SearcharxivSearch

arXiv · 2309.07194

Clinical dichotomania: A major cause of over-diagnosis and over-treatment?

Abstract

Introduction: There have been many warnings that inappropriate dichotomisation of results into positive or negative, high, or normal etc., during medical research could be very damaging. The aim of this paper is to argue that this is the main cause of over-diagnosis and over-treatment. Methods: Illustrative data were taken from a randomised control trial (RCT) that compared the frequency of nephropathy within 2 years in those on treatment with an angiotensin receptor blocker and a control and on patients in whom the numerical value of the albumin excretion rate (AER) was available on all patients before they are randomised. Results: When the RCT results were divided into AER ranges, a negligible proportion developed nephropathy within 2 years and benefited from treatment in the range 20 to 40mcg/min in which 36% of currently treated patients fall (and are thus over-diagnosed and overtreated). Above an AER of 40mcg/min, there was a gradual increase in proportions with nephropathy in each range, with fewer developing nephropathy in each range on irbesartan 150mg daily than on control and fewer still developing nephropathy on 300mg daily. Interpretation: When logistic regression functions were fitted to the data and calibrated, curves were created that allowed outcome probabilities and absolute risk reductions to be estimated for use in shared decision making (illustrated by application to an example patient). This could avoid much overdiagnosis and overtreatment. Conclusion: Careful attention to disease severity by interpreting each numerical diagnostic result provides better application of the principles of diagnosis and treatment decisions that can prevent over-diagnosis and over-treatment.

Explore related subjects

Keep this discovery

BibTeXRIS

Huw Llewelyn. 2023-09-13. Clinical dichotomania: A major cause of over-diagnosis and over-treatment?. https://arxiv.org/abs/2309.07194

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

MarkerScout: A Disease-Agnostic Machine Learning Framework for Biomarker Prediction from Multi-Scale Mechanistic Models

We demonstrate the framework on three infectious diseases derived from a companion mechanistic immune-simulation platform: SARS-CoV-2, Influenza A Virus, and Plasmodium falciparum. Each disease was evaluated across hospitalization and intensive care unit cohorts, yielding six cohorts in total. Best-pipeline cross-validated macro F1 ranged from 0.82 for IAV-HOSP to 0.99 for COV-ICU, and the framework produced tiered, direction-aware biomarker lists for each disease and phase. Interleukin-18 (IL-18) reached the strongest tier in both SARS-CoV-2 phases with consistent direction. When benchmarked against three separate, independently collected clinical ICU datasets, MarkerScout's top-ranked features outperformed 94.4% of randomly selected feature sets of equivalent size for SARS-CoV-2, with a weaker but directionally consistent advantage for Influenza A Virus (66.7%) and Plasmodium falciparum (60.7%).

q-bio.OT

Enhancing Clinical Decision Support and Differential Diagnosis with Knowledge Graphs, and Retrieval Augmented Generation in Generative AI

Diagnostic error carries a burden, while unconstrained large language models (LLMs) remain vulnerable to hallucination and weak integration of quantitative laboratory dynamics. We developed a decision-support pipeline combining disease-specific biomarker correlation graphs, ordinary differential equations (ODEs), deep sequence classification, and retrieval-augmented generation (RAG). For 103 disease classes from a full blood count (FBC) repository, biomarker networks were used as coupling matrices to generate 30 trajectories per disease (3,090 total). A one-dimensional convolutional neural network (CNN) and long short-term memory (LSTM) network classified disease trajectories and six dynamical clusters. A constrained GPT-4o-mini RAG layer used a 19-pattern BMJ Best Practice/NICE corpus to generate differential diagnoses evaluated for diagnostic suitability, evidential grounding, and clinical plausibility. Across five random-seed runs, disease-level accuracy was $0.940 \pm 0.006$ for the CNN (95\% CI 0.933--0.948) and $0.852 \pm 0.019$ for the LSTM (95\% CI 0.828--0.875); the CNN advantage was 8.87 percentage points (95\% CI 6.47--11.27; $t(4)=10.26$, $p=5.1\times10^{-4}$; Hedges' $g=3.67$). Among 100 sampled RAG cases, 96 parsed successfully; evidence was cited in 97.9\%, the true diagnosis was mentioned in 71.9\%, and the composite score was 3.82/5 with a 47.9\% strict pass rate. The central finding was a decoupling between grounding and diagnostic correctness: classifier-correct versus classifier-wrong outputs differed in diagnostic suitability but not evidential grounding. Post-hoc analysis confirmed a 1.02-point diagnostic-score difference (Mann--Whitney $p=0.0024$; Hedges' $g=0.72$), whereas grounding differed by only $-0.02$ points ($p=0.839$; $g=-0.04$).

q-bio.OT

Expanding the Human Ancestry Ontology to include under-represented populations and ethnicities for broader utility in annotations

Successful discovery, integration and reuse of data relies on the availability of rich, well-structured and machine-readable metadata to describe every aspect of the data, from sample sources to collection processes to experimental protocols. The use of standardised terminologies to express concepts in a harmonised fashion lies at the core of high-quality data annotation, increasing the FAIRness of the data, facilitating data integration and promoting reproducibility. Here, we describe the Human Ancestry Ontology (HANCESTRO), originally developed to improve standardised reporting of genetic ancestry genomic resources such as the NHGRI-EBI GWAS Catalog and the Human Cell Atlas through high-level population descriptors, and more recently expanded to include diverse and previously under-represented populations in genomics and genetics research. HANCESTRO provides a framework for population descriptors that includes both ancestry based on the analysis of genetic information and self-reported ethnicity, which is based on social and cultural factors that don't necessarily align with genetic populations. By enabling the accurate and interoperable representation of population-related data, it promotes inclusive, representative and reproducible science.

q-bio.OT