A systematic review of observational studies evaluating costs of adverse drug reactions.
BACKGROUND
The growing evidence of the increased frequency and severity of adverse drug events (ADEs), besides the negative impact on patient's health status, indicates that costs due to ADEs may be steadily rising. Observational studies are an important tool in pharmacovigilance. Despite these studies being more susceptible to bias than experimental designs, they are more competent in assessing ADEs and their associated costs.


OBJECTIVE
To identify and characterize the best available evidence on ADE-associated costs.


METHODS
MEDLINE, Cochrane Library, and Embase were searched from 1995 to 2015. Observational studies were included. The methodological quality of selected studies was assessed by Cochrane Collaboration tool for experimental and observational studies. Studies were classified according to the setting analyzed in "ambulatory", "hospital", or both. Costs were classified as "direct" and "indirect". Data were analyzed using descriptive statistics. The total incremental cost per patient with ADE was estimated.


RESULTS
Twenty-nine (94%) longitudinal observational studies and two (7%) cross-sectional studies were included. Twenty-three (74%) studies were assessed with the highest methodological quality score. The studies were mainly conducted in the US (61%). Twenty (65%) studies evaluated any therapeutic group. Twenty (65%) studies estimated costs of ADEs leading to or prolonging hospitalization. The "direct costs" were evaluated in all studies, whereas only two (7%) also estimated the "indirect costs". The "direct costs" in ambulatory ranged from €702.21 to €40,273.08, and the in hospital from €943.40 to €7,192.36.


CONCLUSIONS
Methodological heterogeneities were identified among the included studies, such as design, type of ADEs, suspected drugs, and type and structure of costs. Despite such discrepancies, the financial burden associated with ADE costs was found to be high. In the light of the present findings, validated methods to measure ADE-associated costs need future research efforts.
CHAD - Centre for Health Technology Assessment and Drug Research, AIBILI - Association for Innovation and Biomedical Research on Light and Image; School of Pharmacy, University of Coimbra, Coimbra, Portugal.
Francisco
F
Batel Marques
CHAD - Centre for Health Technology Assessment and Drug Research, AIBILI - Association for Innovation and Biomedical Research on Light and Image; School of Pharmacy, University of Coimbra, Coimbra, Portugal.
Ana
A
Penedones
CHAD - Centre for Health Technology Assessment and Drug Research, AIBILI - Association for Innovation and Biomedical Research on Light and Image; School of Pharmacy, University of Coimbra, Coimbra, Portugal.
Diogo
D
Mendes
CHAD - Centre for Health Technology Assessment and Drug Research, AIBILI - Association for Innovation and Biomedical Research on Light and Image; School of Pharmacy, University of Coimbra, Coimbra, Portugal.
Carlos
C
Alves
drug costs; drug-related side effects and adverse reactions; health care costs; review