skills/jinko-task-literature-search/evals/files/scientific-use-cases.md

# Scientific Use Cases

This file contains concise scientific briefs for testing `jinko-task-literature-search`. Each use case is limited to scientific context, modeling question, and publication-discovery problem framing.

## Use Case 1 - IL-2 Pathway Modulation In Autoimmune Disease

### Scientific Problem

A pharmacometrics team is preparing a translational model of IL-2 pathway modulation in autoimmune disease. The model focuses on regulatory T-cell expansion and downstream effects on CD8 T cells, helper T-cell subsets, and NK cells.

### Context Of Use

The team needs to understand what public evidence could support model-structure assumptions and later calibration of immune-cell dynamics in healthy and autoimmune disease populations.

## Use Case 2 - Treatment De-Escalation In Metastatic Lung Cancer

### Scientific Problem

Maintenance treatment intensity may be reducible in a front-line metastatic lung cancer regimen, but the risk is loss of clinical efficacy.

### Context Of Use

The team needs evidence to frame treatment de-escalation scenarios, preserve relevant efficacy endpoints, and understand how regimen changes may affect disease-control outcomes.

## Use Case 3 - Long-Term Cardiovascular Outcomes For Market Access

### Scientific Problem

A lipid-lowering therapy has short- and medium-term biomarker effects, but long-term cardiovascular event outcomes may not yet be fully established.

### Context Of Use

The team needs evidence to connect biomarker changes, baseline cardiovascular risk, background therapy, and long-term clinical outcomes for comparative-effectiveness assessment.

## Use Case 4 - Hematological Malignancy Drug Development Support

### Scientific Problem

Early development in hematological malignancies requires translation across preclinical systems, first-in-human evidence, and later-phase clinical endpoints.

### Context Of Use

The team needs evidence to characterize disease dynamics, standards of care, treatment modalities, and response endpoints across hematological malignancy settings.

## Use Case 5 - Patient Population Selection In Acute Myeloid Leukemia

### Scientific Problem

Response variability in acute myeloid leukemia may depend on baseline molecular and cellular characteristics, making broad trial inclusion less efficient.

### Context Of Use

The team needs evidence to understand which baseline descriptors and response markers could support subgroup definition and patient-selection hypotheses.

## Use Case 6 - Trial Design Efficiency In Atopic Dermatitis

### Scientific Problem

Atopic dermatitis has high phenotypic diversity, and treatment response can vary substantially across patient subgroups.

### Context Of Use

The team needs evidence to frame biomarker-informed inclusion strategies and identify disease descriptors relevant to trial enrichment.

## Use Case 7 - Dose-Response For A T-Cell Engager

### Scientific Problem

A bispecific immune-cell engager requires dose selection in combination therapy, balancing tumor response with feasibility for late-stage development.

### Context Of Use

The team needs evidence on target engagement, immune-cell mediated cytotoxicity, tumor dynamics, exposure-response, and combination-treatment context.

## Use Case 8 - Treatment-Induced Neutropenia

### Scientific Problem

A treatment has potential blood toxicity, and alternative regimens may reduce neutropenia while maintaining therapeutic activity.

### Context Of Use

The team needs evidence linking exposure metrics, dosing schedules, neutrophil dynamics, and safety endpoints to evaluate regimen-dependent toxicity risk.

## Use Case 9 - Best-Responder Identification From Heterogeneous Data

### Scientific Problem

Preclinical and early clinical data are heterogeneous, making it difficult to identify patients most likely to benefit before a pivotal trial.

### Context Of Use

The team needs evidence to connect baseline disease features, biomarkers, treatment mechanisms, and clinical response variability for patient-selection hypotheses.

## Use Case 10 - Control-Arm Constraints In Rare Disease Trials

### Scientific Problem

Rare disease trials face recruitment limitations and ethical concerns around assigning scarce patients to control arms.

### Context Of Use

The team needs evidence to characterize natural history, standard-of-care outcomes, patient heterogeneity, and endpoint variability in a small target population.

## Use Case 11 - Comparative Treatment Selection In EGFR-Mutated Lung Cancer

### Scientific Problem

Clinicians need comparative evidence across targeted treatment generations, but new head-to-head trials may be slow, expensive, or impractical.

### Context Of Use

The team needs evidence on disease progression, mutation-defined subgroups, exposure-response, resistance patterns, and clinically relevant time-to-event endpoints.

## Use Case 12 - Combination Treatment In Chronic Hepatitis B

### Scientific Problem

Existing chronic hepatitis B standards of care may be insufficient, and combination regimens introduce many possible dose, duration, and sequence choices.

### Context Of Use

The team needs evidence on viral dynamics, immune response, treatment mechanisms, regimen schedules, and clinical or virological endpoints.

## Use Case 13 - Population Extrapolation Across Age And Region

### Scientific Problem

Regulatory needs may require evidence across age groups or geographic populations when generating complete clinical data in every subgroup is impractical.

### Context Of Use

The team needs evidence on age-dependent physiology, ethnicity- or region-dependent variability, disease progression, PK differences, and endpoint comparability.

## Use Case 14 - Route-Of-Administration Switch During Development

### Scientific Problem

Safety or tolerability observations during development may require switching from one route of administration to another while preserving intended exposure and activity.

### Context Of Use

The team needs evidence on route-specific PK, bioavailability, exposure-response, safety endpoints, and dose-equivalence considerations.

## Use Case 15 - Treatment Regimen Optimization Before A Pivotal Trial

### Scientific Problem

An alternative regimen may be more effective or better tolerated than a classical regimen, but direct comparison in the pivotal trial may not be feasible.

### Context Of Use

The team needs evidence on regimen schedules, exposure patterns, efficacy endpoints, adverse effects, and treatment-duration effects.