Hey @dmauri Great question. As long as the study publication does not contain information suggesting dosing practices inconsistent with Canadian labelling, the manufacturer’s Medical/Regulatory Affairs department can confirm that the dosing in the jurisdiction where the study was conducted is the same as it is in Canada. When it comes to “SoC”, per 1.7 of the Guidance on Real-World Evidence/Data, remember that pooled comparisons are not acceptable which would render the second half of the question moot. However, if you are referring to SoC in a single-arm study (per Advisory: RWE Single-Arm Studies of Previously Treated Patients), we would look to ensure that the overwhelming majority of patients were on a product available in Canada/indicated in the same population in Canada. Regarding "SoC", please note the guidance's remarks on representing the marketplace versus exclusions by design. An opinion can be a great mechanism to get specific guidance on an individual study as it allows for assessment of the study design, therapeutic area, and indicated product(s).

Hi @charlton, Pragmatic trials are interventional in nature, as they involve random assignment to the treatment groups. Given this fact, it would be inaccurate to refer to them as ‘observational’ studies. However, they differ in important ways from randomized control trials (RCTs). RCTs are designed in a manner that prioritizes a highly controlled environment. While this comes at the cost of an artificial environment that can differ from the actual surrounding environment, it reduces the potential for biases that could impair the validity of causal inferences. While their results should be generalized cautiously to the real-world, they have high internal validity when designed, executed, analyzed, and reported properly. Pragmatic trials are designed to prioritize reflecting the surrounding environment. This is why they are said to provide insights about “effectiveness”, which is the benefit that the treatment produces in routine clinical practice. For example, pragmatic trials tend to include patients with comorbidities, the methodology aims to reflect the lower adherence levels that occur in clinical practice, blinding is rarely utilized (as it does not reflect real-life practice), and investigators have more clinical freedom to make therapeutic decisions (i.e., less protocol standardization than in RCTs). Due to the above, PAAB considers pragmatic trials to fall within the realm of RWEs. Please see our RWE guidance document on parameters for acceptability and presentation format.