Improving the Evaluation of Biomedical Question Answering with Few Human Preference Signals
Organizations: Suncorp Bank, Australia · CSIRO, Australia · Monash University, Australia · Commonwealth Bank, Australia
Abstract
Retrieval-Augmented Generation (RAG) systems are increasingly used for biomedical Question Answering (QA). However, evaluating their effectiveness remains challenging due to the lack of reliable reference resources and the frequent misalignment between automatic evaluation metrics and human judgments. One practical question is how evaluation results should be used to guide development decisions, especially when they correlate weakly with human judgments and may even lead to different conclusions. We explore how to use a small amount of human preference signals to calibrate direct assessment evaluation metrics, and show that calibrated metrics consistently outperform baselines that either treat all metrics equally or rely on a single best metric across multiple datasets.
Figures & tables
| Quality | Metric | Evaluation |
| Dimension | Dimension | |
| Semantic Similarity | ROUGE-1 ( Lin, 2004 ) , | , |
| BERTScore ( Zhang et al., 2020 ) , | , | |
| CosSim. ( Reimers and Gurevych, 2019 ) | ||
| Relevance | Context Relevance ( Es et al., 2024 ) | |
| (LLM-based) | Answer Relevance ( Es et al., 2024 ) |
| Prompt Strategy | Cohen’s | Pearson’s |
|---|---|---|
| LLMDirect | 0.46 | 0.409 |
| LLMDomain | 0.55 | 0.530 |
| LLMGeneric | 0.50 | 0.486 |
| LLMAll | 0.53 | 0.515 |
| Setting | Query | Ans | |||||
|---|---|---|---|---|---|---|---|
| LLM | LLM | Avg. | Avg. | Avg. | Avg. | Avg. | |
| SQ | GPT3.5 | GPT4 | 0.606 | 0.154 | 0.465 | 0.793 | 0.408 |
| GPT3.5 | QWEN | 0.813 | 0.497 | ||||
| GPT4 | GPT4 | 0.596 | 0.175 | 0.486 | 0.789 | 0.414 | |
| GPT4 | QWEN | 0.823 | 0.484 | ||||
| GEMMA | GPT4 | 0.596 | 0.183 | 0.471 | 0.774 | 0.422 |
| No Calibration | ||
|---|---|---|
| Uniform weighting | 61.44 5.95 | |
| Random weighting | 55.42 7.21 | |
| W/ Calibration | ||
| DMW | LMW | |
| Human pref. | 64.30 4.34 | 70.00 4.05 |
| LLM pref. | 53.17 2.45 | 62.95 4.10 |
| Eval. Dimension | Uniform | DMW | LMW |
|---|---|---|---|
| All | 61.44 | 64.30 | 70.00 |
| -AlignScore (best) | 66.03 | ||
| 50.92 | 52.88 | 52.17 | |
| 52.84 | 52.85 | 51.88 | |
| 45.07 | 48.54 | 47.64 | |
| + | 48.57 | 49.57 | 48.66 |
| Unif. Weighting | DMW | LMW | |
|---|---|---|---|
| Combined | 53.47 | 59.82 | 60.51 |
| Biomed. | 52.14 | 60.17 | 59.82 |
| Medicine | 53.91 | 58.77 | 58.75 |
| Neuroscience | 54.00 | 61.09 | 62.18 |
| Pharmacy | 52.42 | 60.05 | 60.57 |
| Public Health | 51.77 | 59.00 | 61.23 |
Appendix figures & tables20 assets
Supplementary material from the paper’s appendix.
Appendix
| API/Method | Parameters |
|---|---|
| NCBI API | DB: PubMed, Sort: relevance |
| (Entrez) | Min-year: 1990, Max-year: 2024 |
| Max-articles:30, Filter: PMC open access | |
| PaperQA2 | Top evidences: 5, Evidence summary length: 50 |
| Max answer source: 3, Answer length: 100 | |
| LLM: GPT4o-2024-08-06 |
| Prompt: Query Reformulation— SQ setting |
|---|
| Question: {question} |
| From the above question, your task is to create a search phrase to find relevant articles. The search phrase should contain only one or a few words. Do not include any word that is not present in the question. Do not generate numbers and punctuation. Convert any initials to their full form. |
| Below are some examples: {samples} |
| However, below query term(s) didn’t return any article: |
| Prompt: Query Reformulation— MQ setting |
|---|
| Your task is to create multiple search phrases to find relevant articles that may assist in answering a question. |
| 1. If the question is simple and asking about one single topic, keep the question as it is. |
| 2. If the question is asking a relation between multiple topics, create sub-questions that will be able to help get the final answer. |
| 3. Create the most important search phrases for the questions to be able to search relevant articles. |
| Prompt: Answer Generation |
|---|
| Question: {question} |
| For the above question, we retrieve the following context: |
| Context: {context} |
| Try to answer the question with the help of the given context in a maximum {length} words with citation in the format (citation key - pmid). |
| Question | Answer (GPT4) |
|---|---|
| FrostTolGene —What proportion of Transcriptomic studies on plants found ICE1 Transcription factors to be associated with cold acclimation? [Contains both gene name and trait] | The provided context indicates that ICE1 transcription factors are associated with cold acclimation in multiple plant studies. Specifically, Wu (2021) discusses the regulation of cold acclimation pathways by ICE1 and ICE2 in plants (Wu 2021 - 34639192). Additionally, Xu (2015) identifies ICE gene homologs in grapevines that play a crucial role in cold acclimation, highlighting the involvement of VaICE1 as a transcription factor responding to cold stress (Xu 2015 - 25019620). However, the exact proportion of studies reporting this association is not specified in the context. Thus, while ICE1 transcription factors are recognized for their role in cold acclimation, quantifying the proportion of studies is not possible based on the given information. |
| OzWheatGene —Candidate gene TraesCS4D03G0067100 on genome GCF 018294505.1 has the annotation of being a GAI-like protein 1 gene. Are there any known associations or links between this family of genes and the trait height in wheat research? Please also describe the evidence for the association. [Contains both gene name and connection to pre-existing trait] | Yes, there are known associations between the GAI-like protein family and height traits in wheat. The Reduced height-1 (Rht-B1 and Rht-D1) loci, which are orthologues of the Arabidopsis GAI gene, encode proteins that function as nuclear transcription factors and are implicated in the regulation of plant height by modulating the response to gibberellin, a growth hormone (Peng 1999 - 10421366). The introduction of mutant dwarfing alleles at these loci has led to the development of shorter wheat varieties, significantly contributing to the green revolution’s impact on wheat yields (Peng 1999 - 10421366). Additionally, studies of mutant GAI alleles in other crops, such as rice, demonstrate that they also result in reduced gibberellin responses and dwarfism, suggesting that manipulating GAI-like proteins could be a strategy to enhance yield across various species (Peng 1999 - 10421366). |
| Query & Context (Prompt Setting–Query LLM) | ||
|---|---|---|
| Eval. Dim. | FrostTolGene | OzWheatGene |
| MQ +Stack -GPT4 | SQ -GEMMA | |
| MQ +Stack -Mistral | MQ +Stack -GPT4 | |
| SQ -GEMMA | MQ +Cat -Mistral | |
| Overall | SQ -GPT3.5 | SQ-GPT3.5 |
| Answer ((Prompt Setting–Query LLM–Answer LLM) | ||
| Prompt | Query | Query to Ques. ( ) | Context to Ques. ( ) | Context to Abstracts ( ) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Setting | LLM | ROUGE-1 | BERTSc. | CosSim. | AlignSc. | Query Avg. | AlignSc. | Relev. | Avg. | ROUGE-1 | BERTSc. | AlignSc. | FactCC | Faith. | Avg. | Context Avg. | Overall Avg. |
| SQ | GPT3.5 | 0.072 | 0.877 | 0.817 | 0.659 | 0.606 | 0.202 | 0.106 | 0.154 | 0.070 | 0.772 | 0.461 | 0.879 | 0.142 | 0.465 | 0.376 | 0.460 |
| GPT4 | 0.062 | 0.877 | 0.782 | 0.663 | 0.596 | 0.227 | 0.123 | 0.175 | 0.063 | 0.788 | 0.487 | 0.880 | 0.210 | 0.486 | 0.397 | 0.469 | |
| GEMMA | 0.068 | 0.869 | 0.824 | 0.623 | 0.596 | 0.217 | 0.149 | 0.183 | 0.065 | 0.781 | 0.460 | 0.883 | 0.165 | 0.471 | 0.389 | 0.464 | |
| Mistral | 0.089 | 0.870 | 0.758 | 0.549 | 0.567 | 0.229 | 0.210 | 0.220 | 0.047 | 0.806 | 0.470 | 0.839 | 0.241 | 0.481 | 0.406 | 0.464 | |
| MQ +Cat | GPT4 | 0.029 | 0.884 | 0.843 | 0.670 | 0.607 | 0.228 | 0.300 | 0.264 | 0.043 | 0.826 | 0.455 | 0.935 | 0.347 | 0.521 | 0.448 | 0.505 |
| Prompt | Query | Answer | Ans. to Ques. ( ) | Ans. to Context ( ) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Setting | LLM | LLM | AlignSc. | Relev. | Avg. | AlignSc. | ROUGE-1 | BERTSc. | FactCC | Faith. | Avg. | Avg. |
| SQ | GPT3.5 | GPT4 | 0.710 | 0.875 | 0.793 | 0.676 | 0.013 | 0.818 | 0.345 | 0.187 | 0.408 | 0.518 |
| GPT4 | GPT4 | 0.719 | 0.859 | 0.789 | 0.695 | 0.018 | 0.822 | 0.254 | 0.283 | 0.414 | 0.521 | |
| GEMMA | GPT4 | 0.715 | 0.832 | 0.774 | 0.691 | 0.016 | 0.821 | 0.332 | 0.249 | 0.422 | 0.522 | |
| Mistral | GPT4 | 0.743 | 0.840 | 0.792 | 0.690 | 0.022 | 0.831 | 0.208 | 0.206 | 0.391 | 0.506 | |
| GPT3.5 | QWEN | 0.758 | 0.867 | 0.813 | 0.754 | 0.012 | 0.805 | 0.736 | 0.179 | 0.497 | 0.587 | |
| Prompt | Query | Query to Ques. ( ) | Context to Ques. ( ) | Context to Abstracts ( ) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Setting | LLM | ROUGE-1 | BERTSc. | CosSim. | AlignSc. | Query Avg. | AlignSc. | Relev. | Avg. | ROUGE-1 | BERTSc. | AlignSc. | FactCC | Faith. | Avg. | Context Avg. | Overall Avg. |
| SQ | GPT3.5 | 0.049 | 0.853 | 0.761 | 0.544 | 0.552 | 0.273 | 0.028 | 0.151 | 0.075 | 0.753 | 0.578 | 0.989 | 0.054 | 0.650 | 0.393 | 0.523 |
| GPT4 | 0.046 | 0.839 | 0.696 | 0.483 | 0.516 | 0.280 | 0.085 | 0.183 | 0.032 | 0.760 | 0.584 | 0.912 | 0.083 | 0.634 | 0.391 | 0.509 | |
| GEMMA | 0.046 | 0.839 | 0.696 | 0.483 | 0.516 | 0.280 | 0.112 | 0.196 | 0.032 | 0.760 | 0.584 | 0.995 | 0.083 | 0.651 | 0.407 | 0.519 | |
| Mistral | 0.046 | 0.851 | 0.703 | 0.543 | 0.536 | 0.289 | 0.070 | 0.180 | 0.093 | 0.765 | 0.572 | 0.898 | 0.096 | 0.625 | 0.398 | 0.511 | |
| MQ +Cat | GPT4 | 0.036 | 0.858 | 0.806 | 0.605 | 0.576 | 0.424 | 0.372 | 0.398 | 0.045 | 0.828 | 0.494 | 0.304 | 0.317 | 0.398 | 0.398 | 0.463 |
| Prompt | Query | Answer | Ans. to Ques. ( ) | Ans. to Context ( ) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Setting | LLM | LLM | AlignSc. | Relev. | Avg. | AlignSc. | ROUGE-1 | BERTSc. | FactCC | Faith. | Avg. | Avg. |
| SQ | GPT3.5 | GPT4 | 0.678 | 0.835 | 0.757 | 0.655 | 0.006 | 0.796 | 0.651 | 0.080 | 0.438 | 0.529 |
| GPT4 | GPT4 | 0.688 | 0.798 | 0.743 | 0.671 | 0.006 | 0.797 | 0.633 | 0.091 | 0.440 | 0.526 | |
| GEMMA | GPT4 | 0.688 | 0.801 | 0.745 | 0.671 | 0.006 | 0.797 | 0.633 | 0.091 | 0.440 | 0.527 | |
| Mistral | GPT4 | 0.666 | 0.783 | 0.725 | 0.667 | 0.009 | 0.797 | 0.416 | 0.035 | 0.385 | 0.482 | |
| GPT3.5 | QWEN | 0.687 | 0.816 | 0.752 | 0.593 | 0.004 | 0.788 | 0.592 | 0.089 | 0.413 | 0.510 | |
| Metric | Hum-Metric | Pearson’s | LLM-Metric | Pearson’s |
|---|---|---|---|---|
| Agree. (%) | Agree. (%) | |||
| All | 61.45 | 0.300 (p=0.002) | 47.163 | 0.267 (p=0.005) |
| AlignScore | 59.04 | 0.164 (p=0.035) | 48.27 | -0.044 (p=0.005) |
| ROUGE | 52.41 | -0.010 (p=0.902) | 46.99 | -0.069 (p<0.001) |
| BERTScore | 50.60 | -0.003 (p=0.974) | 46.77 | -0.079 (p<0.001) |
| Rubric: Generic |
|---|
| - Does the response answer the user’s question? |
| - Is the answer easily understandable and complete with non-repetitive information? |
| - Are the references useful to answer the question? |
| - Does the answer cite the references correctly for each claim? |
| - Can the claims in the answers be accurately supported by the given references? |
| Rubric: Domain-specific |
| Prompt: Grouping Human Ratoinals |
|---|
| human reasonings: {reasons} |
| Given the above list of reasons for not preferring some LLM-generated answers, try to group them into reasoning categories. |
| Give a short category name for each category. |
| Subject | Datasize |
|---|---|
| Combined | 2251 |
| Biomed. | 662 |
| Medicine | 801 |
| Neuroscience | 206 |
| Pharmacy | 334 |
| Public Health | 248 |
| Total | Similarity to the Selected Answer | Relevance of Answer | Lack of Details | Lack of Supporting Evidence | Incorrect or irrelevant context | Organization and Structure | Answer Clarity and Fluency | Inaccurate Claims | |
| All | 54 | 16 | 15 | 9 | 4 | 4 | 3 | 2 | 2 |
| Qr2Q | 70 | 15 | 28 | 11 | 7 | 4 | 1 | - | 1 |
| C2Q | 62 | 18 | 22 | 10 | 6 | 3 | 2 | - | 1 |
| C2Ab | 75 | 17 | 30 | 12 | 7 | 6 | 1 | 1 | 1 |
| C2Q+C2Ab | 70 | 18 | 27 | 11 | 6 | 6 | - | 1 | 1 |
| A2Q | 72 | 21 | 26 | 8 | 6 | 5 | 3 | 1 | 2 |
| Criteria | Frequency | Example Reasons |
|---|---|---|
| Relevance of Answer | 54 | ‘the answer is not as relevant’, ‘answer is not relevant to the question’,‘the answer is neither sufficiently relevant nor complete.’, ‘not as relevant to the candidate gene’, ‘the answer is not as relevant and does not provide inline citations’, ‘the answer is very similar to the selected answer but less relevant’, ‘not as relevant does not get to answer’, ‘not as relevant, no description of gene function’, ‘the answer is neither sufficiently relevant nor complete.’ |
| Similarity to the Selected Answer | 35 | ‘the answer is very similar to the selected answer but not as concise.’, ‘the answer has less information about the other reference.’, ‘similar, irrelevant context’, ‘both bad, no description of gene function’, ‘the answer is almost similar to the selected answer’ |
| Lack of details | 16 | ‘the answer is not as detailed. The paragraph structure is not helpful for directly answer the question.’, ‘the answer has less information’, ‘the answer is not as detailed.’, ‘the answer has less information.’, ‘details provided could be misleading to a novice.’, ‘answer is not as detailed’, ‘less detail’, ‘the answer is neither sufficiently relevant nor com plete.’, ‘the answer is not complete’ |
| Incorrect or Irrelevant Context | 11 | ‘incorrect context’, ‘irrelevant context, no description of gene function’, ‘context has low relevance’ |
| Lack of Supporting Evidence | 11 | ‘no supporting evidence’, ‘the answer does not provide inline citations.’, ‘the answer is not as relevant and does not provide inline citations’, ‘did not define function of gene’, ‘irrelevant; did not define function of gene’, ‘not as relevant, no description of gene function’, ‘part of the answer is not as relevant and there is no citations’, ‘the answer is not as relevant, no supporting evidence’ |
| Organization and Structure | 7 | ‘the paragraph structure is not helpful for directly answer the question.’, ‘the paragraph structure and organization are not as useful’, ‘the answer is not as relevant paragraph structure and organization are not helpful (not using topic sentence structure)’, ‘incomplete, intro too long’, ‘The phrasing in the answer is not as fluent.’ |
| Example #1 |
|---|
| Question: What proportion of Transcriptomic studies on plants found Gpcr-type g protein 2 gene to be associated with cold acclimation? |
| Human reason: The answer has less information |
| Human preference: Answer 2 Metric preference: Answer 1 |
| Answer 1: "The provided context does not mention any specific transcriptomic studies on plants that associate the GPCR-type G protein 2 gene with cold acclimation. The cited studies focus on viroid effects on gene expression (Joubert 2022 - 35887025), stress responses via RNA-seq and single-cell RNA-seq (Rurek 2024 - 39524930), and single-cell transcriptomics for plant development (Yu 2023 - 36540021). None of these contexts address GPCR-type G protein 2 gene functionality or its relationship with cold acclimation. Therefore, the proportion cannot be determined.", |
| Anwer 2: "The provided context does not specify the proportion of transcriptomic studies on plants that found the G-protein coupled receptor (GPCR) type G protein 2 gene to be associated with cold acclimation. It emphasizes the general mechanisms of cold acclimation, such as physiological adjustments and changes in gene expression involving C-repeat binding factors (CBFs) (Barrero-Gil 2019 - 30288701), as well as the role of various proteins in regulating this process (Barrero-Gil 2013 - 23498862). However, specific information regarding the GPCR-type G protein 2 gene’s association with cold acclimation is not included in the provided studies. Thus, I cannot provide a definitive answer regarding the proportion." |
| Example #2 |
| Question: | |
| Candidate gene TraesCS6B03G0835400 on genome GCF_018294505.1 has the annotation of being a SBP (S-ribonuclease-binding protein) family protein gene. Are there any known associations or links between this family of genes and the trait spike length in wheat research? Please also describe the evidence for the association. | |
| Answer 1: | |
| The SBP (S-ribonuclease-binding protein) family gene TraesCS6B03G0835400 is linked to spike length in wheat. Research indicates that SBP genes, such as BdSBP1 and BdSBP3, play roles in spike development, with their expression patterns during spikelet initiation and responses to environmental factors like vernalization and temperature (Tripathi 2020 - 32929136). A T-DNA mutant of Bdsbp9 showed reduced spike length, highlighting the functional importance of SBP genes in spike development (Tripathi 2020 - 32929136). | |
| Answer 2: | |
| There is currently no direct evidence linking the SBP (S-ribonuclease-binding protein) family genes, such as TraesCS6B03G0835400, to spike length traits in wheat research based on the provided context. The context discusses the association of specific haplotypes in different genes with spike length traits (Zhang 2023 - 37310852) but does not mention SBP family genes or their role in determining spike length. Additionally, while SPL genes are mentioned in relation to plant growth traits (Zhao 2022 - 36011366), they do not directly address the SBP family or spike length in wheat. Therefore, further research would be necessary to explore any potential associations between SBP genes and spike length in wheat. | |
| Annot. 1 | Annot. 2 |
| Subject: Biomed. Engi. |
|---|
| Question: What recent progress characterises novel monolithic stationary phases for liquid chromatography? |
| Llama-4-Scout: The development of novel monolithic stationary phases has significantly advanced liquid chromatography, offering improved separation efficiency, selectivity, and versatility. Recent progress in this area includes the introduction of nanomaterial-based stationary phases, such as nanoporous silica, zirconia, and graphene, which provide ultra-high surface areas and nanoscale confinement effects (Ratnam et al. 2023b). |
| Monolithic columns, made from organic polymers, inorganic materials, or hybrid structures, have been engineered to offer tailored characteristics for specific analyses (Nechv0̆0e1talov0̆0e1 et al. 2022a). These columns have demonstrated superior permeability, efficiency, and ease of preparation, making them attractive alternatives to traditional particle-packed columns (Gregu0̆161 et al. 2023a). The incorporation of metal ions, such as Co(II), into molecularly imprinted polymers has enhanced selectivity for separating enantiomeric compounds (Amalia et al. 2022b). Additionally, zwitterionic sulfobetaine-based monoliths have been developed for hydrophilic interaction chromatography, exhibiting good selectivity and efficiency (Wang et al. 2022a). |
| The use of bio-inspired materials, like lipase-immobilized monoliths, has also shown potential for chiral separations (Fouad et al. 2023a). Furthermore, the integration of monolithic columns with mass spectrometry has enabled sensitive and high-throughput analysis of complex samples (Shamsi et al. 2022a). Overall, these advancements in monolithic stationary phases are transforming liquid chromatography, enabling faster, more sensitive, and high-resolution separations for a wide range of applications (Ratnam et al. 2023b). |
| Deepseek-R1: Recent advancements in monolithic stationary phases for liquid chromatography (LC) emphasize enhanced selectivity, fabrication techniques, and application-specific designs. Gradient monolithic phases, achieved through controlled chemical modifications like the controlled rate infusion method or photo-grafting, enable gradual changes in surface functionality along the column, improving resolution for complex biological samples (Alla et al. 2022a). Metal-mediated molecularly imprinted polymers (MMIPs) have emerged for chiral separations, with cobalt(II)-based monolithic columns demonstrating high enantioselectivity for racemic citronellal, leveraging metal coordination to enhance template recognition (Amalia et al. 2022b). |
| Hybrid organic-inorganic monoliths, such as polymer-bound silica phases, combine high permeability with exceptional efficiency ( 288,000 plates/m for peptides), addressing challenges in biomolecule separation (Ali et al. 2024b). Innovations in miniaturization include microbore columns (1 mm i.d.) that reduce solvent consumption while maintaining performance, ideal for environmentally friendly LC systems (Amalia et al. 2022a). Zwitterionic sulfobetaine-based monoliths, fabricated via rapid photoinitiated copolymerization, offer superior hydrophilic interaction chromatography (HILIC) capabilities, benefiting polar analyte separations (Wang et al. 2022a). |
RAG Evaluation
Retrieval-augmented generation (RAG) evaluation measures how well systems retrieve, use, and cite evidence while balancing reliability, cost, and speed.
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