Table 3.

Problems encountered and suggested potential solutions

Problems encountered	Potential solutions
Administrative difficulty and resource requirements in contract negotiation, IRB/ethics approval application, and site personnel training	Beware of local legal environment for contracting during site selection Realistic planning of study schedule Timely assessment of progress or lack of progress Minimize the number of sites to increase the general efficiency
Slow patient recruitment	Careful site selection Timely closure of underperforming sites Practical inclusion/exclusion criteria Realistic enrollment targets
Inconsistency in patient enrollment, enrolling ineligible patients, high blood sample missing rate, etc	Standardizing investigator training, e.g., using instruments such as training manual and video, answers to “frequently asked questions”, and standardized sample collection kits Close monitoring of enrollment process and early implementation of corrective measures Careful principal investigator selection
High dropout rate	No clear solution; close monitoring of the situation and striving for high engagement of the study sites (e.g., through newsletters, investigator meetings, site visits)
Heterogeneity of patient population and treatments limiting meaningful analyses	Predefine the infection history and status Anticipate and better define treatment procedures and surgical stages Larger sample size to allow later stratification of patient population according to the predefined infection history and status
Biological sample collection and transport	Standardized sample handling kits Utilizing professional courier service
Language and cultural barrier	Engaging well-trained local monitors Choose outcome measures with validated translations Beware of local regulations