Reasons for Protocol Deviations & Missed Antibiotic Doses in Patients Undergoing Oncological Endoprosthetic Reconstruction

Abstract

Background: Research study protocols are critical in study design, however study implementation can be subject to protocol deviations. The Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial assessed prophylactic intravenous antibiotics on the rate of surgical site infection in patients undergoing oncological endoprosthetic reconstruction of the lower extremity. The objective of this study was to identify the protocol deviations - missed antibiotic doses - in the PARITY trial, and determine the causes of the protocol deviations. Methods: This study is a secondary analysis of the PARITY trial data set. The patients in the original trial were randomized to receive either 24 hours or five days of postoperative intravenous antibiotics, for a total of 15 doses. Patients that missed doses and the reason for each missed dose were recorded in the database and summarized descriptively herein. This data was then compared between clinical sites with high and low volume, between nationalities and between the economic development status of the clinical site location. Results: The PARITY trial included 604 participants with 218 patients missing at least one antibiotic dose. The most common reason across all clinical sites was that patients were discharged earlier than the five-day protocol. This finding was consistent across high and low volume sites and across clinical sites in areas of different economic development. The reasons for protocol deviations varied across clinical sites of different nationalities. Conclusions: Protocol deviations - missed antibiotic doses - were common but of minimal severity in the PARITY trial. The most commonly reported reason for missed antibiotic doses was discharge earlier than the five-day protocol and not due to clinical site personnel error. Nevertheless, this study did identify actionable improvements to study protocol adherence such as careful monitoring of drug administration, investigator equipment, and availability of study drug.