Comment

We read with interest the article by Vu et al, ¹ titled “Intravenous acetaminophen for postoperative pain management in patients undergoing living laparoscopic living-donor nephrectomy,” published in Annals of Pharmacotherapy. The authors conducted a retrospective study to determine whether intravenous (IV) acetaminophen administration post–laparoscopic living-donor nephrectomy influenced length of stay (LOS). They included 90 patients in their analysis. They found that patients receiving IV acetaminophen had no improvements in hospital LOS, average pain score, or opioid requirements compared with patients not receiving IV acetaminophen. Patients who received IV acetaminophen also had higher 30-day readmission rate. ¹

We would like to commend Vu et al ¹ for their insightful research work. We would also like to commend Annals of Pharmacotherapy for publishing this article, which did not show significant positive results. It is commonly seen that positive trial results easily get the headlines in the media and are published in more prestigious journals, whereas negative trial results are less frequently published and with more delays. ² In fact, many investigators abandon negative studies and focus their time elsewhere, leaving these studies unpublished. Worse yet, the omission of critical information such as safety data could be potentially harmful to patients and the general public. ² In addition, ignoring negative trial results can also lead to a huge waste of time and resources because other researchers contemplating the same question may perform the same study.

Thus, negative study results can be just as important as positive ones. Unfortunately, the long-standing focus in the research community on rewarding eye-catching and positive findings has resulted in a significant body of unreproducible work. ³ In 2012, researchers at the biotechnology firm Amgen reported that they could replicate only 6 out of 53 landmark studies in oncology and hematology. ³ Negative study results should, therefore, be made easily available to balance the body of related literature in order to avoid publication bias. This is critical to ensure that future clinical practice guidelines and treatment standards reflect the updated and unbiased evidence base. Furthermore, negative trial results may contain important safety information that would otherwise be lost. In a recent article by Meinlschmidt et al, ⁴ titled “Disseminating justified, well-designed, and well- executed studies despite nonsignificant tests,” published in JAMA Psychiatry, the authors questioned the validity of the statement made by Kraemer ⁵ that “tests that are not statistically significant should be regarded as indicative of poorly justified, designed, or executed hypothesis-testing studies,” arguing that such a statement may trigger undesirable recommendations to scientists, reviewers, and editors. Meinlschmidt et al ⁴ believe that this statement may impede the dissemination of scientific study results, where researchers may decide not to report a statistically nonsignificant test for fear of their study being perceived as poorly justified, designed, or executed.

Unquestionably, a well-designed prospective, randomized, double-blind study is essential to achieve reliable results, and validation in parallel studies of those results, which include negative findings so that there is no deviation from the truth, should not be ignored.