior to initiating clinical trials.

In their BMJ editorial dated Jan. 10, Merel Ritskes-Hoitinga and Kim Wever call for "a cultural shift in which researchers would be rewarded for producing reproducible results that are both relevant to patients, and to the animals used".


"By definition, research means re-searching", searching again, Merel Ritskes-Hoitinga and Kim Wever recall. They believe that "a systematic review of preclinical animal studies is real research and a solid foundation for conducting subsequent clinical trials. If the organizations responsible for [evaluating and validating preclinical studies] are capable of carrying out a cultural change, to demand high-quality reports and systematic reviews of animal studies, the potential of animal studies, which aim to transform human health, will be fully exploited. "


As Fiona Godlee, editor-in-chief of the BMJ points out, savvy readers will understand that this is not about questioning vaccine research, which remain "more necessary than ever", especially as tuberculosis multidrug resistance is gaining grounds. It is about calling into question animal research, still necessary today for clinical research and the development of new treatments. It is simply a question of the urgency to improve the integrity of animal research: its reliability, reproducibility, analysis, reporting and interpretation, with the ultimate aim of improving human and animal health.


Hélène Bour


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