Table 2.

Challenges and limitations of prospective studies.

Characteristic	Limitations/Challenges
Funding	Typically expensive studies. High cost per patient. Federal funding is usually low.
Patient accrual/Monitoring	Typically low. Even more challenging to investigate infrequent adverse effects. Extensive on-site monitoring.
Clinical research personnel	Complex studies may require personnel with expertise in the perioperative environment.
Outcomes	Usually long-term, recurrence or death. Surrogate outcomes do not always correlate with overall survival. Endpoint adjudication can be difficult. Establishing cancer recurrence or progression is subject to error bias. The definition of “clinically meaningful” can be challenging.
Hypothesis	Equipoise between treatment options versus directional hypothesis testing.
Validity	It may lack generalizability since recruited patients may differ from the population of interest (volunteer bias). Loss of follow-up may threaten the validity of outcomes.