Large language model-generated patterns for epidemiological modeling: a multi-benchmark evaluation framework
Organizations: Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, 1603 W. Taylor St., Chicago, IL, USA · Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
Abstract
Representing individual-level behavioral heterogeneity is challenging in epidemiological modeling, particularly when empirical behavioral data are sparse. We assess the potential of large language model (LLM)-generated behavioral outputs in addressing this challenge, using hepatitis C virus-related behaviors among people who inject drugs as a case study. Correspondence with epidemiological patterns was evaluated using external benchmarks: literature-informed association directions, correlations from an agent-based model (ABM), and survey associations. Across three LLMs, unconditional directional recovery across 28 retained literature-informed associations was 46-68%, compared with 82-93% agreement when LLMs were directly asked to classify the same associations. Mean absolute differences from ABM and survey correlation patterns were 0.11-0.13 and 0.15-0.18, respectively. Together, these findings show partial alignment between LLM-generated behavioral relationships and epidemiological evidence, despite higher knowledge-probe agreement. More systematic evaluation is needed before incorporating LLM-generated behavioral outputs into epidemiological models that simulate transmission dynamics.
Figures & tables
| Outcome variable | Definition | Type |
|---|---|---|
| Injection frequency | Average weekly injections | Count |
| Network in-degree | Unique individuals from whom the person received a used syringe | Count |
| Network out-degree | Unique individuals to whom the person gave a used syringe | Count |
| Partners | Unique individuals with at least one shared injection event | Count |
| Non-injection routes | Non-injection use (smoking or snorting) | Count |
| Overdose | Non-fatal overdoses | Count |
| Variable pairs Direction Evidence | |||
|---|---|---|---|
| Homeless | Public injecting | OR = 4.23 (3.17–5.65) (Khezri et al., 2025) (meta-analysis) Positive association reported (Arum et al., 2021) (systematic review) | |
| Homeless | Injection frequency | OR = 1.40 (1.08–1.82) (Ballard et al., 2025) Positive association reported (Arum et al., 2021) (systematic review) | |
| Homeless | Receptive sharing | Positive association reported (Arum et al., 2021) (systematic review) aOR = 1.93 (1.67–2.23) (Hotton et al., 2021) aPR = 1.26 (1.15–1.39) (Kan et al., 2026) (cohort) RR = 1.18 (0.60–2.39) (Morris et al., 2014) (cohort) | |
| Homeless | Positive HCV status | aHR = 1.86 (1.32–2.55) (Morris et al., 2020) (cohort) aRR = 1.64 (1.43–1.89) (Arum et al., 2021) (meta-analysis) aHR = 1.46 (1.21–1.76) (Gahrton et al., 2024) (cohort) aOR = 1.55 (1.50–1.61), currently homeless versus at risk of homelessness among veterans (Byrne et al., 2019) HR = 1.20 (0.60–2.30) (Hahn et al., 2002) (cohort) | |
| Homeless | Overdose | OR = 1.64 (1.49–1.81) (Dunne et al., 2025) (meta-analysis) aPR = 1.64 (1.49–1.79) (Marcus et al., 2022) aOR = 1.36 (0.70–2.63) (Gunaratne et al., 2026) aOR = 1.29 (0.82–2.04) (Guarino et al., 2023) Positive association reported (Arum et al., 2021; Austin et al., 2021) (systematic reviews) | |
| Homeless | Injection partners | aRR = 1.48 (1.25–1.76) (Hotton et al., 2021) | |
| Metric | Claude Sonnet 4.6 | DeepSeek v3.2 | GPT-OSS-120B |
|---|---|---|---|
| LLM outputs vs. literature | |||
| Estimable targets | 22/28 (78.6%) | 17/28 (60.7%) | 28/28 (100.0%) |
| Conditional directional recovery | 18/22 (81.8%) | 13/17 (76.5%) | 19/28 (67.9%) |
| Unconditional directional recovery | 18/28 (64.3%) | 13/28 (46.4%) | 19/28 (67.9%) |
| Knowledge-probe agreement | 26/28 (92.9%) | 25/28 (89.3%) | 23/28 (82.1%) |
| LLM outputs vs. ABM data | |||
| Variable pairs Direction Evidence | |||
|---|---|---|---|
| Public injecting | Positive HCV status | OR = 1.55 (1.18–2.02) (Khezri et al., 2025)(meta-analysis) aOR = 1.91 (1.33–2.75) (Eckhardt et al., 2017) | |
| Public injecting | Overdose | OR = 2.51 (2.01–3.13) (Khezri et al., 2025) (meta-analysis) | |
| Public injecting | Receptive sharing | OR = 2.41 (1.97–2.94) (Khezri et al., 2025)(meta-analysis) | |
| Public injecting | Injection frequency | OR range across studies = 1.96–5.34 (Khezri et al., 2025) (systematic review) | |
| Public injecting | Treatment | OR = 0.61 (0.48–0.76) for methadone maintenance treatment (longitudinal study reported in Khezri et al., 2025) | |
| Receptive sharing | Positive HCV status | HR = 2.1 (1.2–3.7) (Hahn et al., 2002) (cohort) PRR = 1.94 (1.53–2.46) (Pouget et al., 2012) (meta-analysis) aHR = 1.79 (1.44–2.22) (Gahrton et al., 2024) (cohort) Indirect evidence: aRR = 1.53 (1.01–2.31) for syringe sharing, without distinguishing receptive from distributive sharing (Mackesy-Amiti et al., 2023; baseline analysis) aPR = 1.20 (1.09–1.33) (Kan et al., 2026) (cohort) | |
| Model | Variable pair | Original | Paraphrased |
|---|---|---|---|
| Claude Sonnet 4.6 | Homelessness / Non-injection routes | decrease | uncertain |
| DeepSeek v3.2 | Non-injection routes / HCV status | decrease | increase |
| GPT-OSS-120B | Treatment / Non-injection routes | mixed | increase |
| GPT-OSS-120B | Non-injection routes / Overdose | increase | decrease |
| GPT-OSS-120B | HCV status / Overdose | uncertain | mixed |
| GPT-OSS-120B | Receptive sharing / Overdose | mixed | increase |
| Outcome | Claude Sonnet 4.6 | DeepSeek v3.2 | GPT-OSS-120B |
|---|---|---|---|
| Overdose | 49.1 | 100.0 | 32.1 |
| Public injecting | 100.0 | 74.6 | 98.7 |
| Receptive sharing | 69.6 | 94.6 | 40.2 |
| Injection partners | 71.4 | 90.6 | 35.3 |
| Network in-degree | 97.8 | 96.9 | 71.9 |
| Network out-degree | 97.3 | 99.1 | 67.4 |