Large-Scale Biomedical RAG: Corpus Scaling, Document Representation, and Efficiency Trade-offs

Retrieval-Augmented Generation (RAG) offers a well-established path to grounding large language model (LLM) outputs in external knowledge, yet the question of which retrieval strategy works best in a high-stakes domain such as biomedicine has not received the controlled, multi-metric treatment it deserves. This paper presents a systematic empirical comparison of five retrieval strategies -- Dense Vector Search, Hybrid BM25 + Dense retrieval, Cross-Encoder Reranking, Multi-Query Expansion, and Maximal Marginal Relevance (MMR) -- within a biomedical question-answering RAG pipeline. All strategies share a fixed generation model (GPT-4o-mini), a common vector store (ChromaDB), and OpenAI's text-embedding-3-small embeddings, ensuring that observed differences are attributable to retrieval alone. Evaluation is conducted on 250 question-answer pairs drawn from a preprocessed subset of the BioASQ benchmark (rag-mini-bioasq) using four DeepEval metrics: contextual precision, contextual recall, faithfulness, and answer relevancy, each reported with 95% confidence intervals. A no-context ablation is included as a lower bound. Cross-Encoder Reranking achieves the best composite score (0.827) and highest contextual precision (0.852), confirming that query-document interaction yields measurable retrieval gains. Multi-Query Expansion, despite its recall-oriented design, produces the weakest contextual precision (0.671), suggesting naive query diversification introduces retrieval noise. MMR sacrifices answer relevancy for diversity, while the Dense baseline (composite 0.822) falls within 0.005 points of the top strategy. All RAG conditions dramatically outperform the no-context ablation on answer relevancy (0.658-0.701 vs. 0.287), confirming the practical value of retrieval. The full pipeline, hyperparameters, and evaluation code are publicly available.

Retrieval-augmented generation (RAG) spans lexical and dense retrieval, graph-based indexing, and agentic search, but these paradigms are usually evaluated on different benchmarks at one corpus size, leaving their accuracy-cost scaling unclear. To bridge this gap, we present a controlled study that varies corpus size along 28 strictly nested tiers spanning roughly 450-fold, while holding questions and a fixed bedrock of relevant and adversarial documents unchanged. Under one reader model and one judging protocol, we measure official accuracy, construction and query tokens, and latency. The results reveal a scale-dependent crossover rather than an unconditional winner. File-System Agent leads at the smallest shared tiers, but its sequential exploration costs 39 times more query tokens at the bedrock and becomes less effective as the search space grows. Around 10 million corpus tokens, BM25 overtakes it and leads at every larger shared tier, with a margin approaching 20 points at full scale. BM25 also anchors the low-cost end of the Pareto frontier without LLM-based construction. Dense retrieval remains efficient but less accurate, whereas graph-based RAG encounters construction walls before deployment scale and its scalable variants remain below BM25 at shared tiers. Overall, corpus growth increasingly favors global candidate ranking: lexical retrieval is the strongest scalable default, while agentic reasoning works best after ranked discovery rather than in place of it.

Medical question answering is a high-stakes setting where factual errors can have serious consequences. Retrieval-augmented generation (RAG) is widely viewed as a promising solution, and prior work has reported substantial gains for large medical QA models. We revisit this assumption across a broad range of open-weight instruction-tuned models spanning 7B to 72B parameters. Across five models, ten biomedical QA datasets, four retrieval methods, and four retrieval corpora, we find that retrieval yields only small and inconsistent improvements over a no-retrieval baseline, typically within 1-2 points. In contrast, the choice of backbone model has a much larger effect than the choice of retriever or corpus, and expert and layman retrieval sources perform similarly in most settings. These results suggest that the main bottleneck is not retrieval quality alone, but the model's limited ability to use retrieved evidence effectively.