Bridging evidence gaps: the role of real-world data in tobacco harm reduction

The importance of real-world evidence (RWE) is becoming increasingly recognized in the fields. of medicine and healthcare delivery as a complement to evidence from randomized controlled. trials (RCTs). Incorporating RWE - which informs on a treatment's uptake, effectiveness, risks, and benefits under realistic (vs. carefully controlled) conditions among diverse and heterogeneous populations-can specifically benefit efforts to reduce combustible tobacco use, the primary cause of preventable premature death globally. RCTs have shown a variety of quit methods (e.g., nicotine replacement therapy, varenicline, and electronic nicotine delivery systems (ENDS)) to be effective for smoking cessation, but these treatments have varying uptake and success in real-world settings. A likely reason why RCT evidence does not necessarily generalize to real-world settings is that the populations eligible for RCTs do not represent the majority of adults who smoke (e.g., with respect to motivation to quit), underscoring the need for complementary RWE. Accordingly, non-combustible nicotine products (NCNPs) including ENDS that can serve as alternative consumer products and do not require a priori intentions to quit smoking seem to have higher uptake, and therefore greater reach, than traditional medical or pharmaceutical methods. RWE can also advance our limited current understanding of how consumers use reduced-risk products, which could in turn improve generalizability of RCTs in the future, as well as inform clinical communications and regulatory strategies. Since RWE has limitations such as confounding and selection bias, it should be used as a complement, not a replacement for, traditional RCT evidence.