Table 2.
Certainty assessment of the outcomes – application of the GRADE system.
| Outcomes | Certainty assessment |
Certainty | Importance | |||||
|---|---|---|---|---|---|---|---|---|
| Trials | Risk of bias | Inconsistency | Indirectness of evidence | Imprecision | Other considerations | |||
| The absence of complete disease remission | CCG 1962 POG 8866 | Seriousa | Seriousb | Not serious | Not serious | Highly suspicious publication bias All potential confounders would suggest a spurious effect, and yet no effect was observeda |
 LOW |
CRITICAL |
| Number of postdiagnosis events | CCG 1962 DFCI 87-01 DFCI 05-001 DFCI 01-91 |
Seriousd | Not serious | Not serious | Not serious | Highly suspicious publication bias All potential confounders would suggest a spurious effect, and yet no effect was observedc, d |
 MODERATE |
CRITICAL |
| Overall mortality | DFCI 87-01 DFCI 05-001 |
Serious | Seriouse | Not serious | Not serious | Highly suspicious publication bias All potential confounders would suggest a spurious effect, and yet no effect was observedc |
LOW |
CRITICAL |
| Hypersensitivity | CCG 1962 POG 8866 DFCI 05-001 | Serious a | Not serious | Not serious | Seriousf | Highly suspicious publication bias All potential confounders would suggest a spurious effect, and yet no effect was observeda |
LOW |
CRITICAL |
CI: confidence interval; RR: relative risk.
Explanations:
The POG 8866 recruited patients previously treated with native L-Asparaginase and who were in a second bone marrow relapse and included hypersensitive patients, circumstances that may influence the response to treatment.
The analysis of the studies showed an I2 > 70% (high heterogeneity between the trials).
The protocol DFCI 87-01 used only one dose of PEG-Asparaginase; the remainder of the treatment was performed with native L-asparaginase.
The protocol DFCI 91-01 did not report the calculation used for the number of patients randomized in the trial.
The analysis of the studies showed an I2 = 56% (considerable heterogeneity between the trials).
The CI demonstrated in the analysis for the CCG 1962 ([0.25, 101.95]) and POG 8866 ([0.39, 6.47]) are high, bringing imprecision to the effect estimate.