Pharmacologic Therapies for Neuropathic Pain: an Assessment of Reporting Biases in Randomized Controlled Trials

Several different reporting biases cited in scientific literature have raised concerns about the overestimation of effects and the subsequent potential impact on the practice of evidence-based medicine and human health. Up to 7% to 8% of the population experiences neuropathic pain (NP), and established treatment guidelines are based predominantly on published clinical trial results. Therefore, we examined published randomized controlled trials (RCTs) of first-line drugs for NP and assessed the relative proportions with statistically significant (ie, positive) and nonsignificant (ie, negative) results and their rates of citation. We determined the relationships between reported study outcome and the frequency of their citations with journal impact factor, sample size, time to publication after study completion, and study quality metrics. We also examined the association of study outcome with maximum study drug dosage and conflict of interest. We found that of 107 published RCTs, 68.2% reported a statistically significant outcome regarding drug efficacy for chronic peripheral and central NP. Positive studies were cited nearly twice as often as negative studies in the literature (P = 0.01), despite similar study sample size, quality metrics, and publication in journals with similar impact factors. The time to publication, journal impact factor, and conflict of interest did not differ statistically between positive and negative studies. Our observations that negative and positive RCTs were published in journals with similar impact at comparable time-lags after study completion are encouraging. However, the citation bias for positive studies could affect the validity and generalization of conclusions in literature and potentially influence clinical practice.