CLINICAL OPERATIONS & OUTSOURCING
Refer to the risk assessment heat map in Figure 2 on the previous page. Higher risk scores are more acceptable for data/ procedures with lower impact, particularly when combined with lower probability and higher detectability. In my view, variables with a risk score of ≥ 6 are considered critical. Sponsors should determine their acceptable risk threshold and the cost- effectiveness (return on investment [ROI]) of monitoring noncritical data. Non-critical variables may be reclassified as critical if a high frequency of errors is observed. Risk prioritising starts with identifying and
categorising risk events. An effective approach is to review the Schedule of Events for each protocol and assign a Risk Score for each element. Below is an example of a partially completed Risk Assessment Worksheet; unscored items should be evaluated by the sponsor, who has a better understanding of the study intervention and the acceptable level of risk that the sponsor is willing to accept. For example, in the worksheet below,
Informed Consent is identified as a critical element due to its role in safeguarding the safety and well-being of study participants. The risk assessment for Informed Consent includes: • Impact Score 3: » If not obtained (or incorrectly obtained) the impact is high
• Probability Score 1 » Most investigational sites will be familiar
with the informed consent process and will have been trained at the Site Initiation Visit
» Note: if the investigational site has limited experience with GCP-compliant studies or if the Informed Consent Form is complex, the Probability Score may be higher
• Detectability Score 3 » Without monitoring, it is impossible to see if the form was signed and dated correctly. Also, if the form requires initials on each page or contains check boxes, these can only be confirmed with physical inspection.
• Overall Risk Score: 7- Critical The sponsor should consider impact,
probability, and detectability and, where possible, incorporate technology to aid in monitoring critical data and processes. For example, this can include electronic or remote viewing of consent forms (See Section III.B.2.a of the RBM document). Developing a risk-based approach to
overseeing clinical investigations begins with a thorough risk assessment and identifying critical elements. Sponsors should then allocate more time and resources to the training of investigational site staff and monitoring these critical elements. For better utilisation of CRA time on site, many data elements can be centrally monitored to help direct the CRA in a targeted monitoring approach and more critical data should be SDVd with less critical data monitored as time allows.
Figure 3: Risk Assessment and Scoring Worksheet Example (Partially Complete) Impact
Probability Detectability Informed consent
Demographics General medical history Randomization
Primary efficacy endpoint Secondary efficacy endpoint Exploratory endpoints Study Intervention
Safety endpoints (other than AEs) Recording of adverse events
Recording of concomitant medications Outsourcing in Clinical Trials Handbook | 29 3 1 3 Risk
Score 7
Category critical
3 3 2 1 3 3 3
2
1
6
critical
1 1 1
3 3 3
7 7 7
critical critical critical
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