Table 1.

Risks with possible high impact identified in a phase II immunotherapy trial⁶ based on the perspectives of Hall et al.¹ with our approach to mitigation of that risk.

	Type of risk	Risk	Description of risk	Mitigation approach
1.	Risks to patients	No stroma or tumor cells in biopsy	Discomfort and risks associated with a sampling intervention	Take multiple biopsies from one lesion at the same time (a minimum of three biopsies per lesion9) and check amount of tumor cells before analysis of sTILs and inclusion in the trial
2.	Risks to patients	Loss of data confidentiality	Patient samples sent to multiple institutions and reviewers	Pseudonymization should be applied, hide slide labels, implement strict access control, ensure no metadata is linked to a slide
3.	Risks to biomarker development	Inter-laboratory variability and interobserver variability	Different methodologies used to score slides, interrater variability	Use of international guidelines for scoring and training, use consensus score of four expert pathologists from three institutes
4.	Operational risks	Failure of sample collection, processing, and quality	Missing or poor-quality samples resulting in poor consensus scoring	Standardized tissue processing, workflow management
5.	Operational risks	Inadequate image quality or no ability to access image	Missing, poor, or inaccurate scoring	Track the scores of all pathologists and notify when scores are inconsistent
6.	Operational risks/risks to patients	Long turnaround time	Delay in patient randomization and treatment	Timeline tracking incorporated in workflow
7.	Operational risks	Data management failure	Errors in collecting manual scores, typos, data conversion issues	Structured digital scores from pathologist to the analyst