Use of administative claims data to design and emulate a clinical trial in acute stroke patients comparing rehabilitation at inpatient rehabilitation facilities to skilled nursing facilities

Stroke affects nearly 800,000 people every year in the United States and is a leading cause of adult disability. After hospitalization half of stroke patients continue to require medical and rehabilitation services provided at inpatient rehabilitation facilities (IRFs) or skilled nursing facilities (SNFs). In general, IRFs provide time-intensive therapy for two to three weeks, while SNFs provide moderately intensive therapy for four- to five-weeks. There is substantial variation in the utilization of these alternative rehabilitation settings, but their relative comparative effectiveness remains uncertain. A randomized controlled trial (RCT) would provide an unbiased comparative effectiveness estimate, but the design of such a trial is complicated by several practical and ethical issues. The overarching purpose of this dissertation was to use Medicare claims data to inform the design and to emulate such a trial. In the first aim, we sought to identify patient and hospital level factors that were associated with IRF or SNF discharge and characterize the heterogeneity of hospital effects that influenced discharge to an IRF (vs. SNF). From a retrospective cohort of 145,894 stroke patients, we used multi-level multivariable models to identify several patient- and hospital- level factors that were independently associated with discharge setting. We also showed that hospitals contributed around a third of the variation in IRF (vs. SNF) discharge, but there was substantial variation in the effect that specific hospitals had on influencing IRF discharge. The second aim, was to identify a target trial population that optimized the explanatory-pragmatic balance of a subsequent RCT. To identify this population, we profiled hospitals based on their propensity to discharge stroke patients to IRFs (vs. SNFs) and inferred IRF and SNF referral networks for each hospital. The final target trial population included 44,950 patients (30.8% of the starting sample) who were treated at 441 hospitals (14.5%) and subsequently discharged to 745 IRFs (64.8%) and 5,974 SNFs (48.2%).The third aim was to emulate three alternate RCTs that compared patient outcomes at IRFs vs. SNFs. Trial #1 used the target trial population identified in Aim 2, while trials #2 and 3 excluded increasingly infrequently used IRFs and SNFs. Comparative effectiveness was estimated using a matched propensity score analysis. Overall, on a relative basis, patients treated at IRFs were between 18-35% more likely to be successfully discharged home (i.e., alive and at home for >30 days) and were between 11-15% less likely to die within one year of acute care discharge. The variation in the effect size estimates across the trials was driven by poorer outcomes among patients treated at infrequently used SNFs. Finally, we identified that a moderate sized unmeasured confounder would nullify the observed differences.In conclusion, we identified that referring hospitals are a major driver of IRF or SNF use, and that patients treated at IRFs had better outcomes (relative to SNF patients). However, our results were limited by the inability to adjust for potentially important unmeasured confounders. A pragmatic RCT would eliminate such biases and provide a more valid comparative effectiveness estimate of these two alternative rehabilitation settings.