Does Inclusion of Interactions Result in Higher Precision of Estimated Health State Values?

Background: Most preference-based instruments producing overall values for health states are devised on the simplifying assumption that the overall effect of distinct health-related quality of life domains (attributes) of the instrument equals the sum of the attributes. Nevertheless, health attributes are often inter-related and depend on each other. Objectives: To investigate whether inclusion of second-order interactions in the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) value function would result in better fit and lead to different health state values than a model with main effects only. Methods: Using an efficient design, 400 pairs of EQ-5D-3L health states were generated in a pairwise choice format. We analyzed responses of 4000 people from the general population using a conditional logit model, and we tested goodness of fit using pseudo R2, Akaike information criterion, differences in log-likelihood, and likelihood ratio. We compared accuracies of models’ predictions based on root mean square error and mean absolute error. Results: The interaction-effects model showed systematically lower values than the main-effects model. Inclusion of interactions resulted only in a slightly better model fit. Interactions comprising mobility and self-care were the most salient. Conclusions: For the EQ-5D-3L, a value function based on interactions produces systematically lower values than a main-effects model, meaning that the effect of two or more health problems combined is stronger than the sum of the individual main effects

A Review and Classification of Approaches for Dealing with Uncertainty in Multi-Criteria Decision Analysis for Healthcare Decisions

The Author(s) 2015. This article is published with open access at Springerlink.com Abstract Multi-criteria decision analysis (MCDA) is increasingly used to support decisions in healthcare involving multiple and conflicting criteria. Although uncertainty is usually carefully addressed in health eco-nomic evaluations, whether and how the different sources of uncertainty are dealt with and with what methods in MCDA is less known. The objective of this study is to review how uncertainty can be explicitly taken into account in MCDA and to discuss which approach may be appro-priate for healthcare decision makers. A literature review was conducted in the Scopus and PubMed databases. Two reviewers independently categorized studies according to research areas, the type of MCDA used, and the approach used to quantify uncertainty. Selected full text articles wer

Research Priorities to Increase Confidence in and Acceptance of Health Preference Research:What Questions Should be Prioritized Now?

Background and Objective: There has been an increase in the study and use of stated-preference methods to inform medicine development decisions. The objective of this study was to identify prioritized topics and questions relating to health preferences based on the perspective of members of the preference research community. Methods: Preference research stakeholders from industry, academia, consultancy, health technology assessment/regulatory, and patient organizations were recruited using professional networks and preference-targeted e-mail listservs and surveyed about their perspectives on 19 topics and questions for future studies that would increase acceptance of preference methods and their results by decision makers. The online survey consisted of an initial importance prioritization task, a best-worst scaling case 1 instrument, and open-ended questions. Rating counts were used for analysis. The best-worst scaling used a balanced incomplete block design. Results: One hundred and one participants responded to the survey invitation with 66 completing the best-worst scaling. The most important research topics related to the synthesis of preferences across studies, transferability across populations or related diseases, and method topics including comparison of methods and non-discrete choice experiment methods. Prioritization differences were found between respondents whose primary affiliation was academia versus other stakeholders. Academic researchers prioritized methodological/less studied topics; other stakeholders prioritized applied research topics relating to consistency of practice. Conclusions: As the field of health preference research grows, there is a need to revisit and communicate previous work on preference selection and study design to ensure that new stakeholders are aware of this work and to update these works where necessary. These findings might encourage discussion and alignment among different stakeholders who might hold different research priorities. Research on the application of previous preference research to new contexts will also help increase the acceptance of health preference information by decision makers.</p

Single tube liquid biopsy for advanced non-small cell lung cancer

The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAM(high) circulating tumor cells (CTC), EpCAM(low) CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM(high) CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM(low) CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had >= 2 EpCAM(high) CTC, 15% had >= 2 EpCAM(low) CTC, 27% had >= 18 tdEV and 19% had ctDNA with >= 10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAM(high) CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAM(low) CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy

A Review and Classification of Approaches for Dealing with Uncertainty in Multi-Criteria Decision Analysis for Healthcare Decisions

The Author(s) 2015. This article is published with open access at Springerlink.com Abstract Multi-criteria decision analysis (MCDA) is increasingly used to support decisions in healthcare involving multiple and conflicting criteria. Although uncertainty is usually carefully addressed in health eco-nomic evaluations, whether and how the different sources of uncertainty are dealt with and with what methods in MCDA is less known. The objective of this study is to review how uncertainty can be explicitly taken into account in MCDA and to discuss which approach may be appro-priate for healthcare decision makers. A literature review was conducted in the Scopus and PubMed databases. Two reviewers independently categorized studies according to research areas, the type of MCDA used, and the approach used to quantify uncertainty. Selected full text articles wer

Public Preferences for Lung Cancer Screening Policies

Background Because early detection of lung cancer can substantially improve survival, there is increasing attention for lung cancer screening. Objectives To estimate public preferences for lung cancer screening and to identify subgroups in preferences. Methods Seven important attributes were selected using the literature, interviews, and a panel session. Preferences were elicited using a swing weighting questionnaire. The resulting attribute weights indicate the relative importance of swings from the worst to the best level between attributes. Hierarchical clustering was used to identify subgroups with different attribute weights. Results One thousand thirty-four respondents from a representative Dutch panel aged between 40 and 80 years were included. The identified attributes were location of screening (weight = 0.18 ± 0.16), mode of screening (weight = 0.17 ± 0.14), sensitivity (weight = 0.16 ± 0.13) and specificity (weight = 0.13 ± 0.12) of the screening modality, waiting time until results (weight = 0.13 ± 0.12), radiation burden (weight = 0.13 ± 0.12), and duration of screening procedure (weight = 0.10 ± 0.09). Most respondents preferred breath analysis (45%) to giving blood samples (31%) or going through a scanner (24%) as screening modality; 59% preferred screening at the general practitioner’s office instead of at the hospital. There was a significant difference in education between the five identified preference subgroups (P < 0.01). Conclusions There is considerable variation in how people value attributes of lung cancer screening. Different screening policies and implementation strategies may be appropriate for particular preference subgroups. Our results indicate that people prefer breath analysis and that they are more likely to attend screening modalities that can be used at a primary care facility

Assessing Lung Cancer Screening Programs under Uncertainty in a Heterogeneous Population

Background: Lung cancer screening can reduce cancer mortality. Most implementation studies focus only on low-dose computed tomography (LDCT) and clinical attributes of screening and do not include preferences of potential participants. In this study we evaluated the perceived value of screening programs based on LDCT, breath analysis (BA), or blood biomarkers (BB) according to the perspective of the target population. Methods: A multi-criteria decision analysis framework was adopted. The weights of seven attributes of screening (sensitivity, specificity, radiation burden, duration of screening process, waiting time until results are communicated, location of screening, and mode of screening) were obtained from an earlier study that included a broad sample from the Netherlands. Performance data for the screening modalities was obtained from clinical trials and expert opinion. Parameter uncertainty about clinical performances was incorporated probabilistically, while heterogeneity in preferences was analyzed through subgroup analyses. Results: The mean overall values were 0.58 (CI: 0.57 to 0.59), 0.57 (CI: 0.56 to 0.59), and 0.44 (CI: 0.43 to 0.45) for BB, BA, and LDCT, respectively. Seventy-seven per cent of respondents preferred BB or BA. For most subgroups, the overall values were similar to those of the entire sample. BA had the highest value for respondents who would have been eligible for earlier screening trials. Discussion: BB and BA seem valuable to participants because they can be applied in a primary care setting. Although LDCT still seems preferable given its strong and positive evidence base, it is important to take non-clinical attributes into account to maximize attendance

Time-varying covariates and coefficients in Cox regression models

Time-varying covariance occurs when a covariate changes over time during the follow-up period. Such variable can be analyzed with the Cox regression model to estimate its effect on survival time. For this it is essential to organize the data in a counting process style. In situations when the proportional hazards assumption of the Cox regression model does not hold, we say that the effect of the covariate is time-varying. The proportional hazards assumption can be tested by examining the residuals of the model. The rejection of the null hypothesis induces the use of time varying coefficient to describe the data. The time varying coefficient can be described with a step function or a parametric time function. This article aims to illustrate how to carry out statistical analyses in the presence of time-varying covariates or coefficients with R