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Randomized Controlled Trial
. 2023 Jan:124:107035.
doi: 10.1016/j.cct.2022.107035. Epub 2022 Nov 30.

The importance of methods for site performance evaluation in REPRIEVE, a longitudinal, global, multicenter trial

Evelynne S Fulda  1 , Carl J Fichtenbaum  2 , Emma M Kileel  1 , Markella V Zanni  1 , Judith A Aberg  3 , Carlos Malvestutto  4 , Sandra Wagner Cardoso  5 , Baiba Berzins  6 , Rita Lira  7 , Regina Harden  8 , Gregory Robbins  9 , Maria Martinez  10 , Sylvia Davila Nieves  11 , Sara McCallum  1 , Jorge Leon Cruz  12 , Triin Umbleja  12 , Heather Sprenger  13 , Francoise Giguel  14 , Frederic Bone  13 , Ken Wood  13 , Mark Byroads  13 , Kayla Paradis  15 , Michael T Lu  15 , Pamela S Douglas  16 , Heather J Ribaudo  12 , Steven K Grinspoon  1 , Kathleen V Fitch  17 ; REPRIEVE Investigators
Affiliations
Randomized Controlled Trial

The importance of methods for site performance evaluation in REPRIEVE, a longitudinal, global, multicenter trial

Evelynne S Fulda et al. Contemp Clin Trials. 2023 Jan.

Abstract

Background: REPRIEVE, the Randomized Trial to Prevent Vascular Events in HIV, is a multicenter, primary prevention trial evaluating whether a statin can prevent major cardiovascular events in people with HIV. REPRIEVE is conducted at >100 clinical research sites (CRSs) globally. Detailed, comprehensive, and novel methods for evaluating and communicating CRS performance are required to ensure trial integrity and data quality. In this analysis we describe a comprehensive multidimensional methodology for evaluating CRS performance.

Methods: The REPRIEVE Data Coordinating and Clinical Coordinating Centers developed a robust system for evaluation of and communication with CRSs, designed to identify potential issues and obstacles to performance, provide real-time technical support, and make recommendations for process improvements to facilitate efficient trial execution. We describe these systems and evaluate their impact on participant retention, data management, and specimen management from 2019 to 2022, corresponding to the period from end of recruitment to present. This evaluation was based on pre-defined metrics, regular reviews, and bidirectional communication.

Results: Participant retention, data management, and specimen management all remained steady over the three-year period, although metrics varied by country of enrollment. Targeted messaging relating to certain performance metrics was effective.

Conclusion: Site performance is vital to ensure trial integrity and achievement of key trial goals. This analysis demonstrates that utilization of a comprehensive approach allows for a thorough evaluation of CRS performance, facilitates data and specimen management, and enhances participant retention. Our approach may serve as a guidepost for maximizing future large-scale clinical trials' operational success and scientific rigor.

Clinicaltrials: gov Identifier: NCT02344290.

Keywords: Clinical trial management; Data management; Participant retention; Site performance.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
Percentage of enrolled participants off-study or at risk of loss to follow-up by site. Sites at or below the site median. Each bar shows 100% of participants at each CRS. Participants are considered in good follow-up standing (above the x-axis) if contact has been reported within the past 5 months or are known deceased; the bar segments above the x-axis indicate the CRS’s network affiliation within REPRIEVE. The portion of each bar below the x-axis shows the percentage of participants off-study (excluding deaths), or with no contact reported in 5 months or greater; the bar segments below the x-axis indicate the follow-up status (time since last contact or off-study). Network affiliation description: REPRIEVE (international or domestic), no network affiliation; NEAT-ID, The European treatment network for HIV, hepatitis and global infectious diseases; Canadian HIV Trials, Canadian HIV Trials Network; ACTG (international or domestic), AIDS Clinical Trials Group.
Fig. 2.
Fig. 2.
Active REPRIEVE CRSs. Overview of REPRIEVE site activation in each country.
Fig. 3.
Fig. 3.
Retention Metrics April 2019–April 2022. (A) Treatment discontinuation (blue) and study discontinuation (orange) rates for CRSs from April 2019 to April 2022. Trial benchmark (< 5/100PY) is shown by the solid green line. (B) Study discontinuation rates for each country of enrollment from April 2019 to April 2022. (C) Treatment discontinuation rates for each country of enrollment from April 2019 to April 2022. Enrollment for Spain took place from February–July 2019 thus metrics for Spain are shown from April 2020 onwards.
Fig. 4.
Fig. 4.
Data and Specimen Management Metrics April 2019–April 2022. (A) Data entry timeliness (blue), expected data submitted (orange), expected endpoint data submitted (gray), and expected specimens shipped (yellow) for CRSs from April 2019 to April 2022. Trial benchmark (≥ 90%) is shown by the solid green line. (B) Data entry timeliness percentage for each country of enrollment from April 2019 to April 2022. (C) Expected data submitted percentage for each country of enrollment from April 2019 to April 2022. (D) Expected endpoint data submitted percentage for each country of enrollment from April 2019 to April 2022. (E) Expected specimens shipped percentage for each country of enrollment from April 2019 to April 2022. Enrollment for Spain took place from February–July 2019 thus metrics for Spain are shown from April 2020 onwards.
Fig. 4.
Fig. 4.
Data and Specimen Management Metrics April 2019–April 2022. (A) Data entry timeliness (blue), expected data submitted (orange), expected endpoint data submitted (gray), and expected specimens shipped (yellow) for CRSs from April 2019 to April 2022. Trial benchmark (≥ 90%) is shown by the solid green line. (B) Data entry timeliness percentage for each country of enrollment from April 2019 to April 2022. (C) Expected data submitted percentage for each country of enrollment from April 2019 to April 2022. (D) Expected endpoint data submitted percentage for each country of enrollment from April 2019 to April 2022. (E) Expected specimens shipped percentage for each country of enrollment from April 2019 to April 2022. Enrollment for Spain took place from February–July 2019 thus metrics for Spain are shown from April 2020 onwards.
Fig. 5.
Fig. 5.
Impact of Targeted Language in Biannual Evaluations. (A) Change in treatment discontinuation rate from Fall 2021 to Winter 2022 for sites that did or did not receive targeted language in their biannual evaluation. The trial is <5/100PY (green line) and a lower rate indicates better retention. (B) Change in data entry timeliness from Fall 2021 to Winter 2022 for sites that did or did not receive targeted evaluation in their biannual evaluation. The trial benchmark is ≥90% (green line) and a higher percentage indicates better data entry timeliness. 7 sites were not included in this comparison due to missing values for data timeliness.
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