Interferon beta (IFN-beta)

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.
S3728
R8025		 Portaccio, 2018 Major anomalies early pregnancy prospective cohort unexposed, sick Adjustment: No 1.27 [0.13;12.35] C 1/76   3/288 4 76
ref
S3716
R7990		 Thiel (control unexposed, sick), 2016 Major congenital anomalies early pregnancy prospective cohort unexposed, sick Adjustment: Yes 0.72 [0.29;1.80] 7/227   10/181 17 227
ref
S3735
R8028		 Colvin - IFN beta1b, 2010 Birth defects 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 3.40 [0.40;28.00] 1/7   4,994/106,067 4,995 7
ref
S3613
R7362		 Weber-Schoendorfer (control exposed to Glatiramer), 2009 Birth defects (major) at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.09 [0.00;1.90] C
excluded (control group) 		0/54   2/26 2 54
ref
S3614
R7366		 Weber-Schoendorfer (control unexposed, disease free), 2009 Birth defects (major) at least 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 0.55 [0.03;9.17] C
excluded (control group) 		0/54   23/1,405 23 54
ref
S3615
R7370		 Weber-Schoendorfer (control unexposed, sick), 2009 Birth defects (major) at least 1st trimester prospective cohort unexposed, sick Adjustment: No 0.14 [0.01;2.83] C 0/54   3/57 3 54
ref
S3723
R8018		 Boskovic (control unexposed, disease free), 2005 Major malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 1.81 [0.15;21.60] C
excluded (control group) 		2/23   1/20 3 23
ref
S3724
R8023		 Boskovic (control unexposed, sick), 2005 Major malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 1.90 [0.16;22.69] C 2/23   1/21 3 23
ref
Total 5 studies 0.90 [0.44;1.87] 5,022 387
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 Portaccio, 2018Portaccio, 2018 1.27[0.13; 12.35]47610%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Thiel (control unexposed, sick), 2016Thiel, 2016 1 0.72[0.29; 1.80]1722764%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Colvin - IFN beta1b, 2010Colvin - IFN beta1b, 2010 3.40[0.40; 28.00]4,995712%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Weber-Schoendorfer (control unexposed, sick), 2009Weber-Schoendorfer, 2009 2 0.14[0.01; 2.83]3546%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Boskovic (control unexposed, sick), 2005Boskovic, 2005 3 1.90[0.16; 22.69]3239%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 0.90[0.44; 1.87]5,0223870.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: control unexposed, sick; 2: control unexposed, sick; 3: control unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.90[0.44; 1.87]5,0223870%NAPortaccio, 2018 Thiel (control unexposed, sick), 2016 Colvin - IFN beta1b, 2010 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.40[0.41; 28.45]4,9957 -NAColvin - IFN beta1b, 2010 1 unexposed, sickunexposed, sick 0.76[0.35; 1.64]273800%NAPortaccio, 2018 Thiel (control unexposed, sick), 2016 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 4 Tags Adjustment   - No  - No 1.34[0.40; 4.48]5,0051600%NAPortaccio, 2018 Colvin - IFN beta1b, 2010 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 4   - Yes  - Yes 0.72[0.29; 1.79]17227 -NAThiel (control unexposed, sick), 2016 1 All studiesAll studies 0.90[0.44; 1.87]5,0223870%NAPortaccio, 2018 Thiel (control unexposed, sick), 2016 Colvin - IFN beta1b, 2010 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 50.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.63.51.8290.000Portaccio, 2018Thiel (control unexposed, sick), 2016Colvin - IFN beta1b, 2010Weber-Schoendorfer (control unexposed, sick), 2009Boskovic (control unexposed, sick), 2005

Asymetry test p-value = 0.7351 (by Egger's regression)

slope=-0.3944 (0.8857); intercept=0.3963 (1.0671); t=0.3714; p=0.7351

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 3723, 3613, 3614

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.77[0.44; 7.18]5,021840%NAColvin - IFN beta1b, 2010 Weber-Schoendorfer (control unexposed, disease free), 2009 Boskovic (control unexposed, disease free), 2005 3 unexposed, sick controlsunexposed, sick controls 0.76[0.35; 1.64]273800%NAPortaccio, 2018 Thiel (control unexposed, sick), 2016 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls Out of scale0.09[0.00; 1.90]254 -NAWeber-Schoendorfer (control exposed to Glatiramer), 2009 10.510.01.0