The Importance of Economic Perspective and Quantitative Approaches in Oncology Value Frameworks of Drug Selection and Shared Decision Making

The debate around value in oncology drug selection has been prominent in recent years, and several professional bodies have furthered this debate by advocating for so-called value frameworks. Herein, we provide a viewpoint on these value frameworks, emphasizing the need to consider 4 key aspects: (1) the economic underpinnings of value; (2) the importance of the perspective adopted in the valuation; (3) the importance of the difference between absolute and relative measures of risk and measuring patient preferences; and (4) the recognition of multiple quality-of-life (QoL) domains, and the aggregation and valuation of those domains, through utilities within a multicriteria decision analysis, may allow prioritization of QoL above the tallying of safety events, particularly in a value framework focusing on the individual patient. While several frameworks exist, they incorporate different attributes and—importantly—assess value from alternative perspectives, including those of patients, regulators, payers, and society. The various perspectives necessarily lead to potentially different, if not sometimes divergent, conclusions about the valuation. We show that the perspective of the valuation affects the framing of the risk/benefit question and the methodology to measure the individual patient choice, or preference, as opposed to the collective, or population, choice. We focus specifically on the American Society of Clinical Oncology (ASCO) Value Framework. We argue that its laudable intent to assist in shared clinician-patient decision making can be augmented by more formally adopting methodology underpinned by micro- and health economic concepts, as well as application of formal quantitative approaches. Our recommendations for value frameworks focusing on the individual patient, such as the ASCO Value Framework, are 3-fold: (1) ensure that stakeholders understand the importance of the adopted (economic) perspective; (2) consider using exclusively absolute measures of risk and formal patientpreference methodology; and (3) consider foregoing safety parameters for higher-order utility considerations

Non-muscle-invasive bladder cancer surveillance for which cystoscopy is partly replaced by microsatellite analysis of urine: a cost-effective alternative?

OBJECTIVE To determine how good microsatellite analysis (MA) markers in voided urine samples should be to make a surveillance procedure cost-effective in which cystoscopy is partly replaced by MA for patients with non-muscle-invasive urothelial carcinoma (NMI-UC). PATIENTS AND METHODS We constructed a semi-Markov model with a time horizon of 2 years, and a man aged 65 years as reference case. Data were used from a randomized trial (including 448 patients with NMI-UC from 10 hospitals), and from other data sources. The costs and effects (probability of being in a specific health state) were compared for two surveillance strategies: (i) cystos

Cost-Utility Analysis of Venous Thromboembolism Prophylaxis Strategies for People Undergoing Elective Total Hip and Total Knee Replacement Surgeries in the English National Health Service

Background: Major orthopedic surgery, such as elective total hip replacement (eTHR) and elective total knee replacement (eTKR), are associated with a higher risk of venous thromboembolism (VTE) than other surgical procedures. Little is known, however, about the cost-effectiveness of VTE prophylaxis strategies in people undergoing these procedures. Aim: The aim of this work was to assess the cost-effectiveness of these strategies from the English National Health Service perspective to inform NICE guideline (NG89) recommendations. Materials and Methods: Cost-utility analysis, using decision modeling, was undertaken to compare 15 VTE prophylaxis strategies for eTHR and 12 for eTKR, in addition to “no prophylaxis” strategy. The analysis complied with the NICE Reference Case. Structure and assumptions were agreed with the guideline committee. Incremental net monetary benefit (INMB) was calculated, vs. the model comparator (LMWH+ antiembolism stockings), at a threshold of £20,000/quality-adjusted life-year (QALY) gained. The model was run probabilistically. Deterministic sensitivity analyses (SAs) were undertaken to assess the robustness of the results. Results: The most cost-effective strategies were LMWH for 10 days followed by aspirin for 28 days (INMB = £530 [95% CI: -£784 to £1,103], probability of being most cost-effective = 72%) for eTHR, and foot pump (INMB = £353 [95% CI: -£101 to £665]; probability of being most cost-effective = 18%) for eTKR. There was considerable uncertainty regarding the cost-effectiveness ranking in the eTKR analysis. The results were robust to change in all SAs. Conclusions: For eTHR, LMWH (standard dose) for 10 days followed by aspirin for 28 days is the most cost-effective VTE prophylaxis strategy. For eTKR, the results are highly uncertain but foot pump appeared to be the most cost-effective strategy, followed closely by aspirin (low dose). Future research should focus on assessing cost-effectiveness of VTE prophylaxis in the eTKR population.Peer reviewe

The burden of managing pleural effusions in patients with chronic myelogenous leukemia post-imatinib failure: A literature-based economic analysis

Jennifer Stephens, Kimbach Tran Carpiuc, Marc BottemanPharmerit North America LLC, Bethesda, MD, USAObjectives: To develop an economic analysis of the management of pleural effusions in patients with imatinib-resistant/intolerant chronic myelogenous leukemia (CML).Methods: A cost of treatment analysis was conducted from the US payer perspective, based on resource utilization data for 48 patients with dasatinib-related pleural effusions at a large US cancer center. Probabilities of various procedures and treatment events were derived from published resource use data, supplemented with expert opinion. Cost data was derived from median reimbursements for relevant CPT codes for outpatient services and medical literature for inpatient services. Sensitivity analyses were conducted for types of procedures used. All costs were adjusted to US dollars (2007 rates).Results: Sixty percent of pleural effusions were managed medically costing 750 per episode. Forty percent of pleural effusions were more significant (>25% of one lung volume), with half of those requiring invasive procedures. Cost of inpatient procedures was 10,616 for chest tube and $15,170 with pleural catheter. Cost of outpatient procedures was$713 for ultrasound thoracentesis and $4,598 for pleural catheter. The average cost of treating a pleural effusion was$2,062 to >$2,700 for all severity levels and ~$6,400 to >$9,000 for invasive procedures. Key cost drivers were invasive procedures and recurrence.Conclusion: This economic analysis using actually observed treatment patterns suggests that the management of pleural effusion adverse events in CML patients is costly, requires intensive resource utilization, and may be an important factor in treatment selection.Keywords: dasatinib, nilotinib, imatinib, adverse events, safety, cost, and cost analysi

The Use of Decision–Analytic Models in Atopic Eczema: A Systematic Review and Critical Appraisal

Objective: The objective of this systematic review was to identify and assess the quality of published economic decision–analytic models within atopic eczema against best practice guidelines, with the intention of informing future decision–analytic models within this condition. Methods: A systematic search of the following online databases was performed: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, NHS Economic Evaluation Database, EconLit, Scopus, Health Technology Assessment, Cost-Effectiveness Analysis Registry and Web of Science. Papers were eligible for inclusion if they described a decision–analytic model evaluating both the costs and benefits associated with an intervention or prevention for atopic eczema. Data were extracted using a standardised form by two independent reviewers, whilst quality was assessed using the model-specific Philips criteria. Results: Twenty-four models were identified, evaluating either preventions (n = 12) or interventions (n = 12): 14 reported using a Markov modelling approach, four utilised decision trees and one a discrete event simulation, whilst five did not specify the approach. The majority, 22 studies, reported that the intervention was dominant or cost effective, given the assumptions and analytical perspective taken. Notably, the models tended to be short-term (16 used a time horizon of ≤1 year), often providing little justification for the limited time horizon chosen. The methodological and reporting quality of the studies was generally weak, with only seven studies fulfilling more than 50% of their applicable Philips criteria. Conclusions: This is the first systematic review of decision models in eczema. Whilst the majority of models reported favourable outcomes in terms of the cost effectiveness of the new intervention, the usefulness of these findings for decision-making is questionable. In particular, there is considerable scope for increasing the range of interventions evaluated, for improving modelling structures and reporting quality

Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment

Background and purpose An internet-based discrete choice experiment (DCE) was conducted to elicit preferences for a wide range of Dupuytren’s contracture (DC)-related health states. An algorithm was subsequently developed to convert these preferences into health state utilities that can be used to assess DC’s impact on quality of life and the value of its treatments. Methods Health state preferences for varying levels of DC hand severity were elicited via an internet survey from a sample of the UK adult population. Severity levels were deined using a combination of contractures (0, 45, or 90 degrees) in 8 proximal interphalangeal and metacarpophalangeal joints of the index, middle, ring, and little ingers. Right-handed, left-handed, and ambidextrous respondents indicated which hand was preferable in each of the 10 randomly-selected hand-pairings comparing different DC severity levels. For consistency across comparisons, anatomically precise digital hand drawings were used. To anchor preferences onto the traditional 0–1 utility scale used in health economic evaluations, unaffected hands were assigned a utility of 1.0 whereas the utility for a maximally affected hand (i.e., all 8 joints set at 90 degrees of contracture) was derived by asking respondents to indicate what combination of attributes and levels of the EQ-5D-5L proile most accurately relects the impact of living with such hand. Conditional logistic models were used to estimate indirect utilities, then rescaled to the anchor points on the EQ-5D-5L. Results Estimated utilities based on the responses of 1,745 qualiied respondents were 0.49, 0.57, and 0.63 for completely affected dominant hands, non-dominant hands, or ambidextrous hands, respectively. Utility for a dominant hand with 90-degree contracture in t h e metacarpophalangeal joints of the ring and little ingers was estimated to be 0.89. Separately, reducing the contracture of metacarpophalangeal joint for a little inger from 50 to 12 degrees would improve utility by 0.02. Interpretation DC is associated with substantial utility decrements. The algorithms presented herein provide a robust and lexible framework to assess utility for varying degrees of DC severity

Mapping of the Insomnia Severity Index and other sleep measures to EuroQol EQ-5D health state utilities

<p>Abstract</p> <p>Background</p> <p>This study sought to map the Insomnia Severity Index (ISI) and symptom variables onto the EQ-5D.</p> <p>Methods</p> <p>A cross-sectional survey was conducted among adult US residents with self-reported sleep problems. Respondents provided demographic, comorbidity, and sleep-related information and had completed the ISI and the EQ-5D profile. Respondents were classified into ISI categories indicating no, threshold, moderate, or severe insomnia. Generalized linear models (GLM) were used to map the ISI's 7 items (Model I), summary scores (Model II), clinical categories (Model III), and insomnia symptoms (Model IV), onto the EQ-5D. We used 50% of the sample for estimation and 50% for prediction. Prediction accuracy was assessed by mean squared errors (MSEs) and mean absolute errors (MAEs).</p> <p>Results</p> <p>Mean (standard deviation) sleep duration for respondents (N = 2,842) was 7.8 (1.9) hours, and mean ISI score was 14.1 (4.8). Mean predicted EQ-5D utility was 0.765 (0.08) from Models I-III, which overlapped with observed utilities 0.765 (0.18). Predicted utility using insomnia symptoms was higher (0.771(0.07)). Based on Model I, predicted utilities increased linearly with improving ISI (0.493 if ISI = 28 vs. 1.00 if ISI = 0, p < 0.01). From Model II, each unit decrease in ISI summary score was associated with a 0.022 (p < 0.001) increase in utility. Predicted utilities were 0.868, 0.809, 0.722, and 0.579, respectively, for the 4 clinical categories, suggesting that lower utility was related to greater insomnia severity. The symptom model (Model IV) indicated a concave sleep-duration function of the EQ-5D; thus, utilities diminished after an optimal amount of sleep. The MSEs/MAEs were substantially lower when predicting EQ-5D > 0.40, and results were comparable in all models.</p> <p>Conclusions</p> <p>Findings suggest that mapping relationships between the EQ-5D and insomnia measures could be established. These relationships may be used to estimate insomnia-related treatment effects on health state utilities.</p

Assessing the value of orphan drugs using conventional cost-effectiveness analysis:Is it fit for purpose?

Conventional cost-effectiveness analysis-i.e., assessing pharmaceuticals through a cost per quality-adjusted life year (QALY) framework-originated from a societal commitment to maximize population health given limited resources. This "extra-welfarist" approach has produced pricing and reimbursement systems that are not well- aligned with the unique considerations of orphan drugs. This framework has been slow to evolve along with our increased understanding of the impact of rare diseases, which in turn has complicated the assessment of orphan drugs meant to treat rare diseases. Herein, we (i) discuss the limitations of conventional cost-effectiveness analysis as applied to assessing access to, as well as the pricing and reimbursement of, orphan drugs, (ii) critically appraise alternative and supplemental approaches, and (iii) offer insights on plausible steps forward

An Assessment of the Potential Relationship between the Charge of Gd-DTPA Complexes and the Exchange Rate of the Water Coordinated to the Metal

peer reviewedThe residence time of coordinated water (tau(M)), a parameter of paramount importance for relaxivity, is compared in a series of Gd-DTPA derivatives carrying different global charges. The importance of the charge in the first coordination sphere of the metal and in its vicinity is reported. Neutral bisester and bisamide complexes have significantly different tau(M) values. The paradoxical similarity of the exchange rates of bisester complexes and Gd-DTPA, on the one hand, and the large difference between neutral bisester and bisamide complexes, on the other hand, suggest that the charge inside the first coordination sphere is not the factor dominating the water exchange rate, which seems therefore more sensitive to the steric congestion. The study of Gd-(S)-N-6-carboxymethyl-DTPA, Gd-DTPA-BHydroxamide at basic pH, and Gd-DTPA-BAlaA clearly shows that anionic groups located outside the first coordination sphere have a beneficial influence on the value of tau(M), but that this effect strongly decreases with an increasing distance between the anionic group and the coordinated water. These conclusions underline the influence of steric hindrance and of the charged groups present in close proximity of the first coordination sphere on the exchange rate of the coordinated water