Topiramate (All indications)

Oro-facial clefts

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.
S15225
R62458		 Lyons (Topiramate) (Indications NOS), 2023 Oral clefts 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 3.50 [1.64;7.46] -/-   1,314/1,066,086 1,305 -
ref
S10173
R46499		 Blotière (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Oro-facial clefts 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 4.37 [0.97;19.57] C
excluded (control group) 		3/517   4/2,997 7 517
ref
S10048
R46494		 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Oro-facial clefts 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 3.88 [1.25;12.09] C 3/517   2,815/1,875,733 2,818 517
ref
S8605
R28687		 Hernandez-Diaz (Topiramate) (Mixed indications), 2018 Oral clefts 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes 2.69 [1.28;5.64] -/1,790   1,501/1,322,955 1,492 1,790
ref
S8575
R28528		 Tomson (Topiramate), 2018 Cleft lip or palate at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 2.37 [0.12;46.04] C 0/152   3/2,514 3 152
ref
S8616
R28776		 Mines (Topiramate) (Other indications), 2014 Oral cleft 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes 2.20 [0.80;6.40] 5/1,745   20/13,512 25 1,745
ref
S8594
R28608		 Veiby (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Orofacial clefts throughout pregnancy population based cohort retrospective exposed to other treatment, sick Adjustment: No 5.84 [0.23;145.17] C 0/48   1/833 1 48
ref
S10221
R37446		 Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012 Oral clefts 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 3.14 [0.99;9.94] C 5/359   7/1,562 12 359
ref
S8569
R28509		 Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006 Facial cleft 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 23.93 [1.46;392.85] C 1/28   1/647 2 28
ref
Total 8 studies 3.15 [2.12;4.69] 5,658 4,639
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 Lyons (Topiramate) (Indications NOS), 2023Lyons, 2023 1 3.50[1.64; 7.46]1,305-27%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Blotière, 2019 2 3.88[1.25; 12.09]2,81851712%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hernandez-Diaz (Topiramate) (Mixed indications), 2018Hernandez-Diaz, 2018 3 2.69[1.28; 5.64]1,4921,79029%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Tomson (Topiramate), 2018Tomson, 2018 4 2.37[0.12; 46.04]31522%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Mines (Topiramate) (Other indications), 2014Mines, 2014 5 2.20[0.80; 6.40]251,74515%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Veiby (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Veiby, 2014 6 5.84[0.23; 145.17]1482%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012Hernández-Díaz, 2012 7 3.14[0.99; 9.94]1235912%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006Morrow, 2006 8 23.93[1.46; 392.85]2282%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (8 studies) I2 = 0% 3.15[2.12; 4.69]5,6584,6390.950.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Topiramate) (Indications NOS; 2: Topiramate) (Controls unexposed NOS) (Mixed indications; 3: Topiramate) (Mixed indications; 4: Topiramate; 5: Topiramate) (Other indications; 6: Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications; 7: Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications; 8: Topiramate) (Controls exposed to Lamotrigine, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.15[2.12; 4.69]5,6584,6390%NALyons (Topiramate) (Indications NOS), 2023 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Hernandez-Diaz (Topiramate) (Mixed indications), 2018 Tomson (Topiramate), 2018 Mines (Topiramate) (Other indications), 2014 Veiby (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012 Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006 8 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.19[1.98; 5.16]5,6152,3070%NALyons (Topiramate) (Indications NOS), 2023 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Hernandez-Diaz (Topiramate) (Mixed indications), 2018 3 unexposed, sickunexposed, sick 2.20[0.78; 6.22]251,745 -NAMines (Topiramate) (Other indications), 2014 1 exposed to other treatment, sickexposed to other treatment, sick 4.08[1.57; 10.65]185870%NATomson (Topiramate), 2018 Veiby (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012 Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006 4 Tags Adjustment   - No  - No 4.00[1.92; 8.32]2,8361,1040%NABlotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Tomson (Topiramate), 2018 Veiby (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012 Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006 5   - Yes  - Yes 2.86[1.78; 4.58]2,8223,5350%NALyons (Topiramate) (Indications NOS), 2023 Hernandez-Diaz (Topiramate) (Mixed indications), 2018 Mines (Topiramate) (Other indications), 2014 3 All studiesAll studies 3.15[2.12; 4.69]5,6584,6390%NALyons (Topiramate) (Indications NOS), 2023 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Hernandez-Diaz (Topiramate) (Mixed indications), 2018 Tomson (Topiramate), 2018 Mines (Topiramate) (Other indications), 2014 Veiby (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012 Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006 80.550.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.95.01.9680.000Lyons (Topiramate) (Indications NOS), 2023Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Hernandez-Diaz (Topiramate) (Mixed indications), 2018Tomson (Topiramate), 2018Mines (Topiramate) (Other indications), 2014Veiby (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006

Asymetry test p-value = 0.1950 (by Egger's regression)

slope=0.7862 (0.2778); intercept=0.7074 (0.4851); t=1.4583; p=0.1950

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 10173

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.19[1.98; 5.16]5,6152,3070%NALyons (Topiramate) (Indications NOS), 2023 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Hernandez-Diaz (Topiramate) (Mixed indications), 2018 3 unexposed, sick controlsunexposed, sick controls 2.20[0.78; 6.22]251,745 -NAMines (Topiramate) (Other indications), 2014 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 4.16[1.86; 9.34]251,1040%NABlotière (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Tomson (Topiramate), 2018 Veiby (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012 Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006 50.510.01.0