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www.biopharminternational.com Quality and Regulatory Sourcebook eBook March 2024 BioPharm International ® 9 Risk Management • "A failure to recognize where and when subjec- tivity enters and might create problems in risk assessment and risk-based decision-making. • "A failure to implement control on subjectivity where it is known to occur." Several other papers have further highlighted the challenges posed by subjectivity, including a paper by ICH Q9(R1) rapporteur Kevin O'Donnell (10). This paper discusses elements of subjectivity and uncer- tainty such as the impact of human heuristics, which are cognitive behaviors that can introduce bias and errors in judgment during activities like brainstorm- ing and probability estimation. It suggests incorpo- rating design elements into QRM tools to counteract the adverse effects of heuristics and reduce guess- work. Practical strategies and cognitive approaches are presented to improve the accuracy of risk analyses and enhance the outcomes of QRM exercises. These insights can be valuable to facilitators in achieving more accurate risk assessments. In a follow up paper (11), O'Donnell discusses the sig- nificance of risk communication in the QRM process, highlighting potential challenges of subjectivity and uncertainty in this activity. Stakeholders' individual perceptions can lead to subjective differences in risk judgments, introducing uncertainty in risk manage- ment outcomes. To address these issues, O'Donnell suggests adopting a more rigorous approach to risk communication. Practical strategies based on research from experimental psychology and uncertainty analy- sis to improve risk communication and reduce subjec- tivity and uncertainty are presented. These strategies include stakeholder selection, employee roles in risk communication, and essential information to be com- municated within pharmaceutical companies. In a 2016 publication (12), authors Vesper and O'Don- nell highlight multiple issues encountered 10 years after the publication of ICH Q9. One of the issues discussed was the relationship between risk and uncertainty, with risk defined as the "effect of uncertainty on achieving one's objectives." Subjectivity in risk assessment can emerge due to differences in perceptions, values, and experiences among stakeholders. This subjectivity in- fluences the evaluation of potential harms, probabili- ties, and severities in the QRM process. This may be compounded by groupthink during risk assessment activities, leading to difficulties in reaching consensus on risk acceptability and appropriate courses of action. Vesper and O'Donnell emphasize the importance of ad- dressing subjectivity and uncertainty in risk assessment and offer strategies to do so. These strategies include fostering diverse team composition, using key words in scales, acknowledging uncertainty, and relying on validated data. Additionally, this publication suggests integrating good science into risk assessments and doc- umenting current controls before assigning ratings to failure modes or hazards. A 2018 paper by Emma Ramnarine and Kevin O'Don- nell (13) emphasizes the role of subjectivity during risk assessment activities and how subjectivity can nega- tively impact the state of control and the delivery of products with consistent quality throughout their commercial life. In addition to QRM-related literature that directly highlights subjectivity, related research by Valerie Mulholland explores the impact subjectivity plays in effective risk-based decision-making. In a paper on Key Decision Review Points (14), Mulholland proposes that each decision within a QRM process has the potential to be sub-optimal due to subjectivity (among other causes). Furthermore, in another paper from the same four-pa- per series focused on uncertainty (15), Mulholland dis- cusses the presence of high uncertainty, which poses significant challenges in decision-making. In some cases, the risk itself may be uncertainty. Uncertainty can arise from various sources, including variability in data, lack of knowledge, and ambiguity in interpreta- tions. Decision-making under uncertainty may rely on different mental abilities and competencies compared to evidence-based decision-making. Overall, addressing uncertainty in risk management requires a thoughtful and strategic approach, acknowledging the intercon- nectedness of risk and subjectivity. Considering these articles in aggregate, the authors of this paper suggest that Claycamp's 2018 assertion that the problem with subjectivity in QRM arises from two elements (9) captures the essence of an important theme across this literature. The authors propose restating these two challenges more simply as follows: … addressing uncertainty in risk management requires a thoughtful and strategic approach, acknowledging the interconnectedness of risk and subjectivity.