Local Instrumental Variable Methods to Address Confounding and Heterogeneity when Using Electronic Health Records: An Application to Emergency Surgery

BACKGROUND: Electronic health records (EHRs) offer opportunities for comparative effectiveness research to inform decision making. However, to provide useful evidence, these studies must address confounding and treatment effect heterogeneity according to unmeasured prognostic factors. Local instrumental variable (LIV) methods can help studies address these challenges, but have yet to be applied to EHR data. This article critically examines a LIV approach to evaluate the cost-effectiveness of emergency surgery (ES) for common acute conditions from EHRs. METHODS: This article uses hospital episodes statistics (HES) data for emergency hospital admissions with acute appendicitis, diverticular disease, and abdominal wall hernia to 175 acute hospitals in England from 2010 to 2019. For each emergency admission, the instrumental variable for ES receipt was each hospital's ES rate in the year preceding the emergency admission. The LIV approach provided individual-level estimates of the incremental quality-adjusted life-years, costs and net monetary benefit of ES, which were aggregated to the overall population and subpopulations of interest, and contrasted with those from traditional IV and risk-adjustment approaches. RESULTS: The study included 268,144 (appendicitis), 138,869 (diverticular disease), and 106,432 (hernia) patients. The instrument was found to be strong and to minimize covariate imbalance. For diverticular disease, the results differed by method; although the traditional approaches reported that, overall, ES was not cost-effective, the LIV approach reported that ES was cost-effective but with wide statistical uncertainty. For all 3 conditions, the LIV approach found heterogeneity in the cost-effectiveness estimates across population subgroups: in particular, ES was not cost-effective for patients with severe levels of frailty. CONCLUSIONS: EHRs can be combined with LIV methods to provide evidence on the cost-effectiveness of routinely provided interventions, while fully recognizing heterogeneity. HIGHLIGHTS: This article addresses the confounding and heterogeneity that arise when assessing the comparative effectiveness from electronic health records (EHR) data, by applying a local instrumental variable (LIV) approach to evaluate the cost-effectiveness of emergency surgery (ES) versus alternative strategies, for patients with common acute conditions (appendicitis, diverticular disease, and abdominal wall hernia).The instrumental variable, the hospital's tendency to operate, was found to be strongly associated with ES receipt and to minimize imbalances in baseline characteristics between the comparison groups.The LIV approach found that, for each condition, there was heterogeneity in the estimates of cost-effectiveness according to baseline characteristics.The study illustrates how an LIV approach can be applied to EHR data to provide cost-effectiveness estimates that recognize heterogeneity and can be used to inform decision making as well as to generate hypotheses for further research

Clinical effectiveness and cost-effectiveness of emergency surgery for adult emergency hospital admissions with common acute gastrointestinal conditions: the ESORT study

Background: Evidence is required on the clinical effectiveness and cost-effectiveness of emergency surgery compared with non-emergency surgery strategies (including medical management, non-surgical procedures and elective surgery) for patients admitted to hospital with common acute gastrointestinal conditions. Objectives: We aimed to evaluate the relative (1) clinical effectiveness of two strategies (i.e. emergency surgery vs. non-emergency surgery strategies) for five common acute conditions presenting as emergency admissions; (2) cost-effectiveness for five common acute conditions presenting as emergency admissions; and (3) clinical effectiveness and cost-effectiveness of the alternative strategies for specific patient subgroups. Methods: The records of adults admitted as emergencies with acute appendicitis, cholelithiasis, diverticular disease, abdominal wall hernia or intestinal obstruction to 175 acute hospitals in England between 1 April 2010 and 31 December 2019 were extracted from Hospital Episode Statistics and linked to mortality data from the Office for National Statistics. Eligibility was determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis codes, which were agreed by clinical panel consensus. Patients having emergency surgery were identified from Office of Population Censuses and Surveys procedure codes. The study addressed the potential for unmeasured confounding with an instrumental variable design. The instrumental variable was each hospital’s propensity to use emergency surgery compared with non-emergencysurgery strategies. The primary outcome was the ‘number of days alive and out of hospital’ at 90 days. We reported the relative effectiveness of the alternative strategies overall, and for prespecified subgroups (i.e. age, number of comorbidities and frailty level). The cost-effectiveness analyses used resource use and mortality from the linked data to derive estimates of incremental costs, quality-adjusted life-years and incremental net monetary benefits at 1 year. Results: Cohort sizes were as follows: 268,144 admissions with appendicitis, 240,977 admissions with cholelithiasis, 138,869 admissions with diverticular disease, 106,432 admissions with a hernia and 133,073 admissions with an intestinal obstruction. Overall, at 1 year, the average number of days alive and out of hospitals at 90 days, costs and quality-adjusted life-years were similar following either strategy, after adjusting for confounding. For each of the five conditions, overall, the 95% confidence intervals (CIs) around the incremental net monetary benefit estimates all included zero. For patients with severe frailty, emergency surgery led to a reduced number of days alive and out of hospital and was not cost-effective compared with non-emergency surgery, with incremental net monetary benefit estimates of –£18,727 (95% CI –£23,900 to –£13,600) for appendicitis, –£7700 (95% CI –£13,000 to –£2370) for cholelithiasis, –£9230 (95% CI –£24,300 to £5860) for diverticular disease, –£16,600 (95% CI –£21,100 to –£12,000) for hernias and –£19,300 (95% CI –£25,600 to –£13,000) for intestinal obstructions. For patients who were ‘fit’, emergency surgery was relatively cost-effective, with estimated incremental net monetary benefit estimates of £5180 (95% CI £684 to £9680) for diverticular disease, £2040 (95% CI £996 to £3090) for hernias, £7850 (95% CI £5020 to £10,700) for intestinal obstructions, £369 (95% CI –£728 to £1460) for appendicitis and £718 (95% CI £294 to £1140) for cholelithiasis. Public and patient involvement translation workshop participants emphasised that these findings should be made widely available to inform future decisions about surgery. Limitations: The instrumental variable approach did not eliminate the risk of confounding, and the acute hospital perspective excluded costs to other providers. Conclusions: Neither strategy was more cost-effective overall. For patients with severe frailty, nonemergency surgery strategies were relatively cost-effective. For patients who were fit, emergency surgery was more cost-effective. Future work: For patients with multiple long-term conditions, further research is required to assess the benefits and costs of emergency surgery. Study registration: This study is registered as reviewregistry784

Local Instrumental Variable Methods to Address Confounding and Heterogeneity when Using Electronic Health Records: An Application to Emergency Surgery.

BACKGROUND: Electronic health records (EHRs) offer opportunities for comparative effectiveness research to inform decision making. However, to provide useful evidence, these studies must address confounding and treatment effect heterogeneity according to unmeasured prognostic factors. Local instrumental variable (LIV) methods can help studies address these challenges, but have yet to be applied to EHR data. This article critically examines a LIV approach to evaluate the cost-effectiveness of emergency surgery (ES) for common acute conditions from EHRs. METHODS: This article uses hospital episodes statistics (HES) data for emergency hospital admissions with acute appendicitis, diverticular disease, and abdominal wall hernia to 175 acute hospitals in England from 2010 to 2019. For each emergency admission, the instrumental variable for ES receipt was each hospital's ES rate in the year preceding the emergency admission. The LIV approach provided individual-level estimates of the incremental quality-adjusted life-years, costs and net monetary benefit of ES, which were aggregated to the overall population and subpopulations of interest, and contrasted with those from traditional IV and risk-adjustment approaches. RESULTS: The study included 268,144 (appendicitis), 138,869 (diverticular disease), and 106,432 (hernia) patients. The instrument was found to be strong and to minimize covariate imbalance. For diverticular disease, the results differed by method; although the traditional approaches reported that, overall, ES was not cost-effective, the LIV approach reported that ES was cost-effective but with wide statistical uncertainty. For all 3 conditions, the LIV approach found heterogeneity in the cost-effectiveness estimates across population subgroups: in particular, ES was not cost-effective for patients with severe levels of frailty. CONCLUSIONS: EHRs can be combined with LIV methods to provide evidence on the cost-effectiveness of routinely provided interventions, while fully recognizing heterogeneity. HIGHLIGHTS: This article addresses the confounding and heterogeneity that arise when assessing the comparative effectiveness from electronic health records (EHR) data, by applying a local instrumental variable (LIV) approach to evaluate the cost-effectiveness of emergency surgery (ES) versus alternative strategies, for patients with common acute conditions (appendicitis, diverticular disease, and abdominal wall hernia).The instrumental variable, the hospital's tendency to operate, was found to be strongly associated with ES receipt and to minimize imbalances in baseline characteristics between the comparison groups.The LIV approach found that, for each condition, there was heterogeneity in the estimates of cost-effectiveness according to baseline characteristics.The study illustrates how an LIV approach can be applied to EHR data to provide cost-effectiveness estimates that recognize heterogeneity and can be used to inform decision making as well as to generate hypotheses for further research