Modelling health-related quality of life data for economic evaluation of cancer treatments: Applications in lung cancer

INTRODUCTION: The annual economic burden of treating cancer to the National Health Service (NHS) in the United Kingdom (UK) is over £15 billion; and for non small cell lung cancer (NSCLC), one of the leading causes of cancer deaths in the world, this is £2.4 billion. Economic evaluation plays an essential role in assessing the relative value of lung cancer treatments. Modelling (HRQoL) data is fundamental in determining the cost-effectiveness of cancer treatments. This thesis aims to investigate modelling of HRQoL data collected from lung cancer patients for economic evaluation. In particular, the role of modelling to improve utility prediction is investigated. The sensitivity of disease specific and generic HRQoL measures are also explored. In addition, methods to extrapolate utilities beyond cancer progression and identifying a selection procedure from relevant published algorithms are developed. METHODS: Data from two clinical trials and a prospective observational study in NSCLC patients were designed and executed to develop several mapping models (Linear, Non-Linear, Joint, and Bayesian). The sensitivity of EQ-5D-3L and EQ-5D-5L were compared with a cancer specific measure (QLQ-C30). Simulation methods were used to develop an approach for selecting algorithms. RESULTS: Two and three-part Beta-Binomial models improve predictions. Joint models also contribute to improved prediction of utilities. Bayesian Networks may help reduce the over-prediction in poor health states. The EQ-5D-5L offers better mapping and is more sensitive for detecting treatment benefit compared to EQ-5D-3L. It is also viable to develop decision criteria for selecting between several published algorithms. CONCLUSION: Methodological improvements in modelling HRQoL for the economic evaluation of cancer treatments have been demonstrated. Improvements in model structure, prediction and selection are empirically demonstrated

MRI features of spinal fluorosis: Results of an endemic community screening

Objectives: Fluorosis is endemic in many parts of the world. However community studies on MRI features of fluorosis are lacking. The aim of this study was to determine MRI features of spinal changes in a community with endemic fluorosis in the Thar Desert Pakistan.Methodology: Randomly selected adults from the Village Samorindh, district Tharparker, Sindh, Pakistan, with spinal fluorosis diagnosed on plain x-rays and raised serum fluoride levels were studied from June 2008 to January 2009. MRI was carried out on 0.5 T open magnet MRI system. Features of vertebral body, spinal ligaments, intervertebral disc, facet joints, iliac wings and other incidental findings were noted. Sclerosis was defined as low signal intensity on both T1 and T2 weighted images. RESULTS were described as mean and percentage values.Results: All the studied 27 subjects complained of back ache without neurological signs. The average age was 43.33 ± 10.45 years; 21 being male (77.8%). The most frequent findings included generalized vertebral sclerosis (24, 88.8%), ligamentum flavum hypertrophy (23, 85%), anterior (20, 74%) and lateral (17, 62.9%) disc herniation, thickened longitudinal ligaments, and narrowing of spinal foramina. Hemangioma was seen in 04(14.8%). The most commonly involved level was L1-2, L4-5 and lower dorsal spine.Conclusion: Vertebral sclerosis, a combination of premature degeneration with anterior disc herniation and an unusually high frequency of vertebral hemangioma formed the spectrum of MRI findings in subjects with spinal fluorosis having back ache but no neurological findings

Stopping clinical trials early for futility: retrospective analysis of several randomised clinical studies

Background: Many clinical trials show no overall benefit. We examined futility analyses applied to trials with different effect sizes. Methods: Ten randomised cancer trials were retrospectively analysed; target sample size reached in all. The hazard ratio indicated no overall benefit (n=5), or moderate (n=4) or large (n=1) treatment effects. Futility analyses were applied after 25, 50 and 75% of events were observed, or patients were recruited. Outcomes were conditional power (CP), and time and cost savings. Results: Futility analyses could stop some trials with no benefit, but not all. After observing 50% of the target number of events, 3 out of 5 trials with no benefit could be stopped early (low CPless than or equal to15%). Trial duration for two studies could be reduced by 4–24 months, saving £44 000–231 000, but the third had already stopped recruiting, hence no savings were made. However, of concern was that 2 of the 4 trials with moderate treatment effects could be stopped early at some point, although they eventually showed worthwhile benefits. Conclusions: Careful application of futility can lead to future patients in a trial not being given an ineffective treatment, and should therefore be used more often. A secondary consideration is that it could shorten trial duration and reduce costs. However, studies with modest treatment effects could be inappropriately stopped early. Unless there is very good evidence for futility, it is often best to continue to the planned end

Public private partnerships and the poor - case report 1: Karachi, Pakistan

The purpose of the project Public Private Partnerships and the Poor in Water and Sanitation is to determine workable processes whereby the needs of the poor are promoted in strategies which encourage public-private partnerships (PPP) in the provision of water supply and sanitation services. One of the key objectives is to fill some of the gaps which exist in evidence-based reporting of the facts and issues around the impacts of PPP on poor consumers. This report presents the case report from Karachi, Pakistan

Public private partnerships and the poor - case report 3: awami tanks in Orangi Town, Karachi, Pakistan

The purpose of the project Public Private Partnerships and the Poor in Water and Sanitation is to determine workable processes whereby the needs of the poor are promoted in strategies which encourage public-private partnerships (PPP) in the provision of water supply and sanitation services. One of the key objectives is to fill some of the gaps which exist in evidence-based reporting of the facts and issues around the impacts of PPP on poor consumers. This report presents the case report from Karachi, Pakistan

Does Structured Exercise Improve Cognitive Impairment in People with Mild to Moderate Dementia? A Cost-Effectiveness Analysis from a Confirmatory Randomised Controlled Trial:The Dementia and Physical Activity (DAPA) Trial

Background Previous studies suggest that physical exercise could slow dementia progression. However, evidence for the cost effectiveness of structured exercise is conflicting and based on small trials. Objectives The objective of this study was to compare the cost effectiveness of a tailored, structured, moderate- to high-intensity exercise programme versus usual care in people with mild to moderate dementia. Methods An economic evaluation was conducted from the UK National Health Service and personal social services perspective, based on data from a large randomised controlled trial. The primary clinical outcome was the participant reported ADAS-Cog (Alzheimer’s Disease Assessment Scale–Cognitive Subscale) at 12 months. Costs (£; 2014–2015 prices) were collected prospectively over a 12-month follow-up period. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted with the view to estimating the incremental cost per QALY gained and the incremental net monetary benefit (INMB) associated with the exercise programme plus usual care versus usual care. Sensitivity analyses were undertaken to assess the impact of uncertainty surrounding aspects of the economic evaluation, and pre-specified subgroup analyses explored heterogeneity in the cost-effectiveness results. Results Participants (n = 494) were randomised to exercise plus usual care or usual care only. By 12 months the mean ADAS-Cog score had worsened slightly to 25.2 (standard deviation [SD] 12.3) in the exercise arm and 23.8 (SD 10.4) in the usual care: difference − 1.4, 95% confidence interval (CI) − 2.6 to − 0.2 (p = 0.03). The mean (standard error [SE]) costs over 12 months for experimental versus control was £5945 (USD7856) versus £4597 (USD6574), respectively; (difference: £1347 [$1926]; p = 0.0426). Mean (SE) QALY estimates were 0.787 (0.012) versus 0.826 (0.019), respectively (p = 0.090). The probability that the exercise programme is cost effective was  Conclusions Building on the clinical results of the trial, which showed that the structured exercise programme evaluated does not slow cognitive impairment in people with mild to moderate dementia, this economic evaluation shows that the programme is not cost effective.</p

Climatic Changes and Their Effect on Wildlife of District Dir Lower, Khyber Pakhtunkhwa, Pakistan

Climatic changes and their impact are increasingly evident in Pakistan, especially in the mountainous regions. Mountain ecosystems are considered to be sensitive indicators of global warming; even slight variations in temperature can lead to significant shifts in local climate, which can, in turn, drastically affect the natural environment, subsequently altering people’s lifestyle and wildlife habitats. The targeted area for the present research was Lower Dir District, Pakistan. The study gathered the required information from primary and secondary sources. Secondary data on temperature and precipitation were obtained from various sources, i.e., local CBO, including WWF Pakistan. Based on information gathered on climate change and wildlife, a detailed questionnaire was designed. Results showed that no regular pattern of the increase was found in temperature from 2010 to 2018; the same was noticed in the rainfall decrease pattern. Results also showed that the leading causes behind climatic changes are an increase in greenhouse gases due to pollution by industries, vehicles, crushing plants, deforestation, and some natural phenomena such as floods. The study showed that more than 80% of the respondents agreed that climatic effects have a significant impact on wildlife, i.e., the existence of wildlife falls in danger due to climatic changes as it may lead to habitat change, making it difficult for the survival and adaptation of the wildlife. Hence, in consequence, it leads to migration, low growth rate, an increase in morbidity and mortality rate, and finally leading to the extinction of the species or population. It is concluded from the study that people are severely noticing the climatic change and its leading causes are greenhouse gases and deforestation. To control climatic changes and wildlife extinction, we need an appropriate policy for forest conservation, wildlife conservation, prevent hunting, industrial pollution control, vehicle pollution control, increase in plantation, awareness of policy for the control of climatic changes, etc

Comparing the mapping between EQ-5D-5L, EQ-5D-3L and the EORTC-QLQ-C30 in non-small cell lung cancer patients

BACKGROUND: Several mapping algorithms have been published with the EORTC-QLQ-C30 for estimating EQ-5D-3L utilities. However, none are available with EQ-5D-5L. Moreover, a comparison between mapping algorithms in the same set of patients has not been performed for these two instruments simultaneously. In this prospective data set of 100 non-small cell lung cancer (NSCLC) patients, we investigate three mapping algorithms using the EQ-5D-3L and EQ-5D-5L and compare their performance. METHODS: A prospective non-interventional cohort of 100 NSCLC patients were followed up for 12 months. EQ-5D-3L, EQ-5D-5L and EORTC-QLQ-C30 were assessed monthly. EQ-5D-5L was completed at least 1 week after EQ-5D-3L. A random effects linear regression model, a beta-binomial (BB) and a Limited Variable Dependent Mixture (LVDM) model were used to determine a mapping algorithm between EQ-5D-3L, EQ-5D-5L and QLQ-C30. Simulation and cross validation and other statistical measures were used to compare the performances of the algorithms. RESULTS: Mapping from the EQ-5D-5L was better: lower AIC, RMSE, MAE and higher R(2) were reported with the EQ-5D-5L than with EQ-5D-3L regardless of the functional form of the algorithm. The BB model proved to be more useful for both instruments: for the EQ-5D-5L, AIC was –485, R(2) of 75 %, MAE of 0.075 and RMSE was 0.092. This was –385, 69 %, 0.099 and 0.113 for EQ-5D-3L respectively. The mean observed vs. predicted utilities were 0.572 vs. 0.577 and 0.515 vs. 0.523 for EQ-5D-5L and EQ-5D-3L respectively, for OLS; for BB, these were 0.572 vs. 0.575 and 0.515 vs. 0.518 respectively and for LVDMM 0.532 vs 0.515 and 0.569 vs 0.572 respectively. Less over-prediction at poorer health states was observed with EQ-5D-5L. CONCLUSIONS: The BB mapping algorithm is confirmed to offer a better fit for both EQ-5D-3L and EQ-5D-5L. The results confirm previous and more recent results on the use of BB type modelling approaches for mapping. It is recommended that in studies where EQ-5D utilities have not been collected, an EQ-5D-5L mapping algorithm is used

Is protocolised weaning that includes early extubation onto non-invasive ventilation more cost effective than protocolised weaning without non-invasive ventilation? Findings from the Breathe Study

Background Optimising techniques to wean patients from invasive mechanical ventilation (IMV) remains a key goal of intensive care practice. The use of non-invasive ventilation (NIV) as a weaning strategy (transitioning patients who are difficult to wean to early NIV) may reduce mortality, ventilator-associated pneumonia and intensive care unit (ICU) length of stay. Objectives Our objectives were to determine the cost effectiveness of protocolised weaning, including early extubation onto NIV, compared with weaning without NIV in a UK National Health Service setting. Methods We conducted an economic evaluation alongside a multicentre randomised controlled trial. Patients were randomised to either protocol-directed weaning from mechanical ventilation or ongoing IMV with daily spontaneous breathing trials. The primary efficacy outcome was time to liberation from ventilation. Bivariate regression of costs and quality-adjusted life-years (QALYs) provided estimates of the incremental cost per QALY and incremental net monetary benefit (INMB) overall and for subgroups [presence/absence of chronic obstructive pulmonary disease (COPD) and operative status]. Long-term cost effectiveness was determined through extrapolation of survival curves using flexible parametric modelling. Results NIV was associated with a mean INMB of £620 ($US885) (cost-effectiveness threshold of £20,000 per QALY) with a corresponding probability of 58$US6594 per QALY gained). Conclusions The probability of NIV being cost effective relative to weaning without NIV ranged between 57 and 59% overall and between 82 and 87% for the COPD subgroup