Prediction of methotrexate efficacy and adverse events in patients with juvenile idiopathic arthritis: a systematic literature review

van Dijkhuizen, EH Pieter; Wulffraat, Nico M

doi:10.1186/1546-0096-12-51

Pediatric Rheumatology

Table 2 Critical appraisal

From: Prediction of methotrexate efficacy and adverse events in patients with juvenile idiopathic arthritis: a systematic literature review

Reference	Design	Relevance			Validity
Reference	Design	Dom	Det	Out	Blind	Rec	SoC	Loss	Mis
Outcome: MTX efficacy
[16]	Retrospective (validation prospective)	+	+	+/−	+	+	+	+	+
[17]	Mixed retrospective and prospective	+	+	+/−	+	+	+	+	+
[18]	Prospective	+	+	+/−	+	+	+	+	?
[19]	Prospective	+	+	+/−	+/−	+	?	?	+
[20]	Cross-sectional	+	+	+/−	+/−	+	?	?	+
[10]	Retrospective	+	+	+/−	?	+	?	+	+
[21]	Retrospective	+	+	+/−	?	+	?	?	+
[22]	Mixed retrospective and prospective	+	+/−	+/−	?	+	?	+	+
[23]	Prospective (validation unknown)	+	+/−	+/−	?	+	?	?	?
[24]	Prospective (validation unknown)	+	+/−	+/−	?	+	?	?	?
[25]^a	Retrospective	+/−	+/−	+	?	+	?	+/−	+
[26]	Prospective	+/−	+	+/−	?	+	?	+	+
[27]	Prospective	+/−	+	+/−	?	+	?	+	+/−
[28]	Prospective	+/−	+	+/−	?	+	?	+	?
[29]	Retrospective	+/−	+/−	+	?	+	?	+/−	+
[25]^b	Retrospective	+/−	+/−	+/−	?	+	?	+/−	+
[30]	Retrospective	+	+	-	?	+	?	+	+
[31]	Cross-sectional	+	+	-	+/−	+	?	?	?
[32]	Retrospective	+	+/−	-	+/−	+	?	?	?
[33]	Retrospective	+/−	+	-	?	+	?	?	+
Outcome: MTX adverse effects
[34]	Prospective	+	+	+/−	+	+	+	+	+
[18]	Prospective	+	+	+/−	+	+	+	?	?
[10]	Retrospective	+	+	+/−	?	+	?	+	+
[21]	Retrospective	+	+	+/−	?	+	?	?	+
[20]	Cross-sectional	+	+	+/−	+/−	+	?	?	+
[31]	Cross-sectional	+	+	+/−	+/−	+	?	?	?
[32]	Retrospective	+	+/−	+/−	+/−	+	?	?	?
[35]	Cross-sectional	-	+	+	?	-	?	+	+

Abbreviations: Blind blinding, Det determinant, Dom domain, Loss loss to follow up, Mis missing predictors, Ou t outcome, Rec recruitment, SoC standardization of care.
Bold articles were excluded for analysis.
^aPredictors after 6 months for outcome after 5 years; ^bPredictors at baseline for outcome after 6 months.
Criteria: Domain: + Children with confirmed JIA, according to currently valid ILAR criteria, starting MTX +/− Children with JCA/JRA according to previously valid criteria, or children with JIA and additional criteria (e.g. hospitalized, specific categories only), starting MTX - Children without JIA/JCA/JRA, or no MTX; Determinant: + Prediction model or single predictors corrected for confounding in multivariable analysis +/− Single predictors in univariate analysis - No predictors; Outcome: + Efficacy: Any standardized outcome measurement, follow up >1 year. Adverse effects: Any outcome measurement, follow up >1 year +/− follow-up <1 year - Efficacy: No use of standardized outcome criteria; Blinding: + Both patient and physician blinded (or not applicable in case of objective measurements) +/− Patient or physician not blinded - Not blinded; Recruitment: + Predictors determined at time of start of MTX or <6 months (or time of determination does not matter as in genetic evaluations, gender, age at onset, etc.) +/− Predictors determined more than 6 months after start of MTX, but <1 year - Predictors determined after 1 year, or completely at random; Standardization of care: + All participants treated according to standards of care - No standardized care; Loss to follow up (missing outcome): + <20% and unselective loss to follow up; or >20%, unselective and solved with a statistically valid method (imputation) +/− >20% (not imputed) but unselective loss to follow up - Selective loss to follow up; Missing predictors: + <20% and unselective; or >20%, unselective and solved with a statistically valid method (imputation) +/− >20% (not imputed) but unselective - Selective missing predictors.

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ISSN: 1546-0096

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