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.

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.

Risk Based Monitoring- Opportunity or Obstacles

Risk Based Monitoring- Opportunity or Obstacles

“Analyst have been manually examined thousands of data points in clinical research but with the vast and ever increasing amount of data available, the human brain is unable to do it all.”

Data are coming from operational and laboratory which requires technology to bring these together into something meaningful and actionable. What are these technology which enables to work more efficiently on actual performance?

Applicable steps for Risk Based Monitoring

Let’s break the process into steps,

  • Determine risk at both protocol and site level
  • Define performance brink
  • Determine key risk indicators
  • Determine action and response plans
  • Define communication plans
  • Ensure continuous review and reassessment
  • Adjust the plan when necessary
  • Provide midterm performance indicators showing how site compare, enabling action or escalation of action as needed
  • Trend long term site performance, showing what to monitor, and how much to monitor, whether performed on site or remotely

Risk based monitoring has gained considerable scrutiny in recent years hesitation still remains around the approach. In some cases, risk based strategy could replace the need for such frequent site visits to quarterly or even once a year instead of industry standard of every four to six weeks. A risk based approach with good judgment and sound reasoning can greatly curtail the need for CRAs to be road warriors.


What are the things that any mid-size CRO can appliance for RBM?

  1. Develop monitoring plan appropriate for the trial
  2. Conduct early dispute with team members to clearly define
  • How to assess risks
  • Outline statistical analysis
  • Identify what monitors review
  1. Develop robust risk management plan at the beginning of the study
  2. Potential risks and strategies to mitigate them should be reviewed regularly with sponsor/CRO partners throughout the life of trial to optimize efficiency decision making and in taking action when risks become reality.
  3. Establish solid communication pathways for issue discussion and escalation with key team members.
  4. Pull together different values and presptives from various team members and start with the end in mind.
  5. Be actively involved in identifying triggers, trending and modeling and programming for data as it is ongoing.
  6. Frequent ongoing communication with PM, DM CRAs and Biostatician.
  7. Focus less on source verification and more on source data review and analysis.
  8. Support clinical sites in developing their own internal quality management plans.

Obstacles for slower adoption

  • Commercial Interestrsz_changesahead
  • People concerns
  • Technology hurdles



Commercial Interest

Wait for others to move which is first common strategy, effort to reduce risk as you can learn from others mistakes. And most of the CROs are dependent on monitoring visits to generate their revenue, and scared that they will have to face long term losses until it’s established. Let me tell you in very simple language why anyone wants to change wheels while it is already moving?

People concerns

This is something related to industry people, as they are well experienced and have to face process change. Everyone has to be part of change, writing metrics too and most importantly “Expertise” tag. “Expertise” tag is going to change in “learning new model”.

Technology Hurdles

Powerful challenge among all, development of whole new system needs strong IT team which is lacking in every Indian CRO or hire third party developer to establish data integrated system. Clinical trial data are to be regularly reviewed for outliers, errors, or other non-compliances, and large volumes of data need to be processed, and it would be require the use of validated and well-designed computerized to minimize the workload.


Risk-Based Monitoring (RBM) is changing the way companies are conducting clinical trials. Adopting RBM requires changes to a company’s processes and tools for monitoring. Risk Based Monitoring is one solution to combat the continually rising costs of conducting effective clinical trials.  Shifting the costs away from onsite visits and 100 0ercent source data verification toward centralized data collection and monitoring, limited sources and budgets can be better utilized to ensure data quality.

Implementing technology will be critical in strategies to increase efficiency and deliver accurate analyses of clinical study site performance and data quality. However the challenges of moving toward an alternative monitoring approach have slowed industry-wide implementation, the future looks bright for Risk Based Monitoring. The word “risk” is going to reduce risk with “Risk Based Monitoring”.