Table 3.

Strengths and limitations of real‐world evidence about treatment tolerability and adverse events

	Strengths of RWE	Limitations of RWE
Description of rare toxicities	Potentially larger number of patients compared with those enrolled in RCTs	Lack of experience of doctors in clinical practice in appreciating rare drug‐related toxicity
Description of tolerability in “clinical practice” heterogeneous population	Lower selection bias in study population compared with RCTs.	Description of adverse events could be less accurate compared with the close monitoring and prospective collection within RCTs
Description of tolerability in special patient populations	Potential focus on tolerability in special patient populations, often under‐represented in (or excluded from) RCTs
Description of long‐term toxicities	Longer follow‐up compared with primary analysis of RCTs: useful for description of long‐term toxicities
Accuracy of results	If designed as prospective collection of safety data in the “real‐world” setting, good accuracy of results	If designed as retrospective collection of safety data in the “real‐world” setting, lower accuracy of results and risk of “falsely reassuring” data. Establishment of a causal relationship between the drug and the adverse events can be more difficult compared with prospective clinical trials.
Incorporation of PROs into description of toxicity	If designed as prospective collection of safety data in the “real‐world” setting, possibility of inclusion of PROs in the description of AEs	If designed as retrospective collection of safety data in the “real‐world” setting, no possibility of inclusion of patient‐reported outcomes in the description of AEs

Abbreviations: AEs, adverse events; PROs, patient‐reported outcomes; RCT, randomized controlled trial; RWE, real‐world evidence.