Marginal cost per QALY estimates: What are they good for?

Estimates of the marginal cost per quality-adjusted life year (MCPQ) are available for health care systems worldwide. Researchers routinely make claims about these estimates and how they should inform policymaking. This commentary considers these claims by taking a recent article from Health Policy as a case study. Claims are made about the past performance of the health service and about future decisions and relate to such considerations as productivity, the impact of technology approvals, cost-effectiveness thresholds, and budget allocation. We argue that the evidence does not justify these claims and MCPQ estimates should instead inform questions about the consequences of changes in expenditure.

This Dead or That Dead: Framing Effects in the Evaluation of Health States.

OBJECTIVES: Current approaches to health state valuation rely on credible classification of states as either "better than dead" or "worse than dead" (WTD). We investigate how such evaluations of health states are affected by the framing in pairwise comparison tasks. METHODS: We conducted an online survey with 361 participants to compare the propensity to evaluate a state as WTD under 6 frames: (A) using a regular time trade-off (TTO) choice task, (B) using a lead-time TTO choice task, (C) excluding the immediacy of death, (D) avoiding reference to the process of dying, (E) focusing on longevity, and (F) focusing on improvements in quality of life. Each participant evaluated 9 EQ-5D-5L health states using 3 frames. The frames were compared using several statistical approaches to confirm robustness to indirect comparisons or respondent heterogeneity and inattentiveness. RESULTS: The odds of a state being evaluated as WTD, compared with frame A, increase 2.7-fold and 1.5-fold in frame B and E, respectively, and decrease >5-fold in frame F. Frames C and D do not differ significantly from frame A. CONCLUSIONS: Different framings for questions about whether a state is WTD or better than dead, even if theoretically equivalent, yield substantially different results. Notably, whether a state is evaluated as WTD differs greatly between the regular TTO and lead-time TTO choice tasks and when either final outcomes or improvements over time are considered.

Logical Inconsistencies in the Health Years in Total and Equal Value of Life-Years Gained.

OBJECTIVES: This study aimed to assess whether recently proposed alternatives to the quality-adjusted life-year (QALY), intended to address concerns about discrimination, are suitable for informing resource allocation decisions. METHODS: We consider 2 alternatives to the QALY: the health years in total (HYT), recently proposed by Basu et al, and the equal value of life-years gained (evLYG), currently used by the Institute for Clinical and Economic Review. For completeness we also consider unweighted life-years (LYs). Using a hypothetical example comparing 3 mutually exclusive treatment options, we consider how calculations are performed under each approach and whether the resulting rankings are logically consistent. We also explore some further challenges that arise from the unique properties of the HYT approach. RESULTS: The HYT and evLYG approaches can result in logical inconsistencies that do not arise under the QALY or LY approaches. HYT can violate the independence of irrelevant alternatives axiom, whereas the evLYG can produce an unstable ranking of treatment options. HYT have additional issues, including an implausible assumption that the utilities associated with health-related quality of life and LYs are "separable," and a consideration of "counterfactual" health-related quality of life for patients who are dead. CONCLUSIONS: The HYT and evLYG approaches can result in logically inconsistent decisions. We recommend that decision makers avoid these approaches and that the logical consistency of any approaches proposed in future be thoroughly explored before considering their use in practice.

Supply-Side Cost-Effectiveness Thresholds: Questions for Evidence-Based Policy.

There is growing interest in cost-effectiveness thresholds as a tool to inform resource allocation decisions in health care. Studies from several countries have sought to estimate health system opportunity costs, which supply-side cost-effectiveness thresholds are intended to represent. In this paper, we consider the role of empirical estimates of supply-side thresholds in policy-making. Recent studies estimate the cost per unit of health based on average displacement or outcome elasticity. We distinguish the types of point estimates reported in empirical work, including marginal productivity, average displacement, and outcome elasticity. Using this classification, we summarise the limitations of current approaches to threshold estimation in terms of theory, methods, and data. We highlight the questions that arise from alternative interpretations of thresholds and provide recommendations to policymakers seeking to use a supply-side threshold where the evidence base is emerging or incomplete. We recommend that: (1) policymakers must clearly define the scope of the application of a threshold, and the theoretical basis for empirical estimates should be consistent with that scope; (2) a process for the assessment of new evidence and for determining changes in the threshold to be applied in policy-making should be created; (3) decision-making processes should retain flexibility in the application of a threshold; and (4) policymakers should provide support for decision-makers relating to the use of thresholds and the implementation of decisions stemming from their application.

Criteria for developing, assessing and selecting candidate EQ-5D bolt-ons.

PURPOSE: 'Bolt-on' dimensions are additional items added to multi-attribute utility instruments (MAUIs) such as EQ-5D that measure constructs not included in the core descriptive system. The use of bolt-ons has been proposed to improve the content validity and responsiveness of the descriptive system in certain settings and health conditions. EQ-5D bolt-ons serve a particular purpose and thus satisfy a certain set of criteria. The aim of this paper is to propose a set of criteria to guide the development, assessment and selection of candidate bolt-on descriptors. METHODS: Criteria were developed using an iterative approach. First, existing criteria were identified from the literature including those used to guide the development of MAUIs, the COSMIN checklist and reviews of existing bolt-ons. Second, processes used to develop bolt-ons based on qualitative and quantitative approaches were considered. The information from these two stages was formalised into draft development and selection criteria. These were reviewed by the project team and iteratively refined. RESULTS: Overall, 23 criteria for the development, assessment and selection of candidate bolt-ons were formulated. Development criteria focused on issues relating to i) structure, ii) language, and iii) consistency with the existing EQ-5D dimension structure. Assessment and selection criteria focused on face and content validity and classical psychometric indicators. CONCLUSION: The criteria generated can be used to guide the development of bolt-ons across different health areas. They can also be used to assess existing bolt-ons, and inform their inclusion in studies and patient groups where the EQ-5D may lack content validity.

Digital cognitive behavioural therapy for insomnia and primary care costs in England: an interrupted time series analysis.

BACKGROUND: Sleepio is an automated digital program that delivers digital cognitive behavioural therapy for insomnia (dCBT-I). Sleepio has been proven effective in improving sleep difficulties; however, evidence for the possible impact of Sleepio use on healthcare costs in the UK has not, to the authors' knowledge, previously been developed. AIM: To identify the effect of a population-wide rollout of Sleepio in terms of primary care costs in the NHS in England. DESIGN & SETTING: The study was conducted in the Thames Valley region of England, where access to Sleepio was made freely available to all residents between October 2018 and January 2020. The study relies on a quasi-experimental design, using an interrupted time series (ITS) to compare the trend in primary care costs before and after the rollout of Sleepio. METHOD: Primary care data for people with relevant characteristics from nine general practices in Buckinghamshire was used. Primary care costs include general practice contacts and prescriptions. Segmented regression analysis was used to estimate primary and secondary outcomes. RESULTS: For the 10 705 patients included in the sample, the total saving over the 65-week follow-up period was £71 027. This corresponds to £6.64 per person in the sample or around £70.44 per Sleepio user. Secondary analyses suggest that savings may be driven primarily by reductions in prescribing. CONCLUSION: Sleepio rollout reduced primary care costs. National adoption of Sleepio may reduce primary care costs by £20 million in the first year. The expected impact on primary care costs in any particular setting will depend on the uptake of Sleepio.

How symmetry-breaking can amplify the magnetosensitivity of dipolarly coupled n-radical systems.

In systems of more than two reactive radicals, the radical recombination probability can be magnetosensitive due to the mere effect of the inter-radical electron-electron dipolar coupling. Here, we demonstrate that this principle, previously established for three-radical systems, generalizes to n-radical systems. We focus on radical systems in the plane and explore the effects of symmetry, in particular its absence, on the associated magnetic field effects of the recombination yield. We show, by considering regular configurations and slightly distorted geometries, that the breaking of geometric symmetry can lead to an enhancement of the magnetosensitivity of these structures. Furthermore, we demonstrate the presence of effects at low-field that are abolished in the highly symmetric case. This could be important to the understanding of the behavior of radicals in biological environments in the presence of weak magnetic fields comparable to the Earth's, as well as the construction of high-precision quantum sensing devices.

On the magnetosensitivity of lipid peroxidation: two- versus three-radical dynamics.

We present a theoretical analysis of the putative magnetosensitivity of lipid peroxidation. We focus on the widely accepted radical pair mechanism (RPM) and a recently suggested idea based on spin dynamics induced in three-radical systems by the mutual electron-electron dipolar coupling (D3M). We show that, contrary to claims in the literature, lipid peroxides, the dominant chain carriers of the autoxidation process, have associated non-zero hyperfine coupling interactions. This suggests that their recombination could, in principle, be magnetosensitive due to the RPM. While the RPM indeed goes a long way to explaining magnetosensitivity in these systems, we show that the simultaneous interaction of three peroxyl radicals via the D3M can achieve larger magnetic field effects (MFE), even if the third radical is remote from the recombining radical pair. For randomly oriented three-radical systems, the D3M induces a low-field effect comparable to that of the RPM. The mechanism furthermore immunizes the spin dynamics to the presence of large exchange coupling interactions in the recombining radical pair, thereby permitting much larger MFE at magnetic field intensities comparable to the geomagnetic field than would be expected for the RPM. Based on these characteristics, we suggest that the D3M could be particularly relevant for MFE at low fields, provided that the local radical concentration is sufficient to allow for three-spin radical correlations. Eventually, our observations suggest that MFEs could intricately depend on radical concentration and larger effects could ensue under conditions of oxidative stress.

A "Stepping Stone" Approach for Obtaining Quantum Free Energies of Hydration.

We present a method which uses DFT (quantum, QM) calculations to improve free energies of binding computed with classical force fields (classical, MM). To overcome the incomplete overlap of configurational spaces between MM and QM, we use a hybrid Monte Carlo approach to generate quickly correct ensembles of structures of intermediate states between a MM and a QM/MM description, hence taking into account a great fraction of the electronic polarization of the quantum system, while being able to use thermodynamic integration to compute the free energy of transition between the MM and QM/MM. Then, we perform a final transition from QM/MM to full QM using a one-step free energy perturbation approach. By using QM/MM as a stepping stone toward the full QM description, we find very small convergence errors (<1 kJ/mol) in the transition to full QM. We apply this method to compute hydration free energies, and we obtain consistent improvements over the MM values for all molecules we used in this study. This approach requires large-scale DFT calculations as the full QM systems involved the ligands and all waters in their simulation cells, so the linear-scaling DFT code ONETEP was used for these calculations.

Foreign body impaction as presentation of eosinophilic esophagitis.

Esophageal foreign body is a frequent pediatric presentation, and eosinophilic esophagitis (EoE) is an important underlying disease. To determine characteristics common in the presentation of esophageal foreign body indicative of underlying EoE and reach a recommendation for the appropriate scenario in which to obtain esophageal mucosal biopsy, 312 pediatric esophageal foreign bodies requiring operative removal were reviewed. Patients older than 18 years or with a known history of esophageal surgery or pathology were excluded. Eligibility criteria were met in 271 cases. Twenty-seven patients were biopsied, and 18 were diagnosed with EoE. The following factors were identified in the EoE population: food impaction (89%), older age (average 12.2 years), male sex (78%), atopic disease (61%), previous esophageal foreign body or frequent dysphagia (83%), and endoscopic abnormalities (100%). These factors are all associated with an underlying diagnosis of EoE, and patients meeting these criteria should be strongly considered for intraoperative esophageal mucosal biopsy.

Is routine dental prophylaxis effective?

DATA SOURCES: Searches were made for relevant papers using Medline, CINHAL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic reviews, Database of Abstracts of Reviews of Effects, Embase, Health and Psychosocial Instruments, HealthSTAR, International Pharmaceutical Abstracts, and ACP (American College of Physicians) Journal Club. Further articles were identified by reviewing the references and bibliographies of the retrieved articles. STUDY SELECTION: Articles were limited to original human studies assessing rubber cup dental prophylaxis. All other studies, including in vitro studies, reviews and case series, were excluded. Only studies in English with prophylaxis given at a recall appointment at intervals of 4 months were included. DATA EXTRACTION AND SYNTHESIS: The quality of articles was assessed independently and evidence levels rated. A qualitative synthesis is presented. RESULTS: Four articles relating to dental prophylaxis and caries prevention and two articles relating to dental prophylaxis and gingivitis prevention were included. Four studies found that a dental prophylaxis was not warranted before professionally applied topical fluoride (PATF) for caries prevention in children. A generalisation about dental prophylaxis before PATF cannot be applied to adolescents and adults. Available evidence from two other studies fails to demonstrate any benefit in the prevention of gingivitis from further dental prophylaxis at the interval used here for recall examinations. CONCLUSIONS: To prevent caries in children, dental prophylaxis need not be provided either at a recall visit or before PATF. Dental prophylaxis at intervals of 4 months or more is not justified for the prevention of gingivitis in the general population.