Grade summary of findings tables for the observational studies12–17
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No. of participants (studies) | Quality of the evidence (GRADE) | ||
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| Hydroxyurea | ||||||
| Haematological data (HbF) Percentage | Not estimable | Not estimable | Significant increase in HbF after HU use In one study the change was 11.2 (7.1 to 15.4).13 In another HbF changed from 19.8±6.9 to 24.4±6.317 | 45 (3 studies) | ⊕⊝⊝⊝ very low† | |
| Pain episodes (vaso occlusive pain events) Number of events | Study population | RR 0.79 (0.71 to 0.89) | 523 (1 study) | ⊕⊝⊝⊝ very low‡ | ||
| Moderate | ||||||
| Hospitalisation Number of events | Study population | HR 0.65 (0.43 to 0.97) | 312 (1 study) | ⊕⊝⊝⊝ very low§¶ | ||
| Moderate | ||||||
| HRQL PedsQL Score | The mean HRQL using pedsQL self report in the control groups was 69 scale scores | The mean HRQL using pedsQL self report in the intervention groups was 75 higher (62 to 86.4 higher)** | HU group=75 (62.0 to 86.4) No HU group=69 (54.1 to 79.9) | 191 (1 study) | ⊕⊝⊝⊝ very low**,††,‡‡ | |
| Neurological event number of events Follow-up: 111 patient-years | Study population | HR 9.4 (1.3 to 70.6) | 43 (1 study) | ⊕⊝⊝⊝ very low§§ | ||
| 606 per 1000 | 1000 per 1000 (702 to 1000) | |||||
| Moderate | ||||||
*The basis for the assumed risk (eg, the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
†There were no comparison groups, the studies were before and after studies.
‡Patient assignment to groups incompletely reported.
§Before and after design.
¶Downgraded due to indirectness (study done in North Carolina).
**Small sample size (n=191) leading to wide CI (imprecision).
††Selection bias likely as patient selection to comparison study groups done by investigator.
‡‡Downgraded due to indirectness (study conducted in North America).
§§Small sample size (n=43) leading to wide CI (imprecision).
GRADE Working Group grades of evidence; High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
GRADE, Grading of Recommendations Assessment, Development and Evaluation; HbF, fetal haemoglobin; HRQL, health related quality of life; HU, hydroxyurea; PedsQL, paediatric quality of life; RR, rate ratio.