Assessing the cost-effectiveness of precision medicine: protocol for a systematic review and meta-analysis.

INTRODUCTION: Precision medicine (PM) involves gene testing to identify disease risk, enable early diagnosis or guide therapeutic choice, and targeted gene therapy. We aim to perform a systematic review and meta-analysis to quantify the cost-effectiveness profile of PM stratified by intervention type, identify sources of heterogeneity in the value-for-money of PM. METHODS AND ANALYSIS: We will perform a systematic search in Embase, MEDLINE, EconLit and CRD databases for studies published in English language or with translation in English between 1 January 2011 and 8 July 2021 on the topic of cost-effectiveness analysis of PM interventions. The focus will be on studies that reported health and economic outcomes. Study quality will be assessed using the Biases in Economic Studies checklist. The incremental net benefit of PM screening, diagnostic, treatment-targeting and therapeutic interventions over conventional strategies will be respectively pooled across studies using a random-effect model if heterogeneity is present, otherwise a fixed-effect model. Subgroup analyses will be performed based on disease area, WHO region and World Bank country-income level. Additionally, we will identify the potential sources of heterogeneity with random-effect meta-regressions. Finally, biases will be detected using jackknife sensitivity analysis, funnel plot assessment and Egger's tests. ETHICS AND DISSEMINATION: For this type of study ethics approval or formal consent is not required. The results will be disseminated at various presentations and feedback sessions, in conference abstracts and manuscripts that will be submitted to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021272956.

Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy.

Background: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics. Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson's chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons. Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147). Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.