Accuracy of glomerular filtration rate estimation using creatinine and cystatin C for identifying and monitoring moderate chronic kidney disease: the eGFR-C study.

Background: Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS. Objectives: Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies. Design: A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline (n = 1167) and their ability to detect change over 3 years (n = 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components (n = 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs (n = 875). Setting: Primary, secondary and tertiary care. Participants: Adults (≥ 18 years) with stage 3 chronic kidney disease. Interventions: Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations. Main outcome measures: Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated. Results: Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine-cystatin equation (94.9%) was superior (p < 0.001) to other equations. Within each equation, no differences in P30 were seen across categories of age, gender, diabetes, albuminuria, body mass index, kidney function level and ethnicity. All equations showed poor (< 63%) sensitivity for detecting patients showing kidney function decline crossing clinically significant thresholds (e.g. a 25% decline in function). Consequently, the additional cost of monitoring kidney function annually using a cystatin C-based equation could not be justified (incremental cost per patient over 10 years = £43.32). Modelling data showed association between higher albuminuria and faster decline in measured and creatinine-estimated glomerular filtration rate. Reference change values for measured glomerular filtration rate (%, positive/negative) were 21.5/-17.7, with lower reference change values for estimated glomerular filtration rate. Limitations: Recruitment of people from South Asian and African-Caribbean backgrounds was below the study target. Future work: Prospective studies of the value of cystatin C as a risk marker in chronic kidney disease should be undertaken. Conclusions: Inclusion of cystatin C in glomerular filtration rate-estimating equations marginally improved accuracy but not detection of disease progression. Our data do not support cystatin C use for monitoring of glomerular filtration rate in stage 3 chronic kidney disease. Trial registration: This trial is registered as ISRCTN42955626. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.

Chronic kidney disease, which affects approximately 14% of the adult population, often has no symptoms but, in some people, may later develop into kidney failure. Kidney disease is most often detected using a blood test called creatinine. Creatinine does not identify everyone with kidney disease, or those most likely to develop more serious kidney disease. An alternative blood test called cystatin C may be more accurate, but it is more expensive than the creatinine test. We compared the accuracy of these two tests in more than 1000 people with moderate kidney disease. Participants were tested over 3 years to see if the tests differed in their ability to detect worsening kidney function. We also wanted to identify risk factors associated with loss of kidney function, and how much the tests normally vary to better understand what results mean. We compared the accuracy and costs of monitoring people with the two markers. Cystatin C was found slightly more accurate than the creatinine test at estimating kidney function when comparing the baseline single measurements (95% accurate compared to 90%), but not at detecting worsening function over time. This means that the additional cost of monitoring people over time with cystatin C to detect kidney disease progression could not be justified. Kidney test results could vary by up to 20% between tests without necessarily implying changes in underlying kidney function ­ this is the normal level of individual variation. Cystatin C marginally improved accuracy of kidney function testing but not ability to detect worsening kidney function. Cystatin C improves identification of moderate chronic kidney disease, but our results do not support its use for routine monitoring of kidney function in such patients.

Cost-Effectiveness of Plasma Microbial Cell-Free DNA Sequencing When Added to Usual Care Diagnostic Testing for Immunocompromised Host Pneumonia.

INTRODUCTION: Immunocompromised host pneumonia (ICHP) is an important cause of morbidity and mortality, yet usual care (UC) diagnostic tests often fail to identify an infectious etiology. A US-based, multicenter study (PICKUP) among ICHP patients with hematological malignancies, including hematological cell transplant recipients, showed that plasma microbial cell-free DNA (mcfDNA) sequencing provided significant additive diagnostic value. AIM: The objective of this study was to perform a cost-effectiveness analysis (CEA) of adding mcfDNA sequencing to UC diagnostic testing for hospitalized ICHP patients. METHODS: A semi-Markov model was utilized from the US third-party payer's perspective such that only direct costs were included, using a lifetime time horizon with discount rates of 3% for costs and benefits. Three comparators were considered: (1) All UC, which included non-invasive (NI) and invasive testing and early bronchoscopy; (2) All UC & mcfDNA; and (3) NI UC & mcfDNA & conditional UC Bronch (later bronchoscopy if the initial tests are negative). The model considered whether a probable causative infectious etiology was identified and if the patient received appropriate antimicrobial treatment through expert adjudication, and if the patient died in-hospital. The primary endpoints were total costs, life-years (LYs), equal value life-years (evLYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio per QALY. Extensive scenario and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: At a price of $2000 (2023 USD) for the plasma mcfDNA, All UC & mcfDNA was more costly ($165,247 vs $153,642) but more effective (13.39 vs 12.47 LYs gained; 10.20 vs 9.42 evLYs gained; 10.11 vs 9.42 QALYs gained) compared to All UC alone, giving a cost/QALY of $16,761. NI UC & mcfDNA & conditional UC Bronch was also more costly ($162,655 vs $153,642) and more effective (13.19 vs 12.47 LYs gained; 9.96 vs 9.42 evLYs gained; 9.96 vs 9.42 QALYs gained) compared to All UC alone, with a cost/QALY of $16,729. The PSA showed that above a willingness-to-pay threshold of $50,000/QALY, All UC & mcfDNA was the preferred scenario on cost-effectiveness grounds (as it provides the most QALYs gained). Further scenario analyses found that All UC & mcfDNA always improved patient outcomes but was not cost saving, even when the price of mcfDNA was set to $0. CONCLUSIONS: Based on the evidence available at the time of this analysis, this CEA suggests that mcfDNA may be cost-effective when added to All UC, as well as in a scenario using conditional bronchoscopy when NI testing fails to identify a probable infectious etiology for ICHP. Adding mcfDNA testing to UC diagnostic testing should allow more patients to receive appropriate therapy earlier and improve patient outcomes.

Optical penetration models for practical prediction of femtosecond laser ablation of dental hard tissue.

OBJECTIVES: To develop and practically test high-precision femtosecond laser ablation models for dental hard tissue that are useful for detailed planning of automated laser dental restorative treatment. METHODS: Analytical models are proposed, derived, and demonstrated for practical calculation of ablation rates, ablation efficiency and ablated morphology of human dental enamel and dentin using femtosecond lasers. The models assume an effective optical attenuation coefficient for the irradiated material. To achieve ablation, it is necessary for the local energy density of the attenuated pulse in the hard tissue to surpass a predefined threshold that signifies the minimum energy density required for material ionization. A 1029 nm, 40 W carbide 275 fs laser was used to ablate sliced adult human teeth and generate the data necessary for testing the models. The volume of material removed, and the shape of the ablated channel were measured using optical profilometry. RESULTS: The models fit with the measured ablation efficiency curve against laser fluence for both enamel and dentin, correctly capturing the fluence for optimum ablation and the volume of ablated material per pulse. The detailed shapes of a 400-micrometer wide channel and a single-pulse width channel are accurately predicted using the superposition of the analytical result for a single pulse. CONCLUSIONS: The findings have value for planning automated dental restorative treatment using femtosecond lasers. The measurements and analysis give estimates of the optical properties of enamel and dentin irradiated with an infrared femtosecond laser at above-threshold fluence and the proposed models give insight into the physics of femtosecond laser processing of dental hard tissue.

Dynamic Copper Site Redispersion through Atom Trapping in Zeolite Defects.

Single-site copper-based catalysts have shown remarkable activity and selectivity for a variety of reactions. However, deactivation by sintering in high-temperature reducing environments remains a challenge and often limits their use due to irreversible structural changes to the catalyst. Here, we report zeolite-based copper catalysts in which copper oxide agglomerates formed after reaction can be repeatedly redispersed back to single sites using an oxidative treatment in air at 550 °C. Under different environments, single-site copper in Cu-Zn-Y/deAlBeta undergoes dynamic changes in structure and oxidation state that can be tuned to promote the formation of key active sites while minimizing deactivation through Cu sintering. For example, single-site Cu2+ reduces to Cu1+ after catalyst pretreatment (270 °C, 101 kPa H2) and further to Cu0 nanoparticles under reaction conditions (270-350 °C, 7 kPa EtOH, 94 kPa H2) or accelerated aging (400-450 °C, 101 kPa H2). After regeneration at 550 °C in air, agglomerated CuO was dispersed back to single sites in the presence and absence of Zn and Y, which was verified by imaging, in situ spectroscopy, and catalytic rate measurements. Ab initio molecular dynamics simulations show that solvation of CuO monomers by water facilitates their transport through the zeolite pore, and condensation of the CuO monomer with a fully protonated silanol nest entraps copper and reforms the single-site structure. The capability of silanol nests to trap and stabilize copper single sites under oxidizing conditions could extend the use of single-site copper catalysts to a wider variety of reactions and allows for a simple regeneration strategy for copper single-site catalysts.

Subfemtowatt Laser Phase Tracking.

Low power optical phase tracking is an enabling capability for intersatellite laser interferometry, as minimum trackable power places significant constraints on mission design. Through the combination of laser stabilization and control-loop parameter optimization, we have demonstrated continuous tracking of a subfemtowatt optical field with a mean time between slips of more than 1000 s. Comparison with analytical models and numerical simulations verified that the observed experimental performance was limited by photon shot noise and unsuppressed laser frequency fluctuations. Furthermore, with two stabilized lasers, we have demonstrated 100 min of continuous phase tracking of Gravity Recovery and Climate Experiment (GRACE)-like signal dynamics with an optical carrier ranging in power between 1-7 fW with zero cycle slips. These results indicate the feasibility of future interspacecraft laser links operating with significantly reduced received optical power.

Perceptions and Attitudes Regarding Medical Device Development in Canada Among Canadian Innovators: A Qualitative Study.

OBJECTIVES: The Canadian medical device industry presents unique challenges to innovators. However, little attention has been paid to exploring the distinct experience of Canadian medical device innovators in the literature. The objective of this study is to explore the experience of Canadian innovators in navigating this industry, with a focus on their perceptions and attitudes towards the use of health economic evaluation. METHODS: Semi-structured interviews were conducted using virtual conferencing technology. All participants were C-level employees of small- and medium-sized enterprises (SMEs) with adequate knowledge of their company's overall strategy. Qualitative data were analyzed to reveal emerging themes. RESULTS: Interviews were performed with ten participants. Forty percent of participants rated themselves as having either minimal or basic knowledge of health economics. Thirty percent of participants had not pursued early economic evaluation of their device, while 90% rated health economics as being either "Quite important" or "Very important" to their company. The perception of increased barriers to successful device adoption in Canada relative to the USA was a prominent sentiment among participants, with 50% expressing discontentment with either the device approval process or health technology assessment process in Canada. Twenty percent stated that their primary target market involved the USA and/or other international jurisdictions. CONCLUSION: Canadian medical device innovators appear to understand the importance of health economic evaluation in the innovation process. However, they report difficulty with device approval and adoption, with some innovators focusing their efforts outside of Canada altogether. Further research should be directed toward understanding how to better support SMEs, given that they are a tremendous source of growth for the Canadian medical device industry.

Symmetry Breaking for Voting Mechanisms.

Recently, Rowe and Aishwaryaprajna (2019) introduced a simple majority vote technique that efficiently solves Jump with large gaps, OneMax with large noise, and any monotone function with a polynomial-size image. In this paper, we identify a pathological condition for this algorithm: the presence of spin-flip symmetry in the problem instance. Spin-flip symmetry is the invariance of a pseudo-Boolean function to complementation. Many important combinatorial optimization problems admit objective functions that exhibit this pathology, such as graph problems, Ising models, and variants of propositional satisfiability. We prove that no population size exists that allows the majority vote technique to solve spin-flip symmetric functions of unitation with reasonable probability. To remedy this, we introduce a symmetry-breaking technique that allows the majority vote algorithm to overcome this issue for many landscapes. This technique requires only a minor modification to the original majority vote algorithm to force it to sample strings in {0,1}n from a dimension n-1 hyperplane. We prove a sufficient condition for a spin-flip symmetric function to possess in order for the symmetry-breaking voting algorithm to succeed, and prove its efficiency on generalized TwoMax, a spin-flip symmetric variant of Jump, and families of constructed 3-NAE-SAT and 2-XOR-SAT formulas. We also prove that the algorithm fails on the one-dimensional Ising model, and suggest different techniques for overcoming this. Finally, we present empirical results that explore the tightness of the runtime bounds and the performance of the technique on randomized satisfiability variants.

Exploring the approach to parameter uncertainty in early economic evaluations of surgical technology - a systematic review.

INTRODUCTION: The role of early economic evaluation (EEE) in the development of medical technology has been increasingly recognized; however, data on the use of EEE in surgical technology are sparse. The objective of this review was to explore the use of EEE in the development of surgical technologies, with emphasis on how uncertainty has been addressed. AREAS COVERED: A systematic review was conducted, and original articles employing any form of EEE of surgical technology were selected for review, with 10 studies included in the analysis. These studies demonstrated significant variation in the approach to managing parameter uncertainty, specifically regarding the type of analysis used and the inclusion of effectiveness parameters in sensitivity analysis. The conclusions drawn did not appear to factor in uncertainty in the models. EXPERT OPINION: Approaches to handling parameter uncertainty in previous EEEs of surgical technology have been limited, with some studies failing to address parameter uncertainty. In addition, EEEs do not appear to follow established guidelines with respect to the use of sensitivity analyses. It is important that EEEs of surgical technology address parameter uncertainty in order to draw more robust conclusions from the analysis and allow investors to consider this uncertainty when making investment decisions.

Absolute frequency readout derived from ULE cavity for next generation geodesy missions: erratum.

We found a calculation error affecting the scaling of results presented in Figure 7 of our article "Absolute frequency readout derived from ULE cavity for next generation geodesy missions" [Opt. Express2926014 (2021)10.1364/OE.434483] . The corrected Figure 7 is published here.

Detection statistics for coherent RMCW LiDAR.

This paper presents an analytical model and experimental validation for the detection performance and false-alarm rates for phase-encoded random modulation continuous-wave (RMCW) LiDAR. Derivation of the model focuses on propagating the effects of relevant noise sources through the system to determine an analytical expression for the detection rate, expressed by the probability of detection. The model demonstrates that probability of detection depends only on three factors: i) the mean signal-to-noise ratio (SNR) of the measurement; ii) the measurement integration time; and iii) speckle-induced intensity noise. The predicted analytical relationship between measurement SNR and probability of detection was validated by numerical simulations and experimental demonstrations in both a controlled fiber channel and under fully-developed speckle conditions in an uncontrolled free-space channel.

Absolute frequency readout derived from ULE cavity for next generation geodesy missions.

The next generation of Gravity Recovery and Climate Experiment (GRACE)-like dual-satellite geodesy missions proposals will rely on inter-spacecraft laser interferometry as the primary instrument to recover geodesy signals. Laser frequency stability is one of the main limits of this measurement and is important at two distinct timescales: short timescales over 10-1000 seconds to measure the local gravity below the satellites, and at the month to year timescales, where the subsequent gravity measurements are compared to indicate loss or gain of mass (or water and ice) over that period. This paper demonstrates a simple phase modulation scheme to directly measure laser frequency change over long timescales by comparing an on-board Ultra-Stable Oscillator (USO) clocked frequency reference to the Free Spectral Range (FSR) of the on-board optical cavity. By recording the fractional frequency variations the scale correction factor may be computed for a laser locked to a known longitudinal mode of the optical cavity. The experimental results demonstrate a fractional absolute laser frequency stability at the 10 ppb level (10-8) at time scales greater than 10 000 seconds, likely sufficient for next generation mission requirements.

High stability laser locking to an optical cavity using tilt locking.

This paper describes, to our knowledge, the first demonstration of high performance tilt locking, a method of stabilizing laser frequency to an optical reference cavity using a spatial-mode readout technique. The experiment utilized a traveling wave cavity with a finesse of approximately 10,000, housed in a thermally controlled vacuum chamber. The tilt locking method in a double pass configuration has promising performance in the 100 µHz-1 Hz band, including surpassing the Gravity Recovery and Climate Experiment (GRACE) Follow-On laser ranging interferometer requirement. Tilt locking offers a number of benefits such as high sensitivity, low cost, and simple implementation and therefore should be considered for future applications requiring high performance laser locking, such as future laser-based satellite geodesy missions and the Laser Interferometer Space Antenna.

Engineering Challenges of Solution and Slurry-Phase Chemical Hydrogen Storage Materials for Automotive Fuel Cell Applications.

We present the research findings of the DOE-funded Hydrogen Storage Engineering Center of Excellence (HSECoE) related to liquid-phase and slurry-phase chemical hydrogen storage media and their potential as future hydrogen storage media for automotive applications. Chemical hydrogen storage media other than neat liquid compositions will prove difficult to meet the DOE system level targets. Solid- and slurry-phase chemical hydrogen storage media requiring off-board regeneration are impractical and highly unlikely to be implemented for automotive applications because of the formidable task of developing solid- or slurry-phase transport systems that are commercially reliable and economical throughout the entire life cycle of the fuel. Additionally, the regeneration cost and efficiency of chemical hydrogen storage media is currently the single most prohibitive barrier to implementing chemical hydrogen storage media. Ideally, neat liquid-phase chemical hydrogen storage media with net-usable gravimetric hydrogen capacities of greater than 7.8 wt% are projected to meet the 2017 DOE system level gravimetric and volumetric targets. The research presented herein is a collection of research findings that do not in and of themselves warrant a dedicated manuscript. However, the collection of results do, in fact, highlight the engineering challenges and short-comings in scaling up and demonstrating fluid-phase ammonia borane and alane compositions that all future materials researchers working in hydrogen storage should be aware of.

A Multicenter Randomized Controlled Trial Comparing Safety, Efficacy, and Cost-effectiveness of the Surgisis Anal Fistula Plug Versus Surgeon's Preference for Transsphincteric Fistula-in-Ano: The FIAT Trial.

OBJECTIVE: To undertake a randomized comparison of the Biodesign Surgisis anal fistula plug against surgeon's preference in treating cryptoglandular transsphincteric fistula-in-ano. SUMMARY BACKGROUND DATA: The efficacy of the Biodesign Surgisis anal fistula plug in healing anal fistulae is uncertain. METHODS: Participants were randomized to the fistula plug with surgeon's preference (advancement flap, cutting seton, fistulotomy, Ligation of the Intersphincteric Fistula Tract procedure). The primary outcome was faecal incontinence quality of life (FIQoL) at 12-months. Secondary outcomes were fistula healing, incontinence rates, and complication and reintervention rates. RESULTS: Between May 2011 and March 2016, 304 participants were randomized to fistula plug or surgeon's preference. No differences were seen in FIQoL between the 2 groups at 12 months. Clinical fistula healing was reported in 66/122 (54%) of the fistula plug and 66/119 (55%) of the surgeon's preference groups at 12 months. Fecal incontinence rates improved marginally in both the groups. Complications and reinterventions were frequent, with significantly more complications in the fistula plug group at 6-weeks (49/142, 35% vs 25/137, 18%; P=0.002). The mean total costs were £2738 (s.d. £1151) for the fistula plug and £2308 (s.d. £1228) for the surgeon's preference group (mean difference +£430, P=0.0174). The average total quality adjusted life years (QALYs) gained was marginally higher in the fistula plug group. The fistula plug was 35% to 45% likely to be cost-effective across a willingness to pay threshold of £20,000 to £30,000 / QALY. CONCLUSIONS: The Biodesign Surgisis anal fistula plug is associated with similar FIQoL and healing rates to surgeon's preference at 12 months. Higher costs and highly uncertain gains in QALYs mean that the fistula plug may not be considered as a cost-effective treatment in the UK NHS.

Probabilistic One-Way Sensitivity Analysis with Multiple Comparators: The Conditional Net Benefit Frontier.

Although there have been substantial developments in the analysis of uncertainty in economic evaluations of health care programmes, the development of methods for one-way sensitivity analysis has been notably slower. Conditional incremental net benefit was recently proposed as an approach for implementing probabilistic one-way sensitivity analysis for economic evaluations comparing two strategies. In this paper, we generalise this approach to economic evaluations that compare three or more strategies. We find that 'conditional net benefit' may be used to conduct probabilistic one-way sensitivity analysis for economic evaluations comparing any number of strategies. We also propose the 'conditional net benefit frontier', which may be used to identify the most cost-effective of any number of strategies conditional upon the specific value of a parameter of interest.

Cost-effectiveness of a new autoantibody test added to Computed Tomography (CT) compared to CT surveillance alone in the diagnosis of lung cancer amongst patients with indeterminate pulmonary nodules.

Oncimmune's EarlyCDT®-Lung is a simple ELISA blood test that measures seven lung cancer specific autoantibodies and is used in the assessment of malignancy risk in patients with indeterminate pulmonary nodules (IPNs). The objective of this study was to examine the cost-effectiveness of EarlyCDT-Lung in the diagnosis of lung cancer amongst patients with IPNs in addition to CT surveillance, compared to CT surveillance alone which is the current recommendation by the British Thoracic Society guidelines. A model consisting of a combination of a decision tree and Markov model was developed using the outcome measure of the quality adjusted life year (QALY). A life-time time horizon was adopted. The model was parameterized using a range of secondary sources. At £70 per test, EarlyCDT-Lung and CT surveillance was found to be cost-effective compared to CT surveillance alone with an incremental cost-effectiveness ratio (ICER) of less than £2,500 depending on the test accuracy parameters used. It was also found that EarlyCDT-Lung can be priced up to £1,177 and still be cost-effective based on cost-effectiveness acceptance threshold of £20,000 / QALY. Further research to resolve parameter uncertainty, was not found to be of value. The results here demonstrate that at £70 per test the EarlyCDT-Lung will have a positive impact on patient outcomes and coupled with CT surveillance is a cost-effective approach to the management of patients with IPNs. The conclusions drawn from this analysis are robust to realistic variation in the parameters used in the model.

One-Way Sensitivity Analysis for Probabilistic Cost-Effectiveness Analysis: Conditional Expected Incremental Net Benefit.

Although probabilistic analysis has become the accepted standard for decision analytic cost-effectiveness models, deterministic one-way sensitivity analysis continues to be used to meet the need of decision makers to understand the impact that changing the value taken by one specific parameter has on the results of the analysis. The value of a probabilistic form of one-way sensitivity analysis has been recognised, but the proposed methods are computationally intensive. Deterministic one-way sensitivity analysis provides decision makers with biased and incomplete information whereas, in contrast, probabilistic one-way sensitivity analysis (POSA) can overcome these limitations, an observation supported in this study by results obtained when these methods were applied to a previously published cost-effectiveness analysis to produce a conditional incremental expected net benefit curve. The application of POSA will provide decision makers with unbiased information on how the expected net benefit is affected by a parameter taking on a specific value and the probability that the specific value will be observed.

Early Economic Evaluation to Identify the Necessary Test Characteristics of a New Typhoid Test to be Cost Effective in Ghana.

BACKGROUND: In Ghana, there are issues with the diagnosis of typhoid fever; these include delays in diagnosis, concerns about the accuracy of current tests, and lack of availability. These issues highlight the need for the development of a rapid, accurate, and easily accessible diagnostic test. The aim of this study was to conduct an early economic analysis of a hypothetical rapid test for typhoid fever diagnosis in Ghana and identify the necessary characteristics of the test for it to be cost effective in Ghana. METHODS: An early cost-utility analysis was conducted using a decision tree parameterized with secondary data sources, with reasonable assumptions made for unknown parameters. The patient population considered is individuals presenting with symptoms suggestive of typhoid fever at a healthcare facility in Ghana; a time horizon of 180 days and the Ghanaian national health service perspective were adopted for the analysis. Extensive sensitivity analysis was undertaken, including headroom analysis. RESULTS: The results here show that for a hypothetical test to perform better than the existing test (Widal) in terms of QALYs gained and cost effectiveness, it is necessary for it to have a high specificity (at least 70%) and should not be priced more than US$4. The overall value of conducting research to reduce uncertainty (over 5 years) is US$3287. CONCLUSION: The analysis shows the potential for the hypothetical test to replace the Widal test and the market potential of developing a new test in the Ghanaian setting.