Cargando…

The impact of time-window bias on the assessment of the long-term effect of medication adherence: the case of secondary prevention after myocardial infarction

OBJECTIVES: Time-window bias was described in case–control studies and led to a biased estimate of drug effect. No studies have measured the impact of this bias on the assessment of the effect of medication adherence on health outcomes. Our goals were to estimate the association between adherence to...

Descripción completa

Detalles Bibliográficos
Autores principales: Di Martino, Mirko, Kirchmayer, Ursula, Agabiti, Nera, Bauleo, Lisa, Fusco, Danilo, Perucci, Carlo Alberto, Davoli, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466602/
https://www.ncbi.nlm.nih.gov/pubmed/26063569
http://dx.doi.org/10.1136/bmjopen-2015-007866
_version_ 1782376252011708416
author Di Martino, Mirko
Kirchmayer, Ursula
Agabiti, Nera
Bauleo, Lisa
Fusco, Danilo
Perucci, Carlo Alberto
Davoli, Marina
author_facet Di Martino, Mirko
Kirchmayer, Ursula
Agabiti, Nera
Bauleo, Lisa
Fusco, Danilo
Perucci, Carlo Alberto
Davoli, Marina
author_sort Di Martino, Mirko
collection PubMed
description OBJECTIVES: Time-window bias was described in case–control studies and led to a biased estimate of drug effect. No studies have measured the impact of this bias on the assessment of the effect of medication adherence on health outcomes. Our goals were to estimate the association between adherence to drug therapies after myocardial infarction (MI) and the incidence of a new MI, and to quantify the error that would have been produced by a time-window bias. SETTING: This is a population-based study. Data were obtained from the Regional Health Information Systems of the Lazio Region in Central Italy (around 5 million inhabitants). PARTICIPANTS: Patients discharged after MI in 2006–2007 were enrolled in the cohort and followed through 2009. OUTCOME MEASURE: The study outcome was reinfarction: either mortality, or hospital admission for MI, whichever occurred first. DESIGN: A nested case–control study was performed. Controls were selected using both time-dependent and time-independent sampling. Adherence to antiplatelets, β-blockers, ACE inhibitors/angiotensin receptor blockers (ACEI/ARBs) and statins was calculated using the proportion of days covered (PDC). RESULTS: A total of 6880 patients were enrolled in the cohort. Using time-dependent sampling, a protective effect was detected for all study drugs. Conversely, using time-independent sampling, the beneficial effect was attenuated, as in the case of antiplatelet agents and statins, or completely masked, as in the case of ACEI/ARBs and β-blockers. For ACEI/ARBs, the time-dependent approach produced ORs of 0.83 (95% CI 0.57 to 1.21) and 0.72 (0.55 to 0.95), respectively, for ‘0.5<PDC≤0.75’ and ‘PDC>0.75’ versus ‘0≤PDC≤0.5’. Using the time-independent approach, the ORs were 0.96 (0.65 to 1.43) and 1.00 (0.76 to 1.33), respectively. CONCLUSIONS: A time-independent definition of a time-dependent exposure introduces a bias when the length of follow-up varies with the outcome. The persistence of time-related biases in peer-reviewed papers strongly suggests the need for increased awareness of this methodological pitfall.
format Online
Article
Text
id pubmed-4466602
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-44666022015-06-17 The impact of time-window bias on the assessment of the long-term effect of medication adherence: the case of secondary prevention after myocardial infarction Di Martino, Mirko Kirchmayer, Ursula Agabiti, Nera Bauleo, Lisa Fusco, Danilo Perucci, Carlo Alberto Davoli, Marina BMJ Open Pharmacology and Therapeutics OBJECTIVES: Time-window bias was described in case–control studies and led to a biased estimate of drug effect. No studies have measured the impact of this bias on the assessment of the effect of medication adherence on health outcomes. Our goals were to estimate the association between adherence to drug therapies after myocardial infarction (MI) and the incidence of a new MI, and to quantify the error that would have been produced by a time-window bias. SETTING: This is a population-based study. Data were obtained from the Regional Health Information Systems of the Lazio Region in Central Italy (around 5 million inhabitants). PARTICIPANTS: Patients discharged after MI in 2006–2007 were enrolled in the cohort and followed through 2009. OUTCOME MEASURE: The study outcome was reinfarction: either mortality, or hospital admission for MI, whichever occurred first. DESIGN: A nested case–control study was performed. Controls were selected using both time-dependent and time-independent sampling. Adherence to antiplatelets, β-blockers, ACE inhibitors/angiotensin receptor blockers (ACEI/ARBs) and statins was calculated using the proportion of days covered (PDC). RESULTS: A total of 6880 patients were enrolled in the cohort. Using time-dependent sampling, a protective effect was detected for all study drugs. Conversely, using time-independent sampling, the beneficial effect was attenuated, as in the case of antiplatelet agents and statins, or completely masked, as in the case of ACEI/ARBs and β-blockers. For ACEI/ARBs, the time-dependent approach produced ORs of 0.83 (95% CI 0.57 to 1.21) and 0.72 (0.55 to 0.95), respectively, for ‘0.5<PDC≤0.75’ and ‘PDC>0.75’ versus ‘0≤PDC≤0.5’. Using the time-independent approach, the ORs were 0.96 (0.65 to 1.43) and 1.00 (0.76 to 1.33), respectively. CONCLUSIONS: A time-independent definition of a time-dependent exposure introduces a bias when the length of follow-up varies with the outcome. The persistence of time-related biases in peer-reviewed papers strongly suggests the need for increased awareness of this methodological pitfall. BMJ Publishing Group 2015-06-10 /pmc/articles/PMC4466602/ /pubmed/26063569 http://dx.doi.org/10.1136/bmjopen-2015-007866 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Pharmacology and Therapeutics
Di Martino, Mirko
Kirchmayer, Ursula
Agabiti, Nera
Bauleo, Lisa
Fusco, Danilo
Perucci, Carlo Alberto
Davoli, Marina
The impact of time-window bias on the assessment of the long-term effect of medication adherence: the case of secondary prevention after myocardial infarction
title The impact of time-window bias on the assessment of the long-term effect of medication adherence: the case of secondary prevention after myocardial infarction
title_full The impact of time-window bias on the assessment of the long-term effect of medication adherence: the case of secondary prevention after myocardial infarction
title_fullStr The impact of time-window bias on the assessment of the long-term effect of medication adherence: the case of secondary prevention after myocardial infarction
title_full_unstemmed The impact of time-window bias on the assessment of the long-term effect of medication adherence: the case of secondary prevention after myocardial infarction
title_short The impact of time-window bias on the assessment of the long-term effect of medication adherence: the case of secondary prevention after myocardial infarction
title_sort impact of time-window bias on the assessment of the long-term effect of medication adherence: the case of secondary prevention after myocardial infarction
topic Pharmacology and Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466602/
https://www.ncbi.nlm.nih.gov/pubmed/26063569
http://dx.doi.org/10.1136/bmjopen-2015-007866
work_keys_str_mv AT dimartinomirko theimpactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT kirchmayerursula theimpactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT agabitinera theimpactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT bauleolisa theimpactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT fuscodanilo theimpactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT peruccicarloalberto theimpactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT davolimarina theimpactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT dimartinomirko impactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT kirchmayerursula impactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT agabitinera impactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT bauleolisa impactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT fuscodanilo impactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT peruccicarloalberto impactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction
AT davolimarina impactoftimewindowbiasontheassessmentofthelongtermeffectofmedicationadherencethecaseofsecondarypreventionaftermyocardialinfarction