Table 1.
Outcome measures changes in placebo-treated groups with FXS in failed clinical trials – Main Analysis.
| Endpoint | of Studies | Heterogeneity (I2) | Heterogeneity p-Value |
Meta-Analysis Type | Mean Score Change | 95% CI | Change p-Value | |
|---|---|---|---|---|---|---|---|---|
| Lower | Upper | |||||||
| Clinician Rated ‡ | ||||||||
| CGI-I (<12 years) | 3 | 0.97 | 0.00 | Random | −0.45 | −2.00 | 1.10 | 0.570 |
| CGI-I (>12 years) | 4 | 1.00 | 0.00 | Random | 0.46 | −1.83 | 2.76 | 0.693 |
| Caregiver Rated ‡ | ||||||||
| Vineland-II Comp (<12 years) | 2 | 0.00 | 0.47 | Fixed | 1.71 | 0.38 | 3.05 | 0.012 * |
| ABC-CFX Irr (<12 years) | 3 | 0.85 | 0.00 | Random | −3.51 | −8.29 | 1.26 | 0.149 |
| ABC-CFX SU/L (<12 years) | 2 | 0.97 | 0.00 | Random | −2.28 | −7.41 | 2.85 | 0.383 |
| ABC-CFX SA (<12 years) | 2 | 0.98 | 0.00 | Random | −1.44 | −4.07 | 1.20 | 0.284 |
| VAS Comp (<12 years) | 2 | 0.00 | 0.42 | Fixed | 1.56 | 0.94 | 2.18 | <0.001 * |
| Vineland-II Comp (>12 years) | 4 | 0.00 | 0.44 | Fixed | 1.74 | 0.08 | 3.39 | 0.040 * |
| ABC-CFX Total (>12 years) | 2 | 0.00 | 0.72 | Fixed | −8.60 | −12.45 | −4.76 | <0.001 * |
| ABC-CFX Irr (>12 years) ** | 4 | 0.91 | 0.00 | Random | −1.96 | −5.11 | 1.19 | 0.222 |
| ABC-CFX SU/L (>12 years) ** | 4 | 0.93 | 0.00 | Random | −1.90 | −4.51 | 0.71 | 0.154 |
| ABC-CFX Stereo (>12 years) | 2 | 0.00 | 0.69 | Fixed | −1.04 | −1.58 | −0.50 | <0.001 * |
| ABC-CFX Hyper (>12 years) | 2 | 0.00 | 0.84 | Fixed | −1.37 | −2.26 | −0.49 | 0.002 * |
| ABC-CFX SA (>12 years) | 3 | 0.79 | 0.01 | Random | −1.65 | −2.61 | −0.68 | 0.001 * |
| Caregiver Rated † | ||||||||
| Vineland-II Mal (<12 years) | 1 | NA | NA | NA | −0.70 | −1.05 | −0.35 | <0.001 * |
| VAS Anx and Dis (<12 years) | 1 | NA | NA | NA | −15.50 | −22.12 | −8.88 | <0.001 * |
| ABC-CFX Total (<12 years) | 1 | NA | NA | NA | 3.58 | −4.03 | 11.20 | 0.357 |
| ABC-CFX Stereo (<12 years) | 1 | NA | NA | NA | 0.56 | −0.61 | 1.72 | 0.351 |
| ABC-CFX Hyper (<12 years) | 1 | NA | NA | NA | 1.17 | −1.00 | 3.33 | 0.291 |
| SPM-P Soc Part (<12 years) | 1 | NA | NA | NA | −0.90 | −3.99 | 2.19 | 0.568 |
| ABC-FX Speech (<12 years) | 1 | NA | NA | NA | −0.90 | −1.39 | −0.41 | <0.001 * |
| Vineland-II Mal (>12 years) | 1 | NA | NA | NA | −0.60 | −0.91 | −0.29 | <0.001 * |
| VAS Comp (>12 years) | 1 | NA | NA | NA | 2.79 | 1.68 | 3.89 | <0.001 * |
| VAS Dis and Anx (>12 years) | 1 | NA | NA | NA | −14.10 | −49.36 | 21.16 | 0.433 |
| ABC-CFX Speech (>12 years) | 1 | NA | NA | NA | 0.56 | −0.45 | 1.56 | 0.277 |
| ADAMS Total (>12 years) | 1 | NA | NA | NA | −10.63 | −13.55 | −7.71 | <0.001 * |
| SRS (>12 years) | 1 | NA | NA | NA | −6.58 | −10.28 | −2.87 | 0.001 * |
| RBS-S (>12 years) | 1 | NA | NA | NA | −5.35 | −7.60 | −3.09 | <0.001 * |
| Performance Based Assessment † | ||||||||
| MSEL Comp (<12 years) | 1 | NA | NA | NA | 1.47 | −1.7 | 4.64 | 0.364 |
| ADOS (<12 years) | 1 | NA | NA | NA | -0.78 | −2.88 | 1.31 | 0.463 |
| PLS5_ac_rs (<12 years) | 1 | NA | NA | NA | 3.85 | −0.12 | 7.82 | 0.057 |
| PLS5_ec_rs (<12 years) | 1 | NA | NA | NA | 3.41 | −0.55 | 7.36 | 0.091 |
| PLS Composite (<12 years) | 1 | NA | NA | NA | 7.26 | −0.3 | 14.82 | 0.060 |
| RBANS (>12 years) | 1 | NA | NA | NA | 0.69 | −2.29 | 3.67 | 0.650 |
| Memory 10 Test (>12 years) | 1 | NA | NA | NA | 0.05 | −0.02 | 0.12 | 0.188 |
| KiTAP 3 module (>12 years) | 1 | NA | NA | NA | -0.07 | −0.18 | 0.03 | 0.168 |
| KiTAP go no go (>12 years) | 1 | NA | NA | NA | -42.70 | −145.12 | 59.72 | 0.414 |
Abbreviations: FXS, fragile X syndrome; CGI-I, Clinician Global Impression-Improvement; Vineland-II Comp, Vineland Adaptive Behavior Scale-2nd edition, Composite; Vineland-II Mal, Maladaptive Behavior Subscale; ABC-CFX Irr, Aberrant Behavior Checklist-Community Irritability refactored for FXS; ABC-CFX SU/L, Socially Unresponsive/Lethargy; ABC-CFX Hyper, Hyperactivity; ABC-CFX Stereo, Stereotypy; ABC-CFX Speech, Inappropriate Speech; ABC-CFX SA, Social Avoidance; ABC-CFX Total, Total Score; VAS Comp, Visual Analog Scale, Composite; VAS Dis and Anx, Disruptive and Anxiety Behavior Subscales; SPM-P Soc Part, Sensory Processing Measure—Preschool Social Participation Subtest; ADAMS Total, Anxiety Depression and Mood Scale Total Score; SRS, Social Responsiveness Scale™; RBS-S, Repetitive Behavior Scale; MSEL, Mullen Scales of Early Learning-Composite; ADOS, Autism Diagnostic Observation Schedule; PLS-5, Preschool Language Scale, Fifth Ed; ac_rs, auditory comprehension raw score; ec_rs, expressive communication raw score, PLS-5 Comp, Composite Score; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; KiTAP, the Test of Attentional Performance for Children-3 modules, go/no-go subtests. ‡ Meta-Analysis was conducted on subscales that were used in 2 or more papers, using a pre-post correlation of 0.7, † but not on subscales used in 1 paper. * Indicates p-value < 0.05. ** The ABC-C subscale was used for lethargy and irritability in 2 studies, in contrast to the ABC-CFX subscale used in other studies.