Model Reduction on the Wnt Pathway Leads to Biological Adaptation

Complex systems are an unavoidable problem in the field of biology. One of the ways that scientists have tried to overcome this problem is by building mathematical models—manageable representations designed to look at specific physical phenomena. The Wnt Signaling Pathway is a complex system known to regulate cell-to-cell interactions, play a crucial role in Embryonic Development, and has been implicated in the study of cancer. Typically, the Wnt signal is observed through the behavior of a protein called beta-Catenin (β-Catenin). In 2003, Lee et al. built a model of the Wnt pathway which caused β-Catenin to increase over time. However, in 2010, Jensen et al. built a different model of the Wnt pathway which caused β-Catenin to oscillate over time. This project called for model reduction on the Jensen et al. model to identify the phenomenological parameter combinations that determined features of the Wnt oscillations. The method used to reduce the model is called the Manifold Boundary Approximation Method, which is a geometric, parameter-independent method of reducing the model one parameter at a time. Reduction of the model showed that there were 5 variables and 8 parameters which drove the oscillating behavior of the system. After comparing our results to the Lee et al. reduced model of the Wnt pathway done by student Dane Bjork, a minimal model was constructed which predicted a novel class behavior of the Wnt system: biological adaptation

Patent Purchase as a Policy for Pharmaceuticals

We consider a proposal for pharmaceutical patenting policy: namely, for society to grant and purchase the patent of the first of a new class of drug, instead of purchasing the drug, and award no further patents to runner-up drugs, producing or licensing production with price set to maximise welfare subject to cover costs. It is often observed that when the first of a new class of drugs is patented, it does not necessarily halt the development of a second and a third drug of the same class. The result may be a number of rugs with similar efficacy at similar prices well above the production costs. Where this happens, society could substantially reduce the cost of duplicated R&D and the price of the drug by buying the first patent. This would benefit more patients and produce larger health gains. Under this policy social welfare is increased, the winner is fully compensated, while the runner-up firm incurs possible losses - but there are viable conditions under which firms would not lose on average. We take a drug life-cycle approach to the welfare gains of a patent purchase policy. The results are generated based upon a number of stylised facts regarding R&D in the pharmaceutical industry

Case-mix methodology for the NHS outcomes framework GP Patient Survey Questionnaire Data

The objective of the research described in the current report was to explore alternative methodologies which could be used to determine whether the health status of people living with long- term conditions in England is changing over time, all other factors being equal. Data from the Health Survey for England (HSE) were used in the analyses and EQ-5D was used to represent health related quality of life (HRQoL). The proposed case mix ratio approach which utilised ordinary least square regressions (with the EQ-5D preference - based score as the dependent variable) was replicated and alternatives using logistic regressions and two part models (both using the responses to the EQ-5D health dimensions as the dependent variables) were explored. An alternative method using the HSE year as a performance indicator (PI) was explored and results presented for the four most prevalent health conditions. Results were compared in terms of errors in predicted scores and the ability to capture changes in the distributions of the preference-based scores. Both expected and simulated values were compared

Examining productivity losses associated with health related quality of life using patient and general population data

The work described in this report was commissioned by the Department of Health to inform its work on Value-Based-Pricing (VBP), which is due to replace the current Pharmaceutical Pricing Regulation Scheme (PPS) in January 2014 for pricing medicines in the UK. VBP will include additional payments to interventions that are deemed to provide benefit that is of greater social value instead of the current narrow focus on outcomes relevant to the NHS and Personal Social Services (PSS). This requires taking into account wider societal benefits of medicines beyond the health of the patient including productivity. The objective of the analyses was to provide a model to predict productivity losses associated with paid work that were representative of all patients that are likely to be seen in the NHS

The EQ-5D-5L value set for England : response to the “Quality Assurance”

Objectives To respond to the ‘quality assurance’ of the EQ-5D-5L value set for England study. Methods We provide a point-by-point response to the issues raised by the authors of the quality assurance paper, drawing on theoretical arguments, empirical analyses and practical considerations. Results We provide evidence to show that many of the points made by the authors of the quality assurance are misleading, suggest misunderstandings, or are irrelevant. Conclusions The modelling approaches which were used appropriately address the characteristics of the data and provide a reasonable representation of the average stated preferences of general public in England. We provide reflections on the conduct of stated preference studies, and suggestions for the way forward