Effect of Lipid Bilayers on Prion Peptide Aggregation: Insights from Coarse-Grained Molecular Simulations

No. 4841 - No. 484

How are we evaluating the cost-effectiveness of companion biomarkers for targeted cancer therapies? A systematic review.

BACKGROUND: Despite the increasing economic assessment of biomarker-guided therapies, no clear agreement exists whether existing methods are sufficient or whether different methods might produce different cost-effectiveness results. This study aims to examine current practices of modeling companion biomarkers when assessing the cost-effectiveness of targeted cancer therapies. It investigates the current methods in modeling the characteristics of companion diagnostics based on existing economic evaluations of biomarker-guided therapies in cancer. METHODS: A literature search was performed using Medline, Embase, EconLit, Cochrane library for economic evaluations of biomarker-guided therapies with companion diagnostics in cancer. Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Studies were selected using pre-specified eligibility criteria based on the PICO framework. To make the included studies more comparable, we qualitatively synthesized the data under nine domains of methods where consensus was deemed lacking. RESULTS: Only four of the twenty-two studies included in this review were found to be of good quality with respect to incorporating the characteristics of companion biomarkers in economic evaluations. However, many evaluations focused on a pre-selected patient group rather than including all patients regardless of their biomarker status. Companion biomarker characteristics captured in evaluations were often limited to the cost or the accuracy of the test. Often, only the costs of biomarker testing were modelled. Clinical outcomes and health state utilities were often not included due to the limited data generated by clinical trials. Methods of economic evaluation were not applied consistently in assessments of companion cancer biomarkers for targeted therapies. It was also shown that conflicting cost-effectiveness results were likely depending on what comparator arm was chosen and what comparison structure was designed in the model. CONCLUSION: We found no consistent approach applied in assessing the value of companion biomarker tests and including the characteristics of biomarkers in an economic evaluation of targeted oncology therapies. Currently, many economic evaluations fail to capture the full value of companion biomarkers beyond sensitivity/specificity and cost related to biomarker testing

Cost-effectiveness analysis of vaccinating children in Malawi with RTS,S vaccines in comparison with long-lasting insecticide-treated nets

BACKGROUND: New RTS,S malaria vaccines may soon be licensed, yet its cost-effectiveness is unknown. Before the widespread introduction of RTS,S vaccines, cost-effectiveness studies are needed to help inform governments in resource-poor settings about how best to prioritize between the new vaccine and existing malaria interventions. METHODS: A Markov model simulated malaria progression in a hypothetical Malawian birth cohort. Parameters were based on published data. Three strategies were compared: no intervention, vaccination at one year, and long-lasting, insecticide-treated nets (LLINs) at birth. Both health service and societal perspectives were explored. Health outcomes were measured in disability-adjusted life years (DALYs) averted and costed in 2012 US$. Incremental cost-effectiveness ratios (ICERs) were calculated and extensive sensitivity analyses were conducted. Three times GDP per capita ($1,095) per DALY averted was used for a cost-effectiveness threshold, whilst one times GDP ($365) was considered ‘very cost-effective’. RESULTS: From a societal perspective the vaccine strategy was dominant. It averted 0.11 more DALYs than LLINs and 0.372 more DALYs than the no intervention strategy per person, while costing$10.04 less than LLINs and $59.74 less than no intervention. From a health service perspective the vaccine’s ICER was$145.03 per DALY averted, and thus can be considered very cost-effective. The results were robust to changes in all variables except the vaccine and LLINs’ duration of efficacy. Vaccines remained cost-effective even at the lowest assumed efficacy levels of 49.6% (mild malaria) and 14.2% (severe malaria), and the highest price of $15. However, from a societal perspective, if the vaccine duration efficacy was set below 2.69 years or the LLIN duration of efficacy was greater than 4.24 years then LLINs became the more cost-effective strategy. CONCLUSION: The results showed that vaccinating Malawian children with RTS,S vaccines was very cost-effective from both a societal and a health service perspective. This result was robust to changes in most variables, including vaccine price and vaccine efficacy, but was sensitive to the duration of efficacy of the vaccine and LLINs. Given the best evidence currently available, vaccines can be considered as a very cost-effective component of Malawi’s future malaria control programmes. However, long-term follow-up studies on both interventions are needed

Has the development of cancer biomarkers to guide treatment improved health outcomes?

During the last decade, testing the patient’s biomarker status prior to the administration of corresponding co-dependent therapies has been emerging in clinical practice. These biomarker-guided therapies have promoted the promise of more personalized medicine, with the prescription of the right treatment to the right patient, while avoiding expensive ineffective drugs and adverse drug reactions. Cancer treatments have especially taken advantage of this technology. We assess how the introduction of biomarker tests guiding cancer therapy have affected the premature mortality and survival of cancer patients in Norway. Our findings suggest that, in general, cancer patients have benefited from both biomarker testing and more cancer drugs. Furthermore, we find that the total effect of biomarker testing on 3-year survival decreases as the number of drugs available increases, suggesting that the matching of patients with the appropriate treatment is better when fewer drugs are available.publishedVersio

A Practical Guide to Modeling and Conducting a Cost-Effectiveness Analysis of Companion Biomarker Tests for Targeted Therapies Using R: Tutorial Paper.

Despite the increasing number of potential biomarkers identified in laboratories and reported in much literature, the adoption of biomarkers routinely available in clinical practice to inform treatment decisions is very limited. Reimbursement decisions for new health technologies are often informed by economic evaluations; however, economic evaluations of diagnostics/testing technologies, such as companion biomarker tests, are far less frequently reported than drugs. Furthermore, few countries provide the health economic evaluation methods guide specific to co-dependent technologies such as companion diagnostics or precision medicines. Therefore, this paper aims to guide the process of the development of cost-effectiveness models of cancer biomarkers for targeted therapies, focusing on companion diagnostics. This tutorial paper provides practical guidance on how to conduct economic evaluations of cancer biomarkers and how to model the characteristics of the biomarker tests as part of the value for money of corresponding targeted therapies. This paper presents a brief introduction to the methods and data requirements, a step-by-step guide to constructing a health economic model of companion cancer biomarkers, and a discussion of issues that arise in their application to healthcare decision making. This practical guidance is provided in R, and worked examples are provided in this paper with R codes in the accompanying electronic supplementary material

Cancer Biomarkers: Ethics, Economics and Society

publishedVersio

Is point-of-care testing feasible and safe in care homes in England? An exploratory usability and accuracy evaluation of a point-of-care polymerase chain reaction test for SARS-CoV-2

Introduction: Reliable rapid testing for COVID-19 is needed in care homes to reduce the risk of outbreaks and enable timely care. This study aimed to examine the usability and test performance of a point of care polymerase chain reaction (PCR) test for detection of SARS-COV2 (POCKITTM Central) in care homes.Methods: POCKITTM Central was evaluated in a purposeful sample of four UK care homes. Test agreement with laboratory real-time PCR and usability and use errors were assessed.Results: No significant usability-related hazards emerged, and the sources of error identified were found to be amendable with minor changes in training or test workflow. POCKITTM Central has acceptable sensitivity and specificity based on RT-PCR as the reference standard, especially for symptomatic cases.Asymptomatic specimens showed 83.3% (95% CI: 35.9%-99.6%) positive agreement and 98.7% negative agreement (95% CI: 96.2%-99.7%), with overall prevalence and bias-adjusted kappa (PABAK) of 0.965 (95% CI: 0.932– 0.999). Symptomatic specimens showed 100% (95% CI: 2.5%-100%) positive agreement and 100% negative agreement (95% CI: 85.8%-100%), with overall PABAK of 1.Recommendations are provided to mitigate the frequency of occurrence of the residual use errors observed. Integration pathways were discussed to identify opportunities and limitations of adopting POCKIT™ Central for screening and diagnostic testing purposes.Conclusion: Point-of-care PCR testing in care homes can be considered with appropriate preparatory steps and safeguards. Further diagnostic accuracy evaluations and in-service evaluation studies should be conducted, if the test is to be implemented more widely, to build greater certainty on this initial exploratory analysis

Improving Internal Peptide Dynamics in the Coarse-Grained MARTINI Model: Toward Large-Scale Simulations of Amyloid- and Elastin-like Peptides

We present an extension of the coarse-grained MARTINI model for proteins and apply this extension to amyloid- and elastin-like peptides. Atomistic simulations of tetrapeptides, octapeptides, and longer peptides in solution are used as a reference to parametrize a set of pseudodihedral potentials that describe the internal flexibility of MARTINI peptides. We assess the performance of the resulting model in reproducing various structural properties computed from atomistic trajectories of peptides in water. The addition of new dihedral angle potentials improves agreement with the contact maps computed from atomistic simulations significantly. We also address the question of which parameters derived from atomistic trajectories are transferable between different lengths of peptides. The modified coarse-grained model shows reasonable transferability of parameters for the amyloid- and elastin-like peptides. In addition, the improved coarse-grained model is also applied to investigate the self-assembly of β-sheet forming peptides on the microsecond time scale. The octapeptides SNNFGAIL and (GV)4 are used to examine peptide aggregation in different environments, in water, and at the water–octane interface. At the interface, peptide adsorption occurs rapidly, and peptides spontaneously aggregate in favor of stretched conformers resembling β-strands

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]