Centralized Monitoring/Risk-Based Monitoring

Risk-Based Monitoring

Centralized monitoring is a remote evaluation of the study data, carried out by a team including central monitors, and medical reviewers at a location other than the sites at which the clinical investigation is being conducted. The major difference between CRA monitor and centralized monitor is onsite monitoring and centralized monitoring respectively.

Before you appear for an Interview, kindly read the below guidelines;

https://cdsco.gov.in › CDSCO_WEB › Pdf-documents

  • E6(R2) Good Clinical Practice: Integrated Addendum to ICH …

https://www.fda.gov › files › drugs › published

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety, and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are credible.

Careful and frequent monitoring can ensure the early discovery of pitfalls during the course of a clinical trial. Traditionally, monitoring was done through full-scale Source Data Verification( SDV) which involved traditional verification of all collected data from source documents and records. In due course of time, four algorithm-dependent approaches arbitrary SDV approach, the declining SDV approach, the three-tiered SDV approach, and mixed approaches were enforced to reduce the manual trouble and time involved in SDV.

While these ways were an enhancement to the traditional SDV process, the associated trouble, time and costs were still significantly high, charging the collaborative trouble of assiduity and nonsupervisory actors to look out for indispensable approaches.

The following are the major challenges of 100 SDV approach to trial monitoring

  • Since the SDV performed was primarily a manual review process, monitoring is error-prone and was suitable to give 85% review delicacy at stylish.
  • The SDV process involves repeated reviews adding to resource costs as well as significant time investment.
  • The SDV isn’t effective in dealing with the following factors – Recurrent errors within the source document, Misrepresentation of the subject information, or inapplicable data, still, it’s challenging for the controllers to capture that particular information alone and suggest the CAPA for the same, If an anomaly is being observed in the clinical trial process. Hence, the monitoring process is repeated again making the entire cycle tedious and expensive.
  • Managing and maintaining different performances of SDV attestation would be painful for the controllers as well as guarantors and CROs involved in clinical exploration.

So How Does RBM Work?

RBM focuses on high-threat areas – scientifically as well as operationally – and leverages technology and other coffers to alleviate these pitfalls. The first step for successful RBM is threat assessment and defining the high-threat areas. Hence, it’s important to identify the KRIs( crucial threat pointers) and put in place the right triggers, cautions, and responses. After the assessment, threat mitigation and threat operation strategies come in play.

ICH GCP E6 (R2) section 5 indicates risk-based monitoring i.e centralized monitoring under the sponsor’s responsilities. The sponsor should implement a system to manage quality throughout all stages of the trial process. Sponsors should focus on trial activities essential to ensuring human subject protection and the reliability of trial results. Quality management includes the design of efficient clinical trial protocols, tools, and procedures for data collection and processing, as well as the collection of information that is essential to decision making.
The methods used to assure and control the quality of the trial should be proportionate to the risks inherent in the trial and the importance of the information collected. The sponsor should ensure that all aspects of the trial are operationally feasible and should avoid unnecessary
complexity, procedures, and data collection. Protocols, case report forms, and other operational documents should be clear, concise, and consistent.

The quality management system should use a risk-based approach as described below;

  1. Critical Process and Data Identification
  2. Risk Identification
  3. Risk Evaluation
  4. Risk Control
  5. Risk Communication
  6. Risk Review
  7. Risk Reporting

The Transition towards Risk-based Quality Management

The FDA has honored the capabilities of threat-grounded monitoring to ameliorate quality in all phases throughout the course of study trials. The most significant changes in ICH E6( R2) have been enforced to contend on guarantors and CROs to borrow a threat-grounded approach for study prosecution. The ultramodern automated RBM results grease centralized, off-point monitoring with the ideal to minimize the pitfalls associated with study trials coupled with the perpetration of GCP, SDR, and Planning criteria. The ultramodern approach would also exclude the need to suffer the repeated process, by landing the particular information of the threat assessment which needs corrective action for posterior reviews. The system captures all the information and the workflow process which can be validated by the controllers fluently along with time and date stamps.

threat- grounded monitoring has the implicit to dramatically reduce the costs, time, and crimes without any adverse impact on the overall trial quality.

Remote Monitoring -SCOPE

When the RBM team takes over, it “monitors the data in nearly real time to uncover inconsistencies, deviations, and data errors.” It also “conducts performance assessments to unveil poor performance, potential noncompliance, and misconduct.”

If any red flags are raised based on key risk indicators (KRIs), the RBM team deploys an FM to the site for a visit. Adopting this dual approach ensures the time savings and efficiency of RBM with the localized and first-hand analysis of onsite visits.

The monitoring process

As bandied over, the FDA has handed some detailed guidance on how to prepare a monitoring plan, but once the plan is in place, it’s the guarantor’s responsibility( or the guarantor’s delegate, like a CRO) to execute the plan. While specifics will differ extensively between studies, a threat- acquainted monitoring program will generally contain the following conditioning, which all flow through a comprehensive threat dashboard erected for your particular study

  • Data collection and submission. A centralized approach requires a steady and dependable inflow of data from each study point to the central monitoring system. This may do either through manual entry and transfer of applicable data or through an automated connection between the data entry system and the central dashboard.
  • Dashboard monitoring. The function of the dashboard is to give, regard, information about the status of each study point relative to the specific threat factors in your trial. When a point shows a high threat position, your monitoring plan should help you decide whether further disquisition is applicable, from in-depth statistical analysis to on-point data verification.
  • Statistical analysis. In addition to covering your threat dashboard, it can also be useful to perform supplementary statistical analyses to help identify problems. Simple histograms and box plots can be extremely useful for spotting outliers between spots or countries for colorful threat pointers. More advanced ways like clustering can also help identify problematic spots or indeed fraud.
  • Targeted on-point disquisition. Dashboard monitoring and further analysis will occasionally gesture explosively that in-person disquisition is demanded at a particular point. In these cases, it may be applicable to visit and perform a more traditional source data verification exertion, depending on the nature of your study. The key is that formerly a centralized system in place, on- point disquisition should be the exception, not the norm.

Career Opportunities

Any science graduate Msc, B.pharm, M.pharm, PharmD, Diploma in clinical research candidate can apply for this position.

Centralised Monitoring Assistant (CMA): Fresher to 1-year experience

Centralized Monitor (CM): 1-5 years of experience in Centralised monitoring or Onsite monitoring

Associate Centralized Monitoring Lead (ACML): 5-8 years of experience in clinical trials

Centralized Monitoring Lead (CML): 8-12 years of experience

Centralized Monitoring Manager: 12-16 years of experience in clinical trials

Centralized Monitoring Director: 16–20 years of experience in clinical trials

Key Responsibilities of Centralised Monitor

  • Perform centralized monitoring activities on assigned projects and evaluate the quality and integrity of the study as per the protocol, SOPs, respective regulations and guideline.
  • Ensure accurate completion and maintenance of internal systems, databases, tracking tools/reports for the project specific information.
  • Perform Management of triggers and preparation of i-site pack for respective sites and countries for assigned study(ies).
  • May assist in developing required basic data analytics scope and performing the trend analytics for their respective study(ies).
  • Participate on study team meetings and interact with cross functional staff to verify information and/or triage new data issues or prior identified action items.
  • Escalate quality issues pertaining to site to respective Centralized Monitoring Lead/ Sr. Central Monitor.
  • May perform Subject Level Data Review that require further investigation with the clinical site to determine overall accuracy (inclusion & exclusion criteria/ IP/AE/ Labs/EOT/EOS/ End points/SAEs etc.) Review any other information as necessary to determine overall readiness of the patient information for next level review.
  • Interaction with sites/CRA and follow-up on study required milestones from the project start until close out.
  • May act as backup/ perform the activities as per the task list delegated by Central Monitor Expert/Centralized Monitoring Lead.
  • Ongoing/periodic monitoring of patient data, site data centrally using appropriate technology for single or multiple studies to ensure high data quality and patient safety
  • Monitoring of risk reports, data trending related to quality, safety, efficacy (effectiveness), site performances, budget etc., generated by analytical and visualization or risk management tool
  • Facilitating early identification of risk/issue(s) occurring during study conduct and responsible for identification risk alerts, timely escalation of risk/issue(s) to relevant stakeholders ( e.g. study manager, on-site monitors/CRAs) and tracking of risk/issue(s) until resolution
  • Keeping track of site performances and helping on-site monitors/study managers plan timely corrective actions
  • Act as a single point of contact for relevant stake-holders (on-site monitors, study managers, safety/medical monitors, data managers, etc.) for allocated risked based centralized monitoring studies and ensure timely communication, coordination with these stakeholders
  • Keeping on-site monitors well equipped with the details of site related risk/issue(s) to plan timely site intervention ( site visits or telephonic contacts with sites) and to make them more efficient, focused during monitoring visits
  • Supporting in optimization of SDVs and in turn reduce on-site monitoring visits
  • Responsible for documentation of centralized monitoring activities e.g. risk/issue(s) findings, escalation, tracking and resolution etc., during study conduct etc.
  • Attending review meetings with the relevant stakeholders needed for tracking/controlling of risk/issue(s)
  • Supporting in building overall efficiencies in clinical trial monitoring operations

Bonus Tip

Before appearing in the Interview, kindly read about all EDC platforms being used in clinical trials, i.e., eTMF, eCRF, CTMS, subject diaries, and IWRS systems.


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