Citation Impact of Breakthrough Interventions for Malignant Blood Disorders.

Background: Citation count is a widely accepted measure of how much a study has drawn attention of other scientists and clinicians. The studies that have generated new, breakthrough interventions that potentially can affect the lives of many patients are expected to be widely disseminated. In this work, we test hypothesis if the breakthrough interventions as discovered in the NCI sponsored phase III hematological malignancies trials received high citation count. NCI trials account for almost 100% of publicly sponsored phase III trials in the US.

Methods: We evaluated all randomized controlled trials (RCTs) that have been conducted by six NCI sponsored cooperative oncology groups (COGs). We included all trials that were completed by 2002. Here, we focus on hematological malignancies trials. We arbitrarily defined as “breakthrough interventions” those interventions that were judged by the investigators highly preferred so they should become standard of care and/or had an effect size was so large that their log hazard ratio for survival or event-free survival was −1 or less. The study which received more than 1,000 citations is considered as highly-cited clinical research paper. (Ioannidis JPA, JAMA 2005)

Results: We evaluated 133 hematological-malignancy trials/comparisons. Ninety-two trials studied leukemias, 38 lymphomas and 3 either multiple myeloma or myelodysplastic syndrome. 26 (20%) interventions were found to meet the criteria for the “breaktrough interventions”. None of the papers met criteria for highly-cited research. Citation counts ranged from 4–311 (median: 62). The highest-cited paper reported the use of All-trans-retinoic acid for induction and maintanence of acute promyelocytic leukemia. This paper is currently cited in NCCN guidelines and the NCI PQD^® treatment website.

Conclusions: The best clinical research in hematological malignancies has received relatively little scientific attention. Elucidating the factors that could explain these findings may help identify the barriers that prevent generation and dissemination of evidence of vital importance for improving outcomes of patients with malignant blood disorders.