Etanercept updated on 06-01-2019

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.
S4994
R13075		 Drechsel, 2020 Major congenital malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 2.53 [0.10;67.19] C 0/9   1/66 1 9
ref
S4996
R13099		 Fu, 2019 Congenital malformations (majors) 1st trimester randomized controlled trial unexposed, sick Adjustment: Randomisation 0.79 [0.05;12.80] C 1/85   1/67 2 85
ref
S3011
R4360		 Carman (Control unexposed, disease free), 2017 Major malformations during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No 0.95 [0.49;1.85] C
excluded (control group) 		11/210   59/1,078 70 210
ref
S3010
R4350		 Carman (Control unexposed, sick), 2017 Major malformations during pregnancy (anytime or not specified) excluded retrospective cohort (claims database) unexposed, sick Adjustment: No 1.08 [0.57;2.05] C
excluded (exposition period) 		11/210   94/1,932 105 210
ref
S3004
R4288		 Hoxha, 2017 Congenital malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 0.19 [0.01;5.20] C 0/17   1/11 1 17
ref
S4081
R8678		 Bröms (controls unexposed, disease free), 2016 Any major birth defect 3 months or more before pregnancy or1st trimester population based cohort retrospective unexposed, disease free excluded Adjustment: No 1.71 [1.13;2.59] C
excluded (control group) 		24/344   52,592/1,250,192 52,616 344
ref
S3195
R5177		 Bröms (controls unexposed, sick), 2016 Any major birth defect 3 months or more before pregnancy or1st trimester excluded population based cohort retrospective unexposed, sick Adjustment: Yes 1.49 [0.92;2.28]
excluded (exposition period) 		24/344   1,019/21,549 1,043 344
ref
S3137
R4912		 Chambers, 2015 Major birth defects in live born infants at least 1st trimester prospective cohort unexposed, sick Adjustment: Yes 2.77 [1.04;7.35] -/-   -/- - -
ref
S2913
R4114		 Weber-Schoendorfer, 2015 Major birth defects 1st trimester prospective cohort unexposed, disease free Adjustment: No 3.71 [1.47;9.40] C 6/111   21/1,385 27 111
ref
S13722
R53453		 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 0.37 [0.02;6.16] C
excluded (control group) 		0/37   50/1,424 50 37
ref
S13723
R53455		 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 0.41 [0.03;6.70] C
excluded (exposition period) 		0/37   5,000/154,976 5,000 37
ref
S4998
R13107		 Hyrich, 2006 Major fetal abnormalities 1st trimester retrospective cohort unexposed, sick Adjustment: No 0.79 [0.01;44.65] C 0/10   0/8 0 10
ref
Total 6 studies 2.61 [1.40;4.86] 31 232
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 Drechsel, 2020Drechsel, 2020 2.53[0.10; 67.19]194%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Fu, 2019Fu, 2019 0.79[0.05; 12.80]2855%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hoxha, 2017Hoxha, 2017 0.19[0.01; 5.20]1174%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Chambers, 2015Chambers, 2015 2.77[1.04; 7.35]--41%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Weber-Schoendorfer, 2015Weber-Schoendorfer, 2015 3.71[1.47; 9.40]2711145%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hyrich, 2006Hyrich, 2006 0.79[0.01; 44.65]0102%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (6 studies) I2 = 0% 2.61[1.40; 4.86]312320.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.78[1.47; 5.26]291470%NADrechsel, 2020 Hoxha, 2017 Chambers, 2015 Weber-Schoendorfer, 2015 Hyrich, 2006 5 case control studiescase control studies 0 RCTRCT 0.79[0.05; 12.80]285 -NAFu, 2019 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.71[1.47; 9.40]27111 -NAWeber-Schoendorfer, 2015 1 unexposed, sickunexposed, sick 1.96[0.85; 4.53]41210%NADrechsel, 2020 Fu, 2019 Hoxha, 2017 Chambers, 2015 Hyrich, 2006 5 Tags Adjustment   - No  - No 2.43[0.85; 6.96]291478%NADrechsel, 2020 Hoxha, 2017 Weber-Schoendorfer, 2015 Hyrich, 2006 4   - Randomisation  - Randomisation 0.79[0.05; 12.80]285 -NAFu, 2019 1   - Yes  - Yes 2.77[1.04; 7.36]-- -NAChambers, 2015 1 All studiesAll studies 2.61[1.40; 4.86]312320%NADrechsel, 2020 Fu, 2019 Hoxha, 2017 Chambers, 2015 Weber-Schoendorfer, 2015 Hyrich, 2006 60.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.82.4710.000Drechsel, 2020Fu, 2019Hoxha, 2017Chambers, 2015Weber-Schoendorfer, 2015Hyrich, 2006

Asymetry test p-value = 0.0534 (by Egger's regression)

slope=1.7602 (0.3505); intercept=-1.2221 (0.4504); t=2.7132; p=0.0534

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 13722, 4081, 3011

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.71[1.47; 9.40]27111 -NAWeber-Schoendorfer, 2015 1 unexposed, sick controlsunexposed, sick controls 1.96[0.85; 4.53]41210%NADrechsel, 2020 Fu, 2019 Hoxha, 2017 Chambers, 2015 Hyrich, 2006 50.510.01.0