Patient Specific Model

Strand LM, Guerrero RM, Nickman NA, Morley PC. 1990. Integrated patient-specific model of pharmacy practice. Am J Health-Syst Pharm 47 550. 

Simulation of the Gait of a Patient Specific Model of Post Polio Residual Paralysis... 

Keywords— Patient Specific Model, Poliomyelitis, Orthosis, Orthopaedics, Gait Kinematics and Kinetics, Lower Limbs. 

Patient-specific and modelling-aided clinical treatment could, therefore, become a reality within the first decade of this millennium ... 

In silico models will aid both the standardisation and individualisation of medical care. Standardisation of diagnoses, drug and device descriptions, procedures, etc. will make relevant information more readily and more widely available. On the other hand, advanced models will allow development of patient-specific procedures for diagnosis and treatment. This will move the focus from the treatment of diseases to the curing of patients. 

The Stroke-Thrombolytic Predictive Instrument (Stroke-TPI) has recently been developed in order to provide patient-specific estimates of the probability of a more favorable outcome with rt-PA, and has been proposed as a decision-making aid to patient selection for rt-PA." The estimates from this tool should, however, be treated with caution. The prediction rule is dependent on post hoc mathematical modeling, uses clinical trial data from subjects randomized beyond 3 hours who are not rt-PA-eligible according to FDA labeling and current best practice, and has not been externally validated. It is, therefore, not appropriate to exclude patients from rt-PA treatment based solely on Stroke-TPI predictions. 

Kinetic- information is acquired lor two different purposes. Hirst, data are needed lor specific modeling applications that extend beyond chemical theory. These arc essential ill the design of practical industrial processes and are also used io interpret natural phenomena such as Ihe observed depletion of stratospheric ozone. Compilations of measured rate constants are published in the United Stales by the National Institute of Standards and Technology (NISTt. Second, kinetic measurements are undertaken to elucidate basic mechanisms of chemical change, simply to understand the physical world The ultimate goal is control of reactions, but the immediate significance lies in the patients of kinetic behavior and the interpretation in terms of microscopic models. 

CHD or CHD equivalents. Specific models for therapeutic life-style changes and drug therapy in the primary prevention of CHD have been recommended by ATP III (Figures 26-23 and 26-24). As for the management of patients with metabolic syndrome, a combination approach of weight reduction, increased physical activity, and appropriate control of lipid levels is recommended. 

The NPML approach provides an estimate of the whole probability distribution of the PK parameters on a nonparametric basis (67). The method relies on maximization of the likelihood of the set of observations of all individuals to estimate the distribution of the parameters. The basic conceptual framework is similar to that described for NONMEM above. The difference is that no specihc model for the relationship between PK parameters and patient-specific covariates is specified. The individual parameters (pi are assumed to be independent realizations of a given random variable O with probability distribution F([Pg.278]

Complex pharmacokinetic/pharmacodynamic (PK/PD) simulations are usually developed in a modular manner. Each component or subsystem of the overall simulation is developed one-by-one and then each component is linked to run in a continuous manner (see Figure 33.2). Simulation of clinical trials consists of a covariate model and input-output model coupled to a trial execution model (10). The covariate model defines patient-specific characteristics (e.g., age, weight, clearance, volume of distribution). The input-output model consists of all those elements that link the known inputs into the system (e.g., dose, dosing regimen, PK model, PK/PD model, covariate-PK/PD relationships, disease progression) to the outputs of the system (e.g., exposure, PD response, outcome, or survival). In a stochastic simulation, random error is introduced into the appropriate subsystems. For example, between-subject variability may be introduced among the PK parameters, like clearance. The outputs of the system are driven by the inputs... 

Despite the differences with respect to the desired serum concentration goals, evaluation of aminoglycoside levels and pharmacokinetic adjustment of dosing regimens are common to both approaches. Using a first-order pharmacokinetic model, patient-specific elimination and volume of distribution can be calculated based on... 

Fig. 4 Using Human Pluripotent Stem Cells for Disease Modeling. Patient-specific somatic cells (e.g. skin fibroblasts) can be reprogrammed into induced pluripotent stem cells (iPSCs) using specific genetic factors. Neuronal cells with specific disease phenotypes can be differentiated to neural stem cells. The development of in vitro cellular models based on patient-specific cells may lead to personalized medicine approaches with minimal side effects and improved pharmacological efficacy.

Calo VM, Brasher NP, Bazilevs Y, Hughes TJR (2008) Multiphysics model for blood flow and drug transport with application to patient-specific coronary artery fiow. Comput Mech 43 161-177... 

Animal models of disease that might be considered for use in SP shonld be dictated by whether or not they improve predictive value of adverse reactions in patients, bnt of course they may also be valuable/preferred in studies on mechanism of action and efficacy. Scientists may be guided by selection of specific models that are well known to manifest increased sensitivity for adverse reactions in the clinic (e.g., obesity, senility, heart failure, hypertrophy, diabetes). Clinicians already know, and consider in design of clinical trials, many features of subjects (e.g., age, geographical location, sex, somatotype, strain) that inflnence the outcome of smdies. It is likely that diversity of subjects in preclinical smdies is as important as diversity of snbjects in clinical studies. My suspicion is that smdies conducted on one mouse, one rat, one rabbit, one gninea pig, one dog, and one monkey per each of four groups (vehicle, low dose, mid... 

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