Optimizing accrual to a large-scale, clinically integrated randomized trial in anesthesiology: A 2-year analysis of recruitment

Abstract

Background: Performing large randomized trials in anesthesiology is often challenging and costly. The clinically integrated randomized trial is characterized by simplified logistics embedded into routine clinical practice, enabling ease and efficiency of recruitment, offering an opportunity for clinicians to conduct large, high-quality randomized trials under low cost. Our aims were to (1) demonstrate the feasibility of the clinically integrated trial design in a high-volume anesthesiology practice and (2) assess whether trial quality improvement interventions led to more balanced accrual among study arms and improved trial compliance over time.

Methods: This is an interim analysis of recruitment to a cluster-randomized trial investigating three nerve block approaches for mastectomy with immediate implant-based reconstruction: paravertebral block (arm 1), paravertebral plus interpectoral plane blocks (arm 2), and serratus anterior plane plus interpectoral plane blocks (arm 3). We monitored accrual and consent rates, clinician compliance with the randomized treatment, and availability of outcome data. Assessment after the initial year of implementation showed a slight imbalance in study arms suggesting areas for improvement in trial compliance. Specific improvement interventions included increasing the frequency of communication with the consenting staff and providing direct feedback to clinician investigators about their individual recruitment patterns. We assessed overall accrual rates and tested for differences in accrual, consent, and compliance rates pre- and post-improvement interventions.

Results: Overall recruitment was extremely high, accruing close to 90% of the eligible population. In the pre-intervention period, there was evidence of bias in the proportion of patients being accrued and receiving the monthly block, with higher rates in arm 3 (90%) compared to arms 1 (81%) and 2 (79%, p = 0.021). In contrast, in the post-intervention period, there was no statistically significant difference between groups (p = 0.8). Eligible for randomization rate increased from 89% in the pre-intervention period to 95% in the post-intervention period (difference 5.7%; 95% confidence interval = 2.2%-9.4%, p = 0.002). Consent rate increased from 95% to 98% (difference of 3.7%; 95% confidence interval = 1.1%-6.3%; p = 0.004). Compliance with the randomized nerve block approach was maintained at close to 100% and availability of primary outcome data was 100%.

Conclusion: The clinically integrated randomized trial design enables rapid trial accrual with a high participant compliance rate in a high-volume anesthesiology practice. Continuous monitoring of accrual, consent, and compliance rates is necessary to maintain and improve trial conduct and reduce potential biases. This trial methodology serves as a template for the implementation of other large, low-cost randomized trials in anesthesiology.

Keywords: Clinically-integrated randomized trial; day of surgery consent; high accrual; low cost trial; point of care randomization; pragmatic trial; recruitment analysis; regional anesthesia.

Figure 1.

Regional block clinical and study workflow. Shaded steps represent research procedures incorporated into the clinical workflow. ¹Standard practice includes routinely collected perioperative data and post-discharge patient-reported outcomes. ²Patient may be deemed not fit for randomization by the clinician, for example, due to a specific medical condition. ³Monthly assigned block approach may be contraindicated if there is a clinical reason to use a specific block approach or patient request for a specific block approach. ⁴Patient may agree to have a nerve block and be considered fit for randomization but may decline to participate in the trial. ⁵A consented patient may be deemed ineligible for the assigned block approach after initiation of the procedure and a separate block may be performed, for example, an unanticipated challenging block. The patient is still included in the study on an intention-to-treat basis. ⁶Cluster randomization is performed on a per month basis such that each month, one of the three nerve block approaches is the “standard of care” block approach that all study eligible patients receive regardless of trial participation.