This study yielded general population utilities for adjuvant melanoma treatment-related health states, including those associated with IFN and ipilimumab. Utilities are reported for the United Kingdom, Australia, and the overall study population. With respect to the toxicities evaluated, disutilities (negative values) were calculated, facilitating the application of these values to patients who may be experiencing these effects, but may not currently be receiving adjuvant treatment. The utilities from this study can be used to quality-adjust life expectancy, as well as inform the evaluation of melanoma treatment outcomes in future studies.
The utilities obtained in this study are similar to those obtained by Kilbridge et al. , who used standard gamble to obtain utility weights for adjuvant IFN health states from patients with low-risk melanoma. Specifically, they obtained a mean utility for “IFN treatment without side effects” of 0.92; in this study, “adjuvant treatment without toxicity” had a mean utility of 0.89. The mean utilities for “cancer recurrence” in the Kilbridge et al. study and in this study were 0.61 and 0.62, respectively. Finally, “severe side effects” (that did not include hospitalization) had a mean utility of 0.81 in the Kilbridge et al. study; in this study, severe toxicity with an outpatient visit had a mean utility of 0.78.
As may be expected, the utilities obtained for “adjuvant treatment-no toxicities” and “recurrence” were higher in this study relative to comparable states in advanced melanoma reported by Beusterien et al. , which used standard gamble to obtain utilities for advanced melanoma treatment health states from the general UK and Australian populations. Specifically, the utilities for these states were approximately 0.10 points higher than those for “treatment of advanced melanoma with stable clinical response” and “recurrence of advanced melanoma,” respectively.
The disutilities for the toxicities, calculated by subtracting “adjuvant treatment no toxicity” from “adjuvant treatment plus toxicity,” were similar to the disutilities found for the same toxicity states in the Beusterien et al.  study. Specifically, the disutilities for the respective grade 2 toxicities in this study ranged from −0.08 (“rash,” “nausea,” and “flu-like syndrome”) to −0.09 (“diarrhea”). In the Beusterien et al. study, disutilities ranged from −0.06, for “skin reaction/rash” to −0.11 for “flu-like syndrome.” Also, in this study, the mean disutilities for “severe toxicity-outpatient” and “severe toxicity-hospital” were −0.11 and −0.16, respectively; in the Beusterien et al. study, the mean disutilities for these health states were −0.13 and −0.17, respectively. Among the toxicities in this study, hypophysitis was rated as worst. This may have been attributable to the verbiage in the health state description, which could be characterized as more severe than grade 2, as it referred to having headaches, blurred vision, and feeling sluggish.
Compared to the UK participants, the Australian participants reported higher preferences for all of the health states than the UK participants, except for “no treatment.” The higher preferences observed among the Australian participants may be in part attributable to higher familiarity with melanoma. Specifically, knowing someone with melanoma, which more often occurred among Australian participants, was associated with higher preferences for the health states. These participants may have higher preference for adjuvant treatment as well as adjuvant treatment coupled with toxicities because they have greater knowledge of the potentially devastating impact of life-threatening cancer and are thus willing to tolerate higher risks of side effects. This finding also is consistent with previous research that found that patients and caregivers tended to assign higher utilities for health states relative to the general population and non-caregivers, respectively [10, 22]. Age, gender, and perception of overall health largely were not associated with health state preferences, except that, as may be expected, those reporting “excellent” or “very good” health had more favorable utilities for the “current health” state versus those in “good,” “fair,” or “poor” health.
As expected, when asked to identify the maximum risk of a life-threatening side effect that was acceptable for a treatment that would increase the chance of survival over 3 years by 6%, 12%, or 18%, the study participants reported higher risk acceptance as treatment effectiveness increased. In agreement with our findings, more than 50% of low-risk melanoma patients found mild-moderate and severe IFN toxicity tolerable if accompanied by 4% and 10% improvements in 5-year survival .
As this study used a convenience sample of volunteers, it is unknown whether or not utilities among non-volunteers may differ. Also, it is unknown whether or not the magnitude of utility decrements for the toxicities was influenced by coupling the toxicities with taking adjuvant treatment. Nevertheless, this coupling more truly reflects reality. In addition, while our study did not consider health states with multiple toxicities, several studies have explored the estimation of utilities given this scenario and recommend using a minimal model in which joint-state utilities are predicted to be equivalent to the utility of the worse health state [23, 24]. If one was to use this model to interpret the current study findings, a patient receiving adjuvant treatment (average utility = 0.89) experiencing both grade 2 fatigue (average disutility = −0.06) and grade 2 depression (average utility = −0.11) would be assigned a utility of 0.78 (0.89 minus 0.11). The disutility of depression was incorporated instead of fatigue because the former has a lower utility.