Reducing CO2 and improving clinical delivery with novel study designs

Healthcare is responsible for 4%–5% of greenhouse gas (GHG) emissions globally.¹ An analysis concluded the total carbon footprint for the DAPA-HF trial (n=4744 patients) was calculated as 2498 tonnes of emitted CO2 (CO2e), The estimated CO2e for all the globally ongoing Phase III trials (n>2100) is 3–5.2 million tonnes, and phase I–II studies will add more emissions¹. AstraZeneca Sustainability in Clinical Trials Initiative developed a framework to optimize CO2e in clinical trial design.¹ AstraZeneca used CRESCENDO, a Phase 2a clinical trial of the myeloperoxidase (MPO) inhibitor mitiperstat in patients with chronic obstructive pulmonary disease (COPD)as a proof of principle to apply the framework to optimize CO2e. CRESCENDO has demonstrated a reduction in the CO2 footprint in COPD clinical studies in comparison to an equivalent exacerbation study. The design reduced CO2 footprint by 30% (132 versus 192 Tonnes CO2e per study year). Traditional COPD trials utilize exacerbation events as clinical endpoints, making trials large, lengthy and costly. In contrast, CRESCENDO used COPDCompEx² , a composite endpoint combining patient-reported diary events, including peak expiratory flow, exacerbations and study dropouts, to predict treatment effect of mitiperstat on exacerbations, resulting in fewer visits, fewer patients (reduction from 604 to 288 patients), and therefore fewer sites (reduction from around 300 to 110). The CRESCENDO study is recruiting above expectations. The lessons from CRESCENDO are being shared across the enterprise and similar approaches are being implemented in other trials. 1. McKillop et al: BMJ Open 2023;13:e072491. 2. Vogelmeier C et al. Respir Med 2020;173:106175