Improving the measurement of QALYs in dementia: developing patient- and carer-reported health state classification systems using Rasch analysis

Objectives: Cost-utility analysis is increasingly used to inform resource allocation. This requires a means of valuing health states before and after intervention. Although generic measures are typically used to generate values, these do not perform well with people with dementia. We report the development of a health state classification system amenable to valuation for use in studies of dementia, derived from the DEMQOL system, a measure of health-related quality of life in dementia by patient self-report (DEMQOL) and carer proxy-report (DEMQOL-Proxy). Methods: Factor analysis was used to determine the dimensional structure of DEMQOL and DEMQOL-Proxy. Rasch analysis was subsequently used to investigate item performance across factors in terms of item-level ordering, functioning across subgroups, model fit and severity-range coverage. This enabled the selection of one item from each factor for the classification system. A sample of people with a diagnosis of mild/moderate dementia (n=644) and a sample of carers of those with mild/moderate dementia (n=683) were used. Results: Factor analysis found different 5-factor solutions for DEMQOL and DEMQOL-Proxy. Following item reduction and selection using Rasch analysis, a 5-dimension classification for DEMQOL and a 4-dimension classification for DEMQOL-Proxy were developed. Each item contained 4 health state levels. Conclusion: Combining Rasch and classical psychometric analysis is a valid method of selecting items for dementia health state classifications from both the patient and carer perspectives. The next stage is to obtain preference weights so that the measure can be used in the economic evaluation of treatment, care and support arrangements for dementia.quality adjusted life years; health related quality of life; Rasch analysis; preference-based measures of health; health states; dementia

Valuation of preference-based measures: Can existing preference data be used to select a smaller sample of health states?

Background Different countries have different preferences regarding health, and there are different value sets for popular preference-based measures across different countries. However, the cost of collecting data to generate country-specific value sets can be prohibitive for countries with smaller population size or low- and middle-income countries (LMIC). This paper explores whether existing preference weights could be modelled alongside a small own country valuation study to generate representative estimates. This is explored using a case study modelling UK data alongside smaller US samples to generate US estimates. Methods We analyse EQ-5D valuation data derived from representative samples of the US and UK populations using time trade-off to value 42 health states. A nonparametric Bayesian model was applied to estimate a US value set using the full UK dataset and subsets of the US dataset for 10, 15, 20 and 25 health states. Estimates are compared to a US value set estimated using US values alone using mean predictions and root mean square error. Results The results suggest that using US data elicited for 20 health states alongside the existing UK data produces similar predicted mean valuations and RMSE as the US value set, while 25 health states produce the exact features. Conclusions The promising results suggest that existing preference data could be combined with a small valuation study in a new country to generate preference weights, making own country value sets more achievable for LMIC. Further research is encouraged

Improving the measurement of QALYs in dementia: developing patient- and carer-reported health state classification systems using Rasch analysis

Objectives: Cost-utility analysis is increasingly used to inform resource allocation. This requires a means of valuing health states before and after intervention. Although generic measures are typically used to generate values, these do not perform well with people with dementia. We report the development of a health state classification system amenable to valuation for use in studies of dementia, derived from the DEMQOL system, a measure of health-related quality of life in dementia by patient self-report (DEMQOL) and carer proxy-report (DEMQOL-Proxy). Methods: Factor analysis was used to determine the dimensional structure of DEMQOL and DEMQOL-Proxy. Rasch analysis was subsequently used to investigate item performance across factors in terms of item-level ordering, functioning across subgroups, model fit and severity-range coverage. This enabled the selection of one item from each factor for the classification system. A sample of people with a diagnosis of mild/moderate dementia (n=644) and a sample of carers of those with mild/moderate dementia (n=683) were used. Results: Factor analysis found different 5-factor solutions for DEMQOL and DEMQOL-Proxy. Following item reduction and selection using Rasch analysis, a 5-dimension classification for DEMQOL and a 4-dimension classification for DEMQOL-Proxy were developed. Each item contained 4 health state levels. Conclusion: Combining Rasch and classical psychometric analysis is a valid method of selecting items for dementia health state classifications from both the patient and carer perspectives. The next stage is to obtain preference weights so that the measure can be used in the economic evaluation of treatment, care and support arrangements for dementia

Health state utilities associated with attributes of treatments for hepatitis C

BACKGROUND: Cost-utility analyses are frequently conducted to compare treatments for hepatitis C, which are often associated with complex regimens and serious adverse events. Thus, the purpose of this study was to estimate the utility associated with treatment administration and adverse events of hepatitis C treatments. DESIGN: Health states were drafted based on literature review and clinician interviews. General population participants in the UK valued the health states in time trade-off (TTO) interviews with 10- and 1-year time horizons. The 14 health states described hepatitis C with variations in treatment regimen and adverse events. RESULTS: A total of 182 participants completed interviews (50 % female; mean age = 39.3 years). Utilities for health states describing treatment regimens without injections ranged from 0.80 (1 tablet) to 0.79 (7 tablets). Utilities for health states describing oral plus injectable regimens were 0.77 (7 tablets), 0.75 (12 tablets), and 0.71 (18 tablets). Addition of a weekly injection had a disutility of −0.02. A requirement to take medication with fatty food had a disutility of −0.04. Adverse events were associated with substantial disutilities: mild anemia, −0.12; severe anemia, −0.32; flu-like symptoms, −0.21; mild rash, −0.13; severe rash, −0.48; depression, −0.47. One-year TTO scores were similar to these 10-year values. CONCLUSIONS: Adverse events and greater treatment regimen complexity were associated with lower utility scores, suggesting a perceived decrease in quality of life beyond the impact of hepatitis C. The resulting utilities may be used in models estimating and comparing the value of treatments for hepatitis C. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10198-014-0649-6) contains supplementary material, which is available to authorized users

Biomarkers in T cell therapy clinical trials

T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity

RNA-Seq of Human Neurons Derived from iPS Cells Reveals Candidate Long Non-Coding RNAs Involved in Neurogenesis and Neuropsychiatric Disorders

Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs) provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients

Is the EQ-5D fit for purpose in asthma? Acceptability and content validity from the patient perspective

Background The increasing emphasis on patient-reported outcomes in health care decision making has prompted greater rigor in the evidence to support the instruments used. Acceptability and content validity are important properties of any measure to ensure it assesses the relevant aspects of the target concept. The purpose of this study was to evaluate the acceptability and content validity of the EQ-5D 5-Level (EQ-5D-5L) to assess the impact of asthma on patients’ lives. Methods Qualitative interviews were conducted with 40 adults with asthma in the United Kingdom. The first 25 interviews used cognitive-debriefing methods to assess the relevance and acceptability of the EQ-5D-5L and two asthma-specific measures for comparison: an asthma-specific, preference-based measure (the Asthma Quality of Life Utility Index–5 Dimensions) and an Asthma Symptom Diary. The final 15 interviews combined concept elicitation to identify patient-perceived asthma impact, and cognitive debriefing to assess relevance and acceptability of the EQ-5D-5L and the Asthma Symptom Diary. Cognitive-debriefing feedback on the content of the measures was collated and summarized descriptively. The concept-elicitation data were analyzed thematically. Results Participants were aged 20 to 57 years and 62.5% were female. Although some participants expressed positive opinions on aspects of the EQ-5D-5L, only the usual activities dimension was consistently considered relevant to participants’ asthma experiences. The mobility and self-care dimensions prompted strong negative reactions from some participants. Variations in interpretation of the mobility dimension and difficulties with multiple concepts in the pain/discomfort and anxiety/depression dimensions also were noted. Concepts reported by participants as missing included environmental triggers, asthma symptoms, emotions, and sleep. The EQ-5D-5L was the least preferred measure to describe the impact of asthma on participants’ lives. Participants reported shortness of breath and impact on activities as especially salient issues. Conclusions The content of the EQ-5D-5L was poorly aligned with the patient-perceived impact of asthma, and the measure failed to meet basic standards for acceptability and content validity as a measure to assess the impact of asthma from the patient perspective. The shortcomings identified raise concerns regarding the appropriateness of the EQ-5D in asthma and further evaluation is warranted

Mapping the functional assessment of cancer therapy-general or -colorectal to preference-based values measured by SF-6D in patients with colorectal neoplasm

Concurrent Oral Sessions. Oral Session 209: UtilitiesConference Theme: Pushing the boundaries: frontiers of quality of life researc