Automated Thematic Analysis for Clinical Qualitative Data: Iterative Codebook Refinement with Full Provenance

Thematic analysis (TA) is a widely used qualitative approach for uncovering latent meanings in unstructured text data. TA provides valuable insights in healthcare but is resource-intensive. Large Language Models (LLMs) have been introduced to perform TA, yet their applications in high-stakes healthcare settings, particularly for qualitative clinical interview analysis, remain limited. Here, we propose TAMA: A Human-AI Collaborative Thematic Analysis framework using Multi-Agent LLMs for clinical interviews. We leverage the scalability and coherence of multi-agent systems through structured conversations between agents and coordinate the expertise of cardiac experts in TA. Using interview transcripts from parents of children with Anomalous Aortic Origin of a Coronary Artery (AAOCA), a rare congenital heart disease, we demonstrate that TAMA outperforms single-agent LLM TA approaches, achieving higher thematic hit rate, coverage, and distinctiveness. TAMA demonstrates strong potential for automated TA in clinical settings by leveraging multi-agent LLM systems with human-in-the-loop integration by enhancing quality while significantly reducing manual workload. The full implementation is publicly available at https://github.com/Charlie-Yi-SJ/TAMA.

Large Language Models (LLMs) offer new possibilities for scaling qualitative analysis, but existing applications often provide limited methodological transparency regarding how qualitative methods are translated into computational procedures. This paper presents an auditable and privacy-preserving computational operationalization of inductive and latent Thematic Analysis (TA). This paper first derives five design principles from the methodological requirements of TA and the conditions introduced by LLM-based inference: preserving interpretative context, maintaining traceable relationships between empirical material and analytical outputs, representing analytical constructs and reasoning explicitly, constraining LLM inference to interpretative tasks, and enabling privacy-preserving local deployment. Second, it presents a proof-of-concept for a two-phase workflow that operationalizes these principles by combining interpretative LLM inference with deterministic procedural control to generate codes, analytical justifications, themes, and theme descriptions while preserving explicit links to the source material. Third, it proposes an evaluation framework combining structural comparison with human-led TA and independent expert assessment of analytical quality. The evaluation is conducted on semi-structured Danish interview transcripts. and the results shows that the workflow produces code-level outputs with coverage broadly comparable to human annotations and highly rated analytical justifications, while generating a more compressed thematic structure characterized by fewer and broader themes. The findings demonstrate the feasibility of auditable LLM-supported TA through a modular workflow designed to scale to larger datasets, accommodate different LLMs, and support transfer across research domains, with domain adaptation primarily requiring adjustments to the prompting strategy.

Thematic analysis is difficult to scale: manual workflows are labor-intensive, while fully automated pipelines often lack controllability and transparent evaluation. We present CentaurTA Studio, a web-based system for self-improving human--agent collaboration in open coding and theme construction. The system integrates (1) a two-stage human feedback pipeline separating simulator drafting and expert validation, (2) persistent prompt optimization that distills validated feedback into reusable alignment principles, and (3) rubric-based evaluation with early stopping for process control. Across three domains, CentaurTA achieves the strongest performance in both Open Coding and Theme Construction, reaching up to 92.12% accuracy and consistently outperforming baseline systems. Agreement between the rubric-based LLM judge and human annotators reaches substantial reliability (average $κ= 0.68$). Ablation studies show that removing the feedback loop reduces performance from 90% to 81%, while eliminating the Critic or early stopping degrades accuracy or increases interaction cost. The full system reaches peak performance within 10 iterative rounds (about 25 minutes), demonstrating improved efficiency over expert-only refinement.