Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis.
OBJECTIVE
To investigate whether discrepancies in trials of use of bone marrow stem cells in patients with heart disease account for the variation in reported effect size in improvement of left ventricular function.


METHODS
Identification and counting of factual discrepancies in trial reports, and sample size weighted regression against therapeutic effect size. Meta-analysis of trials that provided sufficient information.


METHODS
PubMed and Embase from inception to April 2013.
Randomised controlled trials evaluating the effect of autologous bone marrow stem cells for heart disease on mean left ventricular ejection fraction.


RESULTS
There were over 600 discrepancies in 133 reports from 49 trials. There was a significant association between the number of discrepancies and the reported increment in EF with bone marrow stem cell therapy (Spearman's r=0.4, P=0.005). Trials with no discrepancies were a small minority (five trials) and showed a mean EF effect size of -0.4%. The 24 trials with 1-10 discrepancies showed a mean effect size of 2.1%. The 12 with 11-20 discrepancies showed a mean effect of size 3.0%. The three with 21-30 discrepancies showed a mean effect size of 5.7%. The high discrepancy group, comprising five trials with over 30 discrepancies each, showed a mean effect size of 7.7%.


CONCLUSIONS
Avoiding discrepancies is difficult but is important because discrepancy count is related to effect size. The mechanism is unknown but should be explored in the design of future trials because in the five trials without discrepancies the effect of bone marrow stem cell therapy on ejection fraction is zero.
International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London W2 1LA, UK.
Alexandra N
AN
Nowbar
Michael
M
Mielewczik
Maria
M
Karavassilis
Hakim-Moulay
HM
Dehbi
Matthew J
MJ
Shun-Shin
Siana
S
Jones
James P
JP
Howard
Graham D
GD
Cole
Darrel P
DP
Francis
D016026:Bone Marrow Transplantation / Q000379:methods*; D006331:Heart Diseases / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards; D033581:Stem Cell Transplantation / Q000379:methods*; D013318:Stroke Volume / Q000502:physiology; D014182:Transplantation, Autologous