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Record W3144094543 · doi:10.1101/2021.04.01.21254679

Is convalescent plasma futile in COVID-19? A Bayesian re-analysis of the RECOVERY randomised controlled trial

2021· preprint· en· W3144094543 on OpenAlexaff
Fergus Hamilton, Todd C. Lee, David Arnold, Richard Lilford, Karla Hemming

Bibliographic record

VenuemedRxiv · 2021
Typepreprint
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsMcGill University
Fundersnot available
KeywordsFrequentist inferenceMedicineRandomized controlled trialConfidence intervalPrior probabilityBayesian probabilityClinical trialSubgroup analysisCredible intervalIntensive care medicineStatisticsInternal medicineBayesian inferenceMathematics

Abstract

fetched live from OpenAlex

Introduction Randomised trials are generally performed from a frequentist perspective reporting point estimates and 95% confidence intervals. This approach can confuse “evidence of no effect” with “no evidence of an effect” and does not allow for contextual knowledge. The RECOVERY trial evaluated convalescent plasma for patients hospitalised with COVID-19, the interaction test for the primary outcome was not statistically significant, and the trial concluded no evidence of an effect. From the clinical immunology perspective, there is strong justification to expect differential responses to convalescent plasma in patients who already have their own antibodies to SARS-CoV2 (seropositive) versus those who do not (seronegative). Methods Outcome data was extracted from the RECOVERY trial both overall and for seronegative participants. A Bayesian re-analysis with a wide variety of priors (vague, optimistic, skeptical and pessimistic) was performed calculating the posterior probability for both any benefit or a modest benefit (number needed to treat of 100). Results Across all patients, when analysed with a vague prior the likelihood of any benefit or a modest benefit was estimated to be 64% and 18% respectively. In contrast, in the seronegative subgroup, the likelihood of any benefit or a modest benefit was estimated to be 90% and 74%. Results were broadly consistent across all prior distributions. Conclusion Performing clinical trials during a pandemic is challenging, and RECOVERY has provided high quality evidence for numerous therapies. However, the use of frequentist hypothesis testing in this trial has led to the trialists and governing bodies to conclude a strong evidence of no effect. Based on this trial, and other prior knowledge there remains a strong probability that convalescent plasma provides at least a modest benefit in seronegative patients.

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)0.323
metaresearch head score (Gemma)0.524
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesMetaresearch
DomainCandidate signal: Methods · Consensus signal: Methods
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.677
Threshold uncertainty score0.835

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.3230.524
Meta-epidemiology (narrow)0.0030.002
Meta-epidemiology (broad)0.0160.022
Bibliometrics0.0030.002
Science and technology studies0.0010.003
Scholarly communication0.0060.006
Open science0.0050.003
Research integrity0.0060.010
Insufficient payload (model declined to judge)0.0110.002

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 head0.056
GPT teacher head0.358
Teacher spread0.302 · 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; the direct Gemma label and the distilled Codex classifier agree on what is shown here.

Study designMeta-analysis
DomainMethods
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
Published2021
Admission routes1
Has abstractyes

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