Leflunomide

Major congenital malformations

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S2900
R4091		 Bérard, 2018 Major congenital malformations 1st trimester nested case control unexposed (general population or NOS) Adjustment: Yes 0.97 [0.81;1.16] 5/51   14,363/144,265 14,368 51
ref
S4080
R8677		 Karadag, 2013 Major malformations early pregnancy retrospective cohort unexposed, sick Adjustment: No 5.00 [0.07;366.35] C 0/2   0/8 0 2
ref
S13720
R53449		 Viktil (Controls exposed to other treatments), 2012 Major malformations 3 months or more before pregnancy or1st trimester population based cohort propective exposed to other treatment, sick excluded Adjustment: No 9.30 [0.37;231.05] C
excluded (control group) 		0/2   50/1,459 50 2
ref
S13721
R53451		 Viktil (Controls unexposed, NOS), 2012 Major malformations 3 months or more before pregnancy or1st trimester excluded population based cohort propective unexposed (general population or NOS) Adjustment: No 10.00 [0.41;245.45] C
excluded (exposition period) 		0/2   5,000/154,976 5,000 2
ref
S2970
R4181		 Chambers (Unexposed control, disease free), 2010 Major structural defects (live births and pregnancy losses) 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 1.20 [0.23;6.17] C
excluded (control group) 		3/63   3/75 6 63
ref
S2969
R4168		 Chambers (Unexposed control, sick), 2010 Major structural defects (live births and pregnancy losses) 1st trimester prospective cohort unexposed, sick Adjustment: No 0.71 [0.18;2.84] C 3/63   7/106 10 63
ref
Total 3 studies 0.97 [0.81;1.16] 14,378 116
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Bérard, 2018Bérard, 2018 0.97[0.81; 1.16]14,3685198%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Karadag, 2013Karadag, 2013 5.00[0.07; 366.35]020%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Chambers (Unexposed control, sick), 2010Chambers, 2010 1 0.71[0.18; 2.84]10632%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (3 studies) I2 = 0% 0.97[0.81; 1.16]14,3781160.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Unexposed control, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.85[0.23; 3.19]10650%NAKaradag, 2013 Chambers (Unexposed control, sick), 2010 2 case control studiescase control studies 0.97[0.81; 1.16]14,36851 -NABérard, 2018 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.97[0.81; 1.16]14,36851 -NABérard, 2018 1 unexposed, sickunexposed, sick 0.85[0.23; 3.19]10650%NAKaradag, 2013 Chambers (Unexposed control, sick), 2010 2 Tags Adjustment   - No  - No 0.85[0.23; 3.19]10650%NAKaradag, 2013 Chambers (Unexposed control, sick), 2010 2   - Yes  - Yes 0.97[0.81; 1.16]14,36851 -NABérard, 2018 1 All studiesAll studies 0.97[0.81; 1.16]14,3781160%NABérard, 2018 Karadag, 2013 Chambers (Unexposed control, sick), 2010 30.210.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

Asymetry test p-value = NaN (by Egger's regression)

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 2970, 13720

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.97[0.81; 1.16]14,3741140%NABérard, 2018 Chambers (Unexposed control, disease free), 2010 2 unexposed, sick controlsunexposed, sick controls 0.85[0.23; 3.19]10650%NAKaradag, 2013 Chambers (Unexposed control, sick), 2010 20.510.01.0