Does asymmetry in patient recruitment in large critical care trials follow the Pareto principle?

Abstract

Background: Randomised controlled trials (RCT) may be hindered by slow recruitment rates, particularly in critically ill patients. While statistical models to predict recruitment rates have been described, no systematic assessment has been conducted of the distribution of recruitment across sites, temporal trends in site participation and impact of competing trials on patient recruitment. Methods: We used recruitment and screening logs from the SAFE, NICE-SUGAR, RENAL, CHEST and ADRENAL trials, five of the largest critical care RCTs. We quantified the extent of recruitment asymmetry between sites using Lorenz curves and Gini coefficients and assessed whether the recruitment distribution across sites follow the Pareto principle, which states that 80% of effects come from 20% of causes. Peak recruitment rates and growth in participating sites were calculated. Results: In total, 25,412 patients were randomised in 99 intensive care units (ICUs) for the five trials. Distribution of recruitment was asymmetric, with a small number of ICUs recruiting a large proportion of the patients. The Gini coefficients ranged from 0.14 to 0.52. The time to peak recruitment rate ranged from 7 to 41 months and was variable (7, 31, 41, 10 and 40 months). Over time, the proportion of recruitment at non-tertiary ICUs increased from 15% to 34%. Conclusions: There is asymmetry of recruitment with a small proportion of ICUs recruiting a large proportion of patients. The distributions of recruitment were not consistent with the Pareto principle. There has been increasing participation of non-tertiary ICUs in clinical trials.

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)

“…The patient accrual rate was 3.4 patients per month (~ 1.9 patients/month/site). However, with the exception of the lead site, the other sites were only recruiting for ≤ 5 months, while peak recruitment in critical care RCTs is generally not achieved until at least 7 months after a site initiates recruitment [ 73 ]. Therefore, we believe that a reasonable expected accrual rate for a multi-year, multi-site RCT would be 2 patients/month/site, which is within the range observed in other completed large, multi-centre PICU RCTs performed in the last decade by large research consortiums [ 74 – 81 ].…”

Recruitment characteristics of randomised trials in critical care: A systematic review

“…13 Not all eligible patients at participating sites are randomised into RCTs [14][15][16] and recruitment rates can be highly variable. 17 Projected recruitment rates are often higher than actual recruitment rates. 18 Systematic evaluation of recruitment characteristics of RCTs in critical care has not been reported.…”

Inequality indices to monitor geographic differences in incidence, mortality and fatality rates over time during the COVID-19 pandemic

“…How is the inequality between malaria prevalence among populations [ 13 ]? Inequality studies also concern the distribution of patient recruitment into clinical trials in different settings [ 14 ].…”