Table A3:
GRADE Evidence Profile for Islet Transplantation
| No. of Studies (Design) | Risk of Bias | Inconsistency | Indirectness | Imprecision | Publication Bias | Upgrade Considerations | Quality |
|---|---|---|---|---|---|---|---|
| Glycemic control (non-uremic patients) | |||||||
|
Graft loss/insulin independence 15 (observational): 3 comparative 12 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | Large magnitude of effect (+2) | ⊕⊕⊕⊕ Highc |
|
HbA1c 15 (observational): 4 comparative 11 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
|
Insulin requirements 11 (observational): 3 comparative 8 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
|
C-peptide 11 (observational): 2 comparative 9 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
|
Hypoglycemia 9 (observational): 9 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
| Glycemic control (uremic patients) | |||||||
|
Graft loss/insulin independence 7 (observational): 4 comparative 3 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | Large magnitude of effect (+2) | ⊕⊕⊕⊕ Highc |
|
HbA1c 8 (observational): 4 comparative 4 noncomparative |
Serious limitations (−1)a | Serious limitations (−1)d | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕ Very Low |
|
Insulin requirements 8 (observational): 4 comparative 4 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
|
C-peptide 7 (observational): 4 comparative 3 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
|
Hypoglycemia 2 (observational): 1 comparative 1 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
| Secondary complications of diabetes (non-uremic patients) | |||||||
|
Cardiovascular disease 4 (observational): 3 comparative 1 noncomparative |
Serious limitations (−1)a | Serious limitations (−1)d | Serious limitations (−1)e | Serious limitations (−1)b | Undetected | None | ⊕ Very Low |
|
Retinopathy 5 (observational): 3 comparative 2 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
|
Nephropathy 6 (observational): 3 comparative 3 noncomparative |
Serious limitations (−1)a | Serious limitations (−1)d | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕ Very Low |
|
Neuropathy 5 (observational): 3 comparative 2 noncomparative |
Serious limitations (−1)a | Serious limitations (−1)d | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕ Very Low |
| Secondary complications of diabetes (uremic patients) | |||||||
|
Cardiovascular risk factors 6 (observational): 4 comparative 2 noncomparative |
Serious limitations (−1)a | No serious limitations | Serious limitations (−1)e | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
|
Nephropathy 6 (observational): 4 comparative 2 noncomparative |
Serious limitations (−1)a | No serious limitations | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
| Health-related quality of life (non-uremic patients) | |||||||
| 12 (observational): 2 comparative 10 noncomparative |
Serious limitations (−1)a | Serious limitations (−1)a | Serious limitations (−1)f | Serious limitations (−1)b | Undetected | None | ⊕ Very Low |
| Health-related quality of life (uremic patients) | |||||||
| 2 (observational): 2 noncomparative |
Serious limitations (−1)a | Serious limitations (−1)a | Serious limitations (−1)f | Serious limitations (−1)b | Undetected | None | ⊕ Very Low |
| Adverse events (non-uremic patients) | |||||||
| 21 (observational): 2 comparative 19 noncomparative |
Serious limitations (−1)a | Serious limitations (−1)a | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
| Adverse events (uremic patients) | |||||||
| 5 (observational): 1 comparative 4 noncomparative |
Serious limitations (−1)a | Serious limitations (−1)a | No serious limitations | Serious limitations (−1)b | Undetected | None | ⊕⊕ Low |
Abbreviations: GRADE, Grading of Recommendations Assessment, Development, and Evaluation; HbA1c, glycosylated hemoglobin.
a
Most studies were of low quality owing to their study design. Noncomparative studies introduce bias and possible confounding. Follow-up period was usually less than 3 years, with few studies assessing outcomes of interest in the long term. Observational studies start at low quality according to GRADE.
b
Most studies had small sample sizes (included < 50 patients total).
c
Evidence upgraded because of large magnitude of effect when compared with insulin. Insulin independence is not possible for patients who are on intensive insulin therapy.
d
Inconsistencies in results.
e
Studies included surrogate outcomes for cardiovascular disease.
f
Studies included both generic and disease-specific scales. Scales are not sensitive to transplantation-specific outcomes.