Randomized clinical trials in Hepatology: Predictors of quality

Authors

  • Lise Lotte Kjaergard,

    1. Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark
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  • Dimitrinka Nikolova,

    1. Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark
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  • Christian Gluud M.D.

    Corresponding author
    1. Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark
    • Dr. Med. Sci., Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Institute of Preventive Medicine, Copenhagen University Hospital, H:S Kommunehospitalet DK-1399 Copenhagen, Denmark fax: 45-3332-4410
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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 inHepatologyfrom 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. High-quality trials were most likely to investigate portal hypertension (odds ratio [OR]: 2.4; 95% CI: 1.1-5.5;P= .03), be multicentered (OR: 3.4; 95% CI: 1.3-8.9;P= .01), sponsored by public organizations (OR: 4.2; 95% CI: 2.1-8.6;P = .0001), or the drug and device industry (OR: 4.7; 95% CI: 2.2-10.2;P= .0001) compared with other therapeutic areas, single-center trials, and trials with no external funding. Quality did not improve with time and was not associated with country of origin. The main conclusions are that the quality of RCTs in Hepatology needs improvement and that the probability of high quality increased with the number of centers involved and external funding.

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