System and method for monitoring and identifying posology efficacy for an individual

Abstract

A system provides for monitoring and identifying the efficacy of a posology protocol for a therapeutic composition for the treatment of a health condition in a target subject. The system comprises a system controller and a database of pharmacokinetic (PK) models related to the therapeutic composition. A prescriber communicates to the system controller via an interface the prescribed therapeutic composition, the assigned posology protocol and the profile of the target PK model specific to the target subject. The target subject supplies biological samples at given time stamps to determine the concentrations of the therapeutic composition in the target subject during the given times stamps. It is determined if the sample concentrations correspond to the determined PK model or not to identify the efficacy or non-efficacy of the posology protocol. The foregoing is communicated to the prescriber via the interface providing for readjustment of the assigned posology protocol in case of non-efficacy.

Description

SYSTEM AND METHOD FOR MONITORING AND IDENTIFYING POSOLOGY EFFICACY FOR AN INDIVIDUALCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority on United States Provisional Patent Application Serial Number 63 / 539,016 filed on September 18, 2023 and incorporated herein by reference in its entirety.TECHNICAL FIELD

[0002] The present disclosure relates to identifying posology efficacy as well as a response to pharmacotherapy, including adverse effects and identifying the optimal posology (dosage regimen) for a target subject. More particularly, but not exclusively, the present disclosure relates to a system and method for monitoring and identifying the efficacy of a posology protocol assigned to a target subject having one or more health conditions with respect to administration of one or more therapeutic compositions prescribed to the target subject for treatment of the one or more health conditions,BACKGROUND

[0003] Heterogeneity of treatment effect is the nonrandom, explainable variability in the direction and magnitude of treatment effects for individuals within a population. In randomized controlled trials and observational studies of comparative effectiveness usually report an average treatment effect, even though experience suggests that the same treatment can have varying impacts in different people. The clinical experience and expectation from clinical trials that differences in patient prognostic characteristics will lead to heterogeneous responses to therapy is mainly why medicine requires to be personalized. Similar evidence can also be derived regarding treatment related adverse events. A treatment related adverse event can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding),symptom, or disease temporarily associated with the use of a drug, without any judgment about causality or relationship to the drug. An adverse event can arise from any use of the drug (e.g., off-label use, use in combination with another drug) and from any route of administration, formulation, or dose, including an overdose.

[0004] Pharmacokinetics describes the four stages of how much of a drug is going to be absorbed: 1.) absorption occurs after medications enter the body and travel from the site of administration into the body’s circulation; 2.) distribution is the process by which medication is spread throughout the body; 3.) metabolism involves the breakdown of a drug molecule; 4.) excretion refers to the process in which the body eliminates waste. Pharmacodynamics is the study of a drug's molecular, biochemical, and physiologic effects or actions. Drugs produce their effects by interacting with biological targets, but the time course of the pharmacodynamic effect is dependent on the mechanism and biochemical pathway of the target. Pharmacodynamics emphasizes dose-receptor relationships; these are the interactions between the drug's concentration and its effect. Thus, the pharmacologic response depends on the drug binding to its target as well as the concentration of the drug at the receptor site.34In simple terms, the study of pharmacokinetics and pharmacodynamics in drug is often paired and described in reciprocal terms, where pharmacokinetic is the analysis of how the body affects a drug, while pharmacodynamic is the analysis of how a drug affects the body.

[0005] Healthcare professional team members engaged in the prescribing, dosing, dispensing, or administering of pharmacological therapy must be familiar with pharmacokinetic and pharmacodynamics of drugs which vary from an individual to another. Scientists do not have the ability to visualize where a drug is going or how long it is active. To compensate, they use mathematical models based on biological and morphological measurements. However, no matter how effectively a drug works in a laboratory simulation, the performance in the human body will not always produce the same results, and individualized responses to drugs have to beconsidered. It would be therefore safe to assume that the clinical experience and expectation that differences in patient prognostic characteristics will lead to heterogeneous responses to therapy is mainly why medicine is as much an art as it is science.

[0006] Model-informed precision dosing has been defined as a “state-of-the- art” science that falls under the umbrella of precision medicine. The goal of model- informed precision dosing is to improve drug treatment outcomes in patients by achieving the optimal balance between beneficial effect and toxicity for the individual patient. This goal is achieved by leveraging available clinical data with dedicated pharmacometric software capable of applying mathematical models to recommend a personalized dose. In short, model-informed precision dosing could be defined as an advanced quantitative approach with a focus on individualized dosage optimization. As mentioned earlier, it uses mathematical and statistical models of drugs as well as demographic and clinical patient characteristics. Prescription of certain drugs is mainly guided by physicians’ intuition, drawing on common knowledge and experience or, often, a dose calculated according to certain metrics in accordance with the information provided in the drug monograph, including, without limitation, personal data such as age or body weight. However, there is a recognized need for the rationalization of drug uses in patients undergoing pharmacotherapy, particularly when a drug exhibits wide inter-individual variability in both pharmacokinetics and clinical response (e.g., when side effects of a drug or symptoms of a given health issue are variable from person to person), or when the target individual remains unresponsive to pharmacotherapy, exhibits unexpected side effects or when drug interactions can impact upon the efficacy of treatment. United States Patent Number 11 ,185,282 which incorporated herein by reference in its entirety proposed a system for monitoring and identifying the efficacy of posology for a target individual having a health condition with respect to administration of a therapeutic composition assigned thereto for treatment comprises a user interface, a database and a controller in communication with the user interface and thedatabase. The database includes information of health conditions, symptoms, therapeutic compositions, and side effects. The controller comprises a memory of computer implementable steps for receiving information from the user interface regarding the target individual's health conditions, symptoms, therapeutic compositions and side effects assigned to the target individual; comparing the received information to a match with the health conditions, the therapeutic compositions, the symptoms and the side effects; prompting and receiving user feedback; and determining whether the therapeutic composition administered at a dosage should be modified to be increased or decreased.OBJECTS

[0003] An object of the present disclosure is to provide a system for monitoring and identifying the efficacy of a posology protocol assigned to a target subject having one or more health conditions with respect to administration of one or more therapeutic compositions prescribed to the target subject for treatment of the one or more health conditions,

[0004] An object of the present disclosure is to provide a method for monitoring and identifying the efficacy of a posology protocol assigned to a target subject having one or more health conditions with respect to administration of one or more therapeutic compositions prescribed to the target subject for treatment of the one or more health conditions.SUMMARY

[0004] In accordance with an aspect of the present disclosure there is provided a system for monitoring and identifying the efficacy of a posology protocol assigned to a target subject having one or more health conditions with respect to administration of one or more therapeutic compositions prescribed to the target subject for treatment of the one or more health conditions, the system comprising: a system controller with an associated memory of processor executable code forperforming computer implementable steps when executed, the system controller being associated and / or in operative communication with a database of a plurality of predetermined pharmacokinetic (PK) models related to predetermined parameters comprising respective ones of a plurality of therapeutic compositions for treating respective ones of a plurality of health conditions in respective ones of a plurality of population profiles having been assigned respective ones of a plurality of predetermined posology protocols; a prescriber user interface in operative communication with the system controller for providing a prescriber user to communicate data to the system controller comprising at least one prescribed therapeutic composition for treating at least one assessed health condition, a personal profile of the target subject and an assigned posology protocol for the at least one therapeutic composition for treating the at least one health condition in the target subject; a concentration monitoring system for receiving biological samples from the target subject, determining a concentration of the at least one therapeutic composition administered to the target subject at predetermined time stamps during a time interval of the assigned posology protocol thereby providing time-stamp sample concentrations and providing for communicating the time stamp sample concentrations to the system controller; wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: i- determining a PK model specific to the target subject from the plurality of PK models by comparing the data communicated by the prescriber user to the predetermined parameters for determining matches therebetween thereby selecting respective ones of the predetermined parameters that match with the communicate data, the determined PK model being based on the selected ones of the predetermined parameters, wherein the determined PK model comprises concentration ranges of the at least one therapeutic composition at each time stamp along a posology time interval; ii- determining if each of the time stamp sample concentrations communicated by the concentration monitoring system are within, above or below the determined PK model concentration range for the same time stamp thereof, wherein the time stamp concentrations being within the determined PK model concentration ranges correspond to the determined PK model and areindicative of the efficacy of the assigned posology protocol, wherein the time stamp concentrations being above or below the determined PK model concentration ranges do not correspond to the determined PK model and are indicative of a nonefficacy of the assigned posology protocol; and iii- providing a graphical user interface (GUI) of the determined PK model and the time stamp sample concentrations positioned thereon and displaying the GUI thereof via the prescriber user interface.

[0005] In an embodiment, execution of the processor executable code causes the system controller to perform the computer implementable steps of: providing for communicating to the system controller via the prescriber user interface a selected time range within the time interval of the determined PK model during which efficacy of the therapeutic composition is desired; determining a therapeutic range based on the selected time range communicated thereto and based on a predetermined concentration range within the selected range; providing and displaying a graphical user interface (GUI) via the prescriber user interface of the therapeutic range on the determined PK model; determining and displaying an intersection of the determined PK model and the therapeutic range thereby indicating an efficacy level during the selected time range based on a degree of the intersection, wherein a high degree of the intersection is indicative of a high efficacy level and a low degree of the intersection is indicative of a low efficacy level.

[0006] In an embodiment, execution of the processor executable code causes the system controller to perform the computer implementable steps of: providing the assigned posology protocol to be adjusted via the prescriber user interface to increase the degree of the intersection; modifying the determined PK model based on the adjusted posology protocol to provide a modified PK model; displaying the modified PK model via the prescriber user interface together with the therapeutic range and an adjusted intersection therebetween.

[0007] In an embodiment, execution of the processor executable code causes the system controller to perform the computer implementable steps of:providing the assigned posology protocol to be adjusted by way of input commands therefor via the prescriber user interface to provide for subsequent ones of the time stamp concentrations to be within the determined PK model concentration range; modifying the determined PK model based on the adjusted posology protocol to provide a modified PK model; and displaying the modified PK model via the prescriber user interface.

[0008] In an embodiment, the database comprises predetermined modulators for modulating the determined PK model.

[0009] In an embodiment, the modulators are selected from the group consisting of: an activity status of the target subject, a condition status of the target subject, one or more additional therapeutic compositions and related posology protocols prescribed to the target subject in the treatment of one or more additional health conditions, a target subject impacting event and any combination thereof.

[0010] In an embodiment, execution of the processor executable code causes the system controller to perform the computer implementable steps of: providing one or more of the modulators to be communicated by way of input commands therefor via the prescriber user interface; modulating the determined PK model based on the communicated modulators to provide a modulated PK model; displaying the modulated PK model via the prescribed user interface.

[0011] In an embodiment, the system further comprises a target subject interface in operative communication with the system controller, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: prompting the target subject via the target subject interface to provide biological samples at predetermined time stamps.

[0012] In an embodiment, the system further comprises a target subject interface in operative communication with the system controller, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: prompting the target subject via the target subjectinterface to provide responses to predetermined questions at predetermined time stamps related to the modulators in order to capture modulator related data; modulating the determined PK model based on the captured modulator related data to provide a modulated PK model; displaying the modulated PK model via the prescribed user interface.

[0013] In an embodiment, the database comprises a set of intended effects and a set of adverse effects related to each of the respective ones of the plurality of therapeutic composition.

[0014] In an embodiment, the set of adverse effects comprises subtherapeutic effects and supratherapeutic effects.

[0015] A In an embodiment, the system further comprises a target subject interface in operative communication with the system controller, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: prompting the target subject via the target subject interface to provide responses to predetermined questions at predetermined time stamps related to the set of intended effects and the set of adverse effects related to the at least one prescribed therapeutic composition in order to capture treatment effect data; modulating the determined PK model based on the capture treatment effect data to provide a modulated PK model; displaying the modulated PK model via the prescribed user interface.

[0016] In an embodiment, execution of the processor executable code causes the system controller to perform the computer implementable steps of: providing one or more of the set of intended effects and the set of adverse effects related to the at least one prescribed therapeutic composition to be communicated by way of input commands therefor via the prescriber user interface; modulating the determined PK model based on the communicated sets of intended and adverse effects to provide a modulated PK model; and displaying the modulated PK model via the prescribed user interface.

[0017] In an embodiment, the system further comprises a dosage dispenser in operative communication with the system and providing automatically dispensing via controller commands thereof the at least one prescribed therapeutic composition for intake by the target subject.

[0018] In an embodiment, the dosage dispenser provides for monitoring whether the dispensed therapeutic dosage has been retrieved or not and for communicating retrieval and non-retrieval to the system.

[0019] In an embodiment, execution of the processor executable code causes the system controller to perform the computer implementable steps of: determining a level of adherence of the target subject to the assigned posology based on the communicated retrieval and non-retrieval of the dispensed dosage; modulating the determined PK model based on the communicated sets of intended and adverse effects to provide a modulated PK model; and displaying the modulated PK model via the prescribed user interface.

[0020] In an embodiment, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: controlling the dosage dispenser to dispense a given dosage at a given time stamp based on the assigned posology protocol and any real time adjustment thereof.

[0021] Other objects, advantages and features of the present disclosure will become more apparent upon reading of the following non-restrictive description of illustrative embodiments thereof, given by way of example only with reference to the accompanying drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In the appended drawings:

[0023] Figure 1 is a schematic representation of a system for monitoring and identifying the efficacy of a posology protocol for a therapeutic composition in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0024] Figure 2 is a schematic representation of the database of the system of Figure 1 containing a plurality of pharmacokinetic models in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0025] Figure 3 is a schematic representation of the database of the system of Figure 1 containing modulators for modulating pharmacokinetic models in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0026] Figure 4 shows a graphic of a pharmacokinetic model provided by the system of Figure 1 in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0027] Figure 5 shows the prescriber user interface of the system ofFigure 1 providing for data input in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0028] Figure 6 shows a graphic of therapeutic range window based on a user selected time range input data in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0029] Figure 7 shows a therapeutic range window of Figure 6 superimposed on the pharmacokinetic model of Figure 4 to show intersections therebetween in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0030] Figure 8 shows the prescriber user interface of the system ofFigure 1 providing for data input in accordance with another non-restrictive illustrative embodiment of the present disclosure;

[0031] Figure 9 shows a graphic of two therapeutic range window based on a user selected time range input data in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0032] Figure 10 shows the prescriber user interface of the system ofFigure 1 providing for data input in accordance with a further non-restrictive illustrative embodiment of the present disclosure;

[0033] Figure 11 shows the two therapeutic range windows of Figures 9 superimposed on pharmacokinetic model to show intersections therebetween in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0034] Figure 12 shows the two therapeutic range windows of Figures 9 superimposed on the modified version of pharmacokinetic model of Figure 11 to show modified intersections therebetween in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0035] Figure 13 shows the two therapeutic range windows of Figures 9 superimposed on the modified version of pharmacokinetic model of Figure 12 to show modified intersections therebetween in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0036] Figure 14 shows the two therapeutic range windows of Figures 9 superimposed on the modified version of pharmacokinetic model of Figure 13 to show modified intersections therebetween in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0037] Figure 15 is Figure 4 shows a graphic of a pharmacokinetic model provided by the system of Figure 1 with plotted dots thereon representing concentrations of a therapeutic composition in a target subject at different time stamps of an assigned posology protocol in accordance with a non-restrictive illustrative embodiment of the present disclosure;

[0038] Figure 17 is a schematic representation of the database of the system of Figure 1 containing therapeutic compositions and their related sets of intended and adverse effects in accordance with a non-restrictive illustrative embodiment of the present disclosure; and

[0039] Figure 18 is schematic representation of the sub-groups of adverse effect of Figure 17 in accordance with a non-restrictive illustrative embodiment of the present disclosure.DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0040] Generally stated and in accordance with an aspect of the present disclosure, there is provided a system for monitoring and identifying the efficacy of a posology protocol assigned to a target subject having one or more health conditions with respect to administration of one or more therapeutic compositions prescribed to the target subject for treatment of the one or more health conditions.

[0041] The system comprises a system controller with an associated memory of processor executable code for performing computer implementable steps when executed. The system controller is associated and / or in operative communication with a database of a plurality of predetermined pharmacokinetic (PK) models related to predetermined parameters comprising respective ones of a plurality of therapeutic compositions for treating respective ones of a plurality of health conditions in respective ones of a plurality of population profiles having been assigned respective ones of a plurality of predetermined posology protocols.

[0042] A prescriber user interface is in operative communication with the system controller for providing a prescriber user to communicate data to the system controller comprising at least one prescribed therapeutic composition for treating at least one assessed health condition, a personal profile of the target subject and an assigned posology protocol for the at least one therapeutic composition for treating the at least one health condition in the target subject.

[0043] A concentration monitoring system for receiving biological samples from the target subject, determining a concentration of the at least one therapeutic composition administered to the target subject at predetermined time stamps during a time interval of the assigned posology protocol thereby providing time-stamp sample concentrations and providing for communicating the time stamp sample concentrations to the system controller.

[0044] Execution of the processor executable code causes the system controller to perform the computer implementable steps.

[0045] A PK model specific to the target subject is determined from the plurality of PK models by comparing the data communicated by the prescriber user to the predetermined parameters for determining matches therebetween thereby selecting respective ones of the predetermined parameters that match with the communicate data. The determined PK model is based on the selected ones of the predetermined parameters. The determined PK model comprises concentration ranges of the at least one therapeutic composition at each time stamp along a posology time interval.

[0046] It is determined if each of the time stamp sample concentrations communicated by the concentration monitoring system are within, above or below the determined PK model concentration range for the same time stamp thereof. The time stamp concentrations being within the determined PK model concentration ranges correspond to the determined PK model and are indicative of the efficacy of the assigned posology protocol. The the time stamp concentrations being above or below the determined PK model concentration ranges do not correspond to the determined PK model and are indicative of a non-efficacy of the assigned posology protocol.

[0047] A a graphical user interface (GUI) of the determined PK model and the time stamp sample concentrations positioned thereon is provided and displayed via the prescriber user interface.

[0004] With reference to Figure 1 there is shown a system 10 for monitoring and identifying the efficacy of posology for a target patient having a health condition with respect to administration of a therapeutic composition assigned to the target individual for treatment of this health condition in accordance with a non-restrictive illustrative embodiment of the present disclosure.

[0005] The system 10 includes a system controller 12 with an associated memory of processor executable code for performing computer implementable steps when executed. The configuration of the controller 12 may include a remote controller in operative communication with a local controller such as a local controller associated with the interface 26 discussed further below. The executable code may be executed partially on the remoter controller and partially on the local controller. The executable code may be downloaded on the local controller via the remote controller. The system controller 12 may be a network of controllers. Indeed, the skilled artisan will readily appreciate that a variety of computer configurations and architectures can be contemplated for the system controller 12 within the scope of the present disclosure.

[0006] The system controller 12 is associated with and / or in operative communication with a database 14. The database 14 may be hosted on another controller or a plurality of controllers in operative communication with the system controller 12 or may be hosted directly on the system controller 12 (as shown in dotted line in Figure 1) including the various configurations thereof as previously described. The database 14 may comprise one ore mor storage mediums present on one or more controller systems or networks. Indeed, a variety of computer configurations and architectures can be contemplated by the skilled artisan with the scope of the present disclosure.

[0007] In an embodiment, the controller 12 and the database 14 define a controller assembly 15.

[0008] Turning to Figure 2, the database 14 comprises a memory of plurality of predetermined pharmacokinetic (PK) modules 16 for a plurality of predetermined therapeutic compositions for the treatment of predetermined healthcare conditions.

[0009] Each of the predetermined pharmacokinetic modules 16 is based on the following parameters: a given therapeutic composition 18, a given health condition 20 to be treated by the given therapeutic composition 18, the posology protocol 22 of this given therapeutic composition 18 in treating this given health condition 20 and the patient population profile 24 to receive the treatment (18, 22) for this health condition 20. The intersection between the foregoing parameters (or clusters) provides the pharmacokinetic module 16. Indeed, the database 14 has received input data regarding assessed pharmacokinetics of therapeutic compositions in treating health conditions in various patient populations with respective population profiles following a posology protocol. In an embodiment, the database 14 is updated regularly by data collected by recognized and peer reviewed clinical trials and the like. Thus, the database 14 is dynamic and not static.

[0010] Figure 4 shows an example of a pharmacokinetic PK model 16 which shows the concentration of a therapeutic composition within a patient population 24 over a time interval (t). Since, the pharmacokinetic model 16 is based on a patient population 24 and not a single individual, there is a range (C-R) of concentrations (C) at each give time stamp (ts) within the time interval (t). As such, the PK model 18 includes various PK curves (PK-c) along the time interval (t) with a median curve (C-m) being the median concentration within each concentration range (C-R) at each given time stamp (ts) during the interval (t). As such, the curves above (C-Ra) and below (C-Rb) the median curve (C-m) are the standard concentration deviations. Together these curves (C-Ra, C-m, C-Rb) form the concentration range (C-R) along the time interval (t).

[0011] With reference to both Figures 1 and 2, the system 10 comprises a prescriber user interface 26. The prescriber (health care professional, physician, researcher etc.) communicates data inputs to the system controller 12 via interface 26 concerning the prescribed therapeutic composition, the health condition to be treated, the posology protocol, and the patient profile of the target subject. The posology protocol includes dosage (concentration intake of the therapeutic composition) and time of dosage. The patient profile includes age, gender, weight, and other relevant profile information as is known in the art.

[0012] The system controller 12 receives the data input from prescriber user interface 26 and compares this data to the stored parameters within the database 12. As such, the prescribed therapeutic composition and the health condition of the patient (target subject) will match with a therapeutic composition 18 and a health condition 20 stored in the database 12 . The prescribed posology protocol 22p will also match with a predetermined posology protocol 22 stored within the database 12 or cluster with a posology protocol cluster 22c of similar predetermined posology protocols 22. The patient profile 24t of the target will cluster with a patient population profile cluster 24 of similar patients.

[0013] Once the four parameters are identified, a PK model 16 is produced as explained above and as shown in Figure 2. The produced PK model 16 is displayed via the interface 26 as exemplified in Figure 4 which is a graphical user interface (GUI) representation of the produced PK model 16 graphic i.e. concentration range (C-R) along a time interval (t).

[0014] The prescriber also inputs a desired therapeutic range via the interface 26 as shown in Figure 5 which shows a GUI 28 displayed via the interface 26. In essence, the prescriber selects at least one time range (tr) within the time interval (t) for which it is desired that the therapeutic composition shows efficacy. In the example shown in Figure 5, the time range selected is between 8:00am and 6:00pm. As shown in Figure 6, this selected time range corresponds to a therapeutic range 30 in the form of a box or window as displayed in the graphic 32 via interface 26. The width of window 30 represents the desired time range (8:00pm to 6:00pm) and the height of the window 30 represents a predetermined concentration range of the therapeutic composition that is known to show efficacy, in this example, the predetermined therapeutic concentration range C-RTH is between 6ng / ml to 20ng / ml.

[0015] The selected therapeutic range 30 is superimposed on the PK model 16 of Figure 4 as shown in Figure 7. The system controller 12 determines the degree of intersection between the produced PK model 16 and the selected therapeutic range 30. A score is provided to via the interface indicating how much of the produced PK model 16 falls within the therapeutic range box 30 during the selected time range (tr). In theexample of Figure 7, the efficacy score of the produced PK model 16 is shown to be at 70%. The higher the score the greater the efficacy.

[0016] Therefore, based on these results the prescribed posology shows to have a theoretical acceptable success rate and the prescribed will thus proceed with prescribing the posology to the target subject.

[0017] Turning to Figure 3, the database 14 shows that predetermined modulators 34 modulate a produced PM model 16 from the initially produced model 16’ to the modified version 16”. These modulators 34 have been previously assessed to impact the efficacy of the posology protocol of therapeutic compositions for the treatment of health conditions in patient populations. The efficacy of a produced PK model 14 will be impacted by one or more of these modulators 34 therefore, the concentration ranges (C-R) will be modified during the time interval (t) in order to compensate for this efficacy impact. These modulators 34 can be stored within the database 14, the controller 12 or a combination thereof including the various computer configurations and architectures previously described.

[0018] The system controller 12 receives inputs regarding these modulators 34 and provides for modifying the initially produced model 16’ to the modified version 16” on the basis of the modulator data input. In an embodiment, the modulators 34 comprise activity status 36 of the target subject, a condition status 38 of the target subject, one or more additional therapeutic compositions and related posology protocols 40 prescribed to the target subject in the treatment of one or more additional health conditions, target impacting events 42 that have a statistical impact on the physical and / or mental and / or emotional condition of the target subject. In embodiment, the activity status 36 modulators include meal times, sleep times, exercise times and the like. In an embodiment, the condition status 38 includes without limitation health status (viral infection etc.), mental status (depression etc.), physical condition (fatigue, injury, weight gain / loss). In an embodiment, an impactful event 42 includes without limitation loss of employment, death in the family, accident and the like.

[0019] As mentioned above, the various modulators 34 have been previously assessed in studies to impacts the produced PK models 16 in patient profiles 24 related to the target subject as previously described and this data has been collected and is accessible to system controller 12 via its memory and / or the database 14 and / or another storage medium in operative communication with the system controller 12 and / or the database 14 and the various configurations and architectures thereof.

[0020] As such, when the prescriber enters the therapeutic composition and posology data along with the patent profile data into interface 26, they will also add any additional drugs and related posology protocols 40 prescribed to the patient so that the PK model produced takes modulator 40 into account.

[0021] Turning to the example of Figure 5, the prescriber has inputted two PK model modulators 34 namely activity status 36 modulators (see Figure 3). For example, daily standard activities are meal times and sleep. In the example shown in Figure 45, the prescriber has inputted two modulator standard activities via the GUI 28, namely lunch at 12pm and sleep at 10:00pm.

[0022] As shown in Figure 7, lunch and sleep identified by icons on the graphic 33 shown an impact on the PK model 16 as concentration levels dip during eating activity 36 and fall when sleep activity 36.

[0023] Turning to Figures 8 and 9, the prescriber can select two therapeutic time ranges, for example a first selected time range (tri) is from 9:00am to 11 :30am and a second selected time range (tr2) is from 1 :00pm to 3:15pm thereby creating two therapeutic range windows 30-1 and 30-2. The prescribed selects a therapeutic composition 18 and a posology 22 as shown in Figure 10 and inputs the target subject profile 24 (see Figure 8) and any modulator 34 data (see Figure 8) to produce a PK model 16’ shown in Figure 11 with therapeutic range windows 30-1 and 30-2 superimposed thereon. Since the intersection between PK model 16’ and window 30-1 is nil and very low between PK model 16’ and window 30-2, the efficacy score is very low and the PK model 16’ must be adjusted to fit in windows 30-1 and 30-2.

[0024] The prescriber will adjust the posology i.e. the dosage concentration and / or the dosage time as well as any modulators 34. Figures 12, 13 or 14 show three adjustment attempts before an acceptable efficacy score is obtained. The acceptable efficacy score is determined by a sufficient intersection between the produced PK model and the selected therapeutic ranges which indicates therapeutic efficacy. Figures 12, 13 and 14 show sequentially adjusted or modulated PK models, 16”, 16”’, and 16”” respectively. Each later model in the sequence being an adjustment or a modulation of the previous model of the sequence. PK model 16” increased the intersection with the second window 30-2 but still had an insufficient intersection with the first window 30-1. PK model 16”’ increased the intersection with the first window 30-1 but showed an over dosage (supra dosage) with window 30-2. Finaly, PK model 16”” showed a sufficient intersection with both the first and second windows 30-1 , 30-2 thereby providing an acceptable overall efficacy score. The prescriber therefore prescribes the posology protocol related to PK model 16”” including any modifications in the modulators 34.

[0025] Turning back to Figure 1 , the system 10 includes a target subject user interface 44 in operative communication with the system control 12. The system 10 also includes a monitoring system 46 for monitoring the concentration of the prescribed therapeutic composition in target subject. The controller 12 prompts the target subject via the interface 44 to provide a biological sample (blood, urine, saliva etc.) at a predetermined time stamp (ts).

[0026] Prompting by the system controller 12 is executed by messages, images, sounds, vibrations and the like via the interface 44. The system controller 12 keeps on prompting the target subject until the task requested has been executed or confirmed that it has been executed via the interface 44.

[0027] The biological samples can be taken at home via a home device or by a health care provider or at a health care premises or a laboratory. Each biological sample is monitored by the monitoring system 46 to determine the concentration (C) of the therapeutic composition at the predetermined time stamp (ts). In an embodiment, the monitoring system 46 comprises a reader 48 which determines the therapeutic composition (C) at the predetermined time stamp (ts) and transmits this data to thecontroller 12 via a device controller and / or a monitoring interface 50 and / or the user interface 46 by way of user inputs. In an embodiment, the monitoring system 46 comprises a laboratory which determines the therapeutic composition (C) at the predetermined time stamp (ts) and transmits this data via a device controller and / or a monitoring interface 50 and / or the user interface 46 by way of user inputs.

[0028] The controller 12 receives the communicate data regarding the plurality of determined sample concentrations (C) at the respective predetermined time stamps (ts) during the time interval (t) and compares these sample concentrations (C) to the produced PK model 16. As shown in Figure 15, sample concentrations (C) taken at time stamps (ts) are plotted along on the concentration vs time interval graphic. In this case, all three plotted dots D fall within the PK curve deviation of the PK model 16. Indeed, the plotted dots D when extrapolated by the controller 12 provided for determining a target subject PK curve. In this case, the determined target subject PK curve is within the PK model curve deviation. This graphic is displayed via the prescriber user interface 26 confirming to the prescriber that the prescribed posology shows an acceptable efficacy when taking the actual concentration of the therapeutic composition in the target subject into account.

[0029] If the plotted dots D would be outside the PK model such as D’ and D” which are above and below the concentration range C-R of the PK model 16 of Figure 15, then the posology would have to be adjusted. In the case of dots D’ above the PK model, the dosage would need to be reduced. In the cases of dots D” below the PK model, the dosage would need to be increased.

[0030] The prescriber can thus prescribe a modified posology and enter the data into the system controller 12. Indeed, the system controller 12 can display via interface 26 the determined target subject PK curve based on the sample concentrations it has received and the extrapolations it has calculated as explained above. Moreover, the controller 12 can suggest a recommended posology protocol based on the determined target subject PK curve via the interface 26 to be confirmed by the prescriber. In an embodiment, the controller 12 can automatically prescribe this recommended posology protocol.

[0031] Turning back to Figure 1 , the system 10 includes a dosage dispenser 52. In an embodiment, the dosage dispenser 52 comprises an electronic pill box. The dosage dispenser 52 provides for monitoring whether or not the target subject adheres to the posology protocol as the sample concentrations (C) may not be a case of insufficient dosage but rather of non-adherence to the dosage regimen. The dosage dispenser 52 comprises a controller in operative communication with the system controller 12. Adherence to dosage can be communicated via interfaces 26 and 44. Indeed, the system controller 12 can prompt the target subject via interface 44 to adhere to the posology protocol in real time. In an embodiment, modifications to the posology protocol for the reasons explained herein can be automatically controlled by the system controller 12 which controls the dosage dispenser 52 to dispense a greater dosage or lesser dosage at the dosage time. This control of the dosage dispenser 52 can be executed by the prescriber via their interface 44 which can be in operative communication with the controller of dosage dispenser 52 or via by using their interface 44 to input commands via the system controller 14 to control the dosage dispenser 52 accordingly. With reference to Figure 3, adherence to posology 53 based on dispenser 52 is an additional modulator and the PK model can be modulated accordingly regarding adherence habits 53 of the target subject.

[0032] With respect to Figure 16, the database 14 includes for each therapeutic composition 18 a plurality of intended effects 54 and a plurality of adverse effects 56. Occurrence of intended effects 54 demonstrates efficacy of the therapeutic composition 18 and hence, the therapeutic dosage is being administered in the treatment of the health condition. The intended effects 54 can be graded. Thus a predetermined higher grade is indicative of a sufficient dosage of the therapeutic composition. A predetermined lower grade is indicative of an insufficient dosage of the therapeutic composition and thus although the intended effect is being achieved it is achieved at a sub-optimal level and thus the dosage can be increased. For example, the system controller may prompt a question to the target subject via the interface 44 asking them if their concentration has improved. If the answer is yes, they may ask a series of other questions that are designed to grade this improvement. For example, the subsequent question may be: how many times did you lose concentration during your first classtoday? Between 1-3 times? Between 4-6 times? More than 7 times? The answer will be indicative of an efficacy grade.

[0033] Occurrence of the adverse effect 56 demonstrates inefficacy of the therapeutic composition. As shown in Figure 17, there are two types of adverse effects 56, subtherapeutic effects 56i and supratherapeutic effects 56ii. Subtherapeutic effects 56i include effects related to the health condition the occurrence of demonstrates that the therapeutic composition is not having the intended effect and as such the dosage needs to be increased. Occurrence of supratherapeutic effects 56ii is indicative that the therapeutic composition is administered at levels greater than would normally be used in treatment of the health condition and as such the dosage needs to be lowered.

[0034] Assessment of the intended effects 54 and adverse affects 56 by the system controller 14 will provide a condition status 38 which will modulate the produced PK model accordingly and thus impact the prescribed posology to be reconciled with the PK model modulation.

[0035] As such, the system controller 12 comprises a time sensitive questionnaire and prompts the target subject to respond to specifically designed questions at predetermined time stamps during the time interval in order to capture data related to the intended effects 54 and adverse effects 56 and thus modulate the PK model accordingly. Indeed, it may be the case the sample concentrations collected do fall within the PK model but that actual effects 54 and / or 56 show that the posology protocol is not having a therapeutic effect and / or is having adverse effects. The PK model must therefore be modulated based on the effects 54 and 56 as captured by the controller 12 and the posology protocol must now be adjustment in accordance with the modulated PK model.

[0036] As previously stated, and with reference to Figure 3, modulators 34 will modulate an initial PK model 16’ into a modulated PK model 16”. These modulators include the activity status 36 of the target subject, the condition status 38 of the target subject and the events 42 impacting the target subject. The database 12 is updated with current data regarding the impact of the foregoing on therapeutic compositions aswell as on heath conditions treated by these therapeutic compositions. The system controller 12 prompts the target patient to answer questions related to their activities at specific times of the day, their conditions status at specific times of the day and whether or not any impactful events occurred.

[0037] Interactive interface applications provide for users (patients / health care professionals / monitors) to enter prompted information in order for the prescriber (clinician / physician) to better modulate posology as described in US Patent No. 11 ,185,282. Patients (target subjects) via the use of an app answer prompted questionnaires during various times of day as they follow their drug dosage regimen (posology protocol). In this way, clinical response and treatment related adverse effects are recorded providing the prescriber with additional clinical information to adjust or not the posology protocol which could include modifying the frequency of administration, the dose per a single administration, the time interval between administrations, and / or the time of administration. The foregoing factors synergistically play a role on the metabolic progress of a drug during the course of the day (pharmacodynamics). Based on the posology (dosage, frequency, time interval and time of administration) the concentration of the medicament within the patient’s blood stream can be extrapolated over the course of the day based on a theoretical drug metabolism rate model.

[0038] The present disclosure provides for determining, monitoring, identifying and optimizing posology efficacy as well as a response to pharmacotherapy, including monitoring of side effects and drug interactions, simulating the pharmacokinetic of any dosing regimen specific to a target individual, identifying the variability in both pharmacokinetics, pharmacodynamics and clinical response, such as such as the patient’s inter or intra therapeutic index variability, determining the optimal posology (dosage regimen) for a target individual and identifying dose adjustments that will bring the therapeutic composition’s concentration in a target patient’s bloodstream into a prespecified target range, i.e. , to a patient-specific target range of concentrations associated with maximal efficacy while minimizing toxicity.

[0039] In an embodiment, there is provided a system controller with databases of pharmacokinetic models for a plurality of therapeutic compositions. A user communicates to the system controller via a user interface a dosing regimen (posology protocol) and a medical profile for the target patient being administered therapeutic compositions for treatment of health conditions. For a given dosing regimen and a measured drug concentration in the bloodstream, the controller calculates percentiles for expected concentrations (i.e. , specific pharmacokinetics of a dosing regimen), which helps the user to evaluate the “normality” or expectedness of a concentration at various times after the therapeutic composition was taken. Biofluid samples are collected from the target patient at predetermined time intervals. The sampled concentration of the therapeutic compositions administered at specific time intervals to the target patient in each of the biofluid samples is determined and communicated to the system controller. The system controller then calculates percentiles for expected concentrations of therapeutic compositions in the bloodstream of the target patient and combines this information as well as with the time specific concentrations of administered therapeutic compositions from the biofluid samples collected. The determined concentration range and the given specific concentrations are communicated via the user interface.

[0040] In an embodiment, the physician prepares a posology protocol based on standard medical factors. Supported by the interactivity of the application, the physician can add significant clinical information to the PK modelization and visualize its impact which will support course of action to optimize posology. On the basis of user’s feedback, the physician enters various variables within entry fields (dosage, frequency, interval and time of administration) and the app shows a theoretical concentration level of a medicament during the course of the day. Accordingly, the physician can modify entry variables in order to modulate the to a more desirable concentration versus time stamp curve line.

[0041] Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure to medications. Thecreation of a pharmacokinetic - curve, which follows the plasma concentration of an administered drug as a function of time, is a critical aspect of the drug development process and includes such information as the drug's bioavailability, clearance, and elimination half-life. The PK curve shows the concentration of the drug in the body at given time stamps. The therapeutic index is a ratio that expresses the relationship between the dose expected to elicit some adverse effect and the dose needed to elicit therapeutic effects. In other words, is the range of doses at which a medication is effective without unacceptable adverse events. This range or zone can be calculated using PK analysis during a clinical trial. Again, in clinical practice, the therapeutic index is the range of doses at which a medication appeared to be effective in clinical trials for a median of participants without unacceptable adverse effects. The healthcare professional use this information to select the appropriate posology for their patient. It is possible that a healthcare professional chose to induce acheive a therapeutical index with a patient at a selected time lapse during the day.

[0042] The PK model is not a single curve line but several lines showing a PK variable curve also known as therapeutic index mentioned. This therapeutic index range though may have a different clinical effect for similar patients (i.e. patient with the same / similar age, gender, weight, BMI, condition, and similar responses to the prompted questions etc.). Thus, no two similar patients necessarily have concentrations on the same PK curve lines. This uncertainty in dosage concentration vs. time of day creates the unintentional consequences of not optimizing posology and not optimizing avoidance of side effects. This uncertainty in dosage concentration vs. time of day also creates the unintentional consequences for a certain number of patients to not being able to determine the medication coverage and why the patient remains unresponsive to therapy.

[0043] In an embodiment, the present disclosure provides a kit for allowing the patient to collect body fluid at home or work or at school including saliva, blood, urine, sweat, tears etc. at given times of day in order to have a real time in vivo truereading of the concentration of a given drug within their bloodstream at a given time stamp.

[0044] In an embodiment, the collected sample is sent to a lab and the selected biomarkers concentrations are communicated to the system controller via a user interface.

[0045] In embodiment, the biomarker concentration reading at time stamps for example identify a given PK curve line within the concentration range of those time stamps. Thus, the system extrapolates by only several body fluid readings on the same day or additional readings for several days, on which real PK curve line the patient is actually on. In this way, we can predict with high level of certainty and much less variance the concentration of the drug within a patient’s bloodstream at a given time stamp during the course of the day. By obtaining a series of samples allowing the analysis of the circulating biomaker concentration for a patient at a given time, the system allows to individualized the PK curves to a patient and consequently minimizing inter and intra patient variability. This form of personalized medicine provides essential information to the health care professional to optimized drug posology to acheive better clinical outcomes

[0046] In an embodiment, the present disclosure provides a system, a kit and a method for assisting a health professional or researcher in identifying optimal posology for an individual and to individualize therapy specifically based on the patient’s characteristics and needs.

[0047] In an embodiment, the present disclosure combines the use of (i) a decision support tool that can simulate the specific pharmacokinetics of any dosing regimen of a particular drug and produce graphical representation that summarizes its performance at a given time stamp during the course of the day, with (ii) precise quantification of this drug concentration in plasma or other body fluids such as, saliva, sweat, tears, urine etc., as determined from time to time, over a predetermined period.

[0048] In an embodiment, reviewing the results of this combination provides clinicians with an increased level of accuracy.

[0049] In an embodiment, the data may be reviewed with the patient and caregiver, to inform themabout the impact of inter and intra patient variability has on the therapeutic index of a drug posology including the clinical response.

[0050] In an embodiment, the present disclosure provides for correlating side effects with the role that the the inter and intra patient variability may play in the response, or not, to treatment.

[0051] In an embodiment, the present disclosure provides for correlating clinical response, or lack of clinical response, with the role that the inter and intra patient variability may play in the response, or not, to treatment.

[0052] In an embodiment, the present disclosure provides for targeting the ideal dosage based on an individual’s personal characteristics, individual variability in response to and side effects of pharmaceuticals and needs.

[0053] In an embodiment, the present disclosure provides for individualizing therapy specifically based on the patient’s characteristics and needs.

[0054] In an embodiment, the present disclosure provides for evaluating drug interactions and how such interactions may impact upon the efficacy of treatment.

[0055] In an embodiment, the present disclosure provides for precisely locating and determining the specific pharmacokinetics of any dosing regimen for varying prescriptions as simulated by a support tool.

[0056] In an embodiment, the present disclosure provides for precisely locating and determining the specific pharmacokinetics of any dosing regimen for varying prescriptions as simulated by a decision support tool specifically when the patient remains unresponsive to therapy.

[0057] In an embodiment, the present disclosure provides for precisely locating and determining the specific pharmacokinetics of any dosing regimen for varying prescriptions as simulated by a decision support tool specifically when the patient exhibits treatment related adverse effects.

[0058] In an embodiment, the present disclosure provides for precisely locating and determining the specific pharmacokinetics of any dosing regimen for varying prescriptions as simulated by a decision support tool specifically and identifying dose adjustments that will bring the therapeutic composition’s concentration in a target patient’s bloodstream into a prespecified target range, i.e. , to a patient-specific target range of concentrations associated with maximal efficacy while minimizing toxicity.

[0059] In an embodiment, the present disclosure provides for precisely locating and determining the specific pharmacokinetics of any dosing regimen for varying formulations of prescriptions as simulated by a decision support tool specifically when the use of formulations of medications with varying half-life are prescribed and medication efficacy must be determined.

[0060] Determining the actual PK curve line of a patient within a simulated model as provided herein provides for determining drug efficacy as well as the impact of posology variables (dose per administration, time-stamp of administration, frequency of administration, and time interval between administrations), interactions with other drugs as well as an individual’s metabolism thereby optimizing drug administration regimens.

[0061] The various features described herein can be combined in a variety of ways within the context of the present disclosure so as to provide still other embodiments. As such, the embodiments are not mutually exclusive. Moreover, the embodiments discussed herein need not include all of the features and elements illustrated and / or described and thus partial combinations of features can also be contemplated. Furthermore, embodiments with less features than those describedcan also be contemplated. It is to be understood that the present disclosure is not limited in its application to the details of construction and parts illustrated in the accompanying drawings and described hereinabove. The disclosure is capable of other embodiments and of being practiced in various ways. It is also to be understood that the phraseology or terminology used herein is for the purpose of description and not limitation. Hence, although the present disclosure has been provided hereinabove by way of non-restrictive illustrative embodiments thereof, it can be modified, without departing from the scope, spirit and nature thereof and of the appended claims.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A system for monitoring and identifying the efficacy of a posology protocol assigned to a target subject having one or more health conditions with respect to administration of one or more therapeutic compositions prescribed to the target subject for treatment of the one or more health conditions, the system comprising: a system controller with an associated memory of processor executable code for performing computer implementable steps when executed, the system controller being associated and / or in operative communication with a database of a plurality of predetermined pharmacokinetic (PK) models related to predetermined parameters comprising respective ones of a plurality of therapeutic compositions for treating respective ones of a plurality of health conditions in respective ones of a plurality of population profiles having been assigned respective ones of a plurality of predetermined posology protocols; a prescriber user interface in operative communication with the system controller for providing a prescriber user to communicate data to the system controller comprising at least one prescribed therapeutic composition for treating at least one assessed health condition, a personal profile of the target subject and an assigned posology protocol for the at least one therapeutic composition for treating the at least one health condition in the target subject; a concentration monitoring system for receiving biological samples from the target subject, determining a concentration of the at least one therapeutic composition administered to the target subject at predetermined time stamps during a time interval of the assigned posology protocol thereby providing time-stamp sample concentrations and providing for communicating the time stamp sample concentrations to the system controller; wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: i- determining a PK model specific to the target subject from the plurality of PK models by comparing the data communicated by the prescriber user to thepredetermined parameters for determining matches therebetween thereby selecting respective ones of the predetermined parameters that match with the communicate data, the determined PK model being based on the selected ones of the predetermined parameters, wherein the determined PK model comprises concentration ranges of the at least one therapeutic composition at each time stamp along a posology time interval; ii- determining if each of the time stamp sample concentrations communicated by the concentration monitoring system are within, above or below the determined PK model concentration range for the same time stamp thereof, wherein the time stamp concentrations being within the determined PK model concentration ranges correspond to the determined PK model and are indicative of the efficacy of the assigned posology protocol, wherein the time stamp concentrations being above or below the determined PK model concentration ranges do not correspond to the determined PK model and are indicative of a non-efficacy of the assigned posology protocol; and iii- providing a graphical user interface (GUI) of the determined PK model and the time stamp sample concentrations positioned thereon and displaying the GUI thereof via the prescriber user interface.

2. A system according to claim 1 , wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: providing for communicating to the system controller via the prescriber user interface a selected time range within the time interval of the determined PK model during which efficacy of the therapeutic composition is desired; determining a therapeutic range based on the selected time range communicated thereto and based on a predetermined concentration range within the selected range; providing and displaying a graphical user interface (GUI) via the prescriber user interface of the therapeutic range on the determined PK model; determining and displaying an intersection of the determined PK model and the therapeutic range thereby indicating an efficacy level during the selected time rangebased on a degree of the intersection, wherein a high degree of the intersection is indicative of a high efficacy level and a low degree of the intersection is indicative of a low efficacy level.

3. A system according to claim 2, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: providing the assigned posology protocol to be adjusted via the prescriber user interface to increase the degree of the intersection; modifying the determined PK model based on the adjusted posology protocol to provide a modified PK model; displaying the modified PK model via the prescriber user interface together with the therapeutic range and an adjusted intersection therebetween.

4. A system according to any one of claims 1 or 2, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: providing the assigned posology protocol to be adjusted by way of input commands therefor via the prescriber user interface to provide for subsequent ones of the time stamp concentrations to be within the determined PK model concentration range; modifying the determined PK model based on the adjusted posology protocol to provide a modified PK model; and displaying the modified PK model via the prescriber user interface.

5. A system according to any one of claims 1 to 4, wherein the database comprises predetermined modulators for modulating the determined PK model.

6. A system according to claim 5, wherein the modulators are selected from the group consisting of: an activity status of the target subject, a condition status of the target subject, one or more additional therapeutic compositions and related posology protocols prescribed to the target subject in the treatment of one or more additionalhealth conditions, a target subject impacting event and any combination thereof.A system according to claim 6, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: providing one or more of the modulators to be communicated by way of input commands therefor via the prescriber user interface; modulating the determined PK model based on the communicated modulators to provide a modulated PK model; displaying the modulated PK model via the prescribed user interface.

8. A system according to any one of claims 1 to 7, further comprising a target subject interface in operative communication with the system controller, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: prompting the target subject via the target subject interface to provide biological samples at predetermined time stamps.

9. A system according to any one of claims 5 or 6, further comprising a target subject interface in operative communication with the system controller, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: prompting the target subject via the target subject interface to provide responses to predetermined questions at predetermined time stamps related to the modulators in order to capture modulator related data; modulating the determined PK model based on the captured modulator related data to provide a modulated PK model; displaying the modulated PK model via the prescribed user interface.

10. A system according to any one of claims 1 to 7, wherein the database comprises a set of intended effects and a set of adverse effects related to each of the respective ones of the plurality of therapeutic composition.11 . A system according claim 10, wherein the set of adverse effects comprises subtherapeutic effects and supratherapeutic effects.

12. A system according to any one of claims 10 or 11 , further comprising a target subject interface in operative communication with the system controller, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: prompting the target subject via the target subject interface to provide responses to predetermined questions at predetermined time stamps related to the set of intended effects and the set of adverse effects related to the at least one prescribed therapeutic composition in order to capture treatment effect data; modulating the determined PK model based on the capture treatment effect data to provide a modulated PK model; displaying the modulated PK model via the prescribed user interface.

13. A system according any one of claims 10 or 11 , wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: providing one or more of the set of intended effects and the set of adverse effects related to the at least one prescribed therapeutic composition to be communicated by way of input commands therefor via the prescriber user interface; modulating the determined PK model based on the communicated sets of intended and adverse effects to provide a modulated PK model; and displaying the modulated PK model via the prescribed user interface.

14. A system according to any one of claims 1 to 6, further comprising a dosage dispenser in operative communication with the system and providing automatically dispensing via controller commands thereof the at least one prescribed therapeutic composition for intake by the target subject.

15. A system according to claim 14, wherein the dosage dispenser provides formonitoring whether the dispensed therapeutic dosage has been retrieved or not and for communicating retrieval and non-retrieval to the system.

16. A system according to claim 15, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: determining a level of adherence of the target subject to the assigned posology based on the communicated retrieval and non-retrieval of the dispensed dosage; modulating the determined PK model based on the communicated sets of intended and adverse effects to provide a modulated PK model; and displaying the modulated PK model via the prescribed user interface.

17. A system according to any one of claims 14 to 16, wherein execution of the processor executable code causes the system controller to perform the computer implementable steps of: controlling the dosage dispenser to dispense a given dosage at a given time stamp based on the assigned posology protocol and any real time adjustment thereof.

Images