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Future Issues:

Value in Health 2014 Volume 17 Issue 4


ViH-09-2013-0396-COM.R2 Questioning patient subgroups for benefit assessment: Challenging the German G-BA approach Jörg Ruof, MD, MPH, MBA, Charalabos-Markos Dintsios, PhD, MPH, Friedrich Wilhelm Schwartz, MD

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ViH-03-2013-0109-OM.R2 Long-Term Humidification Therapy is Cost Effective for Patients with Moderate or Severe COPD or Bronchiectasis Richard J. Milne, Hans Hockey, Harry Rea

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Objective. To establish the cost effectiveness of long term humidification therapy (LTHT) added to usual care for patients with moderate or severe COPD.
Methods. Resource usage in a 12-month clinical trial of LTHT was estimated from hospital records, patient diaries and the equipment supplier. Health state utility values were derived from the St Georges Respiratory Questionnaire (SGRQ) total score. All patients who remained in the trial for 12 months and who had at least 90 days of diary records were included (87/108).
Results. Clinical costs were $NZ3973 (95% CI $1614, $6332) for the control group and $NZ3331 (95%CI $948, $6920) for the intervention group. The mean health benefit per patient was minus 6.9 SGRQ units (95%CI -13.0, -7.2; p<0.05) or +0.0678 QALYs (95% CI 0.001, 0.135). With the intervention costing $NZ2059, the mean cost per QALY was $20,902 ($US17,394) and the bootstrap median was $NZ19,749 (2.5th percentile -$40,923, 97.5th percentile $221,275). At a willingness to pay (WTP) threshold of $NZ30,000, the probability of cost effectiveness was 61% ranging from 49% to 72% as the cost of LTHT was varied by ±30%. At a WTP of $20,000 the probability was 49% (range 34% to 61%).
Conclusions. LTHT is moderately cost effective for patients with moderate to severe COPD or bronchiectasis at a WTP threshold that is acceptable for public funding of medicines in NZ. These findings must be interpreted with caution because of the modest size of the clinical study, necessary lack of blinding in the clinical trial and uncertainty in estimating health state utility from the SGRQ.

ViH-07-2013-0281-OM.R2 A retrospective, observational study of patient outcomes for critically ill patients receiving parenteral nutrition Glenn Magee, Gary Zaloga, Robin S Turpin, Myrlene Sanon

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Objective: Evaluate healthcare related utilization for critically ill patients receiving parenteral nutrition (PN) administered via premixed multi-chamber bag (MCB) or compounded solutions (COM).
Design: A retrospective database analysis of critically ill patients (ICU stay > 3 days) receiving PN & discharged between Jan 1, 2010 and June 30, 2011 using the Premier Hospital Database. Patients were identified as receiving MCB or COM based on product description codes. Primary outcomes were length of stay (LOS) and total costs Comorbidities and clinical outcomes were identified using ICD-9 diagnosis codes. All costs reported were for inpatient services only. MCB and COM patients were matched on key patient and hospital characteristics using a propensity score methodology. Multivariate regression models for cost and length of stay used generalized linear models with a log link and gamma distribution.
Results: 42,631 patients met the inclusion criteria (MCB=5,679; COM=36,952) and the final matched population included 3,559 patients from each cohort. Baseline patient and hospital characteristics were well matched between groups. Adjusted multivariate models demonstrated a small difference between groups for length of stay (MCB=9.40 days vs COM=9.65 days, p = 0.014). Additionally, MCB patients incurred approximately 9.1% less in total costs (MCB=$37,790 vs COM=$41,569, p < 0.001).
Conclusions: Overall, patients receiving MCB and COM experienced similar length of stay, though MCB patients had significantly lower overall costs. Interpretation of the study findings are subject to several limitations and additional studies that include explicit identification of the method for compounding are needed.

ViH-07-2013-0286-OM.R2 Cost-effectiveness of second-generation antipsychotics for the treatment of schizophrenia Taehwan Park, MS Pharm, PhD Candidate, Karen M. Kuntz, ScD

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Objective: To compare the cost-effectiveness of alternate treatment strategies using second-generation antipsychotics (SGAs) for patients with schizophrenia.
Methods: We developed a Markov model to estimate the costs and quality-adjusted life years (QALYs) for different sequences of treatments for 40-year-old patients with schizophrenia. We considered first-line treatment with one of the four SGAs: olanzapine (OLZ), risperidone (RSP), quetiapine (QTP), and ziprasidone (ZSD). Patients could switch to another of these antipsychotics as second-line therapy, and only clozapine (CLZ) was allowed as third-line treatment. We derived parameter estimates from the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study and published sources.
Results: The ZSD-QTP strategy (first-line treatment with ZSD, change to QTP if ZSD is discontinued, and switch to CLZ if QTP is discontinued) was most costly while yielding the greatest QALYs, with an incremental cost-effective ratio (ICER) of $542,500 per QALY gained compared with the ZSD-RSP strategy. However, the ZSD-RSP strategy had an ICER of $5,200/QALY gained versus the RSP-ZSD strategy and had the greatest probability of being cost-effective given a willingness-to-pay threshold between $50,000 and $100,000 per QALY. All other treatment strategies were more costly and less effective than another strategy or combination of other strategies. Results varied by different time horizons adopted.
Conclusions: The ZSD-RSP strategy was most cost-effective at a willingness-to-pay threshold between $5,200 and $542,500 per QALY. Our results should be interpreted with caution because they are based largely on the CATIE trial with potentially limited generalizability to all patient populations and doses of SGAs used in practice.
ViH-08-2013-0347-OM.R1 Comparative Cost Analysis of Clinical Reminder For HIV Testing at the Veterans Affairs Healthcare System Leilani Hernandez, MPH, Heidi Yang, MPH, Matthew Bidwell Goetz, MD,  and Kee Chan, PhD

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Objective: To estimate the cost and health outcomes associated with a new HIV testing strategy that utilizes routine-based clinical reminders.
Study Design: We conducted an economic analysis of 1) traditional pre-test/post-test counseling, 2) counseling and a new clinical reminders system and 3) only clinical reminder in the veterans health care system.
Methods: A payer-perspective decision model was conducted to calculate the 1-year budget impact of three HIV testing strategies. Parameter values were obtained from the literature, including patients’ probability of accepting test, and costs associated with HIV testing procedures. De-identified patient data, including total population screened and number of new HIV cases, was collected from one clinic in Los Angeles, CA, from August 2004 to December 2011. Annual total costs and costs per new case were calculated based on parameter values and patient data. Sensitivity analyses were conducted to evaluate the robustness of the critical variable on costs.
Results: The total cost of clinical reminder system with pre-test counseling was $81,726 over one year compared to $109,208 for traditional HIV testing. Under a clinical reminder system with no pre-test counseling, number of HIV tests performed and number of new diagnoses increased for that year. In addition, cost per new diagnoses was the lowest.
Conclusions: The clinical reminder system can reduce the cost per cased identified and promote better performance of HIV testing compared with traditional HIV testing. The fundamental decision model can be used for hospital facilities outside the Veteran Affairs adopting a similar program for improving HIV testing rate.


ViH-05-2013-0212-OM.R1 Development of a Scale to Assess Performance Following Primary Total Knee Arthroplasty Lewis, Sandy BSN, RN, Price Mark, MA, MEd, Dwyer, Kimberly A., PhD, CCRA, O'Brien, Seamus, PhD, BSc, (Hons), Heekin, R. David, MD, FACS, Yates, Piers J., MBBS, BSc, FRCS, FRACS, FAOrthA, Beverland, David, MD, FRCS, Mordin, Margaret, MS

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Objective: Quantitative assessment of postsurgical knee motion provides sensitive measurements, but results are technical and may not be meaningful to patients. While several knee-specific instruments exist, no patient-reported outcome (PRO) measure correlates function with improved stability, motion, satisfaction, and confidence. Therefore, the study objective was to address both limitations by developing a PRO measure to assess the phenomenon of a “normal” knee following primary total knee arthroplasty (TKA).
Methods: A draft conceptual model linking the impact of clinical mechanics to hypothesized functional outcomes was generated following a literature review of available assessment tools. Participants aged 18 to 80 years having undergone TKA within the past 10 to 18 months were identified and screened by clinical sites to participate in phase 1 focus groups or phase 2 in-depth interviews. Participants were asked to describe their TKA experiences, including how their knee feels now, followed by cognitive debriefing of Patient’s Knee Implant Performance (PKIP) draft items.
Results: Phase 1 results indicated that concepts of confidence, stability, and satisfaction in patients’ replacement knee when performing certain activities were distinct and important in the patients’ assessment of their TKA. Phase 2 efforts yielded a final version of the PKIP measure containing nine items assessing the broader concepts of stability, confidence, and satisfaction in association with activities. Pre- and postsurgical versions of the measure were created.
Conclusions: Results of this qualitative study support use of the PKIP as a complementary PRO measure to assess performance following primary TKA. Psychometric evaluation of the PKIP is planned.

ViH-07-2013-0277-OM.R1 The Impact of Differences between Patient and General Population EQ-5D-3L Values on the Mean Tariff Scores of Different Patient Groups Matthew Little, MSc Peter Reitmeir, PhD, Annette Peters, PhD Reiner Leidl, PhD

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Background: Health states can be valued by those who currently experience a health state (EHS) or by the general public, who value a set of given health states (GHS), which are described to them. There has been debate over which method is more appropriate when making resource allocation decisions. This paper informs this debate by assessing whether differences between these methods have an impact on the mean EQ-5D-3L tariff scores of different patient groups.
Methods: The European tariff based on GHS valuations was compared with a German EHS tariff. Comparison was made in the context of EQ-5D-3L health states describing a number of diagnosed chronic diseases (stroke, diabetes, MI and cancer) taken from the Cooperative Health Research in the Augsburg Region (KORA) population surveys. Comparison was made of both the difference in weighting of the dimensions of the EQ-5D-3L and differences in mean tariff scores for patient groups.
Results: Weighting of the dimensions of the EQ-5D-3L were found to be systematically different. The EHS tariff gave significantly lower mean scores for most, but not all patient groups despite tariff scores being lower for 213 out of 243 EQ-5D-3L health states using the GHS tariff. Differences were found to vary between groups with a largest change in difference being 5.45 in the multiple stoke group.
Conclusion: The two tariffs have systematic differences which in certain patient groups could drive the results of an economic evaluation. Therefore the choice as to which is used may be critical when making resource allocation decisions.

ViH-08-2013-0351-OM.R1 Construct Validity of the Swedish version of the Revised Piper Fatigue Scale in an oncology sample – a Rasch analysis Åsa Lundgren-Nilsson, Anna Dencker, PhD, Sofie Jakobsson, PhD, Charles Taft, Alan Tennant

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Objectives: Fatigue is a common and distressing symptom in cancer patients due to both the disease and the treatments of it. The concept of fatigue is multidimensional and includes both physical and mental components. The 22-item Revised Piper Fatigue Scale (RPFS) is a multidimensional instrument developed to assess cancer-related fatigue. This study reports on the construct validity of the Swedish version of the RFPS from the perspective of Rasch measurement.
Methods: The Swedish version of the RPFS was answered by 196 cancer patients fatigued after four to five weeks of curative radiation therapy. Data from the scale were fitted to the Rasch measurement model. This involved testing a series of assumptions, including the stochastic ordering of items, local response dependency, and unidimensionality. A series of fit statistics were computed, Differential Item Functioning (DIF) was tested and local response dependency was accommodated through testlets.
Results: The Behavioral, Affective and Sensory domains all satisfied the Rasch model expectations. No DIF was observed and all domains were found to be unidimensional. The Mood/Cognitive scale failed to fit the model and substantial multidimensionality was found. Splitting the scale between Mood and Cognitive items resolved fit to the Rasch model and new domains were unidimensional without DIF.
Conclusions: The current Rasch analyses add to the evidence of measurement properties of the scale and show that the RPFS has good psychometric properties and works well to measure fatigue. However, the original four-factor structure was not supported.

ViH-08-2013-0326-OM.R2 A Study of the Relationship Between Health and Subjective Well-being in Parkinson’s Disease Patients Patricia Cubí-Mollá, PhD, Jane de Vries, MSc Nancy Devlin, PhD

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Objectives: Governments are turning their attention to evidence on subjective measures of well-being to inform policy decisions. In the context of health, there is therefore growing interest in understanding how measures of health-related quality of life relate to subjective well-being, and whether subjective well-being could provide a basis for resource allocation decisions in the future. This study investigates the relationship between health-related quality of life, as measured by EQ-5D, and subjective well-being in Parkinson’s disease.
Methods: A paper questionnaire including EQ-5D, four key subjective well-being questions taken from the Integrated Household Survey in England and other demographic details was distributed to people with Parkinson’s disease in the UK. Responses were used to estimate multiple regression models explaining subjective well-being using the EQ-5D Index (UK weights), EQ-5D dimensions and EQ-VAS and patient socio-demographic characteristics.
Results: A total of 199 responses were received. Combining EQ-VAS and EQ-5D dimensions, especially anxiety/depression and, to a lesser extent, mobility, yielded the best-fitting models (adjusted R2 range 0.36-0.53). Parkinson’s disease patients living in care homes report lower levels of subjective well-being than those living alone. These effects are not captured by the health-related quality of life measures in the analysis.
Conclusions: Usual health-related quality of life measures can partially explain different well-being dimensions, yet they fail to capture part of the broader impact of disease on subjective well-being. Further empirical research into the relationship between subjective well-being and EQ-5D longitudinally, and in different disease areas, is required, and further standardisation of subjective well-being measures is recommended.

VIH-2013-17R1 A review of FDA Warning Letters and Notices of Violation issued for Patient Reported Outcomes promotional claims between 2006-2012 Tara Symonds; Claire Hackford; Lucy Abraham

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Objective: To ascertain the frequency and types of patient reported outcome (PRO) violations made in US pharmaceutical promotional materials between 2006 and 2012 and determine if there were increases in violation warnings following issuance of the Food and Drug Administration(FDA) draft and final PRO Guidance. Method: All warning letters (WL) or notices of violation (NOV) issued by the FDA's Office of Prescription Drug Promotion (OPDP) were reviewed for PRO violations (n=213). Each letter containing a PRO violation was reviewed to determine the type of violation: (1) PRO measure not fit for purpose; (2) Study design/Interpretation of results; (3) Statistical analysis; (4) No Treatment benefit. Results: 41 (19%) letters contained information about PRO infringements. Noticeable spikes in letters were shown in 2007 (37%) and 2010 (31%) post the issuance of the draft and final PRO Guidance respectively. The most common violation was PRO measure not fit for purpose (54%), specifically: use of individual items (45%), insufficient evidence of content validity (36%), and broadening of the claim beyond what the PRO measures (27%). Issues with Study design/interpretation of results were also high (49%), particularly broadening of claim beyond what was measured in the trial (55%), and no PRO measure used (50%). Conclusion: A fifth of letters issued to companies contained PRO violations with most related to poor selection of the PRO measure used or trying to broaden the claim. More guidance from OPDP about what is considered 'substantial evidence' in this area could help reduce the number of letters issued.


ViH-02-2013-0066-OM.R2 A Discrete Choice Experiment to Estimate Breast Cancer Patients’ Preferences and Willingness-to-Pay for Prophylactic Granulocyte Colony-Stimulating Factors Phaedra Johnson MS, Tim Bancroft PhD, Richard Barron MS, Jason Legg PhD, Xiaoyan Li PhD, Holly Watson MS, Arash Naeim MD, Angela Watkins MA, Deborah A Marshall PhD

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Objectives: Rising out-of-pocket costs for cancer patients has increased shared decision making. Clinical guidelines recommend prophylactic granulocyte colony-stimulating factor (G-CSF) for patients receiving chemotherapy with a ≥20% risk of febrile neutropenia (FN). A discrete choice experiment (DCE) was conducted to explore breast cancer patients’ preferences and willingness-to-pay (WTP) for prophylactic G-CSF to decrease the risk of chemotherapy-induced FN.
Methods: An online DCE-questionnaire of a national United States convenience sample of self-reported breast cancer patients with prior chemotherapy treatment was conducted. Sixteen paired G-CSF treatment scenarios, each with four attributes (risk of disruption to chemotherapy schedule due to low white blood cell counts, risk of developing an infection requiring hospitalization, frequency of administration, and total out-of-pocket cost) were presented with a follow-up “no treatment” option. Participant preferences and WTP out-of-pocket were estimated by logistic regression.
Results: Participants (n=296) preferred G-CSF regimens with lower out-of-pocket costs, lower risk of chemotherapy disruption, lower risk of infection, and greater convenience (one G-CSF injection per chemotherapy cycle). Participants WTP was $1,076 out-of-pocket per cycle to reduce the risk (high to low) of disrupting their chemotherapy schedule, $884 per cycle to reduce the risk (24% (high) to 7% (low)) of infection, and $851 per cycle to decrease (11 to 1) the number of G-CSF injections per cycle.
Conclusions: Participants highly valued specific features of prophylactic G-CSF treatment including: maintaining their chemotherapy schedule, lowering their risk of infection, and reducing the number of injections. Physicians should consider patient preferences to inform the best treatment choices for individual patients.

ViH-08-2013-0313-OM.R1 Patient preferences for treatment of low back pain – a discrete choice experiment Mirja Elisabeth Kløjgaard, PhD Student, Claus Manniche, Lillebaelt, Middelfart, Line Bjørnskov Pedersen, Mickael Bech, Rikke Søgaard

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Objective: Back pain imposes a substantial economic and social burden, and treatment decisions are distorted by conflicting evidence. Thus, it is important to include patient preferences in decision- and policy-making. The paper aims to contribute to the understanding of patient preferences in relation to the choice of treatment for low back pain. Methods: A discrete choice experiment was conducted with consecutive patients referred to a regional spine centre. The respondents (n=348) were invited to respond to a choice of two hypothetical treatment options and an opt-out option. The treatment attributes included the treatment modality, the risk of relapse, the reduction in pain and the expected increase in the ability to perform activities of daily living. In addition, the wait time to achieve the treatment effect was used as a payment vehicle. Mixed logit models were created to perform analysis. Sub-group analysis, dividing respondents into socio-demographic and disease-related categories, further explored the willingness to wait. Results: Respondents assigned positive utilities to positive treatment outcomes and disutility to higher risks and longer waits for effects of treatment and to surgical interventions. The model captured significant heterogeneity within the sample for the outcomes of pain reduction and the ability to pursue activities of daily living and for the treatment modality. The sub-group analysis revealed differences in the willingness to wait, especially with regard to treatment modality, the level of pain experienced at the time of data collection and the respondents’ preferences for surgery.

ViH-07-2013-0302-OM.R2 A comparison of Hong Kong and United Kingdom SF-6D health states valuations using a nonparametric Bayesian method Samer A Kharroubi, John E Brazier, Sarah McGhee

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Background: There is interest in the extent to which valuations of health may differ between different countries and cultures, but few studies have compared preference values of health states obtained in different countries. The present study applies a nonparametric model to estimate and compare two HK and UK standard gamble (SG) values for SF-6D health states using Bayesian methods. Methods: The data set is the HK and UK SF-6D valuation studies where two samples of 197 and 249 states defined by the SF-6D were valued by representative samples of the HK and UK general populations respectively, both using the standard gamble technique. We estimate a function applicable across both countries which explicitly accounts for the differences between them, and is estimated using the data from both countries. Results: The results suggest that differences in SF-6D health state valuations between the UK and HK general populations are potentially important. In particular, the valuations of the HK were meaningfully higher than those of the UK for most of the selected SF-6D health states. The magnitude of these country-specific differences in health state valuation depended, however, in a complex way on the levels of individual dimensions. Conclusion: The new Bayesian nonparametric method is a powerful approach for analysing data from multiple nationalities or ethnic groups, to understand the differences between them and potentially to estimate the underlying utility functions more efficiently.

ViH-09-2013-0374-OM.R2 Modelling a Preference-Based Index for two condition specific measures (asthma and overactive bladder) using a nonparametric Bayesian method Samer A Kharroubi, PhD, John E. Brazier, PhD, and Yaling Yang, PhD

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Background: Conventionally parametric models were used for health state valuation data. Recently researchers started to explore the use of nonparametric Bayesian methods in this area. Objectives: We present a nonparametric Bayesian model to estimate a preference-based index for two condition specific 5-dimensional health state classifications, one for asthma (AQL-5D) and the other for overactive bladder (OAB-5D). Methods: Samples of 307 and 311 members of the UK general population valued 99 health states selected from a total of 3125 health states defined by each of the measures using time trade-off technique. The paper presents the results of the nonparametric model and compares it to the original model estimated using a conventional parametric random effects model. The different methods are compared theoretically and in terms of empirical performance across the two data sets. It also reports the impact of respondent characteristics on health state valuations. Results: The non-parametric models were found to be better at predicting health state values within the estimation sample without in terms of Root Mean Square Error and the patterns of standardised residuals. Some respondent characteristics were found to explain variation in health state values, but these did not significantly impact on the health states values when estimates were adjusted for sample differences with the general population. Conclusion: The nonparametric Bayesian models are theoretically more appropriate than previously used parametric models and provide better utility estimates from the two condition specific measures. Furthermore, the model is more flexible in estimating the impact of covariates.


ViH-08-2013-0336-OM.R1 Bazedoxifene versus oral bisphosphonates for the prevention of non-vertebral fractures in post-menopausal women with osteoporosis at higher risk of fracture: a network meta-analysis Alexandra G. Ellis, MSc; Jean-Yves Reginster, MD, PhD; Xuemei Luo, PhD; Joseph C. Cappelleri, PhD, MPH; Arkadi Chines, MD; Santosh Sutradhar, PhD; Jeroen P. Jansen, PhD

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Purpose: To compare the efficacy of bazedoxifene and oral bisphosphonates for the prevention of non-vertebral fractures (NVF) in higher-risk postmenopausal osteoporosis (PMO) (i.e. FRAX>=20%), based on currently available evidence from randomized controlled trials (RCTs).
Methods: RCTs evaluating the NVF relative risk reduction (RRR) with oral bisphosphonates or bazedoxifene were identified by a systematic literature review and combined by means of a network meta-analysis (NMA). A subgroup of patients with FRAX>=20% in the bazedoxifene Phase III Osteoporosis study was selected as the population of interest based on the bazedoxifene label and the significant effect on NVF in this subgroup. In one analysis (Analysis 1), the placebo response of the FRAX>=20% subgroup was the benchmark to select comparable bisphosphonate trials. Additional analyses incorporated the aggregate data from the bisphosphonate trials with all of the FRAX subgroups (Analysis 2) or with the individual patient data (IPD) from the bazedoxifene trial (Analysis 3).
Results: Nine identified bisphosphonate trials (alendronate, ibandronate, risedronate; N=23,440 patients) were included in Analysis 1. The results of the NMA of this study set suggest bazedoxifene is expected to have a RRR of 0.43 (95%CrI: -0.19, 0.72) versus alendronate, 0.58 (95%CrI: 0.05, 0.81) versus ibandronate, and 0.39 (95%CrI: -0.29, 0.70) versus risedronate. Analyses where treatment effects with bisphosphonates were projected to a FRAX>=20% population with meta-regression approaches (Analysis 2 and Analysis 3) provide similar findings.
Conclusion: Based on an indirect comparison of randomized trials, bazedoxifene is expected to have at least a comparable RRR of NVF as alendronate, ibandronate, and risedronate in higher-risk PMO.

ViH-01-2013-0017-OM.R3 Sharing Risk between payer and provider by leasing health technologies: an affordable and effective reimbursement strategy for innovative technologies? Richard Edlin, PhD, Peter Hall, PhD, Klemens Wallner, BA, and Christopher McCabe, PhD

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The challenge of implementing high cost innovative technologies in health care systems operating under significant budgetary pressure has led to a radical shift in the health technology reimbursement landscape. New reimbursement strategies attempt to reduce the risk of making the wrong decision; i.e. paying for a technology that is not good value for the health care system, whilst promoting the adoption of innovative technologies into clinical practice. However, the remaining risk is not shared between the manufacturer and the health care payer at the individual purchase level; it continues to be passed from the manufacturer to the payer at the time of purchase. In this paper we propose a health technology payment strategy – Technology Leasing Reimbursement Scheme (TLRS) - which allows the sharing of risk between the manufacturer and the payer; the replacing of upfront payments with a stream of payments spread over the expected duration benefit from the technology, subject to the technology delivering the claimed health benefit. Using trastuzumab (Herceptin) in Early Breast Cancer as an exemplar technology we show how a TLRS not only reduces the total budgetary impact of the innovative technology, it also truly shares risk between the manufacturer and the health care system, whilst reducing the value of further research and thus promoting the rapid adoption of innovative technologies into clinical practice.

ViH-07-2013-0279-OM.R1 Searching for indirect evidence and extending the network of studies for network meta-analysis: case study in venous thromboembolic events prevention following elective total knee replacement surgery Pascale Dequen, MSc, Alex J. Sutton, PhD, David A. Scott, MA, MSc, Keith Abrams, PhD

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Objective: We aim to evaluate the impact of study identification methods and network size on the relative effectiveness and cost-effectiveness of recommended pharmacological venous thromboembolic events (VTE) prophylaxis for adult patients undergoing elective total knee replacement surgery in the UK. Methods: A stepwise literature search specifically designed to identify indirect evidence was conducted to extend the original clinical review from the latest National Institute for Health and Care Excellence (NICE) VTE technology appraisal. Different network sizes or network orders, based on the successive searches, informed three network meta-analyses (NMAs) which were compared to a replicated base case. The resulting comparative estimates were inputted in an economic model to investigate the impact of network size on cost-effectiveness probabilities. Results: Searches increased the number of indirect comparisons between VTE interventions, progressively widening the relevant network of studies for NMA. Precision around mean relative treatment effects was increased as the network was extended from base case to first order NMA, but further extensions had limited impact. Cost-effectiveness analysis results were largely insensitive to variation in clinical inputs from the different NMA orders. Conclusions: No standard methodology is currently recommended by NICE to identify the most relevant network of studies for NMA. Our study showed that optimising the identification of studies for NMA can extend the evidence base for analysis and reduce the uncertainty in relative effectiveness estimates. Although in our example network extensions did not impact the acceptability of available treatments in VTE prevention based on cost-effectiveness results, it may in other applications.


ViH-06-2013-0251-OM.R2 Cost-Effectiveness of a Computerized Provider Order Entry System in Improving Medication Safety in Ambulatory Care Sara H. Forrester, PharmD, MS, Zsolt Hepp, PharmD, MS, Joshua A. Roth, PhD, MHA, Heidi S. Wirtz, PhD, PharmD, MS, Emily Beth Devine, PhD, PharmD, MBA

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Background: Computerized provider order entry (CPOE) is the process of entering physician orders directly into an electronic health record. Although CPOE has been shown to improve medication safety and reduce healthcare costs, these improvements have been demonstrated largely in the inpatient setting; the cost-effectiveness in the ambulatory setting remains uncertain.
Objective: To estimate the cost-effectiveness of CPOE in reducing medication errors and adverse drug events (ADEs) in the ambulatory setting.
Methods: We created a decision-analytic model to estimate the cost-effectiveness of CPOE in a midsized (400 providers) multidisciplinary medical group over a five-year time horizon – 2010 to 2014 – the timeframe during which health systems are implementing CPOE to meet Meaningful Use criteria. We adopted the medical group’s perspective, utilized their costs, changes in efficiency, and actual number of medication errors and ADEs. One-way and probabilistic sensitivity analyses were conducted. Scenario analyses were explored.
Results: In the base case, CPOE dominated paper prescribing, that is, CPOE cost $18 million less than paper; and was associated with 1.5 million and 14.5 thousand fewer medication errors and ADEs, respectively, over five years. In the scenario that reflected a practice group of five providers, CPOE cost $265,000 less than paper, was associated with 3,875 and 39 fewer medication errors and ADEs, respectively, over five years, and was dominant in 80% of the simulations.
Conclusion: Our model suggests that adoption of CPOE in the ambulatory setting provides excellent value for the investment, and is a cost-effective strategy to improve medication safety over a wide range of practice sizes.


ViH-08-2012-0328-MA.R3 A programme of methodological research to arrive at the new international EQ-5D-5L valuation protocol Mark Oppe, MSc, Nancy J. Devlin, PhD, Ben van Hout, PhD, Paul F.M. Krabbe, PhD,Frank de Charro, PhD

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Objectives: To describe the research which has been undertaken by the EuroQol Group to improve current methods for health-state valuation, to summarise the results of an extensive international pilot programme, and to outline the key elements of the EQ-5D-5L valuation protocol which is the culmination of that work.
Methods: In order to improve on methods of health state valuation for EQ-5D-5L, we investigated the performance of different variants of time trade-off (TTO) and Discrete Choice (DC) tasks in a multinational setting. We also investigated the impact of three modes of administration on health state valuation: group interviews, online self-completion, and face to face interviews.
Results: The research programme provided the basis for the EQ-5D-5L valuation protocol. Two different types of tasks are included to derive preferences: a newly developed composite TTO task and a forced-choice paired comparisons DC task. Furthermore, standardised blocked designs for the selection of the states to be valued by participants were created and implemented together with all other elements of the valuation protocol in a digital aid, the EuroQol Valuation Technology (EQ-VT), which was developed in conjunction with the protocol.
Conclusions: The EuroQol Group has developed a standard protocol, with accompanying digital aid and interviewer training materials that can be used to create value sets for EQ-5D-5L. The use of a well-described, consistent protocol across all countries enhances the comparability of value sets between countries, and allows the exploration of the influence of cultural and other factors on health-state values.


ViH-03-2013-0115-SR.R2 Review of utility values for economic modeling in type-2 diabetes Amélie Beaudet, B.Pharm, MSc, John Clegg BSc, Per-Olof Thuresson, MPharm, MSc, Adam Lloyd, MPhil, Phil McEwan, BA (Hons), PhD

Word Count: 2697

OBJECTIVES: Economic analysis in type 2 diabetes mellitus (T2DM) requires an assessment of the impact of a wide range of complications. The objective of this paper was to identify a set of utility values consistent with the NICE reference case and to critically discuss and illustrate challenges in creating such a utility set.
METHODS: A systematic literature review was conducted to identify studies reporting utility values for relevant complications. The methodology of each study was assessed for consistency with the NICE reference case. A suggested set of utility values applicable to modelling was derived, giving preference to studies reporting multiple complications and correcting for co-morbidity.
RESULTS: The review considered 21 relevant diabetes complications. A total of 16,574 papers were identified; after screening, 61 papers were assessed for methodological quality. Nineteen papers met NICE criteria, reporting utility values for 20 of 21 relevant complications. For renal transplant, as no papers meeting NICE criteria were identified, two papers using other methodologies were included. Index value estimates for T2DM without complication ranged from 0.711 to 0.940. Utility decrement associated with complications ranged from 0.014 (minor hypoglycaemia) to 0.28 (amputation). Limitations associated with the selection of a utility value for use in economic modelling included variability in patient recruitment, heterogeneity in statistical analysis, large variability around some point estimates and lack of recent data.
CONCLUSIONS: A reference set of utility values for T2DM and its complications in line with NICE requirements was identified. This research illustrates the challenges associated with systematically selecting utility data for economic evaluations.


ViH-03-2013-0119-PS.R1 Patient-centeredness in the design of clinical trials C. Daniel Mullins, PhD, Joseph E Vandigo, MBA, Jason Zheng, PhD, Paul Wicks, PhD

Word Count: 2760

Evidence from clinical trials should contribute to informed decision making and a learning healthcare system. However, people frequently find participating in clinical trials meaningless or disempowering. Moreover, people often do not incorporate trial results directly into their decision making. The lack of patient centeredness in clinical trials may be partially addressed through trial design. For example, Bayesian adaptive trials designed to adjust in a pre-specified manner to changes in clinical practice could motivate people and their healthcare providers to view clinical trials as more applicable to real-world clinical decisions. The way in which clinical trials are designed can transform the evidence generation process to be more patient centered, providing people with an incentive to participate or continue participating in clinical trials. However, in order to achieve the transformation to patient-centeredness in clinical trial decisions, there is a need for transparent and reliable methods and education of trial investigators and site personnel.

ViH-10-2013-0410-PS.R4 Medical device reimbursement coverage and pricing rules in Korea Sang-Soo Lee MBA, Eugene Salole  MPH PhD

Word Count: 3279

The development of healthcare funding policy in Korea has followed the country’s rapid economic development, with a comprehensive National Health Insurance (NHI) system in place by 1989. The funding of medical devices has followed this progression, with incorporation into the NHI reimbursement system in 2000 (several years later than pharmaceuticals), but important issues impacting patient access remain.
Although the impact of devices on the NHI budget is relatively modest (only about 4%), due to concerns about NHI sustainability, attention has increasingly been paid to their management and funding. However, unlike pharmaceuticals, it has been quite challenging to develop clear and fair criteria for reimbursement coverage and pricing of medical devices.
The two key and longstanding issues around the reimbursement of medical devices in Korea are how to expedite market entry of improved or innovative medical devices at appropriate prices, and how to satisfactorily lower the reimbursement levels of older devices, thereby making headroom for new technologies to be reimbursed. Despite protracted discussions over the last decade, industry and government have been unable to reach full agreement. There has been some progress (e.g., introduction of the Value Appraisal and the Revaluation Systems), but there remains urgent need for productive discussion and consensus between government and industry regarding reasonable funding rules, transparency and clarity in the reimbursement pricing process for medical devices.


ViH-08-2013-0332-OM.R2 Estimation of Potential Gain in Quality of Life from Early Detection of Cervical Cancer Mei-Chuan Hung, RN, PhD, Ching-Lin Wu, RN, Yu-Yun Hsu, PhD, Jing-Shiang Hwang, PhD, Ya-Min Cheng, MD, Jung-Der Wang, MD, ScD

Word Count: 2101

Objectives: The aim is to estimate the lifetime gain in the health-related quality of life (HRQL) from early detection of cervical cancer.
Methods: A consecutive, cross-sectional sample of 421 patients with cervical cancer was measured with the World Health Organization Quality of Life- brief version questionnaires. A nationwide sample of 22,543 ICC (invasive cervical cancer) patients was collected from the national cancer registry for estimation of lifetime survival function from 1998 to 2007, which was further multiplied by the ratio of HRQL score functions for ICC and CIS patients, and summed up over lifetime to obtain expected relative-quality-adjusted survival (RQAS). The difference between lifetime survival and the expected RQAS gives the expected total dissatisfied time during life course.
Results: In comparison with CIS post conization, patients with ICC showed consistently lower scores in the physical and psychological domains and that of sexual life after adjustment for other risk factors. The expected years of life lost for an invasive cancer was 6.48 years using the general population as the reference cohort, while the durations of equivalent to living with a very dissatisfied HRQL were 1.71, 0.25 for the physical and psychological domains, respectively, and 1.47 years for sexual life. Validation of the extrapolation method based on a sub-cohort followed from 6th to the 13th year shows a relative bias of 0.4%. Sensitivity analysis with 37,000 CIS cases as the reference cohort yields a similar result.
Conclusions: Early detection of cervical cancer not only avoids premature mortality, but also prevents long-term living under lower HRQL scores, including sexual life.

ViH-09-2013-0388-SR.R2 Is the UK NICE ‘reference case’ influencing the practice of paediatric QALY measurement within economic evaluations? Nick Adlard, MA, MSc, MBA, Philip Kinghorn, MA, PhD, Emma Frew, MSc, PhD

Word Count: 2362

Objectives: This paper reports findings from a systematic review which sought to address two related questions. First, how has the practice of UK paediatric CUAs evolved over time, in particular how are health related outcomes assessed and valued? Second, how do the methods compare to the limited guidance available, in particular, the National Institute for Health and Care Excellence (NICE) reference case(s)?
Methods: Electronic searches of Medline, Embase and Cochrane databases were conducted for the period May 2004 to April 2012 and the PEDE database for May 2004 to December 2010. Identified studies were screened by three independent reviewers.
Results: 43 were studies identified, 11 of which elicit utility values through primary research. A discrepancy was identified between the methods used for outcome measurement and valuation and the methods advocated within the NICE reference case. Despite NICE recommending the use of preference-based instruments designed specifically for children, most studies which were identified had used adult measures. In fact the measurement of QALYs is the aspect of economic evaluation with the greatest amount of variability and the area that most digressed from the NICE reference case.
Conclusions: Recommendations stemming from the review are that all studies should specify the age range of childhood and include separate statements of perspective for costs and effects; as well as the reallocation of research funding away from systematic review studies towards good quality primary research measuring utilities in children.


VIH-2014-16R1 Multicriteria decision analysis in the reimbursement of new medical technologies: real word experiences from Hungary Dóra Endrei; Bálint Molics; István Ágoston


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