Abstract
There is growing interest in regulatory use of randomized pragmatic trials and noninterventional real-world (RW) studies of effectiveness and safety, but there is no agreed-on framework for assessing when this type of evidence is sufficiently reliable. Rather than impose a clinical trial-like paradigm on RW evidence, like blinded treatments or complete, source-verified data, the framework for assessing the utility of RW evidence should be grounded in the context of specific study objectives, clinical events that are likely to be detected in routine care, and the extent to which systematic error (bias) is likely to impact effect estimation. Whether treatment is blinded should depend on how well the outcome can be measured objectively. Qualification of a data source should be based on (1) numbers of patients of interest available for study; (2) if "must-have" data are likely to be recorded, and if so, how and where; (3) the accessibility of systematic follow-up data for the time period of interest; and (4) the potential for systematic errors (bias) in data collection and the likely magnitude of any such bias. Accessible data may not be representative of an entire population, but still may provide reliable evidence about the experience of typical patients treated under conditions of conventional care. Similarly, RW data that falls short of optimal length of follow-up or study size may still be useful in terms of its ability to provide evidence for regulators for subgroups of special interest. Developing a framework to qualify RW evidence in the context of a particular study purpose and data asset will enable broader regulatory use of RW data for approval of new molecular entities and label changes. Reliable information about diverse populations and settings should also help us move closer to more affordable, effective health care.