US 9,852,267 B2Granted

System and method for personalized dosing of pharmacologic agents

AssigneeUniversity of Louisville Research Foundation, Inc.

InventorsAdam E. Gaweda, Michael E. Brier, George R. Aronoff, Alfred A. Jacobs

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Abstract

A system and method for personalized dosing of a pharmacologic agent include: executing, using a processing device, a plurality of dosing regimen program modules to determine a respective plurality of dose sets in response to receiving, from an input device, a target response value for a patient; and executing, using the processing device, a dosing selection algorithm module, following executing the plurality of dosing regimen program modules and in response to receiving from the input device a response profile and a monitoring frequency of the patient, to determine a recommended dose set computed as a combination of the plurality of dose sets weighted by degrees of matching computed using fuzzy sets and the response profile.

Claims2

Dependent claims

A method for treating anemia in a subject using erythropoietic stimulating agents (Epo), comprising:

obtaining a target hemoglobin value (Hbtarget), a current hemoglobin value (Hbk), a rate of change of hemoglobin value (ΔHbk), and an Epo dose received value (Epok) related to an amount of Epo being received by the subject;
determining an initial recommended Epo dose (Epok+1,i*) for each of i dosing regimens based on the target hemoglobin value (Hbtarget), the current hemoglobin value (Hbk), the rate of change of hemoglobin value (ΔHbk), and the previous Epo dose prescribed value (Epok);
determining a next recommended Epo dose (Epok+1) based on the initial recommended Epo doses for the i dosing regimens weighted by degrees of matching computed using fuzzy membership functions;
determining, using a dose-response model, a Hbk+1 value and a predicted hemoglobin response value (ΔHbk+1) for a subject with a respective Epo sensitivity profile based on the Hbk value, the ΔHbk value, and a proposed Epok+1 value;
determining, using an optimization algorithm, the Epok+1,i* value by determining the proposed Epok+1 value using the Hbtarget value, the Epok value, the Hbk+1 value and the ΔHbk+1 value, and then iteratively re-determining the proposed Epok+1 value until the proposed Epok+1 values converge to the Epok+1,i* value;
and
administering the next recommended Epo dose to the subject;
wherein the dose-response model is substantially according to the function:
[
dHb
dt
d
⁢
⁢
Δ
⁢
⁢
Hb
dt
]
=
[
-
2
T
i
1
T
i
2
1
0
]
⁡
[
Hb
Δ
⁢
⁢
Hb
]
+
[
K
i
T
i
2
0
]
⁢
Epo
where:
Ki—erythropoietic response (1,000 Units Epo per 1 g/dL Hb change)
Ti—time constant
Epo—dose (1,000 Units)
Hb—hemoglobin level (g/dL)
ΔHb—hemoglobin rate of change (g/dL per day);
and
wherein the optimization algorithm is substantially according to the function:
OFV
=
∑
k
p
=
1
H
p
⁢
(
Hb
target
-
Hb
k
p
)
2
+
λ
i
⁢
∑
k
c
=
1
H
c
⁢
Δ
⁢
⁢
Epo
k
c
2
where:
kp, kc—time steps (weeks)
Hp—prediction horizon (weeks)
Hc—control horizon (weeks)
λi—dose change suppression (non-dimensional)
Hbkp—hemoglobin at step kp
ΔEpokc—change in dose from step kc-1 to kc;
Subject to constraints:
0≦Epo≦90,000 units per week
0≦Hb≦20 g/dL
−0.5<ΔHb<0.5 g/dL per week
where:
ΔHb=Hbkp−Hbkp-1.

108 more elements

A method for treating anemia in a subject using erythropoietic stimulating agents (Epo), comprising:

obtaining a target hemoglobin value (Hbtarget), a current hemoglobin value (Hbk), a rate of change of hemoglobin value (ΔHbk), and an Epo dose received value (Epok) related to an amount of Epo being received by the subject;
determining an initial recommended Epo dose (Epok+1,i*) for each of i dosing regimens based on the target hemoglobin value (Hbtarget), the current hemoglobin value (Hbk), the rate of change of hemoglobin value (ΔHbk), and the previous Epo dose prescribed value (Epok);
determining a next recommended Epo dose (Epok+1) based on the initial recommended Epo doses for the i dosing regimens weighted by degrees of matching computed using fuzzy membership functions;
determining, using a dose-response model, a Hbk+1 value and a predicted hemoglobin response value (ΔHbk+1) for a subject with a respective Epo sensitivity profile based on the Hbk value, the ΔHbk value, and a proposed Epok+1 value;
and
determining, using an optimization algorithm, the Epok+1,i* value by determining the proposed Epok+1 value using the Hbtarget value, the Epok value, the Hbk+1 value and the ΔHbk+1 value, and then iteratively re-determining the proposed Epok+1 value until the proposed Epok+1 values converge to the Epok+1,i* value;
and
administering the next recommended Epo dose to the subject;
wherein “i” equals 5 such that there are 5 dosing regimens;
and
wherein Epok+1 is determined substantially according to the equation:
Epo
k
+
1
=
w
R
⁢
⁢
1
⁢
Epo
k
+
1
,
1
*
+
w
R
⁢
⁢
2
⁢
Epo
k
+
1
,
2
*
+
w
R
⁢
⁢
3
⁢
Epo
k
+
1
,
3
*
+
w
R
⁢
⁢
4
⁢
Epo
k
+
1
,
4
*
+
w
R
⁢
⁢
5
⁢
Epo
k
+
1
,
5
*
w
R
⁢
⁢
1
+
w
R
⁢
⁢
2
+
w
R
⁢
⁢
3
+
w
R
⁢
⁢
4
+
w
R
⁢
⁢
5
where:
wR1=fMF(Epok, μ1, s1l, s1r) μ1=0 s1l=1.0 s1r=0.9*(Hbtarget−Hb0)
wR2=fMF(Epok, μ2, s2l, s2r) μ2=3*(Hbtarget−Hb0) s2l=s1r s2r=1.35*(Hbtarget−Hb0)
wR3=fMF(Epok, μ3, s3l, s3r) μ3=7.5*(Hbtarget−Hb0) s3l=s2r s3r=2.25*(Hbtarget−Hb0)
wR4=fMF(Epok, μ4, s4l, s4r) μ4=15*(Hbtarget−Hb0) s4l=s3r s4r=s4l
wR5=fMF(Epok, μ5, s5l, s5r) μ5=22.5*(Hbtarget−Hb0) s5l=s4r s5r=100.0 and
where fMF is a fuzzy membership function substantially according to the equation:
f
MF
⁡
(
x
,
μ
,
s
l
,
s
r
)
=
{
exp
(
-
(
x
-
μ
)
2
s
l
2
)
x
<
μ
1
x
=
μ
exp
(
-
(
x
-
μ
)
2
s
r
2
)
x
>
μ
.

171 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/631,112Filed 28 Sep 2012 · us provisional application
Priority: 30 Sep 2011
Published: US 2013/0085772 A14 Apr 2013
Granted: 26 Dec 2017
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

G16H 20/10
ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient…:…
A61B 34/10
Computer-aided surgery; Manipulators or robots specially adapted for use in surgery: computer-aided planning, simulation or modelling of surgical…
G16H 50/20
ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or…: for…
G16H 50/50
ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or…: for…