The Hazards of Scoring the Quality of Clinical Trials for Meta-analysis

TLDR

Many quality assessment scales exist for clinical trials, making it unclear how to best evaluate trial quality. The study aims to determine whether the type of quality assessment scale used affects the conclusions of meta‑analytic studies. The authors performed a meta‑analysis of 17 trials comparing low‑molecular‑weight heparin with standard heparin for postoperative thrombosis prevention, using 25 different quality scales to identify high‑quality trials. The analysis showed that summary quality scores were not consistently associated with treatment effects; some scales indicated no superiority of LMWH, others the opposite, and open outcome assessment exaggerated LMWH’s effect by about 35%, indicating that using summary scores to identify high‑quality trials is problematic.

Abstract

Although it is widely recommended that clinical trials undergo some type of quality review, the number and variety of quality assessment scales that exist make it unclear how to achieve the best assessment.To determine whether the type of quality assessment scale used affects the conclusions of meta-analytic studies.Meta-analysis of 17 trials comparing low-molecular-weight heparin (LMWH) with standard heparin for prevention of postoperative thrombosis using 25 different scales to identify high-quality trials. The association between treatment effect and summary scores and the association with 3 key domains (concealment of treatment allocation, blinding of outcome assessment, and handling of withdrawals) were examined in regression models.Pooled relative risks of deep vein thrombosis with LMWH vs standard heparin in high-quality vs low-quality trials as determined by 25 quality scales.Pooled relative risks from high-quality trials ranged from 0.63 (95% confidence interval [CI], 0.44-0.90) to 0.90 (95% CI, 0.67-1.21) vs 0.52 (95% CI, 0.24-1.09) to 1.13 (95% CI, 0.70-1.82) for low-quality trials. For 6 scales, relative risks of high-quality trials were close to unity, indicating that LMWH was not significantly superior to standard heparin, whereas low-quality trials showed better protection with LMWH (P<.05). Seven scales showed the opposite: high quality trials showed an effect whereas low quality trials did not. For the remaining 12 scales, effect estimates were similar in the 2 quality strata. In regression analysis, summary quality scores were not significantly associated with treatment effects. There was no significant association of treatment effects with allocation concealment and handling of withdrawals. Open outcome assessment, however, influenced effect size with the effect of LMWH, on average, being exaggerated by 35% (95% CI, 1%-57%; P= .046).Our data indicate that the use of summary scores to identify trials of high quality is problematic. Relevant methodological aspects should be assessed individually and their influence on effect sizes explored.