Clinical diagnosis is fundamentally interactive and incremental, yet the dominant paradigm for evaluating Large Language Models (LLMs) in medicine remains static QA benchmarks or template-based dialogues. These benchmarks say little about whether a model can serve as a diagnostic agent in a dynamic clinical encounter, with LLMs showing significant accuracy and reliability degradation in multi-turn settings. To address this issue, we present MTDiag, a large multi-turn diagnostic dialogue dataset constructed from three heterogeneous sources: DDXPlus, MIMIC-IV, and published case reports (AJCR), covering common ED presentations as well as long-tail rare and atypical conditions. All cases are normalized into a canonical PatientVector schema anchored in the most comprehensive and widely-adopted medical knowledge bases (UMLS concept identifiers, with ICD-10 diagnosis codes). We release the PatientVector schema, a UserLM-8B-based utterance-generation pipeline, and the physician-validated dataset that converts structured clinical evidence into natural-language utterances. Importantly, we introduce and motivate clinical knowledge-grounded metrics for evaluating LLMs as diagnostic agents, beyond diagnostic accuracy, for the task of multi-turn differential diagnosis.

With Large Language Model (LLM)-based applications becoming more common due to strong performance across many tasks, prompt optimization has emerged as a way to extract better solutions from frozen, often commercial LLMs that are not specifically adapted to a task. LLM-assisted prompt optimization methods provide a promising alternative to manual/human prompt engineering, where LLM “reasoning” can be used to make them optimizing agents. However, the cost of using LLMs for prompt optimization via commercial APIs remains high, especially for heuristic methods like evolutionary algorithms (EAs), which need many iterations to converge, and thus, tokens, API calls, and rate-limited network overhead. We propose GenDLN, an open-source, efficient genetic algorithm-based prompt pair optimization framework that leverages commercial API free tiers. Our approach allows teams with limited resources (NGOs, non-profits, academics, ...) to efficiently use commercial LLMs for EA-based prompt optimization. We conduct experiments on CLAUDETTE for legal terms of service classification and MRPC for paraphrase detection, performing in line with selected prompt optimization baselines, at no cost.