Projected environmental and public health benefits of extended-interval dosing: an analysis of pembrolizumab use in a US national health system.

BACKGROUND: Health care is a major source of greenhouse gas emissions, leading to climate change and public health harms. Changes are needed to improve the environmental sustainability of health-care practices, but such changes should not sacrifice patient outcomes or financial sustainability. Alternative dosing strategies that reduce the frequency with which specialty drugs are administered, without sacrificing patient outcomes, are an attractive possibility for improving environmental sustainability. We sought to inform environmentally sustainable cancer care by estimating and comparing the environmental and financial effects of alternative, clinically equivalent strategies for pembrolizumab administration. METHODS: We conducted a retrospective analysis using a cohort of patients from the Veterans Health Administration (VHA) in the USA who received one or more pembrolizumab doses between May 1, 2020, and Sept 30, 2022. Using baseline, real-world administration of pembrolizumab, we generated simulated pembrolizumab use data under three near-equivalent counterfactual pembrolizumab administration strategies defined by combinations of weight-based dosing, pharmacy-level vial sharing and dose rounding, and extended-interval dosing (ie, every 6 weeks). For each counterfactual dosing strategy, we estimated greenhouse gas emissions related to pembrolizumab use across the VHA cohort using a deterministic environmental impact model that estimated greenhouse gas emissions due to patient travel, drug manufacture, and medical waste as the primary outcome measure. FINDINGS: We identified 7813 veterans who received at least one dose of pembrolizumab-containing therapy in the VHA during the study period. 59 140 pembrolizumab administrations occurred in the study period, of which 46 255 (78·2%) were dosed at 200 mg every 3 weeks, 12 885 (21·8%) at 400 mg every 6 weeks, and 14 955 (25·3%) were coadministered with infusional chemotherapies. Adoption of weight-based, extended-interval pembrolizumab dosing (4 mg/kg every 6 weeks) and pharmacy-level stewardship strategies (ie, dose rounding and vial sharing) for all pembrolizumab infusions would have resulted in 24·7% fewer administration events than baseline dosing (44 533 events vs 59 140 events) and an estimated 200 metric tons less CO2 emitted per year as a result of pembrolizumab use within the VHA (650 tons vs 850 tons of CO2, a relative reduction of 24%), largely due to reductions in distance travelled by patients to receive treatment. Similar results were observed when weight-based and extended-interval dosing were applied only to pembrolizumab monotherapy and pembrolizumab in combination with oral therapies. INTERPRETATION: Alternative pembrolizumab administration strategies might have environmental advantages over the current dosing and compounding paradigms. Specialty medication dosing can be optimised for health-care spending and environmental sustainability without sacrificing clinical outcomes. FUNDING: None.

The global temperature-related mortality impact of earlier decarbonization for the Australian health sector and economy: A modelling study.

BACKGROUND: Sustained elevated concentration of GHGs is predicted to increase global mortality. With the Australian health sector responsible for 7% of the nation's GHG emissions, the benefits and costs of various decarbonisation trajectories are currently being investigated. To assist with this effort, we model the impact earlier decarbonisation has on temperature-related mortality. DESIGN: We used DICE-EMR, an Integrated Assessment Model with an endogenous mortality response, to simulate Australian GHG trajectories and estimate the temperature-related mortality impact of early decarbonisation. We modelled a linear decline of the Australian health sector's and economy's GHG annual emissions to net-zero targets of 2040 and 2050. MAIN OUTCOME MEASURE: Deaths averted and monetary-equivalent welfare gain. RESULTS: Decarbonisation of the Australian health sector by 2050 and 2040 is projected to avert an estimated 69,000 and 77,000 global temperature-related deaths respectively in a Baseline global emissions scenario. Australian economy decarbonisation by 2050 and 2040 is projected to avert an estimated 988,000 and 1,101,000 global deaths respectively. Assuming a low discount rate and high global emissions trajectory, we estimate a monetary equivalent welfare gain of $151 billion if the Australian health sector decarbonises by 2040, only accounting for the benefits in reducing temperature-related mortality. CONCLUSIONS: Earlier decarbonisation has a significant impact on temperature-related mortality. Many uncertainties exist and health impacts other than temperature-related mortality are not captured by this analysis. Nevertheless, such models can help communicate the health risk of climate change and improve climate policy decision making.

The mortality cost of carbon.

Many studies project that climate change can cause a significant number of excess deaths. Yet, in integrated assessment models (IAMs) that determine the social cost of carbon (SCC) and prescribe optimal climate policy, human mortality impacts are limited and not updated to the latest scientific understanding. This study extends the DICE-2016 IAM to explicitly include temperature-related mortality impacts by estimating a climate-mortality damage function. We introduce a metric, the mortality cost of carbon (MCC), that estimates the number of deaths caused by the emissions of one additional metric ton of CO2. In the baseline emissions scenario, the 2020 MCC is 2.26 × 10‒4 [low to high estimate -1.71× 10‒4 to 6.78 × 10‒4] excess deaths per metric ton of 2020 emissions. This implies that adding 4,434 metric tons of carbon dioxide in 2020-equivalent to the lifetime emissions of 3.5 average Americans-causes one excess death globally in expectation between 2020-2100. Incorporating mortality costs increases the 2020 SCC from $37 to $258 [-$69 to $545] per metric ton in the baseline emissions scenario. Optimal climate policy changes from gradual emissions reductions starting in 2050 to full decarbonization by 2050 when mortality is considered.

Estimates of country level temperature-related mortality damage functions.

Many studies project that climate change is expected to cause a significant number of excess deaths. Yet, in integrated assessment models that determine the social cost of carbon (SCC), human mortality impacts do not reflect the latest scientific understanding. We address this issue by estimating country-level mortality damage functions for temperature-related mortality with global spatial coverage. We rely on projections from the most comprehensive published study in the epidemiology literature of future temperature impacts on mortality (Gasparrini et al. in Lancet Planet Health 1:e360-e367, 2017), which estimated changes in heat- and cold-related mortality for 23 countries over the twenty-first century. We model variation in these mortality projections as a function of baseline climate, future temperature change, and income variables and then project future changes in mortality for every country. We find significant spatial heterogeneity in projected mortality impacts, with hotter and poorer places more adversely affected than colder and richer places. In the absence of income-based adaptation, the global mortality rate in 2080-2099 is expected to increase by 1.8% [95% CI 0.8-2.8%] under a lower-emissions RCP 4.5 scenario and by 6.2% [95% CI 2.5-10.0%] in the very high-emissions RCP 8.5 scenario relative to 2001-2020. When the reduced sensitivity to heat associated with rising incomes, such as greater ability to invest in air conditioning, is accounted for, the expected end-of-century increase in the global mortality rate is 1.1% [95% CI 0.4-1.9%] in RCP 4.5 and 4.2% [95% CI 1.8-6.7%] in RCP 8.5. In addition, we compare recent estimates of climate-change induced excess mortality from diarrheal disease, malaria and dengue fever in 2030 and 2050 with current estimates used in SCC calculations and show these are likely underestimated in current SCC estimates, but are also small compared to more direct temperature effects.