Introduction
The World Health Organization (WHO) estimates that chronic respiratory diseases represent 5% of total disease burden and 8.3% of chronic disease burden worldwide, accounting for more than 4 million deaths each year [
1] of which 28,000 occur in the Nordics, Belgium, Netherlands and Luxembourg (Benelux) [
2,
3]. About 210 million people are estimated to have chronic obstructive pulmonary disease (COPD) worldwide [
4] and an estimated 300 million people suffer from asthma [
5,
6]. The economic burden, including productivity losses, of these diseases in the European Union (EU) has been estimated to be €33.9 billion and €48.4 billion for asthma and COPD, respectively [
2].
Inhalation therapy is the cornerstone of COPD and asthma management [
7] to reduce symptoms and the risk of severe exacerbations. There are a variety of different inhalers which can be grouped into three main categories: (1) breath-actuated or pressurized metered-dose inhalers (MDI, pMDI), (2) dry powder inhalers (DPIs) and (3) liquid multi-dose spray propellant-free devices, such as the soft mist inhaler (SMI™), Respimat
®.
Innovation in the management of respiratory diseases has traditionally focused on the development of new molecules but the choice of inhaler is as important as the selection of drug for inhaling in achieving an optimal treatment outcome [
8]. Poor adherence to therapy is common among patients with asthma and COPD and partly associated with difficulties in managing the inhaler device [
8‐
11]. Patients have expressed preference for inhalers which are easy to use in episodes of breathing difficulties and provide reassurance about the inhaled dose being taken, e.g. a precise dose counter and dose confirmation mechanisms [
12,
13]. Hence, patient satisfaction with the inhaler device is expected to enhance treatment adherence and ultimately improve clinical outcomes and quality of life.
However, the value of an innovation may extend beyond improvements in clinical outcomes and quality of life. Lately, other innovations aimed at avoiding propellants, reducing drug waste and disposable inhalers have been perceived as an additional benefit with the potential to reduce carbon dioxide (CO
2) emissions and thereby have a positive environmental impact. While the current regulated model of health technology assessment (HTA) captures the first two values (improved clinical outcomes and quality of life), it needs to be expanded to capture the last one (environmental impact). For example, 70% of the inhaler users in the UK are on pMDI [
14]. Yet, the UK Treasury estimates that for each pMDI inhaler with a unit cost of 2–4 GBP there is an environmental damage cost of 1–3 GBP [
14].
In total, the healthcare sector contributes 5–8% of the global greenhouse gas (GHG) emissions [
15]. Global and regional organizations and governments have started to design and implement measures to reduce GHG emissions in the healthcare sector, e.g. by green public procurement policies and inclusion of ecological considerations in the decision-making process for purchasing and funding of healthcare technologies. CO
2 reduction targets have become part of corporate goals and sustainability reporting by healthcare companies. In a more patient-centric healthcare ecosystem, patients increasingly act as consumers and prefer eco-friendly products [
16,
17].
pMDIs with propellants (hydrofluoroalkane, HFA) are the most widely used inhalers in COPD and asthma. The National Health Service (NHS) in the UK reports that propellants from inhalers account for 8% of the NHS’s entire carbon footprint [
2]. Globally, 630 million HFA-based pMDIs are used annually resulting in an estimated CO
2e burden of 13 million tCO
2e [
4], equal to the carbon footprint of 2 million EU citizens [
14].
Whilst several national and methodological guidelines encourage the inclusion of the societal perspective in the economic analyses, only a minority of analyses do so [
18]. There is currently a discussion in the scientific and policy community regarding the need for redefining what value means [
19‐
25]. More holistic frameworks are being proposed and piloted which aim to better capture the total value and to better consider the diverse needs of stakeholders [
26‐
28]. Comprehensive “cradle-to-grave” mapping of the product carbon footprint (PCF) expressed as CO
2e is the first step to quantify the ecological impact of a health technology. The second step is to assess the potential ecological benefits of replacing or improving the current technology. This could be done using common health economic evaluation methods such as budget impact analysis (BIA) or cost-effectiveness analysis (CEA). Currently, however, there are few examples where product-related CO
2 burden to society has been quantified.
RESPIMAT® re-usable is a new type of inhaler that is propellant free and re-usable which has the potential to reduce the CO2 burden and the social cost of carbon emissions (SCC) by replacing conventional pMDIs. The objective of this study was to perform a budget impact analysis that incorporates the ecological impact of substituting Respimat disposable with RESPIMAT re-usable in the healthcare system in the Nordics (Denmark, Iceland, Finland, Norway and Sweden) and Benelux.
Methods
Technologies/Interventions
RESPIMAT re-usable is a newly developed inhaler with identical performance in efficacy and safety as its predecessor, Respimat disposable [
29]. However, RESPIMAT re-usable includes a reversible device lock mechanism which makes it re-usable.
Target Patient Population
The drugs developed for use with the Respimat disposable and RESPIMAT re-usable inhalers are indicated for the treatment of patients with respiratory diseases, such as COPD and asthma. Today, approximately 3 million inhalers are used annually together with Spiriva®, Spiolto® and Striverdi® in the studied countries.
Model Design
Given that RESPIMAT re-usable has identical performance levels as Respimat disposable, no direct efficacy gain is expected from switching patients from Respimat disposable to RESPIMAT re-usable [
30]. And although it would be theoretically possible to incorporate possible gains in quality of life due to environmental improvements, currently robust data is missing for this to be a feasible approach and the potential gain in Quality of life would probably be negligible. Also, it is plausible that RESPIMAT re-usable could provide an improved treatment compliance compared to other type of inhalers. However, there are currently no data that would allow a quantification of such a benefit. For these reasons, a budget impact model (BIM) was chosen over a cost-effectiveness model to quantify the budget and environmental impact of RESPIMAT re-usable. The BIM calculates the number of inhalers and refill packages used annually in the study population over 5 years (between 2019 and 2023). Two types of inhalers (Respimat disposable and RESPIMAT re-usable) and three types of drugs (Spiriva, Spiolto and Striverdi) were included in the analysis. Central to the BIM design and outcomes is the treatment pattern, i.e. how often inhalers are replaced by new ones in a scenario RESPIMAT re-usable. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
Treatment Patterns
Respimat disposable comes in two pack sizes, either as a single disposable pack (containing one inhaler and one cartridge) or as a triple disposable pack (containing three inhalers and three cartridges). In either case, in a scenario without RESPIMAT re-usable, 12 inhalers would be used per patient and year.
RESPIMAT re-usable comes in similar pack sizes as Respimat disposable but both the single pack (N1) and the triple pack (N3) contain one single re-usable inhaler, for 1 month and 3 months of treatment, respectively. In addition, two refill packs (without inhalers) are also available containing one refill (R1) and three refills (R3), respectively. Available RESPIMAT re-usable pack sizes enable a patient to cover their yearly usage using fewer inhalers.
Table
1 outlines the different possible combinations of pack sizes and saved inhalers (per patient and year) per different treatment pattern.
Table 1Inhalers per year by pattern label
Current | 12 × D1 | |
Moderately optimised | 6 × N1 + 6 × R1 | 6 |
Highly optimised | 4 × N1 + 8 × R1 | 8 |
Most optimal | 2 × N3 + 2 × R3 | 10 |
In analysis 1, all patients switching to RESPIMAT re-usable were assumed to follow the “Moderately optimised pattern”. In analysis 2, all patients switching to RESPIMAT re-usable were assumed to follow the “Highly optimised pattern”. In analysis 3, all patients were assumed to follow the “Most optimal pattern”. RESPIMAT re-usable is only available as N1 for Striverdi and hence these patients were excepted from these rules and were assumed to use 12 single packs (N1) per year. In addition, input values were tested in a one-way sensitivity analysis and results are presented in Table 5 in the supplementary material.
Economic Valuation
Direct medical costs in terms of treatment costs were calculated per scenario. Treatment costs were derived from ex-factory prices or pharmacy purchasing price of each brand and inhaler and assumed to be constant throughout the BIM horizon. The treatment cost by country and brand is presented in Table 6 in the supplementary material. Price parity between RESPIMAT re-usable and Respimat disposable was assumed in analyses 1 and 2 but an explorative analysis was undertaken in analysis 4 in which a price discount of 2% was applied to the pack size R1. No annual discount factor was applied as is recommended in BIMs [
31]. No other costs to the healthcare system are included given the equivalence in effect and safety between Respimat disposable and RESPIMAT re-usable [
30]. Therefore, substituting the former with the latter is not assumed to affect healthcare consumption. All costs are expressed in 2018 euros. Treatment costs in Sweden, Norway and Denmark were converted to euro using the average exchange rate between euro and respective currency during 2018 [
32‐
34].
Environmental Impact
The life cycle PCF measured as kilos of CO
2 equivalents was derived for each treatment pattern taking into account the PCF of the whole life cycle (cradle-to-grave) of the inhaler product (Table
2). The whole life cycle is typically divided into five stages: (1) material acquisition and pre-processing, (2) production, (3) distribution and storage, (4) use and (5) end of life. Material acquisition and pre-processing starts at the extraction of the raw materials and ends before filling of the containers/capsules. It covers the extraction of materials, production and assembly of the inhaler subparts and treatment of waste created during this stage. The production stage starts at the assembly of the final product and ends before the distribution to the consumer. It includes the mixing of the formulation ingredients, assembly and package of the inhaler product plus treatment of waste created during this process. The distribution and storage stage begins at the gate of the manufacture’s production facilities and ends at the point of sale. The stage covers the PCF created by distribution of the product taking into account average shipping distance and transportation methods. The use stage typically includes the processes associated with actuation of the inhaler but was ignored in this study as the inhaled formulation was assumed to stay in the lungs. The end of life stage starts after use by the consumer and includes the disposal and waste management of the used inhaler and the inhaler packaging and incineration, energy recovery and land filling. The amount of CO
2 equivalents of each process was calculated according to Eq.
1.
$$ {\text{kg CO}}_{2} {\text{e}} = {\text{Activity Data }}\left( {\text{unit}} \right)*{\text{Emission Factor}} \left( {\frac{\text{kg GHG}}{\text{unit}}} \right)*{\text{GWP}} \left( {\frac{{{\text{CO}}_{2} {\text{e}}}}{\text{kg GHG}}} \right) $$
(1)
The global warming potential (GWP) is set to 100 as recommended by the Green Gas Protocol Product Life Cycle Accounting and Reporting Standard [
35].
The estimate complied with the requirements of the Green Gas Protocol Product Life Cycle Accounting and Reporting Standard [
35] as well as the specific sector guidance for pharmaceutical products [
36]. The SCC was set to US$50 (43.65€) per ton of CO
2. This estimate was derived from three economic climate impact models which translate missions into changes in atmospheric carbon concentrations, atmospheric concentrations into temperature changes, and temperature changes into economic damages [
37]. This estimate is in the lower range of available estimates from the literature which reflects the existing uncertainty around modelling the social cost of environmental outcomes [
38].
The approach of SCC was preferred to others such as carbon intensity (amount of CO
2 due to a certain activity) since the former leaves the interpretation of the environmental impact to the reader [
39].
Table 2
Product carbon footprint (kilos of CO2) by treatment pattern
Respimat disposable (D1) | 0.775 |
RESPIMAT re-usable (N1) | 0.798 |
RESPIMAT re-usable (N3) | 1.035 |
RESPIMAT re-usable refill 1 month (R1) | 0.119 |
RESPIMAT re-usable refill 3 months (R3) | 0.358 |
Study Population
The baseline population in 2019 was assumed to reflect the current use of the three brands included in the BIM (Spiriva, Spiolto and Striverdi) in the Nordics and Benelux and was set to 261,980 patients. Of these, 176,642 (67%) were assumed to use Spiriva, 81,909 (31%) to use Spiolto and 3429 (1%) to use Striverdi. The evolution of both the size of the population and the distribution between brands throughout the BIM horizon was based on forecasted market shares. As the focus of this study was on the environmental impact of replacing Respimat disposable with RESPIMAT re-usable, potential dynamic changes in market shares and competitors’ reactions were not considered.
Scenario Analysis
Two scenarios were analysed and compared in terms of costs of inhalers and environmental impact: one scenario (without RESPIMAT re-usable) in which the three brands were used together with a Respimat disposable inhaler and another scenario (with RESPIMAT re-usable) in which Respimat disposable was progressively replaced by a RESPIMAT re-usable inhaler. Market penetration rates of RESPIMAT re-usable varied by country in 2019 (21–70%); from 2020 and onwards, all patients were assumed to have switched to RESPIMAT re-usable. The treatment pattern for patients switching to RESPIMAT re-usable is described in Table
1.
Compliance with Ethics Guidelines
Since this study did not involve any human subject, ethics committee approval was not required.
Acknowledgements
The authors would like to thank Oskar Eklund, a former employee of Quantify Research, for the design of the budget impact model.