A note on the nature of utility in time and health and implications for cost utility analysis

Time Trade-Off valuations of health are widely used in economic evaluation of health care. Current approaches to eliciting TTO values, and their use in economic evaluation, rests on specific assumptions about the way utility relates to time and health. Both the assumptions themselves and evidence of violations of them are discussed in the literature - yet the issues appear not to be widely appreciated by those using and applying TTO. This paper adds to that literature by demonstrating both the requirements of TTO and violations of these assumptions in terms of the underlying indifference curve maps and utility functions. The advantage of this approach is that is demonstrates very clearly a number of fundamental problems for the way TTO values are currently elicited and used in Cost Utility Analysis. In essence, it is extremely unwise to assume that the current "tariffs" of TTO values, such as those routinely used by NICE and other organisations, can be applied irrespective of the duration of the health states to which they are assigned. The estimates of QALYs that result will, quite often, simply be wrong. We suggest a number of solutions, including the provision of multiple value sets, for a range of durations

A uniform Time Trade Off method for states better and worse than dead: feasibility study of the ‘lead time’ approach

The way Time Trade Off (TTO) values are elicited for states of health considered ‘worse than being dead’ has important implications for the mean values used in economic evaluation. Conventional approaches to TTO, as used in the UK’s ‘MVH’ value set, are problematic because they require fundamentally different tradeoffs tasks for the valuation of states better and worse than dead. This study aims to refine and test the feasibility of a new approach described by Robinson and Spencer (2006), and to explore the characteristics of the valuation data it generates. The approach introduces a ‘lead time’ into the TTO, producing a uniform procedure for generating values either >0 or <0. We used this lead time TTO to value 10 moderate to severe EQ-5D states using a sample of the general public (n=109). We conclude that the approach is feasible for use in valuation studies, and appears to overcome the discontinuity in values around 0 evident in conventional methods. However, further research is required to resolve the issue of how to handle participants who ‘use up’ all lead time; to develop ways of controlling for individual time preferences; and to better understand the implications for valuations of states better than dead

Does the value of quality of life depend on duration?

The aims of this study are to investigate the feasibility of eliciting Time Trade Off (TTO) valuations using short durations; to determine the effect of contrasting durations on individuals’ responses to the TTO; to examine variations within and between respondents’ values with respect to duration; and to consider the insights provided by participants’ comments and explanations regarding their reaction to duration in the valuation task. 27 participants provided TTO values using short and long durations for three EQ-5D states. Feedback was sought using a series of open ended questions. Of the 81 opportunities to observe it, strict constant proportionality was satisfied twice. 11 participants had no systematic relationship between duration and value; 11 provided consistently lower valuations in long durations, while 5 had higher valuations in long durations. Comments provided by participants were consistent with the values they provided. Mean TTO values did not differ markedly between alternative durations. We conclude that it is feasible to elicit TTO values for short durations. There is considerable heterogeneity in individuals’ responses to the time frames used to elicit values. Further research is required to ensure that the values used in cost effectiveness analysis adequately represent preferences about quality and length of life

A new chiral electro-optic effect: Sum-frequency generation from optically active liquids in the presence of a dc electric field

We report the observation of sum-frequency signals that depend linearly on an applied electrostatic field and that change sign with the handedness of an optically active solution. This recently predicted chiral electro-optic effect exists in the electric-dipole approximation. The static electric field gives rise to an electric-field-induced sum-frequency signal (an achiral third-order process) that interferes with the chirality-specific sum-frequency at second-order. The cross-terms linear in the electrostatic field constitute the effect and may be used to determine the absolute sign of second- and third-order nonlinear optical susceptibilities in isotropic media.Comment: Submitted to Physical Revie

Actions of Agonists, Fipronil and Ivermectin on the Predominant In Vivo Splice and Edit Variant (RDLbd, I/V) of the Drosophila GABA Receptor Expressed in Xenopus laevis Oocytes

Ionotropic GABA receptors are the targets for several classes of insecticides. One of the most widely-studied insect GABA receptors is RDL (resistance to dieldrin), originally isolated from Drosophila melanogaster. RDL undergoes alternative splicing and RNA editing, which influence the potency of GABA. Most work has focussed on minority isoforms. Here, we report the first characterisation of the predominant native splice variant and RNA edit, combining functional characterisation with molecular modelling of the agonist-binding region. The relative order of agonist potency is GABA> muscimol> TACA> β-alanine. The I/V edit does not alter the potency of GABA compared to RDLbd. Docking calculations suggest that these agonists bind and activate RDLbdI/V through a similar binding mode. TACA and β-alanine are predicted to bind with lower affinity than GABA, potentially explaining their lower potency, whereas the lower potency of muscimol and isoguvacine cannot be explained structurally from the docking calculations. The A301S (resistance to dieldrin) mutation reduced the potency of antagonists picrotoxin, fipronil and pyrafluprole but the I/V edit had no measurable effect. Ivermectin suppressed responses to GABA of RDLbdI/V, RDLbd and RDLbdI/VA301S. The dieldrin resistant variant also showed reduced sensitivity to Ivermectin. This study of a highly abundant insect GABA receptor isoform will help the design of new insecticides

Interprofessional learning in practice: The student experience

Interprofessional learning and the development of teamworking skills are recognised as essential for patient care and are also a government priority for undergraduate education. Sixteen occupational therapy students worked on an interprofessional training ward as part of their practice placement and three of them participated in an evaluation using the nominal group technique. Despite this small number, the evaluation identifies the value of this learning experience in giving the students an opportunity to appreciate the importance of interpersonal skills; to learn about other team members’ roles; and to experience the challenges of working on a busy rehabilitation ward for older people

Cues and knowledge structures used by mental-health professionals when making risk assessments

Background: Research into mental-health risks has tended to focus on epidemiological approaches and to consider pieces of evidence in isolation. Less is known about the particular factors and their patterns of occurrence that influence clinicians’ risk judgements in practice. Aims: To identify the cues used by clinicians to make risk judgements and to explore how these combine within clinicians’ psychological representations of suicide, self-harm, self-neglect, and harm to others. Method: Content analysis was applied to semi-structured interviews conducted with 46 practitioners from various mental-health disciplines, using mind maps to represent the hierarchical relationships of data and concepts. Results: Strong consensus between experts meant their knowledge could be integrated into a single hierarchical structure for each risk. This revealed contrasting emphases between data and concepts underpinning risks, including: reflection and forethought for suicide; motivation for self-harm; situation and context for harm to others; and current presentation for self-neglect. Conclusions: Analysis of experts’ risk-assessment knowledge identified influential cues and their relationships to risks. It can inform development of valid risk-screening decision support systems that combine actuarial evidence with clinical expertise