2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative

2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative Tuhina Neogi Tim Jansen Nicola Dalbeth Jaap Fransen H. Ralph Schumacher Dianne Berendsen Melanie Brown Hyon K. Choi N. Lawrence Edwards M. Janssen Frédéric Lioté Raymond P. Naden George Nuki Alexis Ogdie Fernando Pérez-Ruiz Kenneth G. Saag Jasvinder A. Singh John S. Sundy Anne‐Kathrin Tausche Janitzia Vaquez‐Mellado Steven A. Yarows William J. Taylor

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2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative 2015 Annals of the Rheumatic Diseases 10.1136/annrheumdis-2015-208237 neogi2015-2015-gout-classification-criteria neogi2015-2015-gout-classification-criteria.txt, the project's staged copy a6de34c8855beb8cb506ef91a19a80e67f8d305c cc-by-nc medicine

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them A CLASSIFICATION CRITERIA SET BUILT FROM A GOLD STANDARD, A DELPHI, A 983-SUBJECT DIAGNOSTIC STUDY AND A DISCRETE-CHOICE CONJOINT EXPERIMENT - and published simultaneously in two journals, in two orthographies Quotation withheld because this record is not cleared for redistribution. how to classify gout for enrolment into studies when the gold standard is available but not feasible, and when every existing criteria set trades sensitivity against specificity badly Quotation withheld because this record is not cleared for redistribution. the 2015 ACR/EULAR criteria: an entry criterion, a sufficient criterion, no exclusion criteria, eight weighted domains scored to a maximum of 23 with a threshold of 8, two categories carrying NEGATIVE weights, sensitivity 0.92 and specificity 0.89 in an independent validation set Quotation withheld because this record is not cleared for redistribution. method Quotation withheld because this record is not cleared for redistribution. a disease with a gold standard that cannot be applied to most of the people who have it, so the definition has to work without it Quotation withheld because this record is not cleared for redistribution. expert-consensus expert-consensus Quotation withheld because this record is not cleared for redistribution. A CRITERION EXCLUDED FROM THE DEFINITION BECAUSE INCLUDING IT WOULD DESTROY THE ABILITY TO STUDY IT: `The last three factors [response to treatment, family history, risk factors or associated comorbidities] were NOT CONSIDERED FURTHER as they are not features of gout itself despite their association with gout, and inclusion of risk factors or comorbidities in the definition of gout would preclude future studies evaluating their association with gout.` The clearest statement of definitional circularity in this corpus, and it is a design decision rather than a critique Quotation withheld because this record is not cleared for redistribution. AND THE SAME REFUSAL AGAIN, IN THE VALIDATION: `Quotation withheld` A published sensitivity of 1.00 that is an artefact of the definition, named as such - and three of the sets in the comparison table carry exactly that 1.00 Quotation withheld because this record is not cleared for redistribution. AND EVIDENCE *AGAINST* MEMBERSHIP IS WEIGHTED, NOT DISCARDED: `there are two categories that elicit negative scores. Specifically, if the synovial fluid is MSU negative, 2 POINTS ARE SUBTRACTED from the total score. Similarly, if the serum urate level is <4 mg/dL, 4 POINTS ARE SUBTRACTED. This approach was taken to emphasise that these findings reduce the probability of gout.` A membership score that can go DOWN on evidence - a shape this corpus's `weight` field has no way to express, since weight is bounded below by zero and means confidence, not direction Quotation withheld because this record is not cleared for redistribution. AND A NEGATIVE TEST SCORES THE SAME AS NO TEST, DELIBERATELY: `In the discrete-choice experiments, Quotation withheld, supporting the validity of using the scoring system in the absence of imaging data.` Our own `absent-not-in-staged-text` problem, in a clinical criteria set - and here the collapse is a decision, taken so that the criteria work where the scanner does not exist Quotation withheld because this record is not cleared for redistribution. AND THE WEIGHTS COME FROM A DECISION-SCIENCE EXPERIMENT, NOT FROM A REGRESSION: `the expert panel undertook a series of discrete-choice experiments. This work resulted in weights being assigned to each category and domain, such that the highest category of each domain summed to a total of 100%` - pairwise forced choices in 1000Minds, with the panel told to assume all other parameters equal, and face validity checked against their own pre-meeting ranking of ten cases Quotation withheld because this record is not cleared for redistribution. AND TWO INDEPENDENT ROUTES LANDED ON THE SAME THRESHOLD: `the expert panel performed a threshold identification exercise designed to assess the members' willingness to enrol 47 paper cases ... into a Phase 3 randomised clinical trial of a new urate-lowering agent with unclear efficacy and safety. The score at which the majority considered an individual as having gout or not fell at the same threshold as that identified as the cut-off score that maximised the sum of sensitivity and specificity.` A statistical optimum and a clinical willingness-to-enrol judgement agreeing - which is the only threshold validation of its kind in this corpus Quotation withheld because this record is not cleared for redistribution. AND MEMBERSHIP ACCRUES OVER TIME: `the classification was to apply to the patient's total disease experience, not to classify individual symptomatic episodes ... elements of the criteria could be accrued over time such that individuals could fulfil criteria at a later time point even if they did not at the initial assessment.` The unit of classification is a life, not a visit - and the categories are `hierarchical and mutually exclusive, such that if a higher and a lower category have been fulfilled at different points in time, the higher one should be scored` Quotation withheld because this record is not cleared for redistribution. AND THE EMPTY SLOT IS DELIBERATE, WITH ITS REASON: `Quotation withheld` A criteria set that declines to say what rules the disease out, because both the disease and the instrument allow exceptions Quotation withheld because this record is not cleared for redistribution. CRITERIA USED FOR DECADES OUTSIDE THE SCOPE THEIR AUTHORS DECLARED: `Quotation withheld`. The stated scope was narrower than the use, and the correction comes 38 years later from a different body. Quotation withheld because this record is not cleared for redistribution. AND A DEFINITION MADE OBSOLETE BY AN INSTRUMENT THAT DID NOT EXIST WHEN IT WAS WRITTEN: `Quotation withheld.` The criteria did not become wrong; the measurable world grew - which is the same shape as haas2018 admitting i-IFTA because the population changed. Quotation withheld because this record is not cleared for redistribution. THE DEFINITION DISCLAIMS THE USE EVERYONE WILL PUT IT TO: `It should be recognised that Quotation withheld. Thus, in clinical practice, joint or tophus aspiration remains an essential component of establishing a diagnosis of gout.` The criteria exist to assemble study populations, and the paper says so where a reader is most likely to misuse them Quotation withheld because this record is not cleared for redistribution. AND THE THRESHOLD SHOULD DIFFER BY PURPOSE, WHILE ONE IS PUBLISHED: `While for certain purposes a higher sensitivity (lower score) may be preferable (eg, general population survey to determine the public health burden of gout for resource planning), a higher specificity (higher score) may be desirable for others (eg, genetic association studies in which accurate phenotyping is critical).` One number ships; the paper names two uses that want different ones Quotation withheld because this record is not cleared for redistribution. AND THE CRITERIA DO NOT TRANSFER TO ANOTHER POPULATION: `classification criteria are not intended to characterise the severity of disease, but only its presence. Additionally, classification criteria should be applied only to the intended population - those who meet the entry criteria. Performance characteristics of any classification criteria set will necessarily be altered if the criteria are applied to those other than the intended population.` The sensitivity and specificity are properties of a pairing, not of the criteria Quotation withheld because this record is not cleared for redistribution. AND THE GOLD STANDARD IS NOT USABLE ON MOST PATIENTS: `Quotation withheld.` The reference against which everything is measured cannot be obtained where most of the cases are Quotation withheld because this record is not cleared for redistribution. excluding response to treatment, family history and risk factors/comorbidities from the criteria eliminates: a definition that contains its own correlates, which 'would preclude future studies evaluating their association with gout' · outcome: held Quotation withheld because this record is not cleared for redistribution. not assessing the new criteria on the sufficient criterion (MSU positivity) when comparing performance eliminates: the circularity that makes several existing criteria sets '100% sensitive by definition' · outcome: held Quotation withheld because this record is not cleared for redistribution. a threshold identification exercise in which the panel judged willingness to enrol 47 paper cases into a Phase 3 trial, run separately from the statistical cut-off eliminates: a threshold set only by maximising the sum of sensitivity and specificity, with no clinical meaning attached · outcome: held Quotation withheld because this record is not cleared for redistribution. validating the final criteria in the one-third of the SUGAR data set never used in any earlier analysis eliminates: performance measured on the data that produced the weights · outcome: held Quotation withheld because this record is not cleared for redistribution. classification criteria classification criteria Quotation withheld because this record is not cleared for redistribution. diagnosis diagnosis Quotation withheld because this record is not cleared for redistribution. risk factors risk factors Quotation withheld because this record is not cleared for redistribution. features of gout features of gout Quotation withheld because this record is not cleared for redistribution. lack of imaging data lack of imaging data Quotation withheld because this record is not cleared for redistribution. negative results negative results Quotation withheld because this record is not cleared for redistribution. gold standard gold standard Quotation withheld because this record is not cleared for redistribution. preliminary preliminary Quotation withheld because this record is not cleared for redistribution. `classification criteria` (this paper's sense) - a rule for `enabling STANDARDISED ASSEMBLY OF A RELATIVELY HOMOGENEOUS GROUP of individuals with the disease of interest for enrolment into studies`, explicitly NOT a diagnostic rule and explicitly not a severity scale Quotation withheld because this record is not cleared for redistribution. `entry criterion` / `sufficient criterion` / `exclusion criterion` - three slots defined before any domain: who the criteria apply to, what classifies without scoring, and what rules the disease out. The third was deliberately left EMPTY Quotation withheld because this record is not cleared for redistribution. `gold standard` (gout) - MSU crystal positivity: high specificity, inadequate feasibility and sensitivity, and therefore `not a feasible universal standard` Quotation withheld because this record is not cleared for redistribution. `typical symptomatic episode` - and the SAME criterion reads differently in the twin: `irrespective of ANTI-INFLAMMATORY treatment ... <24 h` in Annals, `irrespective of ANTIINFLAMMATORY treatment ... <24 hours` in Arthritis & Rheumatology. One criterion, two orthographies, two DOIs Quotation withheld because this record is not cleared for redistribution. `preliminary criteria` - A PROVISIONAL LABEL THAT NEVER EXPIRED: `the most widely used being the 1977 American Rheumatism Association (now the American College of Rheumatology (ACR)) preliminary criteria`. The word `preliminary` is still in the name in 2015, the issuing society has since changed its own name, and the criteria remain the field's default. Quotation withheld because this record is not cleared for redistribution. extends → the 1977 American Rheumatism Association preliminary criteria for the classification of the acute arthritis of primary gout, whose gold standard was PHYSICIAN DIAGNOSIS rather than crystal status, and the Rome, New York, Mexico and Netherlands criteria sets measured alongside it Quotation withheld because this record is not cleared for redistribution. extends → ITS OWN TWIN: the identical criteria set published simultaneously as doi:10.1002/art.39254 in Arthritis & Rheumatology (PMC4566153). Same 22 authors, same year, same criteria, BRITISH spelling here and AMERICAN there - one artefact with two DOIs and two citation counts Quotation withheld because this record is not cleared for redistribution. classification criteria —distinct-from→ diagnosis classification criteria diagnosis the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'It should be…' A definition naming a use it will not support, in the place a reader is most likely to misuse it · the relation stated: the criteria are explicitly NOT INTENDED for making a diagnosis; aspiration remains essential for that Quotation withheld because this record is not cleared for redistribution. risk factors —distinct-from→ features of gout risk factors features of gout the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'The last three…' The distinction is drawn to protect a future measurement, not to describe the world · the relation stated: risk factors are ASSOCIATED WITH gout but are NOT FEATURES OF IT, and admitting them to the definition would make their association unstudiable Quotation withheld because this record is not cleared for redistribution. lack of imaging data —same-as→ negative results lack of imaging data negative results the relation itself is separately evidenced · strength of the relation: 0.85 · note: 'In the discrete-choice experiments…' Weight 0.85: this is an equivalence IN THE INSTRUMENT, adopted so the criteria work where imaging is unavailable - not a claim that an absent test and a negative test are the same thing. It is our own 'absent-not-in-staged-text' collapse, made deliberately and for a stated reason · the relation stated: the two are weighted IDENTICALLY in the scoring system, so the criteria cannot distinguish a test not done from a test that found nothing Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says the lack of imaging data was WEIGHTED THE SAME as negative results; same-as is loose. Quotation withheld because this record is not cleared for redistribution. A FEATURE EXCLUDED FROM A DEFINITION TO PROTECT A FUTURE MEASUREMENT: `inclusion of risk factors or comorbidities in the definition of gout would preclude future studies evaluating their association with gout` A FEATURE EXCLUDED FROM A DEFINITION TO PROTECT A FUTURE MEASUREMENT: `inclusion of risk factors or comorbidities in the definition of gout would preclude future studies evaluating their association with gout` Quotation withheld because this record is not cleared for redistribution. AND A PUBLISHED SENSITIVITY OF 1.00 THAT IS AN ARTEFACT OF THE DEFINITION: `For some existing criteria sets, presence of MSU crystals alone is sufficient to fulfil criteria; they are therefore 100% sensitive by definition ... the criteria set was not assessed in that regard, to avoid circularity` AND A PUBLISHED SENSITIVITY OF 1.00 THAT IS AN ARTEFACT OF THE DEFINITION: `For some existing criteria sets, presence of MSU crystals alone is sufficient to fulfil criteria; they are therefore 100% sensitive by definition ... the criteria set was not assessed in that regard, to avoid circularity` Quotation withheld because this record is not cleared for redistribution. AND EVIDENCE AGAINST MEMBERSHIP CARRIES A NEGATIVE WEIGHT: `two categories that elicit negative scores ... MSU negative, 2 POINTS ARE SUBTRACTED ... serum urate <4 mg/dL, 4 POINTS ARE SUBTRACTED ... these findings reduce the probability of gout` AND EVIDENCE AGAINST MEMBERSHIP CARRIES A NEGATIVE WEIGHT: `two categories that elicit negative scores ... MSU negative, 2 POINTS ARE SUBTRACTED ... serum urate <4 mg/dL, 4 POINTS ARE SUBTRACTED ... these findings reduce the probability of gout` Quotation withheld because this record is not cleared for redistribution. AND A TEST NOT DONE SCORES THE SAME AS A TEST THAT FOUND NOTHING: `Quotation withheld` AND A TEST NOT DONE SCORES THE SAME AS A TEST THAT FOUND NOTHING: `Quotation withheld` Quotation withheld because this record is not cleared for redistribution. AND TWO INDEPENDENT ROUTES REACHED ONE THRESHOLD: `The score at which the majority considered an individual as having gout or not fell at the same threshold as that identified as the cut-off score that maximised the sum of sensitivity and specificity` AND TWO INDEPENDENT ROUTES REACHED ONE THRESHOLD: `The score at which the majority considered an individual as having gout or not fell at the same threshold as that identified as the cut-off score that maximised the sum of sensitivity and specificity` Quotation withheld because this record is not cleared for redistribution. MSU crystal positivity is highly specific, but its feasibility and sensitivity may be inadequate, so it is not a feasible universal standard MSU crystal positivity is highly specific, but its feasibility and sensitivity may be inadequate, so it is not a feasible universal standard Quotation withheld because this record is not cleared for redistribution. `enabling standardised assembly of a relatively homogeneous group of individuals with the disease of interest for enrolment into such studies` - and `not intended for use in making a diagnosis in a clinical setting` classification criteria Quotation withheld because this record is not cleared for redistribution. `features such as a gold standard that alone could classify gout without further need to apply the classification criteria scoring system` - and the reason the new criteria are not scored against it sufficient criterion Quotation withheld because this record is not cleared for redistribution. `there would be no exclusion criteria because gout can often coexist with other diseases and because synovial fluid microscopy can sometimes fail to disclose MSU crystals in patients with gout` exclusion criteria Quotation withheld because this record is not cleared for redistribution. `with no single criteria set having excellent sensitivity and specificity` - and the 100% figures are the circular ones sensitivity and specificity of prior criteria sets against the MSU gold standard Quotation withheld because this record is not cleared for redistribution. evidence against membership, subtracted from the score negative weight for MSU-negative synovial fluid Quotation withheld because this record is not cleared for redistribution. the largest single weight in the criteria set is a NEGATIVE one negative weight for serum urate below 4 mg/dL Quotation withheld because this record is not cleared for redistribution. the pair the whole design optimises, with specificity deliberately favoured because `investigators need to have confidence that individuals who are enrolled in a study truly have the condition of interest` sensitivity and specificity Quotation withheld because this record is not cleared for redistribution. the only mandatory element of the score, taken as `The highest value irrespective of timing`, and the one whose low value subtracts four points serum urate Quotation withheld because this record is not cleared for redistribution.

The full text of this article is not redistributable, so it is not included here. The evidence sentences are withheld with it; the tag layer and its grounding status remain. The article itself is at https://doi.org/10.1136/annrheumdis-2015-208237.