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Record W4387297932 · doi:10.1101/2023.10.03.23296132

Predicting individualized treatment effects of corticosteroids in community-acquired-pneumonia: a data-driven analysis of randomized controlled trials

2023· preprint· en· W4387297932 on OpenAlexaff
Jim M Smit, Philip van der Zee, Sara C. M. Stoof, Michel E. van Genderen, Dominic Snijders, Wim Boersma, Paolo Confalonieri, Francesco Salton, Marco Confalonieri, M-C. Shih, G. Umberto Meduri, Pierre‐François Dequin, Amélie Le Gouge, Melanie Lloyd, Harin Karunajeewa, Grzegorz Bartminski, Silvia Fernández-Serrano, Guillermo Suárez-Cuartín, David van Klaveren, Matthias Briel, Ewout W. Steyerberg, Diederik Gommers, Hannelore I. Bax, Willem Jan W. Bos, E.M.W. van de Garde, Esther Wittermans, Jan C. Grutters, C Blum, Mirjam Christ‐Crain, Antoní Torres, Ana Motos, Marcel Reinders, Jasper van Bommel, Jesse H. Krijthe, Henrik Endeman

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldMedicine
TopicPneumonia and Respiratory Infections
Canadian institutionsMcMaster University
Fundersnot available
KeywordsMedicineLogistic regressionOdds ratioPlaceboRandomized controlled trialInternal medicineMissing dataOddsStatistics

Abstract

fetched live from OpenAlex

Abstract Background Corticosteroids could improve outcomes in patients with community-acquired pneumonia (CAP). However, we hypothesize that corticosteroid effectiveness varies among individual patients, resulting in inconsistent outcomes and unclear clinical indication. Therefore, we developed and validated a predictive, causal model based on baseline characteristics to predict individualized treatment effects (ITEs) of corticosteroids on mortality in patients with CAP. Methods We obtained individual patient data from six randomized controlled trials comparing corticosteroid therapy to placebo in 1,869 adult CAP patients. The study endpoint was 30-day mortality. We performed effect modelling through logistic regression and evaluated the predicted ITEs in terms of discrimination and calibration for benefit. Our modelling procedure involved variable selection, missing value imputation, data normalization, encoding treatment variables, creating interaction terms, optimizing penalization strength, and training logistic regression models. We evaluated discriminative performance using the newly proposed ‘AUC-benefit’. Findings The model identified high levels of CRP and glucose, at baseline, as main predictors for benefit of corticosteroid treatment. Using a decision threshold of ITE=0, the model predicted harm in 1,004 patient and benefit in 864 patients. We observed benefit in patients where the model predicted benefit, with an odds ratio of 0.5 (95% CI: 0.3 to 0.9) and a mortality reduction of 3.2% (95% CI: 0.7 to 5.6), and no statistically significant benefit in the patients where the model predicted harm, with an odds ratio of 1.1 (95% CI: 0.7 to 1.8) and a negative mortality reduction (hence, increase) of −0.3% (95% CI: −2.6 to 1.8). The model yielded an AUC-benefit of 184.9 (28.6 to 347.6, 95% CI), underestimated ITEs in the lower ITE region and slightly overestimated ITEs in the higher ITE region. Interpretation Our model has potential to identify patients with CAP who benefit from corticosteroid treatment, and aid in the design of personalized clinical trials. We will prospectively validate the model in two recent CAP trials.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.270
metaresearch head score (Gemma)0.257
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.270
Threshold uncertainty score0.900

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.2700.257
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0090.017
Bibliometrics0.0020.002
Science and technology studies0.0000.002
Scholarly communication0.0040.002
Open science0.0030.002
Research integrity0.0030.004
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.100
GPT teacher head0.382
Teacher spread0.282 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

Study designMeta-analysis
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations6
Published2023
Admission routes1
Has abstractyes

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