Evaluating Wastewater Surveillance for Estimating Pharmaceutical Use

Abstract Regional medicine use data is key for health management and in understanding many aspects of health, still such data is missing in many parts of the world. Here, we aimed to evaluate how well analyses of active pharmaceutical ingredients (APIs) in untreated municipal wastewater could be used to predict regional use. We studied 53 APIs measured at three wastewater treatment plants (WWTPs) in Stockholm, Sweden between 2004-2021 together with corresponding, comprehensive sales data from hospitals, pharmacies and other outlets as proxy for use. Conversion factors (CFs) representing recovered mass per gram of sold API were generated for each API using data from two WWTPs. Median absolute deviation normalized by the median (MADM) was used to evaluate variability of CFs over the years. While CFs ranged more than two orders of magnitude between different APIs, mass loads recovered in wastewater were equal or less than the estimated daily use for all except one API. The variability of CF estimates was below 100% for 43 APIs. When evaluating the predictive performance of the derived CFs on data from the third WWTP, the typical error was <2-fold for 36 APIs (68%). Neither removal efficiency in WWTPs nor lipophilicity were good predictors of CFs. Our findings suggest that use of most APIs can be estimated from traces measured in wastewater with a typical error of <2-fold. This provides support for the development of wastewater surveillance for estimating medicine use to fill existing data gaps, but also suggest limitations in detecting small changes. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was funded by SciLifeLab & Wallenberg Data Driven Life Science Program (grant: KAW 2020.0239). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors.