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Impact of study design decisions on identification of treatment initiators of medications for opioid use disorder

Abstract

Background and Aims

Comparative effectiveness research studies commonly restrict cohorts to individuals who initiate a medication and do not have evidence of prior treatment. This is particularly challenging in research on medications for opioid use disorder (MOUD) because of sporadic use or intermittent adherence. We examined the impact of different lookback windows and washout criteria to identify MOUD initiator cohorts on sample size, cohort characteristics, and misclassification of treatment initiation.

Design and Setting

Cohort study using the Merative™ MarketScan® Multi-State Medicaid Database (2011–2022).

Participants

Medicaid-insured adults aged 18–64 with an MOUD prescription from 01/01/2022 to 12/31/2022 and a history of opioid use disorder (OUD) with at least 3 months of continuous enrollment.

Measurements

We created treatment initiator cohorts with increasingly restrictive lookback windows for inclusion (6-, 12-, 24-, 36-months, all-available). During each lookback window, we required [1] continuous enrollment; [2] continuous enrollment and OUD diagnosis; or [3] continuous enrollment, OUD diagnosis, and no prior treatment with MOUD. We defined prior treatment with MOUD as: (a) ≥ 30 days use (less restrictive definition; allowed for some prior treatment); or (b) ≥ 1 day use (more restrictive definition; did not allow prior treatment). We quantified changes in cohort sample size, demographic characteristics, and proportion of prevalent use episodes misclassified as MOUD treatment initiation (gold standard: 36-month lookback window).

Findings

We identified 103 794 eligible MOUD initiators (64.8% buprenorphine, 24.8% methadone, 10.4% naltrexone). Sample size of the cohorts decreased with increasingly restrictive lookback windows and washout criteria: [1] continuous enrollment (range, 96.9% for 6 months to 51.8% for 36 months); [2] continuous enrollment and less restrictive washout (range, 29.7% to 8.4%); and [3] continuous enrollment and more restrictive washout (range, 22.2% to 5.8%). All-available lookback performed similarly to a 12-month lookback. Longer lookback windows resulted in initiator cohorts with a greater proportion of individuals who were older, female, and of a minoritized race/ethnicity. The proportion of people with prevalent MOUD use misclassified as treatment initiation increased steadily with decreasing duration of lookback windows (24-, 12-, and 6-month); we observed misclassification among 16.1% to 49.2% of individuals (less restrictive washout), and 16.8% to 53.2% of individuals (more restrictive washout).

Conclusions

The choice of lookback window duration and washout criteria in research on medications for opioid use disorder (MOUD) presents tradeoffs between cohort sample size, demographic characteristics, and misclassification of treatment initiation. This study offers practical guidance for researchers planning to perform comparative studies in MOUD.

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Posted in: Journal Article Abstracts on 01/29/2026 | Link to this post on IFP |
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