Disutilities Associated with Intravenous Iron Infusions: Results from a Time Trade-off Survey and Diminishing Marginal Utility Model for Treatment Attributes in China

Abstract

Purpose

Treatment process attributes can affect health state utilities associated with therapy. For intravenous iron, used to treat iron deficiency and iron deficiency anemia, research into process attributes is still lacking. This study estimated utilities associated with process attributes for intravenous iron infusions.

Methods

An online survey including seven health state vignettes and time trade-off tasks was administered to participants, who were not patients living with iron deficiency or iron deficiency anemia, from a Chinese online panel. Vignettes used an identical description of iron deficiency and iron deficiency anemia but differed in the annual number of infusions, infusion duration, and infusion-associated risk of hypophosphatemic osteomalacia. Disutilities and their rate of change as the number of infusions increased were examined using a power model.

Results

The survey was completed by 1091 participants. The highest utilities were observed for one annual infusion of 15–30 minutes or 30–60 minutes, without risk of hypophosphatemic osteomalacia (0.754 and 0.746, respectively). In comparison, more infusions and infusions with a risk of hypophosphatemic osteomalacia were associated with lower utilities. Utility continued to decrease, but at a diminishing rate, as the annual number of infusions increased, with utility decrements of 0.006 and 0.002, respectively, when going from zero to one and from four to five infusions per year. All marginal disutilities were small (values <0.01).

Conclusion

This study suggested that treatment attributes of intravenous iron infusions affect health state utilities. Using intravenous iron formulations that allow for fewer and shorter infusions without the risk of hypophosphatemic osteomalacia can reduce the number of visits required and increase patients’ quality of life.

Plain Language Summary

A lack of iron in the body can be treated successfully using intravenous infusions of iron, but it is not yet known how different intravenous iron formulations affect patients’ quality of life.

Intravenous iron formulations differ in how often and for how long (per infusion) they need to be administered; for example, while one available intravenous iron formulation allows most iron deficits to be corrected in a single visit, others can require several visits. Formulations also seem to differ in the risk of complications relating to low phosphate and bone softening.

This study presented descriptions of treatment options, differing in the number and duration of infusions as well as in risk, to more than 1000 Chinese respondents. Based on their answers, the differences between intravenous iron administration regimes could be valued and linked to quality of life. Intravenous iron treatment with fewer, shorter infusions and without risk of bone softening was found to come with a better quality of life. Each additional infusion reduced quality of life, but less so if treatment already involved several infusions. These findings can help patients and physicians to make clinical decisions that focus not only on efficacy and safety but also on the quality of life.

Keywords:

• China
• disutility
• health-related quality of life
• intravenous iron
• iron deficiency
• time trade-off

Data and Code Availability

Aggregate data derived from the time trade-off survey and the diminishing marginal disutility model are presented in this manuscript and the Supplementary Information. Participant-level data will not be made publicly available and will not be shared.

The R code for the marginal utility model can be obtained from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

Ethical review board approval in China was not required as valuation tasks are not considered to be medical interventions and, as the study was not a clinical trial, it neither included patients nor made use of human or biological samples, or personally identifiable information, as per the “Measures for Ethical Review of Biomedical Research Involving Human Beings” adopted by the National Health and Family Planning Commission of the People’s Republic of China and in effect since December 2016.

All participants had previously agreed to take part in research of the type presented here and had given explicit consent to participate in the present study at the start of the survey. Participants were free to terminate the survey at any point if they wished to do so, remained anonymous throughout the study, and could neither be identified nor linked to answers.

Acknowledgments

The authors would like to thank Henrik Holm Jensen and Cecilie Yssing at Incentive Partners ApS, Holte, Denmark, for their assistance with survey implementation and data analysis.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

SH and DW have received honoraria from Pharmacosmos China for participation in advisory board meetings conducted by Pharmacosmos China. JW and YZ have nothing to disclose. MB is a Managing Partner at Incentive Partners ApS, which received consultancy fees from Pharmacosmos for the development and implementation of the survey. JP is an employee of, and RFP is a director at Covalence Research Ltd., which received consultancy fees from Pharmacosmos for the development of the marginal disutility model and the preparation of this manuscript. The authors report no other conflicts of interest in this work.

Additional information

Funding

The development and implementation of the survey were funded by consultancy fees paid from Pharmacosmos A/S to Incentive Partners ApS. The development of the marginal disutility model and the preparation of this manuscript were funded by consultancy fees paid from Pharmacosmos A/S to Covalence Research Ltd.