Ondansetron

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.
S3471
R6647		 Bérard, 2019 Major malformations 1st trimester population based cohort propective unexposed (general population or NOS) Adjustment: Yes 0.57 [0.13;2.49] 2/31   14,402/179,106 14,404 31
ref
S3852
R8209		 Huybrechts, 2019 Congenital malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Intravenous 1.02 [0.96;1.08] -/23,866   -/1,762,018 - 23,866
ref
S2852
R3862		 Huybrechts (Control exposed to other treatment), 2018 Any congenital malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 1.00 [0.95;1.05]
excluded (control group) 		2,067/55,579   6,137/185,699 8,204 55,579
ref
S2844
R3816		 Huybrechts (Unexposed control), 2018 Any congenital malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.01 [0.98;1.05] 3,275/88,446   54,163/1,727,546 57,438 88,446
ref
S2752
R3660		 Danielsson, 2014 Relatively severe malformation early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.11 [0.81;1.53] 38/1,349   43,658/1,501,434 43,696 1,349
ref
S2753
R3671		 Andersen, 2013 Major congenital malformations 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.30 [1.00;1.70] 58/1,248   31,357/895,770 31,415 1,248
ref
S2775
R3724		 Colvin, 2013 Any major birth defect 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.20 [0.60;2.20] 10/211   3,975/98,062 3,985 211
ref
S2755
R3670		 Einarson (Control exposed to other antiemetics), 2004 Major malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.93 [0.47;7.84] C
excluded (control group) 		6/169   3/160 9 169
ref
S2754
R3666		 Einarson (Unexposed control), 2004 Major malformations 1st trimester prospective cohort unexposed, disease free Adjustment: No 1.95 [0.48;7.94] C 6/169   3/162 9 169
ref
Total 7 studies 1.02 [0.99;1.05] 150,947 115,320
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, 2019Bérard, 2019 0.57[0.13; 2.49]14,404310%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Huybrechts, 2019Huybrechts, 2019 1.02[0.96; 1.08]-23,86625%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Huybrechts (Unexposed control), 2018Huybrechts, 2018 1 1.01[0.98; 1.05]57,43888,44673%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Danielsson, 2014Danielsson, 2014 1.11[0.81; 1.53]43,6961,3491%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Andersen, 2013Andersen, 2013 1.30[1.00; 1.70]31,4151,2481%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Colvin, 2013Colvin, 2013 1.20[0.60; 2.20]3,9852110%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Einarson (Unexposed control), 2004Einarson, 2004 2 1.95[0.48; 7.94]91690%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 0% 1.02[0.99; 1.05]150,947115,3200.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Unexposed control; 2: Unexposed control;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.02[0.99; 1.05]150,947115,3200%moderateBérard, 2019 Huybrechts, 2019 Huybrechts (Unexposed control), 2018 Danielsson, 2014 Andersen, 2013 Colvin, 2013 Einarson (Unexposed control), 2004 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.02[0.99; 1.05]150,947115,3200%moderateBérard, 2019 Huybrechts, 2019 Huybrechts (Unexposed control), 2018 Danielsson, 2014 Andersen, 2013 Colvin, 2013 Einarson (Unexposed control), 2004 7 Tags Adjustment   - No  - No 1.31[0.73; 2.36]3,9943800%moderateColvin, 2013 Einarson (Unexposed control), 2004 2   - Yes  - Yes 1.02[0.98; 1.06]146,953114,9408%moderateBérard, 2019 Huybrechts, 2019 Huybrechts (Unexposed control), 2018 Danielsson, 2014 Andersen, 2013 5 IntravenousIntravenous 1.02[0.96; 1.08]-23,866 -moderateHuybrechts, 2019 1 All studiesAll studies 1.02[0.99; 1.05]150,947115,3200%moderateBérard, 2019 Huybrechts, 2019 Huybrechts (Unexposed control), 2018 Danielsson, 2014 Andersen, 2013 Colvin, 2013 Einarson (Unexposed control), 2004 70.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.81.80.9040.000Bérard, 2019Huybrechts, 2019Huybrechts (Unexposed control), 2018Danielsson, 2014Andersen, 2013Colvin, 2013Einarson (Unexposed control), 2004

Asymetry test p-value = 0.1892 (by Egger's regression)

slope=0.0012 (0.0165); intercept=0.6301 (0.4147); t=1.5192; p=0.1892

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 2755, 2852

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.02[0.99; 1.05]150,947115,3200%NABérard, 2019 Huybrechts, 2019 Huybrechts (Unexposed control), 2018 Danielsson, 2014 Andersen, 2013 Colvin, 2013 Einarson (Unexposed control), 2004 7 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.00[0.95; 1.05]8,21355,7480%NAHuybrechts (Control exposed to other treatment), 2018 Einarson (Control exposed to other antiemetics), 2004 20.510.01.0