Kiran Bhattacharyya, Sreeram Kamabattula · PLOS Digital Health 2026 · 2026
DOI: 10.1371/journal.pdig.0001182
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Deploying large language models (LLMs) in clinical settings is limited by security, reliability, latency, and accessibility concerns that favor smaller, on-device or on-premise models. However, these smaller models may struggle to meet accuracy requirements. While fine-tuning and retrieval-augmented generation (RAG) can improve domain-specific accuracy, these methods require additional labeled data, technical skill, and infrastructure. In contrast, test-time scaling —allocating extra token-budget during inference—offers a training-free alternative to increasing accuracy. However, the trade-offs between these strategies and their interaction with model size remain poorly understood for medical reasoning. To address this gap, we compare three approaches—test-time scaling, fine-tuning, and context grounding—using the Gemma and MedGemma family of LLMs (Gemma-3 1B, Gemma-3 4B, Gemma-3 27B, MedGemma-4B, and MedGemma 27B) and evaluate these systems across common biomedical question-answering (QA) datasets and a set of recently released medical exam questions with the performance of practicing clinicians available for comparison. We test baseline prompts (direct answer, Chain-of-Thought, and self-consistency) while introducing a new prompting method we call “prompt-chaining for continuous reflection” (PCCR) that forces inference time minimum token-generation budgets. We assess accuracy and tokens-generated, allowing us to investigate the accuracy–efficiency trade-offs across prompting, context-grounding, fine-tuning, and model scales. We discover equivalency point configurations where a smaller model’s accuracy falls within one 95% confidence interval of a larger model’s (typically within 1–4 percentage points) reached through increased reasoning budgets, context-grounding, or fine-tuning. Specific effects are apparent and statistically supported: the benefit of medical fine-tuning grew from +4.6 to +15.7 percentage points (non-overlapping 95% CIs) when paired with self-consistency, and enforced extended reasoning raised MedGemma 27B accuracy from 58.1% to 80.1% ( p < 10 -5 ) in the absence of context. We also identify an “overthinking” inflection: when high-quality context is available, extended reasoning beyond roughly 128–256 tokens degrades accuracy by 7–13 percentage points. Using these empirical results, we formulate a general framework with equations to balance cost-benefit trade-offs when engineering LLM-based systems for medical reasoning and QA. We recommend generalizable configurations, designs, and patterns to achieve accuracy and efficiency objectives for example use-cases relevant to healthcare organizations.
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