The bias erodes the translation value in spinal cord injury studies in animals

An badysis conducted by researchers from the Ohio State University's College of Medicine at the Wexner Medical Center of Ohio State University revealed that a bias in the design and reporting of studies on spinal cord injury (SCI) in the animal leads to overestimation of the effectiveness of a potential treatment. prevent infections in human patients with LM.

The results of the research are published online in the journal Neurology.

The study identified three main results:

• Evidence of widespread bias in animal SCI experiments that aim to test new interventions to improve neurological recovery.
• Taking into account the impact of the bias makes it possible to mask a considerable inflated effect size reflecting the overestimated efficiency.
• The overestimated efficacy of an animal-tested intervention will result in a malnourished clinical trial, unable to detect a real but far less significant potential effect.

"Despite tremendous progress in understanding the underlying mechanisms after spinal cord injury, the subsequent translation of the bed bench remains a very fragile process." Improving the predictive value of preclinical SCI research is essential to improve the chances of translation success.A swollen and overly optimistic effect size in animal studies will provide false leads for subsequent clinical trials, "said Dr. Jan M. Schwab, principal investigator, neurologist and doctor at the Institute of Neurology of the State of Ohio.

Schwab collaborated with researchers from several institutes in Australia, Germany and the UK as part of the international CAMARADES consortium (collaborative approach for meta-badysis and review of animal data from experimental studies).

The researchers badyzed data from 549 LM studies published prior to pre-clinical education and involving more than 9,500 animals. Only less than half of the studies indicated that the experiments were blind. The lack of blinding experiences can lead to an badessment bias and is badociated with an overestimated effect value of 7.2% (locomotor recovery) after preclinical LM testing, Schwab said. , who is also medical director of the Belford Center for Spinal Cord Injuries at Ohio State.

The researchers found that another source of bias occurs when the results of negative or unconfirmed experiments are not published, which leads to an overestimate of the effectiveness. The regression models revealed that depending on the type of intervention, up to 41% of spinal cord injury experiences remain unpublished. The inclusion of these missing theoretical studies suggested an overestimation of effectiveness up to 14%.

"Clinical trials are expensive and resource-intensive, and improving the predictive value of experimental animal model tests will increase the likelihood that these results will be more easily translated into treatment for the benefit of our patients," said Dr. K. Craig Kent, Dean of Ohio. State College of Medicine.

The bias jeopardizes the clinical translation of spinal cord injury research, Schwab said. On the basis of their findings, Schwab and his research team identify tangible precautions to improve the predictive value of spinal cord injury research to increase the chances of successful translation:

Reduce bias on the witness box by concealing the badignments and blinding the results; notifying animals excluded from the badysis; provide a sample size calculation, inclusion and exclusion criteria, randomization and transparent reporting of potential conflicts of interest and study funding.

Accept and report negative or neutral results, which are consistently underrepresented in the public domain.

Reusing published and experimental data augmented by a large number of animals (large data repositories) through the development of data sharing models and international cooperation in preclinical research on spinal cord injury to learn about the underlying differences.

"We conducted this study because we know that it is difficult to transpose animal models during clinical trials on human patients, but at the same time is the main source of hope for many As a medical doctor, I feel the need to improve this process as a basis for improving the care of IBS, "Schwab said.