Reacción a "Only 5% of therapies studied in animals are ever approved for use in humans"

Periodically, studies emerge that aim to provide new data on the eternal question of whether animals are useful for developing therapies that can later be effective in humans. There are studies to suit all tastes. Some studies indicate that the transfer of results from animals to humans is unpredictable, comparable, or entirely different. 

Currently, with growing groups in the population opposing animal experimentation, who systematically appeal to community institutions to try to achieve a ban on these practices, these types of studies aimed at deciphering the usefulness of animal experiments for obtaining effective treatments in humans have gained new and unprecedented interest, especially when the results obtained are negative and, therefore, favorable to those who oppose the continued use of animals in biomedical research. 

We must remember that Directive 2010/63/EU, from which all national European legislations for the protection of animals used in research and teaching are derived, already anticipates that the ultimate goal of the regulation is to end animal experimentation, but adds, when this is scientifically possible. And we are not yet at this point. We still need to go through preclinical analyses in animal models for therapeutic proposals aimed at new treatments, which we want to be safe and effective. Safety and efficacy are first evaluated in animals before being analyzed in subsequent clinical trials. It is no coincidence that the vast majority of Nobel Prizes in Medicine or Physiology have been achieved thanks to animal experimentation. 

We must also bear in mind that we are not indistinguishable from other animals, and each animal model has its advantages and disadvantages in biomedical studies. They are very useful to us most of the time, but there are physiological and metabolic differences for which caution is recommended when comparing and drawing conclusions from the responses obtained in animal models and humans. For example, chocolate is tolerated by humans without problems but can kill a dog, which is unable to process some of its components that become toxic to the animal. Therefore, studies in more than one animal model are often required for the development of gene therapies and vaccines. 

A group of Swiss and British researchers have just published in the journal PLoS Biology the results of analyzing many publications describing preclinical analyses with animals and their subsequent follow-up in patients, in the form of some type of human study, randomized controlled clinical trials, or authorization by regulatory authorities. The strict selection criteria applied to these publications result in only 122 out of the initial 5,228 publications being retained (which may be one of the weakest points of this study, the limited number of cases finally studied). The rest of the study is conducted solely on these 122 publications. These articles describe 54 different human diseases and 367 therapeutic interventions. 

The study's conclusions are that 50% of animal studies progress to human studies, and 40% progress to randomized controlled clinical trials. These figures are significantly higher than those usually published by this type of study. However, only 5% of animal studies progress to obtain the corresponding regulatory approval. They also conduct a meta-analysis and conclude that there is concordance in the positive results in animal models and humans in 86% of cases. The median waiting time between animal studies and human studies, randomized controlled trials, or approvals by authorities is set at 5, 7, and 10 years, respectively. 

To explain the low rate (5%) of animal studies that reach approval in humans, they propose two possible explanations: 

• Either the requirements for randomized controlled clinical trials are very strict, causing some potentially promising animal studies to fail to overcome this barrier; 

• Or there are limitations in the design of both animal experiments and human trials. The authors lean towards the second option. And I agree with this interpretation. 

The regulatory pressure of the 3Rs (replacement, reduction, and refinement) ensures a focus on maintaining animal welfare, but it can force, in some cases, suboptimal experimental designs, which may include perhaps fewer individuals per experimental group or fewer experimental groups than would be objectively necessary (for example, conducting experiments only with males and not including females in the analyses, something highly discouraged). The standardization of environments and animals (mostly inbred, if we talk about mice) usually presented as an advantage, can also be a source of problems, given that it is obvious that humans live in diverse environments and are generally not inbred. All this can produce results in animals that are not robust enough and, therefore, generate therapeutic expectations that later are not confirmed in humans. The same occurs with the first Phase I/II clinical trials, with extraordinary costs, which may not have the adequate design or the necessary statistical power to draw conclusive results. 

Animal experiments remain necessary in biomedicine to advance the development of therapies to treat diseases that affect both animals and us, humans. But surely we should try to improve experimental designs, both at the preclinical and clinical levels, to increase the percentage of animal studies that are confirmed in humans