Systems and methods for quantification and presentation of medical risk arising from unknown factors
Example methods of quantifying known and unknown risks of an adverse drug event in an individual based on various factors are disclosed. In some embodiments, factors include known drug-drug interactions and unknown phenotypes of cytochromes. Quantification may be based on severity of the adverse drug event/and or probability of occurrence in some embodiments. Example methods of displaying the quantified risk are also disclosed. In one embodiment, the risk of individuals is aggregated to display the risk of a population.
1 . A computer implemented method of determining a quantified risk of a drug-drug-gene interaction occurring in an individual, the method comprising:
(a) receiving, by a processor, data specifying a set of drugs for the individual, the set of drugs for the individual comprising two or more drugs considered for use by or used by the individual;
(b) receiving, by the processor, a first matrix comprising drug-drug interactions for pairs of drugs in the set of drugs for the individual, wherein each drug-drug interaction specifies an expected effect on metabolism for a pair of drugs in the set;
(c) receiving, by the processor, a second matrix comprising drug-gene interactions and drug-drug-gene interactions for the set of drugs for the individual,
wherein for each genotype combination in a population, the second matrix comprises:
(i) drug-gene interactions for the drugs in the set, each drug-gene interaction comprises an expected effect on metabolism of one of the drugs in the set by a protein encoded by the genotype combination, and
(ii) drug-drug-gene interactions for the pairs of drugs in the set, each drug-drug-gene interaction comprises a cumulative expected effect on metabolism of a pair of drugs in the set by the protein encoded by the genotype combination;
wherein a probability of the individual having the genotype combination is determined according to a probability of occurrence of the genotype combination in the population;
(d) determining, by the processor, a numerical representation of a known risk of an adverse drug event occurring in the individual based on the first matrix and a numerical representation of an unknown risk of the adverse drug event occurring in the individual based on the second matrix and probabilities of the individual having the genotype combinations;
(e) determining, by the processor, a genetic testing commendation for the individual based on the numerical representation of the known risk of the adverse drug event occurring in the individual and the numerical representation of the unknown risk of the adverse drug event occurring in the individual, and
(f) causing, by the processor, the genetic testing recommendation for the individual to be displayed.
2 . The computer-implemented method of claim 1 , wherein the numerical representation of the unknown risk is determined by a process comprising combining quantified risks for two or more of the drug-drug-gene interactions occurring in the individual.
3 . The computer-implemented method of claim 1 , wherein the genetic testing recommendation for the individual is displayed to confirm a presence or absence of one or more of the drug-gene or drug-drug-gene interactions.
4 . The computer-implemented method of claim 1 , wherein one or more of the drug-drug-gene interactions are weighted.
5 . The computer-implemented method of claim 4 , wherein each of the drug-drug-gene interactions is weighted according to ethnicity or gender.
6 . The computer-implemented method of claim 4 , wherein each of the drug-drug-gene interactions is weighted according to severity.
7 . The computer-implemented method of claim 4 , wherein each of the drug-drug-gene interactions is weighted according to one or more indicators of health status of the individual.
8 . The computer-implemented method of claim 7 , wherein the one or more indicators comprise the individual's liver function, kidney function, weight, or age.
9 . The computer-implemented method of claim 1 , wherein each of the drug-drug interactions or each of the drug-gene interactions is weighted.
10 . The computer-implemented method of claim 1 , wherein the unknown risk of the adverse drug event occurring in the individual comprises a probability of the risk.
11 . The computer-implemented method of claim 1 , wherein the protein is selected from the group consisting of a cytochrome p450, a drug transporter and a glucuronosyltransferase.
12 . The computer-implemented method of claim 1 , wherein the expected effect on the metabolism of the one of the drugs in the set comprises an expected change in blood concentration of the one of the drugs in the set over time.
13 . The computer-implemented method of claim 1 , wherein the expected effect on the metabolism of the one of the drugs in the set by the protein is determined by a process comprising identifying a metabolic route used to metabolize the one of the drugs in the set.
14 . The computer-implemented method of claim 1 , wherein (a)-(f) is repeated for a plurality of individuals.
15 . The computer-implemented method of claim 14 , further comprising displaying a genetic testing recommendation for two or more of the plurality of individuals.
16 . A non-transitory computer-readable storage medium with an executable program stored thereon, which program is configured to instruct the processor to conduct the receiving of (a), the receiving of (b), the receiving of (c), the determining of (d), the determining of (e) and the causing to be displayed of (f) of claim 1 .
17 . A system configured to determine a quantified risk of a drug-drug-gene interactions occurring in an individual, the system comprising one or more processors and memory configured to conduct the receiving of (a), the receiving of (b), the receiving of (c), the determining of (d), the determining of (e), and the causing to be displayed of (f) of claim 1 .
18 . The computer-implemented method of claim 1 , further comprising causing, by the processor, the numerical representation of the known risk and the numerical representation of the unknown risk to be displayed.
19 . The computer-implemented method of claim 18 , wherein the numerical representation of the known risk and the numerical representation of the unknown risk are displayed as a numerical element on a display.
20 . The computer-implemented method of claim 18 , wherein the numerical representation of the known risk and the numerical representation of the unknown risk are displayed as a graphical element on a display.