Proven Solutions for the Real World
Since 2015, Target RWE has proven real-world evidence solutions across the drug development life cycle for an array of partners
Drug & Clinical Product Development Lifecycle Phases
Pre-Clinical
Includes proof of concept, feasibility, biomarker validation
Clinical
Includes external control arms, natural disease progression, validation studies
In-Market
Includes post-marketing commitments, label expansions
Pre-Clinical
Includes proof of concept, feasibility, biomarker validation
Clinical
Includes external control arms, natural disease progression, validation studies
In-Market
Includes post-marketing commitments, label expansions
Case Studies
Biomarkers and Response to Therapy
Samples to Evaluate Viral Resistance to HCV Treatment Outcomes
Samples and Data Used to Support Development of Self-Testing & Point of Care Diagnostic Platform for Early Detection of HCV RNA Infection
Biomarkers and Response to Therapy
Challenge
In clinical research, a significant challenge arises from the variability in patient responses to treatments. Some patients may show positive results, while others do not respond at all. The uncertainty of therapeutic response makes it difficult to identify, in advance of treatment, which individuals are likely to require alternative therapies, leading to inefficient trial designs, wasted resources, and potentially compromised outcomes.
Furthermore, the inability to accurately select participants can increase trial costs and unnecessarily expose patients to treatments that may not provide any benefit. Partners sought to understand factors of non-response to advanced first line therapies in patients with atopic dermatitis.
Solution
- The solution included pairing detailed analyses of clinically characterized patients (events of interest, lab results, and key clinical outcomes endpoints) with biomarker testing from tape strip samples of both lesional and non-lesional skin.
Impact
This data-driven strategy accelerated the identification of relevant biomarkers, aiding in the stratification of patients based on their risk and potential for therapeutic response. This approach can enhance patient outcomes, reduce trial costs, and contribute to faster drug development cycles.
Samples to Evaluate Viral Resistance to HCV Treatment Outcomes
Challenge
In the rapidly developing HCV treatment landscape, several targets for antiviral therapy were coming to market in a short time period. Despite the availability of multi-targeted combination therapies, some patients did not respond with viral failure attributed to both advanced disease and resistant variants. Availability of resistance testing was limited in clinical use despite clinical trial data demonstrating that baseline resistance could play a role in HCV treatment response. This created challenges for clinicians to select regimens for patients that would offer the highest chance for viral eradication.
Solution
- Rapid evaluation of baseline serum samples that assessed for the presence and type of baseline vial resistant variants from patients enrolled in HCV-TARGET as new therapies came into clinical use and were presented in the study.
- Baseline resistance results were paired with HCV treatment data and therapy outcomes.
Impact
The study confirmed baseline resistance findings observed in clinical trials among multiple subpopulations of patients with HCV. The study also demonstrated new findings that could impact clinical decision-making both in therapy selection (some patients had baseline resistance to 2 or more available drug classes) and for treatment management (longer treatment duration strategies resulted in higher cure rates than patients managed strictly to the labeled duration).
Related Resource
- Wang, G.P., Terrault, N., Reeves, J.D. et al. Prevalence and impact of baseline resistance-associated substitutions on the efficacy of ledipasvir/sofosbuvir or simeprevir/sofosbuvir against GT1 HCV infection. Sci Rep 8, 3199 (2018). https://doi.org/10.1038/s41598-018-21303-2
Samples and Data Used to Support Development of Self-Testing & Point of Care Diagnostic Platform for Early Detection of HCV RNA Infection
Challenge
With multiple available highly effective HCV therapies, the field and health organizations focused in HCV adopted a test and treat strategy to quickly identify and treat infected patients to prevent transmission to others and disease sequelae. Most available screening tests are based in antibody detection which can take 2 months post-infection to detect (negatively impacting treatment for acute infection). Direct viral detection testing is faster, but still lacks sensitivity and specificity and requires access to expensive instrumentation.
Clinicians and patients need a rapid detection system that can be easily and cost effectively deployed to provide results within minutes to direct early clinical action and treatment decisions. CRISPR technology offers the potential to develop viral detection assays that are highly sensitive and specific and point of care diagnostic tools for a simplified viral testing application.
Solution
- Validate CRISPR-based technology paper assay tool developed by collaborative researchers for rapid HCV diagnosis in well-characterized patients with HCV.
- HCV-infected serum samples and clinical data from HCV-TARGET studies were evaluated against the assay with healthy control samples to evaluate proof of concept and further validate the work to determine sensitivity and specificity.
Impact
HCV sample validation work demonstrated feasibility of the proof of concept SPLENDID assay (single-pot LAMP-mediated engineered BrCas12b for nucleic acid detection of infectious diseases). The simplicity of the test would enable performance in low-resource areas and quickly offer robust sensitivity and specificity (in about 20 mins.). The assay could also be configured for other viruses and still needs refinements to optimize for practical use.
Related Resources
- Santosh R. Rananaware, Katelyn S. Meister, Grace M. Shoemaker, Emma K. Vesco, Luke Samuel W. Sandoval, Jordan G. Lewis, August P. Bodin, Vedant N. Karalkar, Ian H. Lange, Brianna Lauren Maria Pizzano, Minji Chang, M. Reza Ahmadimashhadi, Sarah J. Flannery, Long. T. Nguyen, Gary P. Wang, Piyush K. Jain. PAM-free diagnostics with diverse type V CRISPR-Cas systems. medRxiv 2024.05.02.24306194; doi: https://doi.org/10.1101/2024.05.02.24306194
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Nguyen, Long T. et al. Engineering highly thermostable Cas12b via de novo structural analyses for one-pot detection of nucleic acids. Cell Reports Medicine, Volume 4, Issue 5, 101037