Developing health-related quality-of-life instruments for use in Asia: the issues.

About half of the world's population live in Asia. Mandarin (the official language of China), Hindi and Japanese are among the ten languages spoken by the largest number of primary speakers. The numbers of Tamil and Malay speakers are expected to grow rapidly in the next few decades. Most health-related quality-of-life (HR-QOL) instruments currently used in Asia are translations and/or adaptations of instruments developed in North America and Western Europe. We illustrate and discuss several major issues in the development of HR-QOL instruments for use in Asia. We have seen insufficient quality in translation and semantic equivalence, which is not a uniquely Asian problem. This problem will be alleviated by putting recently proposed guidelines for translation and adaptation of patient-reported outcomes into practice and formally conducting equivalence studies. For copyright or other reasons it is rare to see major adaptations, such as exclusion of a domain in the original instrument or inclusion of a new domain, made to existing instruments. Evidence is limited and mixed as to whether there are differences in the concepts of HR-QOL between Asian and North American/Western European cultures that are important enough to justify such major adaptations, or the development of indigenous instruments, as opposed to the translation/adaptation of existing instruments. There are substantial cultural differences concerning what questions are appropriate to ask and answer. Many HR-QOL instruments are designed for self-completion. This mode of administration is often not feasible in Asia because of low literacy rates and the presence of many different regional languages. Alternative administration methods and analytic strategies that allow for pooling data collected by different modes are needed. The availability of HR-QOL instruments in various Asian countries seems to reflect the status of economic development of the countries rather than their disease burden. For instance, many important HR-QOL instruments are available in Japanese but not in Hindi or Tamil

Estimation of summary protective efficacy using a frailty mixture model for recurrent event time data.

Recurrent event time data are common in experimental and observational studies. The analytic strategy needs to consider three issues: within-subject event dependence, between-subject heterogeneity in event rates, and the possibility of a nonsusceptible fraction. Motivated by the need to estimate the summary protective efficacy from recurrent event time data as seen in many infectious disease clinical trials, we propose a two-part frailty mixture model that simultaneously accommodates all the three issues. In terms of vaccine action models, the proposed model is a combination of the 'all-or-none' and the 'leaky' models, and the summary protective efficacy is a unified measure of the vaccine's twofold effects in completely or partially protecting the vaccinated individuals against the study event. The model parameters of interest are estimated using the expectation-maximization algorithm with their respective variances estimated using Louis's formula for the expectation-maximization algorithm. The summary protective efficacy is estimated by a composite estimand with its variance estimated using the delta method. The performance of the proposed estimation approach is investigated by a simulation study. Data from a trial of malaria prophylaxis conducted in Ghana are reanalyzed

Supplementary feeding with fortified spread among moderately underweight 6-18-month-old rural Malawian children.

We aimed to analyse growth and recovery from undernutrition among moderately underweight ambulatory children receiving micronutrient-fortified maize-soy flour (Likuni Phala, LP) or ready-to-use fortified spread (FS) supplementary diet. One hundred and seventy-six 6-18-month-old individuals were randomized to receive 500 g LP or 350 g FS weekly for 12 weeks. Baseline and end of intervention measurements were used to calculate anthropometric gains and recovery from underweight, wasting and stunting. Mean weight-for-age increased by 0.22 (95% CI 0.07-0.37) and 0.28 (0.18-0.40) Z-score units in the LP and FS groups respectively. Comparable increase for mean weight-for-length was 0.39 (0.20-0.57) and 0.52 (0.38-0.65) Z-score units. Recovery from underweight and wasting was 20% and 93% in LP group and 16% and 75% in FS group. Few individuals recovered from stunting and mean length-for-age was not markedly changed. There were no statistically significant differences between the outcomes in the two intervention groups. In a poor food-security setting, underweight infants and children receiving supplementary feeding for 12 weeks with ready-to-use FS or maize-soy flour porridge show similar recovery from moderate wasting and underweight. Neither intervention, if limited to a 12-week duration, appears to have significant impact on the process of linear growth or stunting

Mapping and direct valuation: Do they give equivalent EQ-5D-5L index scores?

© 2015 Luo et al. Objective: Utility values of health states defined by health-related quality of life instruments can be derived from either direct valuation ('valuation-derived') or mapping ('mapping-derived'). This study aimed to compare the utility-based EQ-5D-5L index scores derived from the two approaches as a means to validating the mapping function developed by van Hout et al for the EQ-5D-5L instrument. Methods: This was an observational study of 269 breast cancer patients whose EQ-5D-5L index scores were derived from both methods. For comparing discriminatory ability and responsiveness to change, multivariable regression models were used to estimate the effect sizes of various health indicators on the index scores. Agreement and test-retest reliability were examined using intraclass correlation coefficient (ICC). Whenever appropriate, the 90 % confidence intervals (90 % CI) were compared to predefined equivalence margins. Results: The mean difference in and ICC between the valuation- and mapping-derived EQ-5D-5L index scores were 0.015 (90 % CI = 0.006 to 0.024) and 0.915, respectively. Discriminatory ability and responsiveness of the two indices were equivalent in 13 of 15 regression analyses. However, the mapping-derived index score was lower than the valuation-derived index score in patients experiencing extreme health problems, and the test-retest reliability of the former was lower than the latter, for example, their ICCs differed by 0.121 (90 % CI = 0.051 to 0.198) in patients who reported no change in performance status in the follow-up survey. Conclusion: This study provided the first evidence supporting the validity of the mapping function for converting EQ-5D-5L profile data into a utility-based index score.published_or_final_versio

Complementary feeding with fortified spread and incidence of severe stunting in 6- to 18-month-old rural Malawians.

OBJECTIVE: To compare growth and incidence of malnutrition in infants receiving long-term dietary supplementation with ready-to-use fortified spread (FS) or micronutrient-fortified maize-soy flour (likuni phala [LP]). DESIGN: Randomized, controlled, single-blind trial. SETTING: Rural Malawi. PARTICIPANTS: A total of 182 six-month-old infants. INTERVENTION: Participants were randomized to receive 1 year of daily supplementation with 71 g of LP (282 kcal), 50 g of FS (FS50) (256 kcal), or 25 g of FS (FS25) (130 [corrected] kcal). OUTCOME MEASURES: Weight and length gains and the incidences of severe stunting, underweight, and wasting. RESULTS: Mean weight and length gains in the LP, FS50, and FS25 groups were 2.37, 2.47, and 2.37 kg (P = .66) and 12.7, 13.5, and 13.2 cm (P = .23), respectively. In the same groups, the cumulative 12-month incidence of severe stunting was 13.3%, 0.0%, and 3.5% (P = .01), of severe underweight was 15.0%, 22.5%, and 16.9% (P = .71), and of severe wasting was 1.8%, 1.9%, and 1.8% (P > .99). Compared with LP-supplemented infants, those given FS50 gained a mean of 100 g more weight and 0.8 cm more length. There was a significant interaction between baseline length and intervention (P = .04); in children with below-median length at enrollment, those given FS50 gained a mean of 1.9 cm more than individuals receiving LP. CONCLUSION: One-year-long complementary feeding with FS does not have a significantly larger effect than LP on mean weight gain in all infants, but it is likely to boost linear growth in the most disadvantaged individuals and, hence, decrease the incidence of severe stunting

Order effects: a randomised study of three major cancer-specific quality of life instruments

BACKGROUND: In methodological studies and outcomes research, questionnaires often comprise several health-related quality of life (HRQoL) measures. Previous psychological studies have suggested that changing the sequential order of measurement scales within a questionnaire could alter the pattern of responses. Yet, information on the presence or absence of order effects on the assessment of HRQoL in cancer patients is limited. METHODS: An incomplete block design was used in this study of 1277 cancer patients. Each patient filled out a questionnaire package that contained two of the three major cancer-specific HRQoL instruments, namely the Functional Assessment of Cancer Therapy – General, the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire and the Functional Living Index – Cancer. Within a questionnaire package the sequential order of the instruments contained were randomised. Measurement properties of the instruments, including the number of missing values, mean HRQoL scores, known-groups validity and internal consistency were compared between samples of different presentation orders. RESULTS: No effect of presentation order on the four properties aforementioned was found. CONCLUSION: Presentation order is unlikely to alter the responses to these HRQoL instruments administered in cancer patients when any two of them are used together

Bias control in the analysis of case-control studies with incidence density sampling.

BACKGROUND: Previous simulation studies of the case-control study design using incidence density sampling, which required individual matching for time, showed biased estimates of association from conditional logistic regression (CLR) analysis; however, the reason for this is unknown. Separately, in the analysis of case-control studies using the exclusive sampling design, it has been shown that unconditional logistic regression (ULR) with adjustment for an individually matched binary factor can give unbiased estimates. The validity of this analytic approach in incidence density sampling needs evaluation. METHODS: In extensive simulations using incidence density sampling, we evaluated various analytic methods: CLR with and without a bias-reduction method, ULR with adjustment for time in quintiles (and residual time within quintiles) and ULR with adjustment for matched sets and bias reduction. We re-analysed a case-control study of Haemophilus influenzae type B vaccine using these methods. RESULTS: We found that the bias in the CLR analysis from previous studies was due to sparse data bias. It can be controlled by the bias-reduction method for CLR or by increasing the number of cases and/or controls. ULR with adjustment for time in quintiles usually gave results highly comparable to CLR, despite breaking the matches. Further adjustment for residual time trends was needed in the case of time-varying effects. ULR with adjustment for matched sets tended to perform poorly despite bias reduction. CONCLUSIONS: Studies using incidence density sampling may be analysed by either ULR with adjustment for time or CLR, possibly with bias reduction

The impact of diabetes mellitus and other chronic medical conditions on health-related Quality of Life: Is the whole greater than the sum of its parts?

BACKGROUND: Diabetes mellitus (DM) is an important public health concern, the impact of which is increased by the high prevalence of co-existing chronic medical conditions among subjects with DM. The aims of this study were therefore to (1) evaluate the impact of DM and co-existing chronic medical conditions on health-related quality of life (HRQoL) (which could be additive, synergistic or subtractive); (2) to determine the extent to which the SF-6D (a single-index preference measure) captures the multidimensional information provided by the SF-36 (a profile measure). METHODS: Using data from a cross-sectional, population-based survey of Chinese, Malay and Indians in Singapore, we developed 9 separate multiple linear regression models, with each SF-36 scale or SF-6D index score being the dependent variable for one model. The influence of DM and a second chronic medical condition (hypertension (HTN), heart disease (HD), musculoskeletal illnesses (MS)) and their interactions were studied after adjusting for the influence of potential confounding variables. RESULTS: Among 5,224 subjects, the prevalence of DM, HTN, HD and MS were 5.9%, 10.7%, 2.4% and 26.6% respectively. DM lowered SF-36 scores by more than 2 points on 3 SF-36 scales and lowered SF-6D scores by 0.03 points. Subjects with DM and HTN, DM and HD or DM and MS experienced further lowering of SF-36 scores exceeding 2 points on at least 6 scales and further lowering of SF-6D scores by 0.05, 0.08 and 0.10 points respectively. Generally, DM and co-existing medical conditions exerted additive effects on HRQoL, with the exception of DM and heart disease, where a subtractive effect was noted. SF-6D index scores generally reflected the patterns of influence of DM and chronic medical conditions on SF-36 scores. CONCLUSION: DM and chronic medical conditions generally reduced HRQoL in this multiethnic general population in an additive, rather than synergistic or subtractive fashion. In this study, the SF-6D was a reasonably good summary measure for the SF-36

Estimation of the primary, secondary and composite effects of malaria vaccines using data on multiple clinical malaria episodes.

BACKGROUND: An effective malaria vaccine affects the risk of malaria directly, through the vaccine-induced immune response (the primary effect), and indirectly, as a consequence of reduced exposure to malaria infection and disease, leading to slower acquisition of natural immunity (the secondary effect). The beneficial primary effect may be offset by a negative secondary effect, resulting in a smaller or nil composite effect. Reports of malaria vaccine trials usually present only the composite effect. We aimed to demonstrate how the primary and secondary effects can also be estimated from trial data. METHODS: We propose an enhancement to the conditional frailty model for the estimation of primary effect using data on disease episodes. We use the Andersen-Gill model to estimate the composite effect. We consider taking the ratio of the hazard ratios to estimate the secondary effect. We used directed acyclic graphs and data from a randomized trial of the RTS,S/AS02 malaria vaccine to illustrate the problems and solutions. Time-varying effects were estimated by partitioning the follow-up into four time periods. RESULTS: The primary effect estimates from our proposed model were consistently stronger than the conditional frailty model in the existing literature. The primary effect of the vaccine was consistently stronger than the composite effect across all time periods. Both the primary and composite effects were stronger in the first three months, with hazard ratios (95% confidence interval) 0.62 (0.49-0.79) and 0.68 (0.54-0.84), respectively; the hazard ratios weakened over time. The secondary effect appeared mild, with hazard ratio 1.09 (1.02-1.16) in the first three months. CONCLUSIONS: The proposed analytic strategy facilitates a more comprehensive interpretation of trial data on multiple disease episodes. The RTS,S/AS02 vaccine had modest primary and secondary effects that waned over time, but the composite effect in preventing clinical malaria remained positive up to the end of the study. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT00197041

Mapping the Functional Assessment of Cancer Therapy - Breast (FACT-B) to the 5-level EuroQoL group’s 5-dimension questionnaire (EQ-5D-5L) utility index in a Multi-ethnic Asian population

Purpose To develop an algorithm for mapping the Functional Assessment of Cancer Therapy – Breast (FACT-B) to the 5-level EuroQoL Group’s 5-dimension questionnaire (EQ-5D-5L) utility index. Methods A survey of 238 breast cancer patients in Singapore was conducted. Models using various regression methods with or without recognizing the upper boundary of utility values at 1 were fitted to predict the EQ-5D-5L utility index based on the five subscale scores of the FACT-B. Data from a follow-up survey of these patients were used to validate the results. Results A model that maps the physical, emotional, functional well-being and the breast cancer concerns subscales of the FACT-B to the EQ-5D-5L utility index was derived. The social well-being subscale was not associated to the utility index. Although theoretical assumptions may not be valid, ordinary least square outperformed other regression methods. The mean predicted utility index within each performance status level at follow-up deviated from the observed mean less than the minimally important difference of EQ-5D for cancer patients. Conclusions The mapping algorithm converts the FACT-B to the EQ-5D utility index. This enables oncologists, clinical researchers and policy makers to obtain a quantitative utility summary of a patient’s health status when only the FACT-B is assessed.BioMed Central open acces