Why published studies of the cost-effectiveness of PCSK-9 inhibitors yielded such markedly different results

Real-world cardiovascular disease burden in patients with atherosclerotic cardiovascular disease: a comprehensive systematic literature review

“…Elliot et al 12 found that rates of hypoglycemia were consistently higher in real-world studies compared to RCTs in patients with type 1 or type 2 diabetes. Toth et al 34 found that cost-effectiveness analyses based on real-world rather than RCT data are more likely to conclude that a treatment is cost-effective, because RCTs are more likely to underestimate the true benefit of lipid-lowering therapies. Because of this, several national and international clinical and research organizations endorse the use of RWE in the evaluation of new technologies 34 .…”

“…Toth et al 34 found that cost-effectiveness analyses based on real-world rather than RCT data are more likely to conclude that a treatment is cost-effective, because RCTs are more likely to underestimate the true benefit of lipid-lowering therapies. Because of this, several national and international clinical and research organizations endorse the use of RWE in the evaluation of new technologies 34 . Together with prior research and evidence generated in this study, this data underscores the importance of conducting and considering observational population studies in CVD to produce generalizable disease burden estimates in a real-world setting.…”

“…This is demonstrated by the stringent patient selection criteria (e.g. exclusion of high risk patients) and highly controlled clinical settings typically employed by RCTs, leading to limited generalizability of disease burden to the general population and routine clinical practices 12,[32][33][34] . Elliot et al 12 found that rates of hypoglycemia were consistently higher in real-world studies compared to RCTs in patients with type 1 or type 2 diabetes.…”

“…We compared the MACE rates observed in real-world studies with those reported in a recent comprehensive meta-analysis of 26 clinical trials 15 . According to the CTTC, The importance of considering RWE has been discussed in prior studies 12,[32][33][34] . Although RCTs are considered the "gold standard" for establishing the efficacy of specific interventions, this methodological approach is probably not sufficient for describing the epidemiology and real-world disease burden in the general population.…”

“…Differences in results observed in RCTs versus observational studies are primarily associated with differences in the study populations, settings and outcomes 34,35 . RCTs typically examine highly selected patient populations in tightly controlled and monitored settings and often focus on time-tofirst-event outcomes, while observational studies include patients that may be excluded from RCTs and focus on realworld conditions with greater variation in practice and patient settings and examine all relevant events 34,35 .…”