Health utility values associated with pharmaceutical treatment process attributes: a systematic review and...

In cases where clinical efficacy and safety profiles are similar, patient preferences for the treatment process become a critical determinant of therapeutic adherence and health-related quality of life (HRQoL). However, current research on the utility of treatment process attributes (such as administration route, frequency, and time) show significant heterogeneity. Moreover, the results are often influenced by confounding factors, making it difficult to quantify their independent utility impact.

This study aims to deconstruct prevalent confounding biases through a systematic review and multivariable meta-regression. The goal is to isolate the independent effects of various treatment process attributes on health utility values, thereby providing more precise evidence for pharmacoeconomic evaluations.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this study systematically searched PubMed, Cochrane Library, Web of Science, and EBSCO databases for relevant English-language literature published up to December 2024. Original research reporting health utility values (on a 0-1 scale) associated with pharmaceutical treatment process attributes was included. Extracted disutility values, defined as Disutility=Utility - 1, were analyzed using random-effects models. Univariate, bivariate, and multivariable meta-regression models were constructed to control for key confounders, such as disease type and respondent population (patients vs. general public), and to investigate the independent effects of administration route, frequency, and duration on utility values.

Nineteen studies (providing 81 utility values) met inclusion criteria. In fully adjusted models, administration route emerged as a primary determinant of utility. Injection (versus oral) conferred a significant disutility (β = - 0.092; 95% CI - 0.127 to - 0.056; p < 0.001). Administration durations > 1 h also imposed significant disutility (β = - 0.172; 95% CI - 0.289 to - 0.055; p < 0.005). Disease severity was the strongest predictor overall: utilities for neoplasms were over 0.4 lower than for metabolic conditions (p < 0.001). Patients consistently reported higher utilities than the general public. An apparent "frequency paradox" (greater disutility for lower dosing frequency) emerged in unadjusted analysis, but this effect disappeared after adjusting for route, indicating it was a statistical artifact of confounding by route. No independent effect of dosing frequency remained in multivariable analysis.

Injectable route and prolonged administration duration are significant, independent drivers of health disutility. The apparent negative effect of dosing frequency is a statistical artifact of confounding by the administration route, which carries the actual disutility. These findings highlight the interconnectedness of treatment attributes and underscore that a holistic, multivariable measurement approach is necessary to avoid erroneous conclusions from confounding bias in pharmacoeconomic evaluations.