An umbrella review of randomized evidence in the field of solid organ transplantation

Article type
Authors
Rapti I1, Christou M1, Kosmoliaptsis V2, Lavasidis G1, Markozannes G1, Tsilidis K1, Ntzani E1
1University of Ioannina, Greece
2University of Cambridge, United Kingdom
Abstract
Background: Following technology breakthroughs and the introduction of new drug categories, the field of solid organ transplantation has experienced a considerable expansion in randomized evidence.
Objectives: In order to summarise the evidence and evaluate the validity of the associations in the field, we performed an umbrella review of meta-analyses of randomized controlled trials (RCTs) examining associations between any intervention and outcome related to solid organ transplantation.
Methods: We searched MEDLINE and the Cochrane Library, and performed manual reference screening up to Feb 2015 with no language limits. For each meta-analysis we estimated the summary effect size by use of random-effects and fixed-effect models, the 95% CI, and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I2, evidence of small-study effects, and evidence of excess significance bias.
Results: We included 94 meta-analyses out of 2725 potentially eligible titles assessing 941 comparisons (median 14 comparisons per meta-analysis; IQR 7 to 27). The median number of RCTs per meta-analysis was 5 (range 3 to 53) involving a median of 750 (range 53 to 10,712) participants. Most studies were conducted on renal (47%) and liver transplant recipients (28%) while only a small number of studies assessed other solid organ recipients. In the 94 meta-analyses, 257 comparisons (34%) compiled evidence on more than 1000 participants with an I2 < 50%. Eight percent of the assessed comparisons showed an I2 larger than 75%. The majority of publications (51%) examined the effectiveness of different immunosuppressive protocols, followed by studies assessing prophylactic antiviral regimes (9%) and osteoporosis prevention (5%). On the basis of the available evidence, the main outcomes assessed were acute rejection, graft loss, patients' or graft survival, serum creatinine, levels of serum lipids and presence of adverse effects.
Conclusions: Though the field of solid organ transplantation has been extensively studied, especially in the domain of immunosuppression regimes, only a minority of associations have robust supporting evidence without hint of bias.