The relationship between EQ-5D, HAQ and pain in patients with rheumatoid arthritis: further validation and development of the limited dependent variable, mixture model approach

Objective To provide robust estimates of EQ-5D as a function of the Health Assessment Questionnaire (HAQ) and pain in patients with rheumatoid arthritis. Method Repeated observations of patients diagnosed with RA in a US observational cohort (n=100,398 observations) who provided data on HAQ, pain on a visual analogue scale and the EQ-5D questionnaire. We use a bespoke mixture modelling approach to appropriately reflect the characteristics of the EQ-5D instrument and compare this to results from linear regression. Results The addition of pain alongside HAQ as an explanatory variable substantially improves explanatory power. The preferred model is a four component mixture. Unlike the linear regression it exhibits very good fit to the data, does not suffer from problems of bias or predict values outside the feasible range. Conclusions It is appropriate to model the relationship between HAQ and EQ-5D but only if suitable statistical methods are applied. Linear models underestimate the QALY benefits, and therefore the cost effectiveness, of therapies. The bespoke mixture model approach outlined here overcomes this problem. The addition of pain as an explanatory variable greatly improves the estimates

A comparison of direct and indirect methods for the estimation of health utilities from clinical outcomes

Background: Analysts often need to estimate health state utility values as a function of other outcome measures. Utility values like EQ-5D have several unusual characteristics that make standard statistical methods inappropriate. We have developed a bespoke approach based on mixture models to directly estimate EQ-5D. An indirect method, “response mapping”, first estimates the level on each of the five dimensions of the EQ-5D descriptive system and then calculates the expected tariff score. These methods have never previously been compared. Methods: We use a large observational database of patients diagnosed with Rheumatoid Arthritis (n=100,398 observations). Direct estimation of UK EQ-5D scores as a function of Health Assessment Questionnaire (HAQ), pain and age was performed using a limited dependent variable mixture model. Indirect modelling was undertaken using a set of generalized ordered probit models with expected tariff scores calculated mathematically. Linear regression was reported for comparison purposes. Results: The linear model fits poorly, particularly at the extremes of the distribution. Both the bespoke mixture model and the generalized ordered probit approach offer improvements in fit over the entire range of EQ-5D. Mean average error is 10% and 5% lower compared to the linear model respectively. Root mean squared error is 3% and 2% lower. The mixture model demonstrates superior performance to the indirect method across almost the entire range of pain and HAQ. Limitations: There is limited data from patients in the most extreme HAQ health states. Conclusions: Modelling of EQ-5D from clinical measures is best performed directly using the bespoke mixture model. This substantially outperforms the indirect method in this example. Linear models are inappropriate, suffer from systematic bias and generate values outside the feasible range

Valuing health at the end of life: A review of stated preference studies in the social sciences literature

A source of debate in the health care priority setting literature is whether to weight health gains to account for equity considerations, such as concern for those with very short life expectancy. This paper reviews the empirical evidence in the published social sciences literature relevant to the following research question: do members of the public wish to place greater weight on a unit of health gain for end-of-life patients than on that for other types of patients? An electronic search of the Social Sciences Citation Index for articles published until October 2017 was conducted, with follow-up of references to obtain additional data. Hierarchical criteria were applied to select empirical studies reporting stated preferences relating to hypothetical health care priority setting contexts. Twenty-three studies met the inclusion criteria and were included in the review. Choice exercises were the most common method used to elicit preferences; other approaches included budget allocation, person trade-off and willingness-to-pay. Some studies found that observed preferences regarding end-of-life patients are influenced by information about the patients’ ages. Overall, the evidence is mixed, with eight studies that report evidence consistent with a ‘premium’ for end-of-life treatments and 11 studies that do not. Methodological and design aspects that appear to influence the findings of end-of-life-related preference studies are identified and discussed. The findings of the UK studies have particular relevance for assessing the legitimacy of the National Institute for Health and Care Excellence’s policy for appraising life-extending end-of-life treatments

The feasibility of early pulmonary rehabilitation and activity after COPD exacerbations: external pilot randomised controlled trial, qualitative case study and exploratory economic evaluation

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects > 3 million people in the UK. Acute exacerbations of COPD (AECOPD) are the second most common reason for emergency hospital admission in the UK. Pulmonary rehabilitation is usual care for stable COPD but there is little evidence for early pulmonary rehabilitation (EPR) following AECOPD, either in hospital or immediately post discharge. OBJECTIVE: To assess the feasibility of recruiting patients, collecting data and delivering EPR to patients with AECOPD to evaluate EPR compared with usual care. DESIGN: Parallel-group, pilot 2 × 2 factorial randomised trial with nested qualitative research and an economic analysis. SETTING: Two acute hospital NHS trusts. Recruitment was carried out from September 2015 to April 2016 and follow-up was completed in July 2016. PARTICIPANTS: Eligible patients were those aged ≥ 35 years who were admitted with AECOPD, who were non-acidotic and who maintained their blood oxygen saturation level (SpO2) within a prescribed range. Exclusions included the presence of comorbidities that affected the ability to undertake the interventions. INTERVENTIONS: (1) Hospital EPR: muscle training delivered at the patient's hospital bed using a cycle ergometer and (2) home EPR: a pulmonary rehabilitation programme delivered in the patient's home. Both interventions were delivered by trained physiotherapists. Participants were allocated on a 1 : 1 : 1 : 1 ratio to (1) hospital EPR (n = 14), (2) home EPR (n = 15), (3) hospital EPR and home EPR (n = 14) and (4) control (n = 15). Outcome assessors were blind to treatment allocation; it was not possible to blind patients. MAIN OUTCOME MEASURES: Feasibility of recruiting 76 participants in 7 months at two centres; intervention delivery; views on intervention/research acceptability; clinical outcomes including the 6-minute walk distance (6WMD); and costs. Semistructured interviews with participants (n = 27) and research health professionals (n = 11), optimisation assessments and an economic analysis were also undertaken. RESULTS: Over 7 months 449 patients were screened, of whom most were not eligible for the trial or felt too ill/declined entry. In total, 58 participants (76%) of the target 76 participants were recruited to the trial. The primary clinical outcome (6MWD) was difficult to collect (hospital EPR,n = 5; home EPR,n = 6; hospital EPR and home EPR,n = 5; control,n = 5). Hospital EPR was difficult to deliver over 5 days because of patient discharge/staff availability, with 34.1% of the scheduled sessions delivered compared with 78.3% of the home EPR sessions. Serious adverse events were experienced by 26 participants (45%), none of which was related to the interventions. Interviewed participants generally found both interventions to be acceptable. Home EPR had a higher rate of acceptability, mainly because patients felt too unwell when in hospital to undergo hospital EPR. Physiotherapists generally found the interventions to be acceptable and valued them but found delivery difficult because of staffing issues. The health economic analysis results suggest that there would be value in conducting a larger trial to assess the cost-effectiveness of the hospital EPR and hospital EPR plus home EPR trial arms and collect more information to inform the hospital cost and quality-adjusted life-year parameters, which were shown to be key drivers of the model. CONCLUSIONS: A full-scale randomised controlled trial using this protocol would not be feasible. Recruitment and delivery of the hospital EPR intervention was difficult. The data obtained can be used to design a full-scale trial of home EPR. Because of the small sample and large confidence intervals, this study should not be used to inform clinical practice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18634494. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 11. See the NIHR Journals Library website for further project information

Shifting Winds: Using Ancestry DNA to Explore Multiracial Individuals\u27 Patterns of Articulating Racial Identity

This study explored how genotype information affects identification narratives of multiracial individuals. Twenty-one multiracial individuals completed individual interviews before and after receiving a DNA analysis to clarify their genetically based racial ancestry. Based on results, this article proposes patterns of articulating racial identity by multiracial individuals. Four patterns extend evolving research in multiracial identification, namely (1) the individual articulates a monoracial identity; (2) the individual articulates one identity, but this can shift in response to various conditions; (3) the individual articulates an extraracial identity, opting out of traditional categories applied to race; and (4) the person distinguishes traditional categories of race from culture and owns the two identities in different ways. Implications of these findings are discussed. First, adding new ancestry DNA information further muddles the neat categories of race, consistent with the view of race as socially constructed. Second, results emphasize the fluidity of identification for multiracial individuals. Third, DNA information challenges the neat percentages people tend to associate with their backgrounds. Particularly for younger multiracial individuals, there was less of a sense that race was a real thing and more that culture played a big part in how they saw themselves

The politics of health services research: health professionals as hired hands in a commissioned research project in England

Previous health services research has failed to account for the role played by clinical staff in the collection of data. In this paper we use the work of Roth on hired hand research to examine the politics of evidence production within health services research. Sociologies of work predict lack of engagement in the research tasks by subordinated groups of workers. We examine the role of midwives in researching ante-natal screening for sickle cell and thalassaemia in England, and construct three ideal types: repairers, refractors, and resisters to account for the variable engagement of health staff with research. We find some features of the hired hand phenomenon predicted by Roth to be in evidence, and suggest that the context of our project is similar to much health services research. We conclude that without concerted attempts (1) to change the social relations of research production; (2) to mitigate hired hand effects; (3) to assess the impact of the hired hand effect on the validity and reliability of findings, and (4) to report on these limitations, that health services research involving large teams of subordinated clinical staff as data collectors will be prone to produce evidence that is of limited trustworthiness. Keywords: evidence-based research; health services research; hired hands; politics of evidence; screening; midwives; research methodology; work and employment

The HTA risk analysis chart: visualising the need for and potential value of managed entry agreements in health technology assessment

Background Recent changes to the regulatory landscape of pharmaceuticals may sometimes require reimbursement authorities to issue guidance on technologies that have a less mature evidence base. Decision makers need to be aware of risks associated with such health technology assessment (HTA) decisions and the potential to manage this risk through managed entry agreements (MEAs). Objective This work develops methods for quantifying risk associated with specific MEAs and for clearly communicating this to decision makers. Methods We develop the ‘HTA risk analysis chart’, in which we present the payer strategy and uncertainty burden (P-SUB) as a measure of overall risk. The P-SUB consists of the payer uncertainty burden (PUB), the risk stemming from decision uncertainty as to which is the truly optimal technology from the relevant set of technologies, and the payer strategy burden (PSB), the additional risk of approving a technology that is not expected to be optimal. We demonstrate the approach using three recent technology appraisals from the UK National Institute for Health and Clinical Excellence (NICE), each of which considered a price-based MEA. Results The HTA risk analysis chart was calculated using results from standard probabilistic sensitivity analyses. In all three HTAs, the new interventions were associated with substantial risk as measured by the P-SUB. For one of these technologies, the P-SUB was reduced to zero with the proposed price reduction, making this intervention cost effective with near complete certainty. For the other two, the risk reduced substantially with a much reduced PSB and a slightly increased PUB. Conclusions The HTA risk analysis chart shows the risk that the healthcare payer incurs under unresolved decision uncertainty and when considering recommending a technology that is not expected to be optimal given current evidence. This allows the simultaneous consideration of financial and data-collection MEA schemes in an easily understood format. The use of HTA risk analysis charts will help to ensure that MEAs are considered within a standard utility-maximising health economic decision-making framework

Assessing methods for dealing with treatment switching in randomised controlled trials: a simulation study

<p>Abstract</p> <p>Background</p> <p>We investigate methods used to analyse the results of clinical trials with survival outcomes in which some patients switch from their allocated treatment to another trial treatment. These included simple methods which are commonly used in medical literature and may be subject to selection bias if patients switching are not typical of the population as a whole. Methods which attempt to adjust the estimated treatment effect, either through adjustment to the hazard ratio or via accelerated failure time models, were also considered. A simulation study was conducted to assess the performance of each method in a number of different scenarios.</p> <p>Results</p> <p>16 different scenarios were identified which differed by the proportion of patients switching, underlying prognosis of switchers and the size of true treatment effect. 1000 datasets were simulated for each of these and all methods applied. Selection bias was observed in simple methods when the difference in survival between switchers and non-switchers were large. A number of methods, particularly the AFT method of Branson and Whitehead were found to give less biased estimates of the true treatment effect in these situations.</p> <p>Conclusions</p> <p>Simple methods are often not appropriate to deal with treatment switching. Alternative approaches such as the Branson & Whitehead method to adjust for switching should be considered.</p

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. DISCUSSION: The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.MRC Funding: MC_UP_1302/3 NIHR Funding: RP-PG-0610-1006