Quantifying the impact of real-world evidence: the sacubitril/valsartan experience

Background: The impact of RWE publication on use of approved therapies, including the existence of an effect and timing of impact, is unknown. Methods: We assessed the relationship between the cadence of RWE publications and sales of sacubitril/valsartan (Entresto) following launch. Publication data were derived from a PubMed search over 7/01/2015-12/31/2023 for English-language, human subject studies with the drug name (Entresto or sacubitril) and indication (heart failure) in the title or abstract. Quarterly RWE publication data were combined with quarterly information on sacubitril/valsartan sales over the 34-quarter period spanning Q3 2015 through Q4 2023. Quarter-to-quarter change in total sales was modeled with linear regression as a function of counts of previously published RWE-related studies, adjusting for a linear time trend to control for any underlying trends in sales growth; change in total sales from the quarter prior to publication to the quarter of publication to control for recent sales changes; and the cumulative count of RWE publications from Q3 2015 through the previous quarter to control for the contribution of previous RWE publications to future sales. Results: The PubMed search identified 888 studies; of these, 333 (37.5%) were classified as RWE-related. An additional RWE-related publication (in quarter q) was associated with an estimated mean increase in quarterly sales of $1.8M (from quarter q to q+1 following publication), $3.5M (from q+1 to q+2), and $2.7M (from q+2 to q+3). In adjusted models, an additional RWE publication was associated with a mean gain in sales from quarter q+1 to q+2 of $2.6M (95% CI -$0.2M to $5.4M). RWE publications were not associated with an increase in sales in the quarter following publication, and the association was attenuated by third quarter following publication. Conclusion: RWE studies were associated with increased use of sacubitril/valsaratan, providing preliminary evidence of RWE's ability to support therapy adoption.