The Value of Tracking Clinical Trial Results for Preclinical In Vivo Study Design
Promising preclinical results don't always translate into clinical success, leaving researchers with uncertainties when it comes to preclinical study design. However, outcomes from previous clinical trials can provide valuable insights into which approaches are most likely to succeed. This blog explores how examining clinical trial results can inform preclinical study design, reduce translational risk, and improve research efficiency throughout drug development.
Understanding the Preclinical to Clinical Translation Gap
Researchers are fully aware that only a small proportion of therapies showing promise in preclinical studies successfully translate to the clinic. In fact, only around 5% of therapies tested in animals ultimately receive regulatory approval for human use1. Researchers may view the translation of preclinical findings into clinical success as unpredictable, with limited scope for anticipating outcomes or understanding why some therapies succeed while others fail. However, often-overlooked information can provide valuable insights to guide preclinical study design and potentially remove some of the uncertainty.
Published scientific literature can provide researchers with valuable information about available preclinical models, their suitability for specific research questions, and how best to implement them. However, research and methods papers offer limited insight into which approaches have translated to successful (or unsuccessful) human clinical trials. Understanding how projects built on different preclinical study designs have fared in the clinical pipeline can help researchers make more informed decisions when designing their own work.
Clinical Trial Results as a Validation Signal
Whether a trial succeeds or fails, its results offer useful insight for researchers working with similar models, indications, or mechanisms of action. If a trial is successful, it can point researchers towards an appropriate model for a specific indication or help to guide dosage regimens where a test compound has a similar mechanism of action.
Failed trials may offer even greater value by allowing researchers to learn the lessons of unsuccessful projects without paying the price in lost time and resources to discover them firsthand. These trials highlight the outcomes that preclinical work failed to predict and can reveal unsuitable models, poorly chosen endpoints, or unanticipated safety issues.
Examining results across multiple similar clinical trials can provide even deeper insights. By comparing the outcomes of trials that were informed by similar preclinical study designs, researchers can better assess the strengths and limitations of those approaches and identify how subtle differences may influence clinical success.
H2: Preclinical Study Design Factors Informed by Trial Results
Reviewing clinical trial outcomes alongside the preclinical study designs that informed them can provide valuable insights into the factors that may influence clinical success or failure.
- Model selection: Clinical trial results can help researchers identify which species, strains, or disease models most accurately reflect human responses to a given target or indication, informing more effective in vivo study design. Conversely, they can highlight models that looked convincing preclinically but did not predict clinical outcomes.
- Dose and exposure: Researchers can compare preclinical dosing and exposure with the doses that were tolerated and effective in humans and refine dose ranges and exposure targets earlier in the pipeline for preclinical drug development.
- Endpoints: Teams can see which preclinical endpoints correlated with clinical endpoints and avoid relying on measures that have not translated.
- Safety: Researchers can gain a better understanding of which toxicities appeared in humans and whether animal studies flagged them. This helps to inform better monitoring protocols for preclinical study design.
- Target indication: Teams can use clinical outcomes to see which indications a mechanism has actually worked in, not just where it looked promising preclinically.
The Benefits of Translational Insights for Preclinical Research
The clearest benefit of assessing clinical outcomes and their associated preclinical development studies is avoiding designs that have already failed to translate, which saves time and resources in preclinical to clinical translation. Insights may reveal opportunities where a small tweak could enhance translatability rather than forcing teams to go back to the drawing board. Simply being aware of issues that may emerge can mean a smoother and more efficient development process, which in turn leads to greater resource efficiency.
The 3Rs
By making more informed decisions about preclinical study design, researchers can align more closely with the 3Rs (Replacement, Reduction, and Refinement) and improve animal welfare2. Knowing what has already been tested helps teams avoid unnecessarily repeating previous studies, which supports the Reduction principle. It also shows where New Approach Methodologies (NAMs) could replace animal models or complement them. Finally, it can highlight opportunities to refine experimental setups, leading to more reliable outcomes.
Translational Insights Aren’t Everything
While translational insights can be extremely valuable, they do not guarantee success. Reporting bias, for example, means the results of failed trials may not always be available. Greater clinical trial transparency is improving this, but researchers should not assume that a lack of published failures means a genuine lack of failures. Secondly, preclinical design is not the only factor that drives clinical trial success. Thus, researchers should be wary of attributing failed translation solely to preclinical study design when the reasons for failure could lie in trial design, patient selection, or other clinical factors.
Combining Translational Insights With a Comprehensive Literature Review
Researchers can make more informed preclinical study design decisions by drawing on a diverse range of evidence, including clinical trial insights and published scientific literature. The ModernVivo platform automatically notes when a preclinical paper that appears in a user’s search for their preclinical study design has been cited in a human clinical trial. It also lists all clinical trials for any intervention that was cited in a preclinical dataset for study design. By providing this information, ModernVivo helps teams optimize preclinical study design and can improve their chances of bringing important therapies to the clinic to benefit patients.
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References
1. Ineichen BV, Furrer E, Grüninger SL, Zürrer WE, Macleod MR. Analysis of animal-to-human translation shows that only 5% of animal-tested therapeutic interventions obtain regulatory approval for human applications. PLoS Biol. 2024;22(6):e3002667. doi:10.1371/journal.pbio.3002667
2. Center for Drug Evaluation and Research. CDER Streamlined Nonclinical Studies and Acceptable New Approach Methodologies (NAMs). FDA. September 18, 2026. Accessed October 21, 2026. https://www.fda.gov/drugs/science-and-research-drugs/cder-streamlined-nonclinical-studies-and-acceptable-new-approach-methodologies-nams