Patient reported outcomes (PRO) assessing multiple gastrointestinal symptoms are central to characterizing the therapeutic benefit of novel agents for irritable bowel syndrome (IBS). Common approaches that sum or average responses across different illness components must be unidimensional and have small unique variances to avoid aggregation bias and misinterpretation of clinical data. This study sought to evaluate the unidimensionality of the IBS Symptom Severity Scale (IBS-SSS) and to explore person centered cluster analytic methods for characterizing multivariate-based patient profiles.
Ninety-eight Rome-diagnosed IBS patients completed the IBS-SSS and a single, global item of symptom severity (UCLA Symptom Severity Scale) at pretreatment baseline of an NIH funded clinical trial. A k-means cluster analyses were performed on participants symptom severity scores.
The IBS-SSS was not unidimensional. Exploratory cluster analyses revealed four common symptom profiles across five items of the IBS-SSS. One cluster of patients (25%) had elevated scores on pain frequency and bowel dissatisfaction, with less elevated but still high scores on life interference and low pain severity ratings. A second cluster (19%) was characterized by intermediate scores on both pain dimensions, but more elevated scores on bowel dissatisfaction. A third cluster (18%) was elevated across all IBS-SSS sub-components. The fourth and most common cluster (37%) had relatively low scores on all dimensions except bowel dissatisfaction and life interference due to IBS symptoms.
PRO endpoints and research on IBS more generally relying on multicomponent assessments of symptom severity should take into account the multidimensional structure of symptoms to avoid aggregation bias and to optimize the sensitivity of detecting treatment effects.
disease severity; questionnaire development; outcome research; health status indicators; rating scale; psychometric properties; global assessment
An article by Lu et al. in this issue of Value in Health addresses the mapping of treatment or group differences in disease-specific measures (DSMs) of health-related quality of life onto differences in generic health-related quality-of-life scores, with special emphasis on how the mapping is affected by the reliability of the DSM. In the proposed mapping, a factor analytic model defines a conversion factor between the scores as the ratio of factor loadings. Hence, the mapping applies to convert true underlying scales and has desirable properties facilitating the alignment of instruments and understanding their relationship in a coherent manner. It is important to note, however, that when DSM means or differences in mean DSMs are estimated, their mapping is still of a measurement error–prone predictor, and the correct conversion coefficient is the true mapping multiplied by the reliability of the DSM in the relevant sample. In addition, the proposed strategy for estimating the factor analytic mapping in practice requires assumptions that may not hold. We discuss these assumptions and how they may be the reason we obtain disparate estimates of the mapping factor in an application of the proposed methods to groups of patients.
cross-walk; HRQOL; mapping; reliability
In health technology assessment, decisions about reimbursement for new health technologies are largely based on effectiveness estimates. Sometimes, however, the target effectiveness estimates are not readily available. This may be because many alternative instruments measuring these outcomes are being used (and not all always reported) or an extended follow-up time of clinical trials is needed to evaluate long-term end points, leading to the limited data on the target clinical outcome. In the areas of highest priority in health care, decisions are required to be made on a short time scale. Therefore, alternative clinical outcomes, including surrogate end points, are increasingly being considered for use in evidence synthesis as part of economic evaluation.
To illustrate the potential effect of reduced uncertainty around the clinical outcome on the utility when estimating it from a multivariate meta-analysis.
Bayesian multivariate meta-analysis has been used to synthesize data on correlated outcomes in rheumatoid arthritis and to incorporate external data in the model in the form of informative prior distributions. Estimates of Health Assessment Questionnaire were then mapped onto the health-related quality-of-life measure EuroQol five-dimensional questionnaire, and the effect was compared with mapping the Health Assessment Questionnaire obtained from the univariate approach.
The use of multivariate meta-analysis can lead to reduced uncertainty around the effectiveness parameter and ultimately uncertainty around the utility.
By allowing all the relevant data to be incorporated in estimating clinical effectiveness outcomes, multivariate meta-analysis can improve the estimation of health utilities estimated through mapping methods. While reduced uncertainty may have an effect on decisions based on economic evaluation of new health technologies, the use of short-term surrogate end points can allow for early decisions. More research is needed to determine the circumstances under which uncertainty is reduced.
Bayesian analysis; health technology assessment; meta-analysis; multiple end points; rheumatoid arthritis; surrogate end points
To examine cost responsiveness and total costs associated with a simulated “value based” insurance design (VBID) for statin therapy in a Medicare population with diabetes.
Four-year panels constructed from the 1997–2005 Medicare Current Beneficiary Survey selected by self-report or claims-based diagnoses of diabetes in Year 1, and use of statins in Year 2 (N= 899). We computed number of 30-day statin prescription fills, out-of-pocket (OOP) and third party drug costs, and Medicare Part A and B spending.
Multivariate ordinary least squares regression models predicted statins fills as a function of OOP costs, and a generalized linear model with log link predicted Medicare spending as a function of number of fills, controlling for baseline characteristics. Estimated coefficients were used to simulate changes in fills associated with copayment caps from $25 to $1, and to compute changes in 3rd-party payments and Medicare cost offsets associated with incremental fills. Analyses were stratified by patient cardiovascular event risk.
A simulated OOP price of $25[$1] increased plan drug spending by $340[$794], and generated Medicare Part A/B savings of $262[$531]. Medicare Part A/B savings were greater for higher risk patients, generating a net savings for the plans.
Reducing statin copayments for Medicare beneficiaries with diabetes resulted in modestly increased use, and reduced medical spending. The VBID simulation strategy met financial feasibility criteria, but only for higher risk patients.
diabetes; Medicare; medication adherence; cost offsets
To describe rank reversal as a source of inconsistent interpretation intrinsic to indirect comparison (Bucher et al., 1997) of treatments and to propose best practice.
We prove our main points with intuition, examples, graphs, and mathematical proofs. We also provide software and discuss implications for research and policy.
When comparing treatments by indirect means and sorting them by effect size, three common measures of comparison (risk ratio, risk difference, and odds ratio) may lead to vastly different rankings.
The choice of risk measure matters when making indirect comparisons of treatments. The choice should depend primarily on the study design and conceptual framework for that study.
risk ratio; risk difference; odds ratio; indirect comparisons; risk
To develop a set of EQ-5D health state values for the Argentine general population.
Consecutive subjects attending six primary care centers in Argentina were selected based on quota sampling and interviewed using the EuroQol Group protocol for measurement and valuation of health studies. Initially respondents were randomly assigned a unique card set; however, to improve efficiency, subjects were later randomly assigned to one of three fixed sets of EQ-5D states. Using the VAS and TTO responses for these states, we estimated a valuation model using ordinary least squares regression clustered by respondent. Predicted values for EQ-5D health states are compared to published values for the United States.
Six hundred eleven subjects were interviewed by 14 trained interviewers, rendering 6,887 TTO and 6,892 VAS responses. The model had an R2 of 0.897 and 0.928 for TTO and VAS respectively. The mean absolute difference between observed and predicted values was 0.039 for TTO and 0.020 for VAS, each showing a Lin’s concordance coefficient above 0.98. United States and Argentine TTO predicted values were highly correlated (Pearson’s rho=0.963), though the average absolute difference was clinically meaningful (0.06), rejecting the US values for nearly two thirds of the states (62.8%). The Argentine population placed lower values on mild states and higher values on severe states.
This study provides an Argentine value set that could be used locally or regionally, with meaningful and significant differences with that of the US. Health policy in Latin America must incorporate local values for sovereignty and validity.
utility measurement; HRQOL; patient preference; cost effectiveness analysis
The EORTC QLQ-C30 is one of the most commonly used measures in cancer but in its current form cannot be used in economic evaluation as it does not incorporate preferences. We address this gap by estimating a preference-based single index for cancer from the EORTC QLQ-C30 for use in economic evaluation.
Factor analysis, Rasch analysis and other psychometric analyses were undertaken on a clinical trial dataset of 655 patients with Multiple Myeloma to derive a health state classification from the QLQ-C30 that is amenable to valuation. A valuation study was conducted of 350 members of the UK general population using ranking and time trade-off. A series of regression models were fitted to the data, including the episodic random utility model (RUM) to derive preference weights for the classification system.
The resulting health state classification system has 8 dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue and sleep disturbance, nausea, and constipation and diarrhoea) with 4 or 5 levels each. Mean and individual level additive multivariate regression models were estimated and compared. Mean absolute error ranges from 0.050 to 0.054 with no systematic errors. All models have few inconsistencies (0 to 2) in estimated preference weights.
It is feasible to derive a preference-based measure from the EORTC QLQ-C30 for use in economic evaluation, but this work needs to be extended to other countries and replicated across other conditions.
Preference-based measures; QALYs; EORTC QLQ-C30
It is well established that there are problems with the EQ-5D. This is in part due to the scoring methods used for the original UK EQ-5D (TTO) and in particular how negative-Time Trade Off (TTO) values were treated. [1–3] A revised scoring method has been published and this paper has used this to calculate utility estimates in an inflammatory arthritis cohort.
To examine the impact of a revised scoring system for the EQ-5D(UK) TTO on the utility estimates and compare these to estimates produced using the original scoring and the SF-6D. In the case of RA, to explore the impact of using different utility metrics on the on the ICER results of an economic model.
504 patients with inflammatory arthritis were rescored using a revised scoring system for the EQ-5D, which uses an episodic random utility model to deal with negative TTO values. Differences in utility scores were compared and the mapping coefficients were used in an economic model, to examine the impact on the ICER estimate.
In rheumatoid arthritis the overall change is less for the revised EQ-5D scoring than with the original EQ-5D (TTO) but greater than the SF-6D: EQ-5D UK −0.22 (95% CI −0.30, −0.15), revised EQ-5D UK −0.16 (95% CI −0.21, −0.10) and SF-6D −0.08 (95% CI −0.11, −0.05). A similar trend is seen in the psoriatic arthritis group. The economic model produced different ICERS, when different utility measures were used; EQ-5D (TTO) €42,402, SF-6D €111,788 and revised EQ-5D (TTO) €57,747.
In the context of inflammatory arthritis this article demonstrates that choice of utility measure may impact significantly on the output of the economic model and the subsequent reimbursement decision. In order to examine the heterogeneity between utility measures it may be useful to refit a cost effectiveness model using multiple metrics and produce a range of ICER estimates, to explore the uncertainty due to the choice of utility measure used.
To project the potential economic impact of pandemic influenza mitigation strategies from a societal perspective in the United States.
We use a stochastic agent-based model to simulate pandemic influenza in the community. We compare 17 strategies: targeted antiviral prophylaxis (TAP) alone and in combination with school closure as well as prevaccination.
In the absence of intervention, we predict a 50% attack rate with an economic impact of $187 per capita as loss to society. Full TAP is the most effective single strategy, reducing number of cases by 54% at the lowest cost to society ($127 per capita). Prevaccination reduces number of cases by 48% and is the second least costly alternative ($140 per capita). Adding school closure to full TAP or prevaccination further improves health outcomes, but increases total cost to society by approximately $2700 per capita.
Full targeted antiviral prophylaxis is an effective and cost-saving measure for mitigating pandemic influenza.
Influenza; Human Disease Outbreaks; Cost-Benefit Analysis; Economics; Pharmaceutical Models; Theoretical; Computer Simulation
To evaluate cost effectiveness of a socio-culturally adapted collaborative depression care program among low-income Hispanics with diabetes.
RESEARCH DESIGN AND METHODS
A randomized controlled trial of 387 diabetes patients (96.5% Hispanic) with clinically significant depression followed over 18 months evaluated the cost-effectiveness of the Multifaceted Diabetes and Depression Program (MDDP) aimed at increasing patient exposure to evidenced-based depression psychotherapy and/or pharmacotherapy in two public safety net clinics. Patient medical care costs and utilization were captured from Los Angeles County Dept. of Health Services claims records. Patient reported outcomes included SF-12 and PHQ-9-calculated depression-free days (DFDs).
Intervention patients had significantly greater SF-12 utility improvement from baseline compared to controls over the 18 month evaluation period (4.8%; P<.001) and a corresponding significant improvement in DFDs (43.0; P<.001). Medical cost differences were not statistically significant in OLS and log-transformed cost regressions. The average costs of the MDDP study intervention were $515 per patient. The program cost effectiveness averaged $4,053/QALY per MDDP recipient and was more than 90% likely to fall below $12,000/QALY.
Socio-culturally adapted collaborative depression care improved utility and quality of life in predominantly low income Hispanic diabetes patients and was highly cost effective.
depression; Diabetes-related complications; Direct care health costs; Cost-utility analysis; randomized clinical trial
effectiveness; evidence-based; hypertension; RECORD trial
Inverse probability of treatment weighted (IPTW) Kaplan-Meier estimates have been developed to compare two treatments in the presence of confounders in observational studies. Recently, stabilized weights were developed to reduce the influence of extreme IPTW weights in estimating treatment effects. The objective of this paper was to use adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests to examine the effect of a treatment which varies over time in an observational study.
In this paper, we propose stabilized weight (SW) adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests when the treatment is time-varying over the follow-up period. We applied these new methods in examining the effect of an anti-platelet agent, clopidogrel, on subsequent events, including bleeding, myocardial infarction, and death after a Drug-Eluting Stent was implanted into a coronary artery. In this population, clopidogrel use may change over time based on patients' behavior (e.g., non-adherence) and physicians' recommendations (e.g., end of duration of therapy). Consequently, clopidogrel use was treated as a time-varying variable.
We demonstrate that 1) the sample sizes at three chosen time points are almost identical in the original and weighted datasets, and 2) the covariates between patients on and off clopidogrel were well balanced after SWs were applied to the original samples.
The SW-adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests are useful in presenting and comparing survival functions for time-varying treatments in observational studies while adjusting for known confounders.
Observational study; Kaplan Meier estimates; Stabilized weights; Time-varying treatment; Stents
The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Roadmap initiative is a cooperative group program of research designed to develop, evaluate, and standardize item banks to measure patient-reported outcomes relevant across medical conditions. For adults, 11 domains have been developed in physical, mental, and social health.
The objective of the current study was to assess feasibility and construct validity of PROMIS item banks versus legacy measures in a observational study in systemic sclerosis (SSc).
Patients with SSc in a single academic center completed computerized adaptive technology (CAT) administered PROMIS item banks during the clinic visit and legacy domains (using paper-and-pencil). The construct validity of PROMIS items was evaluated by examining correlations with corresponding legacy measures using multitrait-multimethod analysis.
Participants consisted of 143 SSc patients with an average age of 51.5 years; 71% were female and 68% were Caucasian. The average number of items completed for each CAT-administered item bank ranged from 5 to 8 (69 CAT items per patient), and the average time to complete each CAT-administered item bank ranged from 48 seconds to 1.9 minutes per patient (average time= 11.9 minutes/per patient for 11 banks). All correlations between PROMIS domains and respective legacy measures were large and in the hypothesized direction (ranged from .61 to .82).
Our study supports the construct validity of the CAT-administered PROMIS item banks and shows that they can be administered successfully in a clinic with support staff. Future studies should assess the feasibility of PROMIS item banks in a busy clinical practice
Systemic sclerosis; PROMIS; health-related quality of life; construct validity
Health state valuation exercises can be conducted online, but the quality of data generated is unclear.
To investigate whether responses to binary choice health state valuation questions differ by administration mode: online versus face to face.
Identical surveys including demographic, self-reported health status, and seven types of binary choice valuation questions were administered in online and computer-assisted personal interview (CAPI) settings. Samples were recruited following procedures employed in typical online or CAPI studies. Analysis included descriptive comparisons of the distribution of responses across the binary options and probit regression to explain the propensity to choose one option across modes of administration, controlling for background characteristics.
Overall, 422 (221 online; 201 CAPI) respondents completed a survey. There were no overall age or sex differences. Online respondents were educated to a higher level than were the CAPI sample and general population, and employment status differed. CAPI respondents reported significantly better general health and health/life satisfaction. CAPI took significantly longer to complete. There was no effect of the mode of administration on responses to the valuation questions, and this was replicated when demographic differences were controlled.
The findings suggest that both modes may be equally valid for health state valuation studies using binary choice methods (e.g., discrete choice experiments). There are some differences between the observable characteristics of the samples, and the groups may differ further in terms of unobservable characteristics. When designing health state valuation studies, the advantages and disadvantages of both approaches must be considered.
CAPI; health state valuation; online
The Commonwealth of Massachusetts increased the copayment for prescription drugs by $1.50 for Medicaid (MassHealth) beneficiaries in 2003. We sought to determine the likely health outcomes and cost shifts attributable to this copayment increase using the example of inhaled corticosteroids (ICS) use among adult asthmatic Medicaid beneficiaries.
We compared the predicted costs and health outcomes projected over a 1-year time horizon with and without the increase in copayment from the perspective of MassHealth, providers, pharmacies, and MassHealth beneficiaries by employing decision analysis simulation model.
In a target population of 17,500 adult asthmatics, increased copayments from 50¢ to $2.00 would result in an additional 646 acute events per year, caused by increased drug nonadherence. Annual combined net savings for the state and federal governments would be $2.10 million. Projected MassHealth savings are attributable to both decreased drug utilization and lower pharmacy reimbursement rates; these more than offset the additional costs of more frequent acute exacerbations. Pharmacies would lose $1.98 million in net revenues, MassHealth beneficiaries would pay an additional $0.28 million, and providers would receive additional $0.16 million.
Over its first year of implementation, increase in the prescription drug copayment is expected to produce more frequent acute exacerbations among asthmatic MassHealth beneficiaries who use ICS and to shift the financial burden from government to other stakeholders.
asthma; copayment; medicaid; prescription drug
Computed tomography colonography (CTC) is an alternative diagnostic test to colonoscopy for colorectal cancer and polyps. The aim was to determine test characteristics important to patients and to examine trade-offs in attributes that patients are willing to accept in the context of diagnosis of colorectal cancer.
A discrete choice study to assess preferences of patients with clinical indications suspicious of colorectal cancer who experienced both CTC and colonoscopy as part of a diagnostic accuracy study in South Australia. Results were analysed using a mixed logit model and presented as odds ratios (OR) for preferring CTC over colonoscopy
Colonoscopy was preferred over CTC as the need for a second procedure after CTC increased (odds ratio of preferring CTC to colonoscopy=0.013), as the likelihood of missing cancers or polyps increased (OR of CTC: colonoscopy=0.62) and as CTC test cost increased (OR of CTC: colonoscopy=0.65–0.80). CTC would be preferred to colonoscopy if a minimal bowel preparation was available (OR=1.7). Some patients were prepared to trade-off the diagnostic and therapeutic advantage of colonoscopy for a CTC study with a less intensive bowel preparation. Preferences also varied significantly with sociodemographic characteristics.
Despite CTC often being perceived as a preferred test, this may not always be the case. Informed decision making for diagnostic tests for colorectal cancer should include discussion of the benefits, downsides and uncertainties associated with alternative tests, as patients are willing and able to make trade-offs between what they perceive as the advantages and disadvantages of these diagnostic tests.
discrete choice experiments; patient preference; colorectal cancer; colonoscopy; CT colonography
Limited studies consider the effect of differential item functioning (DIF) on health-related quality of life (HRQOL) comparisons between ill and health children. The objective is to assess DIF and compare HRQOL between children with special health care needs (CSHCN) and children without needs.
Data were collected from 1195 families of children enrolled in Florida’s public insurance programs. HRQOL was measured using physical, emotional, social, and school functioning of the PedsQL. We identified CSHCN using the CSHCN Screener and assessed DIF related to CSHCN using a multiple group-multiple indicator-multiple cause (MG-MIMIC) method. We assessed the impact of DIF by examining expected item/test scores and item/test information function. We tested the discrepancy between underlying HRQOL scores of both groups before and after DIF calibration (allowing parameters of DIF items to be different and DIF-free items to be the same across both groups).
Two (25%) and 3 items (60%) of physical and school functioning, respectively, were identified with non-uniform DIF, and two items (40%) of social functioning were identified with uniform DIF. Expected item/test scores and item/test information function suggest the impact of DIF is minimal. Before DIF calibration, HRQOL in CSHCN was more impaired than children without needs (effect size −1.04, − 0.74, −0.96, and −0.98 for physical, emotional, social and school functioning, respectively). After DIF calibration, the discrepancy was increased slightly.
Although 30% of items in the PedsQL were identified with DIF related to CSHCN and children without needs, the impact of DIF is minimal.
Children; differential item functioning; health-related quality of life; item response theory
Clopidogrel’s effectiveness is likely reduced significantly for prevention of thrombotic events after acute coronary syndrome (ACS) in patients exhibiting a decreased ability to metabolize clopidogrel into its active form. A genetic mutation responsible for this reduced effectiveness is detectable by genotyping. Ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. In 2011, clopidogrel will lose its patent protection and likely will be substantially less expensive than ticagrelor.
To determine the cost-effectiveness of ticagrelor compared with a genotype-driven selection of antiplatelet agents.
A hybrid decision tree/Markov model was used to estimate the 5-year medical costs (in 2009 US$) and outcomes for a cohort of ACS patients enrolled in Medicare receiving either genotype-driven or ticagrelor-only treatment. Outcomes included life years and quality-adjusted life years (QALYs) gained. Data comparing the clinical performance of ticagrelor and clopidogrel were derived from the Platelet Inhibition and Patient Outcomes trial.
The incremental cost-effectiveness ratio (ICER) for universal ticagrelor was $10,059 per QALY compared to genotype-driven treatment, and was most sensitive to the price of ticagrelor and the hazard ratio for death for ticagrelor compared with clopidogrel. The ICER remained below $50,000 per QALY until a monthly ticagrelor price of $693 or a 0.93 hazard ratio for death for ticagrelor relative to clopidogrel. In probabilistic analyses, universal ticagrelor was below $50,000 per QALY in 97.7% of simulations.
Prescribing ticagrelor universally increases quality-adjusted life years for ACS patients at a cost below a typically accepted threshold.
acute coronary syndrome; clopidogrel; ticagrelor; cost-benefit analysis; secondary prevention
The objective of this analysis was to estimate costs for lung cancer care and evaluate trends in the share of costs that are the responsibility of Medicare beneficiaries.
SEER-Medicare data from 1991–2003 on n=60,231 lung cancer patients were used to estimate monthly and patient-liability costs for clinical phases of lung cancer care (pre-diagnosis, staging, initial, continuing, and terminal), stratified by treatment, stage, and non- vs. small cell lung cancer. Lung cancer-attributable costs were estimated by subtracting each patient's own pre-diagnosis costs. Costs were estimated as the sum of Medicare reimbursements (payments from Medicare to the service provider), co-insurance reimbursements, and patient-liability costs (deductibles and `co-pays' that are the patient's responsibility). Costs and patient-liability costs were fit with regression models to compare trends by calendar year, adjusting for age at diagnosis.
For a 72-year old diagnosed with lung cancer in 2000, monthly costs in the first 6 months of care ranged from $2,687 (no active treatment) to $9,360 (chemo-radiotherapy), and varied by stage at diagnosis and histologic type. Patient-liability costs represented up to 21.6% of care costs and increased over the period 1992–2003 for most stage and treatment categories, even when care costs decreased or remained unchanged. The greatest monthly patient liability was incurred by chemo-radiotherapy patients ranging across stages from $1,617 to $2,004 per month.
Costs for lung cancer care are substantial and Medicare beneficiaries are responsible for an increasing share of the cost.
Lung cancer; Cost Analysis; Medicare; Treatment Costs
This review examines generic preference-based measures and their ability to reflect health-related quality of life in patients with visual disorders.
A systematic search was undertaken to identify clinical studies of patients with visual disorders where health state utility values were measured and reported. Data were extracted to assess the validity and responsiveness of the measures. A narrative synthesis of the data was undertaken due to the heterogeneity between different studies.
There was considerable heterogeneity in the 31 studies identified in terms of patient characteristics, visual disorders, and outcomes reported. Vision loss was associated with a reduction in scores across the preference-based measure, but the evidence on validity and responsiveness was mixed. The EQ-5D health-related assessment instrument's performance differed according to condition, with poor performance in age-related macular degeneration (AMD) and diabetic retinopathy. The more limited evidence on the HUI-3 instrument found it performed best in differentiating between severity groups of patients with glaucoma, AMD, cataracts, and diabetic retinopathy. One study reported data on the SF-6D instrument and showed it was able to differentiate between patients with AMD.
The performance of the EQ-5D in visual disorders was mixed. The HUI-3 seemed to perform better in some conditions, but the evidence on this and SF-6D is limited. More head to head comparisons of these three measures are required. The new five-level version of EQ-5D may do better at the milder end of visual function.
Health-related quality of life; quality of life; QALYs; utilities; vision
The US Centers for Disease Control and Prevention (CDC) recently revised their HIV screening guidelines to promote testing and earlier entry to care. Prior analyses have examined the policy’s cost-effectiveness but have not evaluated its impact on government budgets.
We used a simulation model of HIV screening, disease, and treatment to determine the budget impact of expanded HIV screening to US government discretionary, entitlement, and testing programs. We estimated total and incremental testing and treatment costs over a five-year time horizon under current and expanded screening scenarios. We used CDC estimates of HIV prevalence and annual incidence, and considered variations in screening frequency, test return rates, linkage to care, test characteristics, and eligibility for government screening and treatment programs.
Under current practice, 177,000 new HIV cases will be identified over five years. Expanded screening will identify an additional 46,000 cases at an incremental five-year cost of $2.7 billion. The financial burden of expanded HIV screening will fall disproportionately on discretionary programs that fund care for newly identified patients and will not be offset by entitlement program savings. Testing will represent a small proportion (18%) of the total budget increase. Costs are sensitive to the frequency of screening and the proportion linked to care.
The expanded HIV screening program will have a large downstream impact on government programs that fund HIV care. Expanded HIV screening will not meet early treatment goals unless government programs have sufficient budgets to expand testing and provide care for newly-identified cases.
Self-versus proxy- perspectives may produce different results that are important for clinical decision-making and for assessing outcomes in research studies. We examined differences in child versus parent-report of the child's health-related quality of life (HRQOL) in a large prospective, community-based study of newly diagnosed childhood epilepsy that included children with epilepsy (case) and sibling controls.
HRQOL was assessed 8–9 years after initial diagnosis of epilepsy in a subset of 143 case-control matched pairs using the Child Health Questionnaire (CHQ), a generic HRQOL measure with child (CHQ-CF87) and parent (CHQ-PF50) versions.
There were no significant differences between self-reported case and sibling control HRQOL scores on 9 of 11 scales or 2 global-items. However, parent ratings were significantly better (higher HRQOL) for sibling controls compared to epilepsy cases on 10 of 12 scales, global behavior and general health items, and the physical and psychosocial summary scores (p≤0.05). Parent-child agreement was low for cases and controls (kappa 0.27–0.33) for three single-item questions with the same wording on parent and child versions. Parent ratings of the case’s HRQOL were often significantly associated with 5-year remission status and current anti-epileptic drug use, but the case’s self-reported HRQOL scores were not. In contrast, current pharmacoresistance was often associated with the child and parent ratings of the child’s HRQOL.
Children with epilepsy report HRQOL that is comparable to that of sibling controls while parents rate children with epilepsy as having lower HRQOL than sibling controls. Measuring outcomes in studies of this population should incorporate both perspectives.
child and adolescent health; epilepsy; outcomes research; health-related quality of life (HRQOL); patient-reported outcomes; proxy; Child Health Questionnaire (CHQ)
Generic health status measures such as the short form health survey (SF-36) and EuroQol-5D (EQ-5D) are increasingly being used to inform health policy. They are claimed to be applicable across disease areas and have started to be used within mental health research. This review aims to assess the construct validity and responsiveness of four generic health status measures in schizophrenia, including the preference-based SF-6D and EQ-5D.
A systematic review of the literature was undertaken. Ten databases were searched from inception to August 2009 and reference lists scrutinized to identify relevant studies. Studies were appraised and data extracted. A narrative synthesis was performed of the evidence on construct validity including known groups validity (detecting a difference in health-related quality of life (HRQL) scores between two different groups such as samples from the general population and people with schizophrenia), convergent validity (strength of association between generic HRQL and other measures (e.g., symptom or functional), and responsiveness. Responsiveness was considered by: 1) differences in generic HRQL measure scores in responders/non-responders and 2) correlation between changes on generic HRQL measures and changes in specific measures obtained from patients and clinicians.
Thirty-three studies were identified that provided data on the validity and/or responsiveness of the instruments. Most of the evidence concerns the SF-36 and EQ-5D, and for these instruments there was evidence for known group validity. The evidence for convergent validity and responsiveness was mixed, with studies presenting contradictory results.
Although the evidence base is limited in a number of important respects, including problems with the measures used to develop constructs in the validation studies, it is sufficient to raise doubts about the use of generic measures of health like the EQ-5D and SF-36 in patients with schizophrenia.
EQ-5D; generic health status measures; health-related quality of life; preference-based measures; quality of life; schizophrenia; SF-36; SF-12; SF-6D
Decisions about the use of new technologies in health care are often based on complex economic models. Decision makers frequently make informal judgments about evidence, uncertainty, and the assumptions that underpin these models.
Transparent interactive decision interrogator (TIDI) facilitates more formal critique of decision models by decision makers such as members of appraisal committees of the National Institute for Health and Clinical Excellence in the UK. By allowing them to run advanced statistical models under different scenarios in real time, TIDI can make the decision process more efficient and transparent, while avoiding limitations on pre-prepared analysis.
TIDI, programmed in Visual Basic for applications within Excel, provides an interface for controlling all components of a decision model developed in the appropriate software (e.g., meta-analysis in WinBUGS and the decision model in R) by linking software packages using RExcel and R2WinBUGS. TIDI's graphical controls allow the user to modify assumptions and to run the decision model, and results are returned to an Excel spreadsheet. A tool displaying tornado plots helps to evaluate the influence of individual parameters on the model outcomes, and an interactive meta-analysis module allows the user to select any combination of available studies, explore the impact of bias adjustment, and view results using forest plots. We demonstrate TIDI using an example of a decision model in antenatal care.
Use of TIDI during the NICE appraisal of tumor necrosis factor-alpha inhibitors (in psoriatic arthritis) successfully demonstrated its ability to facilitate critiques of the decision models by decision makers.
bias adjustment; decision model; interactive; meta-analysis; RExcel; software; TIDI
The decrement in utility attributable to side effects from combination antiretroviral therapy (CART) is unknown and likely to influence clinical decisions regarding CART initiation and cost-effectiveness.
To quantify the decrement in utility attributable to side effects from CART.
We estimated SF-6D utilities (quality-of-life weights on a scale from 0.29 [worst possible health] to 1.00 [perfect health]) from SF-12 scores among patients with HIV in the Veterans Aging Cohort Study by using a published and validated conversion algorithm. We then compared utilities among patients who: 1) did not have bothersome symptoms while taking CART; 2) had bothersome symptoms that they thought might be due to CART; and 3) had bothersome symptoms that they were confident were due to CART; we controlled for other characteristics known to influence quality of life and stratified analyses by CD4 count.
Among 1864 patients with available data, symptoms perceived to be attributable to CART were associated with a mean (95% confidence interval) decrement in utility of 0.06 (0.05, 0.08) points in univariate analyses and 0.08 (0.06, 0.10) in multivariable analyses, clinically significant differences that are comparable to utility decrements reported for partial impotence or mild angina. Other significant predictors of changes in SF-6D utilities were hazardous alcohol consumption, recent drug use, cigarette smoking, homelessness, and African American race (R2 = 0.12). Stratifying by CD4 count, symptoms attributable to CART side effects decreased utility by 0.03 to 0.08 points.
Symptoms perceived to be related to CART are associated with a substantial decrement in utility.
cost-effectiveness analysis; quality of life; utility assessment