Reexamining the data used in the 2012 guidelines of the American Association for the Study of Liver Diseases for the management of adult patients with ascites due to cirrhosis
Background In 2012, the American Association for the Study of Liver Diseases published practice guidelines for the management of patients with ascites caused by cirrhosis, using data from randomized controlled trials (RCTs) and observational studies. We reexamined the strength of these RCTs by calculating the fragility index (FI), a novel metric proposed for evaluating the robustness of RCTs.
Methods We screened all RCTs referenced in the guidelines for specific criteria. We calculated the FI and fragility quotient (FQ), and analyzed the correlation between FI and several variables.
Results Twenty-one RCTs were included. The median (25th, 75th) FI and FQ were 1 (interquartile range [IQR] 0.5-6) and 0.070 (IQR 0.008-0.166), respectively. For studies that reported the number of patients lost to follow up (12 RCTs), the median of patients lost was 2 (IQR 0-6.5). There was no significant correlation between FI and sample size (rs=0.357), P-value (rs=-0.299), number lost to follow up (rs=0.355), Science Citation Index (rs=0.347), year of publication (rs=-0.085), blinding (rpb=-0.18) or number of centers (rpb=0.10). However, a significant correlation was seen between FI and number needed to treat (rs=-0.549; P=0.015).
Conclusions RCTs in the field of cirrhosis-related ascites are fragile. Of the 21 trials analyzed, 13 had an FI of 3 or below and these trials influenced 13 of the 49 recommendations in the guidelines. We recommend the incorporation of FI and FQ in addition to P-value to better understand the meaning of the results in gastroenterological studies.
Keywords Clinical practice guideline; gastroenterology, randomized clinical trial; biostatistics; fragility index
Ann Gastroenterol 2019; 32 (6): 642-649