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- Centralised Monitoring and Risk-Based approach : Case study and live implementation of methodical green-field transition – Part 1
Background: Given the recent implementation timelines (23 Jul 2025) for ICH-E6(R3) for the EMA region (EU) and the US and Indian dates yet to be announced, we thought it appropriate start this series to help the industry colleagues who may be in a dilemma that YouV team in India has expertise within its team to help with implementation of the above guidance, here from the India shores and for the globe.
Purpose and Scope: This series of articles provides practical, live examples of best practices for transitioning from a legacy to a risk-based approach in clinical trial management. Principles of change management, combined with transparent and objective reporting of key KPIs/KRIs/KQIs, are discussed as we initiate from identifying issues in the legacy system and moving into adapting to a risk-based approach. Since the concepts are explained in some details we have several parts so that we can read in 6-7 minutes, as manageable chunks.
The Part 1 of this article will focus on a limited scope of identifying and analyzing issues (the problem) with the legacy monitoring in a multinational live study (covering seven countries and 65+ sites) that was in bad shape, and was causing trouble in managing the study progress and sites, CRO as well as the Sponsors were deeply dissatisfied.
The Case (flashback): A global study, involving a total of 65+ sites spread across major developed markets around the globe and two protocols (a placebo-control and the other active-control), with a target of 3500+ patient enrolment, has been ongoing for the past 15 months.
This study faced numerous challenges in managing the study, including low transparency in clinical monitoring, data quality issues (external data mapping into EDC), and recruitment difficulties. Regional Project managers (PM) attempted to overcome these challenges in a manual and siloed manner, more as ad hoc and reactive responses. The Project Director (PD) in the EU region was responsible for the whole study management. Due to unmanageable issues and the study following a legacy project management system, two resource changes occurred within about 6 months, causing further escalations and delays in diagnosing and fixing the problems.
Since this study was managed using a legacy project management and monitoring methodology, there was all-around chaos and challenges that were causing discordance with sites, clinical monitors and data management teams due to a lack of standardization, transparency, disjointed communications, decentralized metrices and decision-making, causing varying interpretations of data metrics based on regional PMs’ diagnostics and experiences versus the sponsors’. The issue seemed to be building up because each region was dealing with its own issues in isolation, with few learnings being shared. Centrally, the Project Director was not able to control all study aspects to channel major issues upwards to the higher management for the sponsor to get a view of the issues, which started to lead to lot of discordance, inefficiencies and slowing of recruitments and root cause analysis missing, reactive steps and quick fixes in most cases. This situation was taking a toll on widespread discontent and demotivation across the board, leading to heated arguments and discord, with unprofessional language occasionally used by the Sponsor out of frustration during meetings, further escalating the situation.
The process and project management reporting gaps raised risks of data quality and data management issues, cleaning and querying backlog, which cascaded to clinical monitoring and data managers. Since each function was decentralised, no one had unified information on which regions and sites were lagging or delaying the query responses. There were no uniform and standard metrics across regions and for the overall study management, except for meetings with clients to address specific issues that project managers or sponsors identified during their site visits. However, these issues were addressed without the right metrics and transparency on what data elements matter. The study PD and regional PMs focused on individual problems rather than segregating study-level, regional, and site-level problems. This led to heated personal arguments and interpretations, leading to discordance between the Sponsor and CRO management. Conversely, the sites also started to complain to the Sponsors.
Due to complex issues and a strained relationship, the CRO attempted to change the PDs multiple times but was unable to resolve the overall situation.
CRO Outreach for Consulting and gap analysis: To help resolve this longstanding problem, the CRO engaged a highly experienced Operations and Project Management expert who could help analyse the situation and create an open ecosystem that could clarify the issues objectively, systematically, and transparently. They also wanted the PD to focus on the operations and data elements that matter to the primary and secondary objectives of the study.
The first couple of months were spent on identifying and listing issues as well as classifying the issues to Study level, Regional and site level issues and the operations and process level adjustments implemented at the CRO, Site and Sponsor levels.
Identification of issues and classification: This was done to help the study managers and the PD to focus and detailed discussions conducted at appropriate level meeting agenda. The template of the agenda, action items and primary and secondary owners were also introduced for accountability along with start date, target date and end date to help in closures and monitor them closely and objectively.
The following were top few conclusions from the gap analysis and issues mapped:
| Focus | Issue (s) | Proposed monitoring & root cause analysis | Owner P=Primary, S=Secondary T=Tertiary |
|---|---|---|---|
| Study-level | |||
| Recruitment rates were very low | Dashboard requirements and weekly targets for sites and regions fixed and monitored | Sponsor (P) CRO (S) Site (T) | |
| Protocol Screen failure ratio too high | I/E criteria analysed and monitored for insights | Sponsor (P) Site (S) | |
| Data query: – Open query backlog – Open queries ageing beyond specified SOP limits – No key metric tracking publicly available for study teams – Automated queries were firing the wrong query, hence the site did not respond, leading to ageing | – Dashboards from eCRF, CTMS, eTMF, DM query resolution tracking – Discussed reasons at weekly meetings using near-live dashboards and KPIs – Key metrics were used at weekly all-hands meetings and the deep dive at regional meetings, which cascaded to the site-level meeting, as required – Revised the PMP, CMP, DMP, CCG and Edit checks | CRO (P) Site (S) Sponsor (T) | |
| IoT medical device outputs not mapped correctly into EDC uniformly for all patients | Several technical issues with remote reader medical devices we left on the parent server as they were not transmitted to the eCRF | CRO (P) Sponsor (S) | |
| IoT medical devices were reused when patients completed/discontinued/lost to followup/screen failed | This led to unidentified mapping beyond patient participation and missing new patient data. Process change requested to discontinue patient participation and the IoT device. | CRO (P) Sponsor (S) | |
| Operation-level | |||
| Backlogs in: – clinical monitoring – automated data queries – manual data queries | Monitoring was changed from legacy to centralized monitoring (CzM), and a combination of remote visits as well as on-site visits was planned Separate CzM Plan createdSeparate visualisation Vz Plan created (for dashboards standardization and drill down capabilities to site and patient level)Reports for meetings fixed Separate regional meetings for deep dives into specific issues | CRO (P) Sponsor (S) | |
| CzM Monitoring introduced with reduced SDV (targeted) | Legacy monitoring curtailed, target data SDV introduced, CzM remote check introduced per CzM plan | CRO (P) Sponsoir (S) | |
| e-TMF backlog | Due to a resource crunch at sites, and a legacy monitoring backlog, documentation checks | Sponsor (P) CRO (S) | |
| Site- level | |||
| Site Payments | Negotiated rates at academic study budget levels, below commercial market ratesDelay in settlements and invoicing by sites | Sponsor (P) Site (S) CRO (T) | |
| Low resourcing | Low budgets had allowed only limited resourcing even at high potential sites. | Sponsor (P) CRO (S) Site (T) |
Note: Please forward your questions, suggestions and comments to LkdIn-feedback@youvresearch.com
Await the Part-2 in the coming weeks Where we explain how and what changes listed above were implemented and which new tracking and monitoring helped the sponsor, sites and the CRO get back on track.
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