Health Economic Analyses Alongside Clinical Trials: Research from Intensive Care Units & Specialised Palliative Care Teams

This thesis aims to contribute to the field of health economics alongside randomised clinical trials by answering four methodological, clinical and policy relevant questions concerning critically ill and palliative care patients. This is done through three empirical papers based on evidence from three randomised clinical trials and one protocol paper on valuing patient-specific preferences for health states used to estimate quality-adjusted life years (QALYs). All four papers explore different perspectives of health economic analyses, e.g. economic evaluations. Choices relating to the perspective applied in the evaluation are important and can be crucial for the conclusions derived from economic evaluations. Choice of perspective may relate to cost, timespan and preferences for health states. For example, how broad should the economic evaluation be in terms of costs? Is informal caregiving important to include for these patient groups? What time horizon should be applied? How can QALYs be estimated when baseline health-related quality of life is not available, which is most often the case for critical ill patients? Whose perspective is most important – the patient’s or the general public’s? The four research questions examined in the four research journal papers (Papers I-IV) included in this thesis are as follows:


I. Is a systematic fast-track transition from oncological treatment to specialised palliative care at home cost-effective for patients and their caregivers?

Specialised palliative care (SPC) supplemented with a psychological intervention at home was used in an attempt to improve the quality of life for patients with incurable cancer (9). In the randomised clinical trial called the Danish Palliative Care Trial (DOMUS), no significant differences were found in time spent at home, and survival time between the intervention and the control group, but anxiety and depression was lower for caregivers in the SPC group (10). A sub-study in the DOMUS trial examined costs, health-related resource use, and quality of life in a costeffectiveness analysis, where quality of life and length of life were combined. The current paper examined exactly this. As QALYs were collected for both patients and relatives, a cost-utility analysis could be performed with a comprehensive societal perspective (including the perspective of the caregivers through the costs associated with informal caregiving). It was concluded that this model of fast-track SPC yielded QALY gains relative to usual care, but with a large increase in costs (10). Thus, the intervention was not perceived as cost-effective. The costs relating to informal care were shown to represent a substantial part of the total costs for palliative care patients, albeit this cost item was not found to be statistically significantly different between the two groups of interest (10). 

II. Are long-term outcomes, resource use, and labour marked status affected in critically ill patients by using prophylactic pantoprazole versus placebo?

Critically ill patients in the intensive care unit (ICU) are at increased risk of stress-related gastrointestinal (GI) bleeding (11). Pantoprazole is widely used to prevent GI bleeding (12,13), but the long-term consequences associated with this treatment are unknown. The objective of the randomised clinical trial Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) was to assess the benefits and adverse effects of pantoprazole in adult ICU patients (14). In this sub-study of the SUP-ICU trial, we assessed long-term outcomes, resource use and labour market status. We found that despite a reduction in the risk of GI bleeding after one year, health care resource use and labour market status at one-year post ICU stay was unchanged. This questions continued routine use of prophylactic pantoprazole in critically ill patients in the ICU.

III.Are high or low oxygenation targets in the ICU cost-effective in a one-year cost-utility analysis with a societal perspective? 

This paper presents a health economic evaluation alongside a randomised clinical trial of supplementary oxygen therapy for patients admitted to the ICU with acute hypoxaemic respiratory failure. The trial was called ‘Handling Oxygenation Targets in adults with acute hypoxaemic respiratory failure in the Intensive Care Unit’ (HOT-ICU). Severe hypoxaemia is life-threatening and a frequent cause of acute admission to the ICU (15-18). Oxygen is the primary therapy for hypoxaemia in ICU patients (19). Paradoxically, high concentrations of oxygen may cause lung injury, which means that oxygen can be harmful in some cases. HOT-ICU investigated low vs high oxygenation targets (19). The primary outcome measure was mortality 90 days after randomisation, but a part of the assessment also investigated the health economic consequences. The long-term (one-year) implications on resource use and the accompanied costs of different oxygenation targets were examined through a costutility analysis with a broad societal perspective. Data on somatic hospitals were only available for a subpopulation, why the study is considered a pilot study. Conclusions must therefore be interpreted with caution. In overall terms, we find that the various oxygenation targets in the HOT-ICU trial are not associated with long-term health and economic consequences with a follow-up horizon of one year.

IV.Does critical illness alter patient preferences for health states? A protocol

This protocol paper describes a project aiming to derive the first EQ-5D-5L valuation for patients who have survived a critical illness requiring intensive care, socalled patient-based preferences for health states or EQ-5D-5L value set. This protocolled study will test whether preferences for health states of prior ICU patients are significantly different to those of the general public. Most decision-making bodies recommend the use of preferences derived from the general public (8,20-23). The aim of the described protocol is to contribute to the literature by discussing difficulties when deriving preferences from patients. Further contributions are made by the analysis of underlying determinants that affect the potential differences in preferences for health states. As a start, the demographic characteristics and self-reported healthrelated quality of life will be investigated. Other factors might also influence the potential differences in preferences for health states. We will investigate three potential contributing explanations: 1) the phenomenon ‘health state reference dependency’ (24); 2) the willingness to trade-off between longevity and quality of life; and 3) whether ICU patients have larger deviation in preference in the dimensions where the patient has gained experience in terms of the patient’s own illness. Moreover, we will have different time gaps from the ICU stay until the time of the interview about preferences for health states. This allows us to investigate adaptation and the stability of preferences. These topics are elaborated on throughout the thesis and in the protocol.