Randomized clinical trials inHepatology: Predictors of quality

Abstract

Evidence shows that the quality of randomized clinical trials (RCTs) affects estimates of intervention efficacy, which is significantly exaggerated in low-quality trials. The present study examines the quality of all 235 RCTs published in HEPATOLOGY from the initiation in 1981 through August 1998. Quality was assessed by means of a validated 5-point scale and separate quality components associated with empirical evidence of bias. Only 26% of all RCTs reported sample size calculations, 52% adequate generation of the allocation sequence, 34% adequate allocation concealment and 34% double-blinding. The median quality score of all trials was 3 points (range, 1-5 points). Multiple logistic regression analysis explored the association between quality and therapeutic areas, number of centers, external funding, year of publication, and country of origin. Highquality trials were most likely to investigate portal hypertension (odds ratio Randomized clinical trials (RCTs) and systematic reviews of RCTs are the most reliable tools in estimating intervention efficacy. 1 However, deficiencies in the quality of the design, conduct, and report of RCTs may bias the estimates of intervention efficacy. [2][3][4][5] To quantify the quality of RCTs, a number of scales have been developed. 6 A main limitation of quality assessments is that there is no comparative gold standard. However, one quality scale 7 has been validated against the quantitative results of RCTs. 4,8 A low-quality score was associated with 34% exaggeration of the estimated intervention efficacy. 4 Furthermore, estimates of intervention efficacy are exaggerated by 30% to 37% in RCTs with unclear or inadequate allocation concealment 3,4 and by 17% in RCTs without double-blinding. 3 The quality of RCTs has been shown to improve with time 9,10 and to differ between intervention areas in primary health care. 11 An increasing number of RCTs are multicentered and sponsored by the industry. 12 The quality of RCTs in relation to the number of participating centers has not previously been examined, but the quality of trials sponsored by drug companies was not significantly different when compared with trials with other sponsors. 13 One study found the peer reviewing in Gastroenterology biased against nonAmerican authors. 14 It is not known whether this nationality bias is reflected in the quality of published RCTs.[Insufficient registration of RCTs 9,15-18 and publication bias 19 limit the precision in estimates of intervention efficacy. 20 The specialist literature is being handsearched by the Cochrane Hepato-Biliary Group* 21-23 to identify RCTs 9,16,18 and expand the basis on which systematic reviews are performed. 16 The main objective of the present study was to describe the quality of all RCTs published as original articles in HEPATOL-OGY. † The quality assessment describes the confidence that the design, conduct, and report of a RCT will restrict bias. Quality was assessed by means of a validated scale 7 and separate components, which have been associated with empiri...

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“…Articles published in symposia were also similar in quality to those published in the parent journal, although articles published in symposia sponsored by a drug company compared with other symposia articles were less likely to contain a methods section that enabled readers to critically evaluate a study. Finally, a study that assessed the quality of 235 RCTs published in Hepatology from 1981 through 1998 found that higher quality trials were more likely to be sponsored by public organizations (OR=4.2) or by drug or device companies (OR=4.7) than not, although the overall quality of trials in the study was only moderate (i.e., mean of 3 on a validated 5-point scale) (Kjaergard et al 1999).…”