Related Experiment Video
Updated: Jan 6, 2026
Quantitative Immunofluorescence to Measure Global Localized Translation
Published on: August 22, 2017
Building Robustness into Translational Research
Betül R Erdogan1, Martin C Michel2
1Department of Pharmacology, School of Pharmacy, Ankara University, Ankara, Turkey.
Abstract:
Nonclinical studies form the basis for the decision whether to take a therapeutic candidate into the clinic. These studies need to exhibit translational robustness for both ethical and economic reasons. Key findings confirmed in multiple species have a greater chance to also occur in humans. Given the heterogeneity of patient populations, preclinical studies or at least programs comprising multiple studies need to reflect such heterogeneity, e.g., regarding strains, sex, age, and comorbidities of experimental animals. However, introducing such heterogeneity requires larger studies/programs to maintain statistical power in the face of greater variability. In addition to classic sources of bias, e.g., related to lack of randomization and concealment, translational studies face specific sources of potential bias such as that introduced by a model that may not reflect the full spectrum of underlying pathophysiology in patients, that defined by timing of treatment, or that implied in dosing decisions and interspecies differences in pharmacokinetic profiles. The balance of all these factors needs to be considered carefully for each study and program.
Insights
Preclinical studies require careful design to ensure therapeutic candidates translate to human patients. Incorporating animal model heterogeneity and addressing potential biases are crucial for ethical and economic success in drug development.
Area of Science:
- Preclinical research
- Translational science
- Drug development
Background:
- Nonclinical studies are foundational for advancing therapeutic candidates to clinical trials.
- Ensuring translational robustness in these studies is vital for ethical and economic considerations.
- Heterogeneity in patient populations necessitates reflection in preclinical study designs.
Purpose of the Study:
- To highlight the importance of translational robustness in nonclinical studies.
- To identify key factors influencing the predictive value of preclinical research for human outcomes.
- To emphasize the need for careful consideration of biases in translational studies.
Main Methods:
- Review of principles for designing robust preclinical studies.
- Analysis of factors contributing to translational success or failure.
- Discussion of sources of bias specific to translational research.
Main Results:
- Findings confirmed across multiple species increase the likelihood of human relevance.
- Incorporating heterogeneity (e.g., animal strains, sex, age, comorbidities) enhances model translatability but requires larger sample sizes.
- Potential biases include model limitations, treatment timing, dosing, and pharmacokinetic differences.
Conclusions:
- Translational robustness in nonclinical studies is paramount for successful drug development.
- Preclinical study designs must account for biological variability and potential biases.
- A balanced approach considering all factors is essential for each study and program.
Related Concept Videos
02:07Improving Translational Accuracy
02:07Improving Translational Accuracy
01:29Translational Regulation
02:28Leaky Scanning
01:20Cotranslational Protein Translocation
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
02:24Ribosome Profiling
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...