Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis

Abstract

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.Design 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. Data sources PubMed and Embase from inception to April 2013.Eligibility for selecting studies 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.

Doubts over heart stem-cell therapy

“…But a comprehensive study that looked at discrepancies in trials investigating treatments that use patients' own stem cells, published this week in the journal BMJ (ref. 1), finds that only trials containing flaws, such as design or reporting errors, showed positive outcomes. Error-free trials showed no benefit at all.…”

Engineering Cardiovascular Regeneration

“…Advantages of BMC that explain their fast and widespread clinical application in cardiology is their already established clinical use (for bone marrow transplantation in hematological indications), the autologous approach, simple access, and apparent lack of side effects. The main disadvantages are the lack of convincing evidence that BMC can form new cardiomyocytes [13,14] and lack of clinically relevant effects [15]. Moreover, the concept of a Bparacrine^mechanism of action, generally employed to explain positive effects on heart function in the absence of new myocardium, is controversial in light of the fact that BMC that are infused into the coronary circulation do not even remain in the myocardium for extended periods at a relevant rate [16].…”

Mesenchymal stem cells seem too good to believe!

“…What cell types did they generate and how were the effects mediated? Not all the recent news on stem cells has been good [11]. The findings will need to be replicated.…”