Risk Based Monitoring and it’s impact on Quality

RBM requires the ability for CRA to prioritize task and evaluate the performance of site which may involve auditing approach in monitoring.
image

Auditors for identifying error and risk in clinical trials and they find the issues which missed by monitors. And that’s why auditors focus on identifying error with critical data and they are not pre occupied with less impactful activities like 100%SDV.

In five to 10 years, I believe that monitors will be trained to think and perform like auditors and relationship managers. Monitoring will still remain a necessary part of the industry, as important GCP concepts such as delegation of PI responsibilities and drug accountability cannot be performed remotely. However, monitors will be trained to evaluate the operations of a site, thus providing a far more reliable and valuable input into risk-based systems.

Training aspects are lacking with CRAs, and Impact on Clinical Trial Quality

Many years ago, in order to be a monitor, you had to go through several types of training. There was therapeutic training that provided baseline knowledge of the anatomy and physiology one should know in order to read medical charts. Training was provided on the investigational product so that the mechanism of action, anticipated side effects or other scientifically relevant information was shared.  This training also included a review of non-clinical and clinical data known to date.

Monitors were educated about the scientific measures used in a study, such as a rating scale, a clinical lab or a pathology outcome. Aside from the more therapeutically focused training, monitors were taught job skills such as how to review a medical chart so that the review not only ensured the data on the CRF was accurate but also required some logic checking. I do not sense that operations teams are conducting these types of trainings today.

To elaborate, I have seen trials where blood pressures of 180/110 were verified by the monitor, and the monitor didn’t ask the PI if that BP should be considered an adverse event. No clinical significance was recorded in the source. The monitor didn’t think to see if there was a history of hypertension in the medical history or to see if the blood pressure had been within normal limits initially but gradually increased. Could this be a drug effect? Today, monitors are being trained simply to verify that the data in the source matches the data in the CRF.

Additionally, monitors aren’t trained on time management. There has to be clear understanding that the six to eight hours on site cannot be spent strictly performing SDV. Monitors must be able to quickly evaluate if there have been changes in site personnel, ensure the associated training and regulatory documents have been updated, ensure the drug accountability is being performed, ensure patients were consented properly, assess how work is being delegated, ensure the source meets ALCOA standards and that adverse events are being evaluated and reported in a timely manner. Without this kind of training, the quality of monitoring diminishes significantly.

Consolidate RBM with Quality Management

I think the industry has to move in this direction; people in quality management see it but I think something is lost in translation when it comes to the functional areas such as clinical operations, data management, programming and pharmacovigilance. Timelines are becoming more and more aggressive.  Headcount and budgets are growing leaner, yet the regulatory standards are not being reduced. The system has to be more efficient.

The switch is going to require a proactive approach to understanding where the data is being collected and how to access it. Very little of the key primary and secondary endpoints are being collected at the site. With the development of electronic diaries to capture rating scales, patient reported drug compliance and other endpoints such as clinical labs and pathology, we can get at the data much sooner than an on-site monitoring visit. Through programming, we can pull out outliers and trends. However, nothing can replace a monitor going on-site, periodically, to ensure the overall performance of a site is acceptable with regards to GCP standards.

The industry needs to redefine the roles we have working on clinical trials. We need programmers who can pull this data out well before programming tables, listings and figure/graphs and we need medically qualified people reviewing data outliers and trends, weekly and monthly, not at database lock. We also need hybrid roles that are doing some cross logic checking and evaluating the data for any safety trends or errors in interpretation of the protocol, which could be detected through these types of efforts.

Before we can do any of that, though, we need to think about how we are capturing the data in order to fully leverage eClinical technologies. CRFs need to be designed to capture information, so that errors and outliers can be found. Through proper EDC programming and RBM, the sponsor can easily determine if the data support compliance. This approach allows study teams to detect and alert sites to issues early, such as a patient over- or under-dosing sooner than the site might realize or sooner than that eight to 12 week monitoring visit.

 If monitors were trained to work like auditors, the input would be more robust.  If we are having a failure on the front line, so to say, where the monitoring is failing to detect the risk, then the input into the Quality Management is not thorough or accurate and risk cannot be appropriately or adequately assessed. Without proper training and leveraging the technology, we will continue to struggle.

I don’t want believe that this was the spirit and intent encouraging from regulatory agencies for risk based approach. Risk based Monitoring has not succeed the way name was derived, it certainly reduced Monitoring Visits and that’s it.

Advertisements