Time Trade-off Methodology Research Articles

Valuing selected WAItE health states using the Time Trade-Off methodology: findings from an online interviewer-assisted remote survey

PurposeThe Weight-Specific Adolescent Instrument for Economic Evaluation (WAItE) is a physical weight-specific patient reported outcome measure for use in adolescence. The purpose of this study was to use the Time Trade-Off (TTO) methodology, administered using an online interviewer-assisted remote survey, to obtain utility values for several health states from the WAItE descriptive system from a sample of the UK adult general population.MethodsThe adult sample was gathered using a market research company and a sample of local residents. All participants completed the same interviewer-assisted remote survey, which included rating WAItE states of varying impairment using the TTO.Results42 adults completed the survey. Utility values were gathered for four health states, ranging from low impairment to the most severe health from the WAItE descriptive system (the Pits state). Consistent orderings of the WAItE health states were observed; the health state with the lowest level of impairment was valued highest and the Pits state was valued lowest. Several respondents (n = 7, 17%) considered the Pits state to be worse than death; however, the mean value of this health state was 0.23.ConclusionsThe utility value of the Pits state relative to death generated from this study will be used to anchor latent values for WAItE health states generated from a Discrete Choice Experiment onto the 0 = death, 1 = full health Quality Adjusted Life Year (QALY) scale as part of a valuation study for the WAItE in the UK population. This study also provides further evidence that interviewer-assisted digital studies are feasible for collecting TTO data.

Time and lexicographic preferences in the valuation of EQ-5D-Y with time trade-off methodology

In the valuation of EQ-5D-Y-3L, adult respondents are asked to complete composite time trade-off (cTTO) tasks for a 10-year-old child. Earlier work has shown that cTTO utilities elicited in such a child perspective are generally higher than when adults take their own perspective. We explore how differences in time preference in child and adult perspectives could explain this effect. Furthermore, as cTTO valuation in a child perspective involves explicit consideration of immediate death for a child, we also consider how cTTO utilities could be affected by decision-makers lexicographically avoiding death in children. We report the results of an experiment in which 219 respondents valued 5 health states in both adult and child perspectives with either a standard cTTO or a lead-time TTO only approach, in which immediate death is less focal. Time preferences were measured in both perspectives. Our results suggest that utilities were lower when lead-time TTO, rather than cTTO, was used. We find large heterogeneity in time preference in both perspectives, with predominantly negative time preference. The influence of time preferences on utilities, however, was small, and correcting for time preferences did not reduce differences between utilities elicited in both perspectives. Surprisingly, we found more evidence for differences in utilities between adult and child perspectives when lead-time TTO was used. Overall, these results suggest that time and lexicographic preferences affect time trade-off valuation in child and adult perspectives, but are not the explanation for differences between these perspectives. We discuss the implications of our findings for EQ-5D-Y-3L valuation.

PCN90 ASSESSMENT OF UTILITIES FOR ADVERSE EVENTS (AES) ASSOCIATED WITH CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY IN LARGE B-CELL LYMPHOMA (LBCL)

CAR T-cell therapy is a promising treatment for LBCL. Cost-utility analyses are needed to examine and compare the value of these therapies, and these models require health state utilities representing the key AEs associated with therapy, including cytokine release syndrome (CRS) and neurological events (NEs). This study estimated utilities for various severity levels of CRS and NEs associated with CAR T-cell therapy. We used time trade-off methodology—a widely used methodology for assessing preference-based health-related quality of life—to conduct interviews with general population participants in the United Kingdom (London and Edinburgh). Participants valued 6 health state vignettes that were drafted based on literature review and clinician input. The first health state represented LBCL treated with CAR T-cell therapy without AEs. The other 5 health states described CRS or NEs of varying severity following CAR T-cell therapy. The disutilities (i.e., utility decrease) associated with these AEs were calculated by subtracting the utility of the health state without AEs from those of the other health states. Interviews were conducted with 218 participants (London, n=113; Edinburgh, n=105; 50% male; mean age, 49 years). The mean (standard deviation [SD]) utility for CAR T-cell therapy without AEs was 0.73 (0.30). Mean (SD) disutilities associated with CRS were −0.01 (0.04) for grade 1, −0.05 (0.09) for grade 2, and −0.23 (0.24) for grade 3/4. Mean (SD) disutilities associated with NEs were −0.04 (0.07) for grade 1/2 and −0.18 (0.22) for grade 3/4. More severe AEs were associated with greater disutilities. Because the AEs were added to health states valued with a 1-year time horizon, these disutilities can be applied as quality-adjusted life-year decrements in cost-utility analyses. The health state utilities estimated in this study would be useful in cost-effectiveness models of CAR T-cell therapy in patients with LBCL.

Community perspectives on difference of sex development (DSD) diagnoses: A crowdsourced survey

Differences of sex development (DSD) engender ethical, social and psychosexual complexities that can complicate medical decision-making. We performed a web-based pilot study to estimate the utility value of a DSD diagnosis and to identify community concerns regarding DSD management. A cross-sectional survey was posted on Amazon's Mechanical Turk, an online crowdsourcing platform. Respondents were ≥18y and were randomized to receive information on one of three common DSD conditions: Congenital Adrenal Hyperplasia (CAH), Mixed Gonadal Dysgenesis (MGD), and Partial Androgen Insensitivity Syndrome (PAIS). Time trade-off methodology was used to estimate utility values. Likert scale and statement-ranking questions were used to assess respondent perceptions. Of 1,628 respondents, median age was 34y; most respondents were parents (59.1%), white (77.1%), and previously unfamiliar with DSD (60.4%). The median overall utility value was 0.70 (IQR 0.50-0.90), similar to moderately severe chronic health conditions. Utility estimates varied based on the DSD scenario presented (0.80 CAH vs. 0.70 MGD vs. 0.80 PAIS, p=0.0006), respondent gender (p<0.0001), race (p=0.002), religion (p=0.005), and prior knowledge of DSD (p<0.0001). Reported concerns included gender identity (23.4%), urinary function (20.5%) and surgical complications (17.4%). Most (67.5%) supported early surgical intervention at 6-18mo; 10.4% thought surgery should occur ≥18 y. Limitations of this study include that survey participants were aware of the nature of the study, thus some respondents may have participated to skew the results. Given the nature of this pilot study, the representation of families with children with DSD within the study is severely limited given the rarity of DSDs. This means that their opinions may be diluted by the large sample size. However, because utility values are classically estimated according to community opinions, the utility data presented should be taken to reflect that of the specific sample studied and is not reflective of that of families with a vested interest in such cases. Community-based respondents perceived that DSD conditions were associated with a reduction in utility values (0.70-0.80), on par with moderately severe chronic health conditions. Estimates varied based on respondents' gender, race, religion and prior knowledge of DSD. Gender identity was the most concerning aspect for respondents.

Disease State Adaptation Experienced By Patients with Hemophilia: Literature Review and Expert Consensus

Introduction Hemophilia is an inherited disorder that causes a deficiency of a blood clotting factor resulting in a lifelong bleeding diathesis. People with hemophilia (PWH) may experience significant morbidity including potentially life-threatening hemorrhages and accumulation of joint damage and require burdensome and costly chronic treatment with factor replacement therapies. Gene therapies aimed at providing endogenous production of the missing clotting factor have the potential to yield significant health benefits for PWH. Economic evaluation is an important component for the commissioning and funding of new treatments like gene therapies. In economic evaluation, quality-of-life (QoL) is measured using health state utility valuations (HSUV). However, people with inherited and long-term health conditions may adapt to their given health state and adjust their expectations, therefore biasing the estimates of QoL/HSUV (i.e., disease state adaptation (DSA) or "disability paradox"; Albrecht and Devlieger, 1999). Here, we describe the first stages of research to evaluate DSA experienced by PWH. Methods To facilitate the selection of research methodology, a systematic litearure review (SLR) was performed to examine existing studies on QoL/HSUVs for PWH. A SLR was conducted to identify full-text studies by searching electronic databases (e.g. MEDLINE, Web of Science, Cochrane Library). Studies were included in the review using predefined inclusion/exclusion criteria for population, study type, language (English). Additionally, a manual search (last three years) for conferences abstracts was performed to capture the most up-to-date research. Findings from the SLR informed the conceptualisation of a study framework. The proposed research approach was then discussed with an expert panel consisting of clinicians, patient advocacy representatives, and Health Technology Assessment (HTA) specialists. Results The SLR identified 32 studies reporting HSUVs in hemophilia. The studies identified applied a mix of direct and indirect HSUV elicitation techniques. Two studies applied direct time trade-off methodology and the remaining 30 studies adopted indirect valuation methodologies. Utility values were found to vary by disease severity, musculoskeletal damage, bleed frequency, inhibitors, hemophilia subtype, treatment regimen, and adherence. Interestingly, HSUVs derived from valuations from the general public were found to be valued lower than those derived from PWH for the same health states. For example, in Carlsson et al. (2017), general public participants consistently rated significantly lower HSUVs for hemophilia disease states compared to PWH (range: 0.54-0.60 vs. 0.67-0.73), suggesting DSA might exist for PWH. Based on SLR findings, an expert panel discussed the feasibility and acceptability of an approach for conducting a preference elicitation study to directly evaluate DSA in PWH. Preference elicitation is an established research framework that is widely used in health economics. A comparative preference elicitation study was proposed to describe and quantify DSA by comparing responses from PWH, caregivers of PWH, and the general public. Conclusion Based on the SLR and expert panel inputs from clinicians, patients and HTA experts, an agreement was achieved about the research methodology for a new study directly assessing DSA experienced by PWH. Experts agreed that a comparative preference elicitation approach among PWH, caregivers of PWH, and the general public was fit-for-purpose for this research. The impact of DSA on QoL/HSUV should be characterized within economic evaluations of novel treatments with transformative impact on patients' lives, such as gene therapies. Disclosures Martin: HCD Economics: Employment. Mulhern:HCD Economics: Consultancy. Shaikh:HCD Economics: Employment. Asghar:HCD Economics: Employment. O'Hara:HCD Economics: Employment, Equity Ownership. Pedra:HCD Economics: Employment. Sawyer:uniQure Inc.: Employment. Li:uniQure Inc.: Employment.

Preference-based valuation of treatment attributes in haemophilia A using web survey.

Clinical trials have shown promising results for extended half-life factor VIII concentrates but little is known about individuals' valuation of haemophilia treatment attributes. To assess patient/caregiver and population valuation of treatment attributes of prophylactic regimens for people with severe haemophilia A. Members ≥16years of the Swedish Haemophilia Society (FBIS) and of a web-panel representative of the Swedish population were invited to participate in a web-survey investigating preferences for haemophilia treatment attributes using the Time Trade-Off methodology which ranks health states on a scale 0 (dead) to 1 (full health). All respondents assessed the same four treatment scenarios for severe haemophilia A, each described by three stylized attributes: injection interval (every 2nd or 5th day); participation in physical activity (Y/N); annual risk of bleed (1-2 or 5-6 bleeds). The survey had 1657 respondents (68% complete responses; 184/1233 from FBIS/web-panel gave informed consent; mean age 52years, 51% men). Respondents from FBIS and from the web-panel had the same preference ranking of the four treatment scenarios, but members of FBIS consistently rated significantly higher health utilities; range 0.67-0.73 vs 0.54-0.60. Participation in physical activity implied +0.023 (95% confidence interval 0.015-0.030); a longer injection interval implied +0.038 (0.03; 0.45); and fewer bleeds implied +0.022 (0.015-0.029) utility points. Patient/caregiver and population preferences indicate that treatment attributes such as frequency of injections and the possibility of participating in physical activity are important attributes impacting quality of life in addition to the control and prevention of bleeding episodes.

Quantifying Worry in the Face of Uncertainty: Radiation Exposure from Medical Imaging

BackgroundThe degree to which people worry about radiation exposure from medical imaging has not been quantified. Such concern is important for clinical decision making and policy generation. ObjectiveThe aim of this study was to quantify the degree of worry as a consequence of radiation exposure. DesignA time trade-off methodology was used to estimate health state utilities associated with radiation exposure from computed tomography scans in an inclusive sample of physicians. Health state utilities were elicited from in-person interviews using a software-guided, hypothetical scenario in which the subject is exposed to two separate computed tomography scans. ResultsOne hundred and eighteen interviews were conducted. The overall mean and median utility values for the health state of concern due to radiation exposure were 0.95 (95% confidence interval: 0.94–0.96) and 0.98 (interquartile range: 0.91–1.00), respectively. The utility score distribution was highly skewed toward higher values. Five respondents (4.3%) recorded a utility score of ≤0.8 and 17 respondents (14.5%) were willing to sacrifice at least 5 or more years of life to live free of the radiation-exposure worry. Conclusions and relevanceThe physician respondents generally demonstrated low levels of disutility; however, a subset of physicians expressed much greater disutility for the future risk of malignancy. Given the potential for physicians to influence health care decisions and policies, further study of radiation-related concerns seems warranted. Physicians, patients, and the general public should be aware of the potential impact such differing views held by physicians may have on their clinical recommendations.

Health state utilities for chronic lymphocytic leukemia: importance of prolonging progression-free survival

Chronic lymphocytic leukemia (CLL) is a largely incurable disease which affects patients’ health related quality of life (HRQL). Treatment is often initiated when symptoms affect HRQL, and patients can experience many rounds of treatment throughout their life. Therefore, the economic burden of CLL can be high. Utility or preference weights for health states reflect the value of HRQL of a given health state and range from 1 (full health) to 0 (dead) and below (negative values possible). Nine health states were developed representing different CLL treatment lines or disease stages. One hundred members of the UK general public valued each health state using the time trade-off methodology. Progression-free survival (PFS) without therapy (mean utility = 0.82) was the least burdensome, with relapsed lines of treatment (mean utility = 0.42) representing the greatest burden. The results underline the value in maintaining a state of PFS for as long as possible.

Elicitation of health state utilities in neuroendocrine tumours

Background:Neuroendocrine tumours (NETs) are a rare form of neoplasm that can arise in most organs of the body and which share many common pathologic features. Although curative surgery can be conducted for patients with localised disease, once progression occurs and the disease becomes metastatic or un-resectable, treatment aims to extend life and maintain quality-of-life for as long as possible. The aim of the study was to elicit utilities for health state vignettes describing the burdens associated with receiving therapy for advanced NETs.Methods:Health state vignettes were developed by reviewing published literature and conducting in-depth interviews with patients and clinical experts. These states described the burden associated with both stable and progressive disease, in addition to the experience of a number of serious toxicities commonly associated with treatments (grade III/IV diarrhoea, hand-foot syndrome, hyperglycaemia, nausea/vomiting, pneumonitis, rash, stomatitis, and thrombocytopenia). One hundred members of the UK general public valued the states using the time trade-off methodology to determine utility values.Results:Stable disease had a utility value of 0.77 whilst disease progression was associated with a significant decline in health-related quality-of-life (HRQoL) and a value of 0.61. Toxicities experienced in the context of stable disease exhibited varying degrees of impact, with several being deemed as debilitating as disease progression (such as hand-foot syndrome [0.58] and stomatitis [0.56]).Conclusion:Although vignette studies have been criticised for the difficulty in establishing their validity, the collection of health utilities in rare populations is challenging. The findings from this study suggest that advanced NETs is associated with a considerable HRQoL burden, both as a direct result of the disease and the potential of experiencing a number of severe adverse events. These values could assist in future economic evaluation processes.

Comment on the value of vision by Knauer et al.,

s Archive for Clinical and Experimental Ophthalmol-ogy (2008) 246:477-482 entitled “The value of vision.” Theauthors use, as the basis for their commentary, work that hasbeen done to evaluate how much patients with ophthalmicdiseases are concerned about their visual loss. One methodof estimating this is to use the technique discussed by theauthors, “the time trade-off method,” in which patientsdecide how many years of their life they would give up toachieve the desired outcome [6]. Knauer and Pfeiffercomment correctly that some of the studies that have beendone on ophthalmic disease indicate that vision is of greatimportance to patients [1–3].They compare the valuesobtained for other conditions such as AIDS and stroke, andconclude that the relative value of the patient’s vision is trulyextraordinarily great [ 4, 5].The authors, however, do not consider an extremelyimportant issue, which may well invalidate their conclu-sion. Time trade-off studies related to the value of visionask the question, “What is the maximum number of years—if any—you would be willing to give up if you could have anormal vision in both of your eyes for the remainder ofyour life?” Note, the question has to do with recoveringvision. But in contrast, in the standard time trade-offmethodology patients are asked, “What is the maximumnumber of years—if any—you would be willing to give upif you could have perfect health for the remainder of yourlife?”“Vision ” and “health” arenotthesamething.Presumably, vision influences a person’s health. It may bethat some individuals consider vision the most importantaspect of their health. It may also be that some individualsconsider vision an unimportant aspect of their health. But itis not proper to compare the results of those studies done bythe Browns, in which they are asking patients aboutrecovering vision, with those of the great majority of timetrade-off studies, in which subjects are asked aboutrecovering health.As an ophthalmologist, I would love to believe that theBrowns, and Knauer and Pfeiffer are correct in commentingthat patients value vision ahead of being hospitalized withtuberculosis for 3 months, or having a stroke that results ina level of disability causing the person to be unable to walkand unable to wash himself or herself; however, that this isthe case is speculation, and cannot be supported bycomparing two different methodologies, one studyingvision, and the other studying health.References

An Oral Iron Chelator and Quality of Life.

The impact on patients' quality of life (QoL) is an important consideration in both decisions of individual patient care, and in allocating health care resources between competing treatments. This study aims to better inform those decisions by investigating the differential impact on patients' QoL of two equally safe and effective iron chelators: one a subcutaneous infusion, the other a dispersible tablet. The current standard of care in patients with chronic iron overload secondary to haematological conditions such as the thalassaemias, myelodysplastic syndrome and sickle cell disease is the subcutaneous administration of desferrioxamine (DFO), for 8 to 12 hours per day, 5 to 7 days a week. The burden of this treatment regimen in some cases leads not only to poor compliance, and hence a reduction in the extent of effective iron chelation, but also to a reduction in patients' QoL. Novartis Pharmaceuticals AG has developed a once daily oral iron chelator (deferasirox, DFX) shown to be as safe and effective as DFO in treating iron overload. To investigate the differential impact of DFO and DFX on patients' QoL, a community sample of 110 individuals were asked to participate in a time trade off (TTO) exercise to elicit community utility values, or preferences, for their different modes of administration. Following standard TTO methodology, participants were asked how they value ten years of full health compared with time in each of three health states for patients with thalassaemia:an anchor/base state that described a patient who has iron chelation without describing the treatment itself;the anchor state plus iron chelation via a subcutaneous infusion;the anchor state plus iron chelation via a once daily oral medication.To avoid ordering bias, respondents were randomised to respond to either scenario (2) or (3) first after the anchor state. Scenarios were not labelled in terms of the iron chelator included and differed only in their description of the mode of treatment administration. Maximum possible utility values are 1 for perfect health and 0 for death. Preliminary results based on the first 32 respondents showed an average utility value of 0.73 for the anchor state, 0.57 for the subcutaneously infused iron chelator and 0.82 for the once a day oral iron chelator. The difference of 0.25 in the utility value for the two treatments was statistically significant (Wilcoxon-signed rank test, p=0.002). Treatment with the subcutaneously infused agent was associated with a lower QoL value, being 0.16 below that for the anchor state (p=0.025). In contrast, treatment with a once daily oral iron chelator had a utility value that was 0.08 (p=0.002) higher than the anchor state. While data collection is ongoing (completion date late Sept), these preliminary results indicate that society associates oral administration of an iron chelator such as DFX with an improvement in the QoL of patients requiring such treatment. Assuming equal safety and efficacy, a once daily oral treatment may therefore be preferred to a burdensome subcutaneous infusion due to the benefits it confers on patients' QoL.

Changes in Quality of Life for Pregnant Women in Substance User Treatment: Developing a Quality of Life Index for the Addictions

Using preference weights from a community sample, items from the Addiction Severity Index (ASI) were converted into a quality of life index (QOLI) and used to compare the cost-effectiveness of five addiction treatment modalities for pregnant women. Methods: Interviews using the time trade-off methodology were conducted with 143 members of Massachusetts local health planning boards to determine preference weights for different health states resulting from active addiction. A multi-attribute utility formula was used to convert these seven preference weighted scores into a single QOLI. To apply the QOLI, these preference weights were combined with the number of problem days reported in each ASI domain by a sample of 439 pregnant women in MA in five treatment modalities, 1992–1996. Results: Starting at 10 years with an addiction problem, board members indicated that they would give up between 0.83 and 3.96 years to avoid the problems in one domain caused by addiction. The average QOLI was 0.68 at intake but increased by 0.19 points by 6-month follow-up to 0.87. All five treatment groups showed notable improvement in their quality of life. Mean improvements ranged from a high of 0.23 QOLIs for clients who received both residential and outpatient treatment to a low of 0.16 for clients who received only detoxification. Treatment costs ranged from $10,187 for residential and outpatient combined to $2,535 for detoxification only, with costs per QOLI ranging from $14,912 to $44,291. Conclusions: Although this QOLI could benefit from further refinement and development, it showed promise as a single outcome measure for CEAs in the chemical dependency field. This QOLI was sensitive enough to distinguish between the treatment groups, it correlated well with other outcome measures and can be easily converted from the ASI using spreadsheet software and a simple formula.

Are QALYs based on time trade-off comparable?--A systematic review of TTO methodologies.

A wide range of methods is used to elicit quality-of-life weights of different health states to generate 'Quality-adjusted life years' (QALYs). The comparability between different types of health outcomes at a numerical level is the main advantage of using a 'common currency for health' such as the QALY. It has been warned that results of different methods and perspectives should not be directly compared in QALY league tables. But do we know that QALYs are comparable if they are based on the same method and perspective?The Time trade-off (TTO) consists in a hypothetical trade-off between living shorter and living healthier. We performed a literature review of the TTO methodology used to elicit quality-of-life weights for own, current health. Fifty-six journal articles, with quality-of-life weights assigned to 102 diagnostic groups were included. We found extensive differences in how the TTO question was asked. The time frame varied from 1 month to 30 years, and was not reported for one-fourth of the weights. The samples in which the quality-of-life weights were elicited were generally small with a median size of 53 respondents. Comprehensive inclusion criteria were given for half the diagnostic groups. Co-morbidity was described in less than one-tenth of the groups of respondents. For two-thirds of the quality-of-life weights, there was no discussion of the influence of other factors, such as age, sex, employment and children. The different methodological approaches did not influence the TTO weights in a predictable or clear pattern. Whether or not it is possible to standardise the TTO method and the sampling procedure, and whether or not the TTO will then give valid quality-of-life weights, remains an open question.This review of the TTO elicited on own behalf, shows that limiting cost-utility analysis to include only quality life weights from one method and one perspective is not enough to ensure that QALYs are comparable.