Under-recording of hospital bleeding events in UK primary care: a linked Clinical Practice Research Datalink and Hospital Episode Statistics study

Laura McDonald,1,* Cormac J Sammon,2,* Mihail Samnaliev,2 Sreeram Ramagopalan1 1Centre for Observational Research and Data Sciences, Bristol-Myers Squibb, Uxbridge, UK; 2PHMR, Berkeley Works, London, UK *These authors contributed equally to this work Background: Primary care databases represent a rich source of data for health care research; however, the quality of recording of secondary care events in these databases is uncertain. This study sought to investigate the completeness of recording of hospital admissions for bleeds in primary care records and explore the impact of incomplete recording on estimates of bleeding risk associated with antithrombotic treatment.Methods: The study population consisted of adults with non-valvular atrial fibrillation who had at least one bleed recorded in either the Clinical Practice Research Datalink (CPRD) or Hospital Episode Statistics (HES) while receiving prescriptions for an oral anticoagulant. The proportion of bleeds recorded in HES that had a corresponding bleed recorded in the subsequent 12 weeks in CPRD was calculated, and factors associated with having a corresponding record were identified. Cox proportional hazards analyses investigating the hazard of subsequent bleeding associated with antithrombotic treatment were carried out using linked CPRD-HES data and using CPRD only data, and the results were compared.Results: Less than 20% of the 14,361 bleeds recorded in the HES data had a corresponding bleed coded in the CPRD in the subsequent 12 weeks. This proportion varied by bleed characteristics, calendar time, day of week of admission (weekday vs weekend) and oral anticoagulant treatment at the time of the bleed. The hazard of subsequent bleeding associated with vitamin K antagonists (VKAs) and antiplatelet agents (APAs) relative to no antithrombotic treatment were similar using the linked primary and secondary care dataset (VKA HRadj 1.06 CI95 0.96–1.16; APA HRadj 1.08 CI95 0.96–1.21) and the unlinked primary care data (VKA HRadj 1.12 CI95 1.01–1.24; APA HRadj 1.06 CI95 0.95–1.20).Conclusion: Secondary care bleeding events are not completely recorded in primary care records and under-recording may be differential with respect to a variety of factors, including antithrombotic treatment. While the impact of under-recording on estimates of the comparative safety of antithrombotic drugs was limited, the extent of the under-recording suggests its potential impact should be considered, and ideally evaluated in future studies utilizing stand-alone primary care data. Keywords: real-world data, data linkage, comparative effectiveness, secondary care, atrial fibrillatio

Effect of School Integrated Pest Management or Classroom Air Filter Purifiers on Asthma Symptoms in Students with Active Asthma: A Randomized Clinical Trial

IMPORTANCE: School and classroom allergens and particles are associated with asthma morbidity, but the benefit of environmental remediation is not known. OBJECTIVE: To determine whether use of a school-wide integrated pest management (IPM) program or high-efficiency particulate air (HEPA) filter purifiers in the classrooms improve asthma symptoms in students with active asthma. DESIGN, SETTING, AND PARTICIPANTS: Factorial randomized clinical trial of a school-wide IPM program and HEPA filter purifiers in the classrooms was conducted from 2015 to 2020 (School Inner-City Asthma Intervention Study). There were 236 students with active asthma attending 41 participating urban elementary schools located in the Northeastern US who were randomized to IPM by school and HEPA filter purifiers by classroom. The date of final follow-up was June 20, 2020. INTERVENTIONS: The school-wide IPM program consisted of application of rodenticide, sealing entry points, trap placement, targeted cleaning, and brief educational handouts for school staff. Infestation was assessed every 3 months, with additional treatments as needed. Control schools received no IPM, cleaning, or education. Classroom portable HEPA filter purifiers were deployed and the filters were changed every 3 months. Control classrooms received sham HEPA filters that looked and sounded like active HEPA filter purifiers. Randomization was done independently (split-plot design), with matching by the number of enrolled students to ensure a nearly exact 1:1 student ratio for each intervention with 118 students randomized to each group. Participants, investigators, and those assessing outcomes were blinded to the interventions. MAIN OUTCOMES AND MEASURES: The primary outcome was the number of symptom-days with asthma during a 2-week period. Symptom-days were assessed every 2 months during the 10 months after randomization. RESULTS: Among the 236 students who were randomized (mean age, 8.1 [SD, 2.0] years; 113 [48%] female), all completed the trial. At baseline, the 2-week mean was 2.2 (SD, 3.9) symptom-days with asthma and 98% of the classrooms had detectable levels of mouse allergen. The results were pooled because there was no statistically significant difference between the 2 interventions (P = .18 for interaction). During a 2-week period, the mean was 1.5 symptom-days with asthma after use of the school-wide IPM program vs 1.9 symptom-days after no IPM across the school year (incidence rate ratio, 0.71 [95% CI, 0.38-1.33]), which was not statistically significantly different. During a 2-week period, the mean was 1.6 symptom-days with asthma after use of HEPA filter purifiers in the classrooms vs 1.8 symptom-days after use of sham HEPA filter purifiers across the school year (incidence rate ratio, 1.47 [95% CI, 0.79-2.75]), which was not statistically significantly different. There were no intervention-related adverse events. CONCLUSIONS AND RELEVANCE: Among children with active asthma, use of a school-wide IPM program or classroom HEPA filter purifiers did not significantly reduce symptom-days with asthma. However, interpretation of the study findings may need to consider allergen levels, particle exposures, and asthma symptoms at baseline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0229130

Choice Certainty and Consistency in Repeated Choice Experiments

Choice certainty, Choice experiment, Learning, Choice consistency, C35, D83, Q25, Q51,

Mitigating hypothetical bias in willingness to pay studies: post-estimation uncertainty and anchoring on irrelevant information

One possible source of hypothetical bias in willingness to pay (WTP) estimates is response uncertainty, referring to subject’s uncertainty about the value of the good under assessment. It has been argued that uncertainty can be measured using the post-valuation ‘certainty question’ that asks: ‘How certain are you about your stated WTP?’ and marks the degree of certainty on a quantitative or a qualitative scale. Research has shown that the self- reported certainty evaluations can help mitigate hypothetical bias and obtain increasingly accurate WTP estimates. These study reports present a simple test of reliability of post-valuation certainty assessment and then looks at the empirical evidence for clues regarding the general usefulness of certainty adjustment in mitigating hypothetical bias in WTP studies. We find that the post-estimation uncertainty scores are malleable, i.e., significantly correlated with entirely irrelevant information. We conclude that more robust evidence could justify the routine inclusion of certainty evaluation in WTP studies although in the meantime the interpretation of certainty- adjusted WTP values should be approached cautiously