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Centralized monitoring is the core of RBM and helps study teams decide on on-site monitoring activities and site intervention. Thus, the right mix of KRIs and Central Statistical Monitoring Reports is crucial for trial success.
Centralized monitoring is the core of RBM and helps study teams decide on on-site monitoring activities or any site intervention. The types of risks reports selected for centralized monitoring related to site performance, data quality or patient safety outlines the comprehensiveness of central monitoring activities. One needs to ensure that the risk reports used for central monitoring covers all important risks for a study and will not leave any gaps in monitoring which may compromise the validity and integrity of critical data collected. Also, this is very vital to make the RBM plan full proof and compelling especially in terms of getting right trigger on time and also for deciding rational for on-site visits or change in monitoring plan. Therefore, based on risk identification and assessment, one needs to have right mix in terms of type of reports and number of reports for KRI (Key Risk Indicators) and CSM (Central Statistical Monitoring) as a part of central monitoring activities. For each study the mix of KRIs and CSM reports would be specific and based on the critical aspects of the study to be monitored e.g for diabetes study CSM reports related HbA1c or FBS (Fasting Blood Sugar) are important reports to be monitored and for epilepsy study reports related to parameter such monthly seizure frequency would be critical. Similarly, KRI and CSM reports that are used for centralized monitoring should be selected in such way that either individually or collectively brings some key insights which direct study team on timely site intervention to control or mitigate those risks. For example if KRI report related to patient recruitment shows high recruitment rate at a site than expected and site level AE report shows that per patient AE rate for this site is very much lower as compared to other sites then this site needs to be contacted or visited to see the site is not missing to capture AEs due to high number of patients at the site. Also, it is important to check if the site is following other critical study protocol specific procedures as per requirement or deviating from the study protocol. Similarly, the report showing a site with low patient randomization rate but high screening failure rate also need attention to see if the site need better understanding of protocol in identifying and selecting right pool of patients for the study.
Key Risk Indicators (KRIs) – These are mainly used to monitor risks related to site performance in study conduct. Based on the study requirement, site selection and expected performance of the sites, one can decide the threshold to monitor those performance risks and plan timely corrective actions in case of any triggers or risk alerts.
The examples of these KRI or Site Performance reports are - Patient recruitment/randomization rate per month across sites, % Screening failure rate over patient recruited, % CRF completion/incompletion based on patient visits completed, DCF generation, response and aging across sites, and protocol deviation rate etc.
Central Statistical Monitoring (CSM) Reports - These are critical data quality reports to monitor quality of data in terms of consistencies, trends, data distribution patterns and outlier etc. The CSM reports helps to:
Some of the examples of CSM reports are like data outliers for critical variables at patient level or site level, under or over reporting of AEs & SAEs per patient per site wise study duration, site level correlation checks for some critical data points to see any site appears different from others within the same study.
The CSM reports help to identify data quality issues, systematic errors in trial conduct at sites which may be due to inadequate understanding of study protocol or protocol not being followed correctly or incorrect measurement/recording of some critical data points or adverse events are over or under-reported or potential data integrity issues etc.
Based on risks seen in KRI & CSM reports further medical & safety review of patient profiles of those problematic sites and patients will be helpful to understand data quality or patient safety issue further and to implement corrective & preventive measures on time if needed .
The right mix of KRI and CSM reports is important to strengthen centralized monitoring activities and ensure adequate amount of monitoring of key aspects to support RBM approaches. The types and number of KRI and CSM reports should be selected in such way that they individually or together ensure quality study conduct, high data quality and subject protection.
Ashok Ghone, Ph.D. is Vice-President, Global Services at MakroCare USA. He has around 20 years of experience in pharmaceutical and clinical research industry. He carries good knowledge & understanding of global clinical research with hands-on experience in clinical operations, project management, clinical trial management, process development, site management and patient recruitment activities. He has led various cross functional teams successfully by providing strategic direction, guidance for accomplishment of local, regional and global projects involving early & late phase clinical studies in various therapeutic areas. Ashok has been involved in development of process, system and training related to risk-based monitoring and centralized monitoring at MakroCare, which offers these specialized services to biopharmaceutical & medical device companies to support their endeavors in implementation of RBM approach. Email: firstname.lastname@example.org