Prophylactic antibiotic regimens in tumour surgery (PARITY): a pilot multicentre randomised controlled trial
The PARITY Investigators
Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours.
We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens.
We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol.
It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up.
Levels of Evidence Presented at the Musculoskeletal Tumor Society and Orthopaedic Trauma Association Annual Meetings
Daniel M. Lerman, MD, Matthew G. Cable, MD, Patrick Thornley, BHSc, Nathan Evaniew, MD, Gerard P. Slobogean, MD, Mohit Bhandari, MD, MSc, PhD, John H. Healey, MD, R. Lor Randall, MD, Michelle Ghert, MD
Level of evidence (LOE) determination is a reliable tool which ranks the strength of research based on a study’s design. Improvements in LOE are necessary for the advancement of evidence-based clinical care.
(1) Has the LOE presented at the Musculoskeletal Tumor Society (MSTS) annual meeting improved over time? (2) How does the LOE for MSTS annual meetings compare to that of the Orthopaedic Trauma Association (OTA) annual meetings over the past decade?
We reviewed abstracts from MSTS and OTA annual meeting podium presentations from 2005 to 2014. Three independent reviewers evaluated a total of 1222 abstracts for study type and LOE. Changes in the distributions of study type and LOE over time were evaluated by Pearson Chi-Squared test.
There were 577 abstracts from MSTS and 645 from OTA. Of the MSTS therapeutic studies, 0.5% (2/376) were level I, while 74.7% (281/376) were level IV. There was a seven- fold higher proportion of level I studies (3.42% [14/409]) and less than half as many level IV studies (31.7% [130/409]) presented at OTA. There was no improvement in MSTS LOE for all study types (p=0.13) and therapeutic (p=0.36) study types during the reviewed decade. In contrast, OTA LOE increased significantly over this time for all study types (p<0.01). The proportion of controlled therapeutic studies (LOE I through III) versus uncontrolled studies (LOE IV) increased significantly over time at OTA (p<0.021), but not at MSTS (p=0.10).
Uncontrolled case series continue to dominate the MSTS scientific program, limiting research progress in evidence-based clinical care.