Critical Path Generator
The Critical Path Generator tool will assist scientist in planning and structuring a target assessment project. The CP Generator will help to arrange important target assessment blocks into a project-specific Critical Path. Using a query form and different sets of guiding questions (Critical Path Questions (CPQs) & Experimental Approach Questions (EAQs)), the CP Generator identifies strengths and weaknesses of a translational project and provides support how to invest critical resources in an optimal way.
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Target-Related Safety (TRS)
On-target or target-related toxicity refers to exaggerated and adverse effects, that result from manipulating the inherent biological function of the target of interest that is different from therapeutic intervention. In contrast, off-target toxicity refers to adverse effects based on modulation of other targets, related or not to the biological target of interest
Early identification of potential target-related safety risks and increased understanding of underlying molecular mechanisms can guide drug development and help derive mitigation strategies to facilitate project progression .
Thus, the purpose of this Assessment Block is to identify potential unintended consequences of target modulation and to confirm and characterize unavoidable on-target toxicities in a timely manner as well as to facilitate anticipation, monitoring and management of potential clinical adverse events.
 Guengerich FP. Mechanisms of drug toxicity and relevance to pharmaceutical development. Drug Metabolism and Pharmacokinetics (2011)
Drug discovery and development & Safety and toxicity Abstract PMID: 20978361
 Rudmann DG. On-target and off-target-based toxicologic effects. Toxicologic Pathology (2013)
Safety and toxicity Abstract PMID: 23085982
 Roberts RA. Understanding drug targets: no such thing as bad news. Drug Discovery Today (2018)
Target identification and validation Abstract PMID: 29803936
Microbial Targets (MT)
This assessment block addresses general aspects and attributes of non-human drug targets, with special emphasis on bacterial and viral target molecules.
Identification and validation of the role of a molecular target in the observed phenotypic responses (target deconvolution) can greatly facilitate subsequent target-specific optimization of pharmacological properties through structure–activity relationship (SAR) studies. In addition, it can enable species-selectivity as well as target-based side effects to be addressed, thereby potentially reducing later-stage attrition.
Thus, in cases where antimicrobial targets have been established, the aspects discussed in this Assessment Block may need to be considered.
Strategic Issues (SI)
One key question is how to favourably position validated targets for the large-scale (external) investment required to develop new therapeutic products.
Thus, it is important to analyse strategic options for managing and protecting IP associated with validated targets, the competitor landscape, and medical as well as commercial needs. The aim is to generate valuable data for business and commercialization plans, attractive licensing propositions for commercial partners, as well as for potential investors.
For a successful translational target assessment project, some of the decision-making needs to be led by drug discovery concerns, e.g. the protection of intellectual property. Therefore, the aspects discussed in this Assessment Block should be considered when bridging the translational gap between where university research often ends, and commercial drug development begins.
Data Quality and Robustness (DQaR)
Several steps in drug discovery and development need to be compliant with established GxP-based quality requirements such as GLP toxicology, but analogous standards for non-regulated areas of drug discovery and target assessment are not available. A specialized set of quality guidelines is needed that specifically focuses on study design, unbiased conduct, statistical analysis and transparent reporting and that will support academic-industry interactions by aligning quality criteria in preclinical research.
Consequently, questions related to data quality are crucial for the success of translational projects and need to be addressed especially for decision-enabling processes.
The data quality questions highlight the importance of increasing the internal validity of key experiments, including crucial processes such as blinding and randomisation, appropriate statistical power analyses and primary endpoint definitions. They also emphasize the need to establish external validity by multiple independent replicates as well as several orthogonal technologies, which provide greater confidence and converging evidence for the therapeutic relevance of a target.
In addition, a major requirement to ensure robust research outcomes is that researchers routinely question reagent purity, authenticate cell lines, validate antibodies and animal models, and include appropriate controls when planning and conducting an experiment.