Background: A randomized, controlled trial (RCT) should not be started or interpreted without accounting for evidence from preceding RCTs addressing the same question. Research has suggested that evidence from prior trials is often not accounted for in reports of subsequent RCTs.
Objective: To assess the extent to which reports of RCTs cite prior trials studying the same interventions.
Design: Meta-analyses published in 2004 that combined 4 or more trials were identified; within each meta-analysis, the extent to which each trial report cited the trials that preceded it by more than 1 year was assessed.
Measurements: The proportion of prior trials that were cited (prior research citation index), the proportion of the total participants from prior trials that were in the cited trials (sample size citation index), and the absolute number of trials cited were calculated.
Results: 227 meta-analyses were identified, comprising 1523 trials published from 1963 to 2004. The median prior research citation index was 0.21 (95% CI, 0.18 to 0.24), meaning that less than one quarter of relevant reports were cited. The median sample size citation index (0.24 [CI, 0.21 to 0.27]) was similar, suggesting that larger trials were not selectively cited. Of the 1101 RCTs that had 5 or more prior trials to cite, 254 (23%) cited no prior RCTs and 257 (23%) cited only 1. The median number of prior cited trials was 2, which did not change as the number of citable trials increased. The mean number of preceding trials cited by trials published after 2000 was 2.4, compared with 1.5 for those published before 2000 (P < 0.001).
Limitation: The investigators could not ascertain why prior trials were not cited, and noncited trials may have been taken into account in the trial design and proposal stages.
Conclusion: In reports of RCTs published over 4 decades, fewer than 25% of preceding trials were cited, comprising fewer than 25% of the participants enrolled in all relevant prior trials. A median of 2 trials was cited, regardless of the number of prior trials that had been conducted. Research is needed to explore the explanations for and consequences of this phenomenon. Potential implications include ethically unjustifiable trials, wasted resources, incorrect conclusions, and unnecessary risks for trial participants.
Primary funding source: None.