Table 3. Heterogeneity associated with methodological characteristics.
| Study design characteristic | Average bias (95% CI) | Increase in between-trial heterogeneity* (95% CI) | Variation in average bias (95% CI) |
|---|---|---|---|
| Inadequate/unclear sequence generation (versus adequate) | |||
| Armijo-Olivo 2015: All outcomes | dSMD -0.02 (-0.15, 0.12) | NR | tau 0.10 |
| BRANDO (Savović 2012): All outcomes | ROR 0.90 (0.82, 0.99) | tau 0.06 (0.01, 0.20) | tau 0.05 (0.01, 0.15) |
| BRANDO (Savović 2012): Mortality | ROR 0.86 (0.69, 1.06) | tau 0.08 (0.01, 0.31) | tau 0.06 (0.01, 0.28) |
| BRANDO (Savović 2012): Other objective | ROR 1.00 (0.84, 1.20) | tau 0.07 (0.01, 0.30) | tau 0.07 (0.01, 0.27) |
| BRANDO (Savović 2012): Subjective | ROR 0.88 (0.76, 1.00) | tau 0.05 (0.01, 0.21) | tau 0.06 (0.01, 0.24) |
| Papageorgiou 2015: All outcomes | dSMD -0.01 (-0.26, 0.25) | NR | tau 0.46 |
| Inadequate/unclear allocation concealment (versus adequate) | |||
| Armijo-Olivo 2015: All outcomes | dSMD -0.12 (-0.30, 0.06) | NR | tau 0.21 |
| BRANDO (Savović 2012): All outcomes | ROR 0.89 (0.81, 0.99) | tau 0.06 (0.01, 0.19) | tau 0.05 (0.01, 0.18) |
| BRANDO (Savović 2012): Mortality | ROR 1.03 (0.82, 1.31) | tau 0.07 (0.01, 0.30) | tau 0.07 (0.01, 0.33) |
| BRANDO (Savović 2012): Other objective | ROR 0.92 (0.76, 1.12) | tau 0.06 (0.01, 0.24) | tau 0.06 (0.01, 0.29) |
| BRANDO (Savović 2012): Subjective | ROR 0.82 (0.70, 0.94) | tau 0.08 (0.01, 0.27) | tau 0.07 (0.01, 0.30) |
| Herbison 2011: All outcomes | ROR 0.91 (0.83, 0.99) | NR | tau 0.19 |
| Nuesch 2009a: Subjective outcomes | dSMD -0.15 (-0.31, 0.02) | NR | tau 0.24 |
| Lack of/unclear blinding of participants (versus blinding) | |||
| Hrobjartsson 2014b: Subjective | dSMD -0.56 (-0.71, -0.41) | NA | I2 60% |
| Nuesch 2009a: Subjective | dSMD -0.15 (-0.39, 0.09) | NR | tau 0.26 |
| Lack of/unclear blinding of outcome assessor (versus blinding) | |||
| Hrobjartsson 2012: Subjective | ROR 0.64 (0.43, 0.96) | NA | I2 45% |
| Hrobjartsson 2013: Subjective | dSMD -0.23 (-0.40, -0.06) | NA | I2 46% |
| Hrobjartsson 2014a: Subjective (standard trials) | RHR 0.73 (0.57, 0.93) | NA | I2 24% |
| Hrobjartsson 2014a: Subjective (atypical trials) | RHR 1.33 (0.98, 1.82) | NA | I2 0% |
| Lack of/unclear double blinding (versus double blinding) | |||
| BRANDO (Savović 2012): All outcomes | ROR 0.86 (0.73, 0.98) | tau 0.20 (0.02, 0.39) | tau 0.17 (0.03, 0.32) |
| BRANDO (Savović 2012): Mortality | ROR 1.07 (0.78, 1.48) | tau 0.09 (0.01, 0.44) | tau 0.08 (0.01, 0.42) |
| BRANDO (Savović 2012): Other objective | ROR 0.91 (0.64, 1.33) | tau 0.10 (0.01, 0.50) | tau 0.20 (0.02, 0.85) |
| BRANDO (Savović 2012): Subjective | ROR 0.77 (0.61, 0.93) | tau 0.24 (0.02, 0.45) | tau 0.20 (0.04, 0.39) |
| Attrition (versus no or minimal attrition) | |||
| Abraha 2015: All outcomes | ROR 0.80 (0.69, 0.94) | NR | tau 0.28 |
| Abraha 2015: Objective | ROR 0.80 (0.60, 1.06) | NR | tau 0.42 |
| Abraha 2015: Subjective | ROR 0.84 (0.70, 1.01) | NR | tau 0.33 |
| BRANDO (Savović 2012): All outcomes | ROR 1.07 (0.92, 1.25) | tau 0.07 (0.01, 0.24) | tau 0.06 (0.01, 0.24) |
| BRANDO (Savović 2012): Mortality | ROR 1.07 (0.80, 1.42) | tau 0.10 (0.01, 0.32) | tau 0.09 (0.01, 0.75) |
| BRANDO (Savović 2012): Other objective | ROR 1.35 (0.63, 2.94) | tau 0.13 (0.01, 1.05) | tau 0.13 (0.01, 1.15) |
| BRANDO (Savović 2012): Subjective | ROR 1.03 (0.79, 1.36) | tau 0.07 (0.01, 0.38) | tau 0.07 (0.01, 0.35) |
* tau is on the log scale for RORs, but not for dSMDs
CI = confidence interval; dSMD = difference in standardised mean differences; NA = not applicable; NR = not reported; RHR = ratio of hazard ratios; ROR = ratio of odds ratios. dSMD < 0 and ROR and RHR < 1 = larger effect in trials with inadequate characteristic (or at high/unclear risk of bias)