Abstract
Given the low prevalence of sarcoma, international cooperation is necessary to recruit sufficient numbers of patients for surgical trials. The PARITY (Prophylactic Antibiotic Regimens in Tumour Surgery) trial is the first international multicentre trial in orthopedic oncology and successfully achieved target enrollment of 600 patients across 12 countries. It is important to reflect upon the challenges encountered and experiences gained to inform future trials. The objective of this study is to describe recruitment patterns and examine the differences in enrollment across different PARITY sites and identify variables associated with varying levels of recruitment.
Data from this study was obtained from the PARITY trial Methods Centre and correspondence data. We performed descriptive statistics to demonstrate the recruitment patterns over time. We compared recruitment, time to set up, and time to enroll the first patient between North American and international sites, and sites that had dedicated research personnel. Two-tailed non-paired t-tests were performed to compare average monthly recruitment rates between groups with significance being set at alpha=0.05.
A total of 600 patients from 48 clinical sites and 12 countries were recruited from January 2013 through to October 2019. Average monthly enrollment increased every year of the study. There were 36 North American and 12 international sites. North American sites were able to set up significantly faster than international sites (19.3 vs. 28.3 months p=0.037). However, international sites had a significantly higher recruitment rate per month once active (0.2/month vs. 0.62/month, p=0.018). Of active sites, 40 (83%) had research support personnel and 8 (17%) sites did not. Sites with research personnel were able to reach ‘enrolment ready’ status significantly faster than sites without research support (19.6 vs. 30.7 months, p=0.032). However, there was no significant difference in recruitment rate per month once the sites began enrolling (0.28/month vs. 0.2/month, p=0.63). Trial sites that took longer than 1 year to recruit their first patient had 3x lower average recruitment rate compared to sites that were able to recruit their first patient within a year of being enrolment ready.
The PARITY trial is the first multicentre RCT in orthopaedic oncology. The PARITY investigators were able to increase the recruitment levels throughout the trial and generally avoid trial fatigue. This was a North American based trial which may explain the longer start up times internationally given the different regulatory bodies associated with drug-related trials. However, international sites should be considered critical as they were able to recruit significantly more patients per month once active. The absence of research support personnel should not preclude a site from inclusion. These sites took longer to setup but had no difference in monthly recruitment once active. This study will create a framework for identifying and targeting high yield sites for future randomized control trials within orthopaedic oncology to maximum recruitment and resource allocation. Data quality is another consideration that will be addressed in future analyses of the PARITY trial.
