Risk Based Monitoring and Central Monitoring
A centralized approach to the clinical trials
The Risk-Based Monitoring (RBM) is a monitoring technique for the execution of successful and safe clinical trials. The method aims to fulfill the regulatory requirements without the 100% SDV (Source Data Verification) of the participant data. The clinical trial monitoring plays a vital role in the drug development within the parameters of safety, protocol compliance, data quality, and regulations by working on the sponsor oversight on the essential aspects of the conduct. Risk-Based Monitoring means that the frequency and the volume of monitoring are decreased at a few points and the data is only verified at the sites which have high risk on the triggered events or the critical events. During the execution of the clinical trials, a number of things are exposed to risk. The medications may show adverse effects, there may be any serious adverse events occurring at the time of the conduct, and the health and well being of the subject participating in the trial may be exposed to many risks. In the past years, the industry consortia, non-profit collaborations between regulators and industries and regulatory agencies have been striving hard to advocate a new and safe risk-based approach for the monitoring of the clinical trials. The industries and agencies aim at finding the approach which lays emphasis on the critical processes and collected data with the use of centralized monitoring. However, the subject of risk-based monitoring is very vast and remains unclear with the wide range of variations at the times of different trials in the methodologies and tools. The security of the participant should be the primary point on the checklist. There must be every possible way to mitigate the risk factors related to clinical trials. The risk assessments and risk-based monitoring even helps in the cost reduction of the clinical trials. The rate of the serious adverse events are reduced to high extents; therefore there may be no need to execute further clinical trials in the case of adverse events. The efficient risk-based monitoring systems must work on the centrally with the faster rate of data flow for the more efficient, improved and quicker outcomes of trials. The following will, in turn, enables faster-informed decisions. It allows the team to concentrate on more high valued tasks and targets the resources on the trial related methods. The quality of the corresponding trial data can be enhanced by assessing, identifying, mitigating and monitoring the related risks.
The official regulatory authorities have recognized the potential of Risk-Based Management in improvising the conduction of the clinical trials of various phases. The authorities have even published certain guidance documents in context with the RBM to encourage the sponsors to imply the risk-based approach in the study management. However, Risk-Based Management has not been absolutely decreed by any specific regulator. Both EMA and FDA accept that review of less data is relevant in studies posing lower risks in lower risk periods of firstly high-risk study. The RBM can be executed in a convenient manner which targets to the sites and patients based on inlaying, outlying, operationally deficient, potentially, or erroneous, fraudulent data.
The FDA guidance outlines mainly three steps in the Risk-Based Management approach:
1. Perform a Risk Assessment
A risk assessment is a necessary part of the RBM approach. The risk must be analyzed before the next step or the initiation of the clinical trial. When the investigators have identified the related risks, a “traffic light system” can be used for the visualization for the clinical operations. The risk assessment must be managed which concerns with the investigation of the risk along with the origin and perform several measures to prevent the future risks involved with the resolution of the existing risks. The measures may consist of the motivational visits, issuance of several warning letters, studying the site again, and reworking on the recruitment plan.
2. Detection of critical processes and data
The sponsor must identify the acceptable or expected parameters and values to flag the critical data as the potential risk in the conduction of the clinical trial. The studies from the previous sessions or trials must be used as the quantifying metrics as low, medium or high risks. In case, of the initial trials or studies, the metrics must be quantified by the older studies of other investigators. The mitigation of the flagged risk can be changed throughout the trial as per the situations when working with the risk assessment categorization tool(RACT) for the first time. The instances for high-risk data can include the points which may affect the safety of the patient, use of sites with little experience of clinical trials, and endpoint data categories.
3. Developing a Monitoring Plan for the integration of the risk-based approach
The FDA guidance characterizes that a good clinical trial monitoring plan must describe the requirements of the trial, monitoring methods of the trial. The critical document will land to the stipulations on the required data points which need to be monitored with the certain frequency of monitoring. The frequency of the respective monitoring shall be coupled with the escalation and communication plans for the stakeholders who are involved in the clinical trial. A proper high-quality Data Quality Oversight (DQO) which enables Centralized Statistical Monitoring (CSM) must be set up to perform the high-end Risk-Based Monitoring for clinical trials.
The strategy of Risk-Based Monitoring has become a vital part of the clinical researches. It has great potential in reducing the clinical costs by 25% and improve the quality of collected data. Therefore, it also helps in the reduction time of the approval of any certain Investigational Medicinal Product (IMP). FDA, which plays a great role in the approvals of the products has also advised integrating the degree of statistical management and RBM to meet the modern standards. The RBM is one of the best tools for the safety and well being of the participants. RBM creates a lower risk environment which ensures the lower rates of the adverse events.