Toward comprehensive value assessment for Alzheimer's disease innovations.

INTRODUCTION: Assessing medical technologies for Alzheimer's disease (AD) creates challenges for current methods of value assessment. New value assessment approaches for AD are also needed. METHODS: We adapted concepts from health economics to help guide decision makers to more informed decisions about AD therapies and diagnostics. RESULTS: We propose a value framework based on five categories: perspective, value elements, analysis, reporting, and decision making. AD value assessments should include the perspective of the patient-caregiver dyad. We propose a broader array of value elements than currently used. Analytics and decision methods can synthesize evidence for all elements of value. Decisions should use a "deliberative appraisal" approach informed by the composite evidence and be transparently reported. DISCUSSION: Using the proposed framework, the value of forthcoming innovations for AD may be more thoroughly assessed for and by all stakeholders. It can guide decision makers to carefully consider all relevant elements of value contributing to more holistic and transparent decision making. RESEARCH HIGHLIGHTS: Alzheimer's disease challenges common methods of evaluating medical technology. Using current methods, new AD innovations might not be appropriately valued. Poor value assessments will adversely affect patient access to AD innovations. A full AD value framework expands perspective, elements, analysis, decision-making, reporting.

Assessing the Cost-effectiveness of a Hypothetical Disease-modifying Therapy With Limited Duration for the Treatment of Early Symptomatic Alzheimer Disease.

PURPOSE: Clinical trials have produced promising results for disease-modifying therapies (DMTs) for Alzheimer's disease (AD); however, the evidence on their potential cost-effectiveness is limited. This study assesses the cost-effectiveness of a hypothetical DMT with a limited treatment duration in AD. METHODS: We developed a Markov state-transition model to estimate the cost-effectiveness of a hypothetical DMT plus best supportive care (BSC) versus BSC alone among Americans living with mild cognitive impairment (MCI) due to AD or mild AD. AD states included MCI due to AD, mild AD, moderate AD, severe AD, and death. A hypothetical DMT was assumed to confer a 30% reduction in progression from MCI and mild AD. The base case annual drug acquisition cost was assumed to be $56,000. Other medical and indirect costs were obtained from published literature or list prices. Utilities for patients and caregivers were obtained from the published literature and varied by AD state and care setting (community care or long-term care). We considered 3 DMT treatment strategies: (1) treatment administered until patients reached severe AD (continuous strategy), (2) treatment administered for a maximum duration of 18 months or when patients reached severe AD (fixed-duration strategy), and (3) 40% of patients discontinuing treatment at 6 months because of amyloid plaque clearance and the remaining patients continuing treatment until 18 months or until they reached severe AD (test-and-discontinue strategy). Incremental cost-effectiveness ratios (ICERs) were calculated as the incremental cost per quality-adjusted life-year (QALY) gained. FINDINGS: From the health care sector perspective, continuous treatment with a hypothetical DMT versus BSC resulted in an ICER of $612,354 per QALY gained. The ICER decreased to $157,288 per QALY gained in the fixed-duration strategy, driven by large reductions in treatment costs. With 40% of patients discontinuing treatment at 6 months (test-and-discontinue strategy), the ICER was $125,631 per QALY gained. In sensitivity and scenario analyses, the ICER was the most sensitive to changes in treatment efficacy, treatment cost, and the initial population AD state distribution. From the modified societal perspective, ICERs were 6.3%, 20.4%, and 25.1% lower than those from the health care sector perspective for the continuous, fixed-duration, and test-and-discontinue strategies, respectively. IMPLICATIONS: Under a set of assumptions for annual treatment costs and the magnitude and duration of treatment efficacy, DMTs used for a limited duration may deliver value consistent with accepted US cost-effectiveness thresholds.

An in vitro bacterial surface migration assay underneath sterile barrier material commonly found in a hospital setting.

OBJECTIVE: To determine what barrier material used in hospital neonatal intensive care units most effectively blocks bacterial migration. STUDY DESIGN: Bacterial migration distance was compared across simple and complex solid media using Escherichia coli, an early and common neonatal gut colonizer, and Staphylococcus aureus, a common skin bacterium, across polystyrene, medical-grade silicone, hydrocolloid dressing and transparent film dressing as barrier materials on complex solid media. RESULTS: Bacterial migration was significantly greater on complex versus simple solid media. Bacteria migrated farthest beneath hydrocolloid dressing and transparent film dressing, while migration underneath polystyrene and medical-grade silicone was generally comparable to no barrier. CONCLUSIONS: Commonly used hydrocolloid dressing and transparent film dressing surprisingly increases bacterial migration, possibly by providing a wet capillary surface for bacteria to attach to or inducing biofilm formation. Using polystyrene or silicone to interface with the site of catheter insertion may best avoid a bacterial wicking phenomenon.

Phytochrome action in light-grown plants: the influence of light quality and fluence rate on extension growth in Sinapis alba L.

Using light-grown plants of Sinapis alba an analysis has been made of the effect on extension growth of adding far red light to a background photosynthetic source. It has been possible to distinguish between the increase in fluence rate and the reduction of the amount of phytochrome present as Pfr, which are both consequences of the addition of supplementary far red light, and to determine that the response of increased extension growth is due only to the latter. It is shown that the degree of fluence rate dependency varies with photoequilibrium and the significance of this interaction is discussed in terms of the mode of action of phytochrome and of its role in the natural light environment.

An analysis of phytochrome action in the 'high-irradiance response'.

Using a model based on spectrophotometric measurements of the phytochrome of Sinapis alba L. seedlings we have used the published rate constants for the component reactions of this system to calculate the behaviour of the far-red absorbing form of phytochrome (Pfr), and other parameters, over a period of continuous irradiation. We have then analysed two of the most intensively studied photomorphogenetic responses, hypocotyl extension and anthocyanin synthesis, of these seedlings in terms of various parameters of the model. The results show that many of the main features of the high-irradiance response are correlated with Pfr level. However, a more detailed analysis leads to the conclusion that Pfr alone cannot account for some critical aspects of the response. In particular, it is necessary to hypothesize an additional 'active' component which is a function of the rate of photoconversion.

Temperature- and seed-batch-related variation in the kinetic behaviour of phytochrome under 'high-irradiance-response' conditions.

The characteristics of the 'high-irradiance response' (HIR) of plant photomorphogenesis are thought to be the result of the interaction of both the light and dark reactions of phytochrome. Thus any variation in the rates of the dark reactions may be expected to lead to variation in the characteristics of the HIR. We report here substantial differences in the rates of the dark reactions between different seed batches of a single species (Sinapis alba L.), and also between different organs of seedlings from each of the batches of seed. Calculations of phytochrome dynamics from the measured dark-reaction rates show that the behaviour of Pfr under HIR conditions will vary considerably according to seed batch and seedling organ. Much larger differences in dark-reaction rates, and the resulting phytochrome dynamics, were found between 25° and 10° C. These lead to the prediction that the HIR will be much reduced at the lower temperature, and may be absent in some cases.