Systems and methods for clinical decision support

Abstract

Systems and methods are described herein for the prioritization of possible treatment options based on biomarkers, such as (but not limited to) tumor and germline-based genomic variants. The system and methods may thereby identify patient and the status of a biomarker in the treatment options tailored to a patient, in particular to his/her clinical, molecular, and/or genetic condition. Furthermore, the system and method provides a means for prioritizing the possible treatment options based on the extraction and contextualization of clinical and molecular knowledge. The system gathers and/or accesses biomarker information and transforms the information into prioritized, clinically actionable options identified for a specific patient case.

1 . A method for prioritization of patient treatment options based on an analysis of biomarker information, comprising:
 retrieving the results of measurements of a set of one or more biomarkers of the patient,   identifying a plurality of treatments associated with any of the set of one or more biomarkers in a database,   generating a score for each of the identified plurality of treatments, the score being based on:
 a) whether predictive rules for each of the one or more biomarkers are associated with response to the treatment, resistance to the treatment, or risk of adverse effects from the treatment, and 
   ordering at least a portion of the identified plurality of treatments according to the generated score to provide a treatment option or treatment contraindication prioritization for the patient.   
     
     
         2 . The method of  claim 1 , wherein generating a score for each of the identified plurality of treatments further comprises, for each generated score:
 generating a sub-score for each biomarker, and   aggregating the sub-scores to generate the score.   
     
     
         3 . The method of  claim 1 , wherein generating the score for each of the identified plurality of treatments further comprises generating two or more separate scores for each of the identified plurality of treatments, said separate scores corresponding to categories that relate to responsiveness, resistance, and/or risk, and aggregating the two or more separate scores. 
     
     
         4 . The method of  claim 3 , comprising specifying, by a user, treatment risk/benefit preferences and wherein scoring and ordering at least a portion of the identified plurality of treatments comprises weighting the two or more separate scores according to the treatment risk/benefit preferences. 
     
     
         5 . The method of  claim 1 , wherein the score is further based on
 b) effect sizes of the predictive rules for each of the one or more biomarkers.   
     
     
         6 . The method of  claim 5 , wherein the effect sizes of the predictive rules for each of the one or more biomarkers comprise a measure of likelihood of response or resistance, a measure of a hazard ratio, a measure of likelihood odds of response or resistance, or a measure of a quotient of hazard ratios. 
     
     
         7 . The method of  claim 1 , further comprising retrieving an identification of an indication of the patient, and wherein the score is further based on
 c) whether the predictive rules for each of the one or more biomarkers have been observed in the indication of the patient, in related indications, or in unrelated indications.   
     
     
         8 . The method of  claim 1 , wherein the score is further based on
 d) clinical validation levels of the predictive rules for each of the one or more biomarkers.   
     
     
         9 . The method of  claim 1 , wherein the clinical validation level is one out of the following list: endorsed, clinical, pre-clinical, inferred. 
     
     
         10 . The method of  claim 1 , wherein the information about the predictive rules for the set of one or more biomarkers with respect to the identified plurality of treatments is stored in one or more curated databases. 
     
     
         11 . The method of  claim 10 , wherein the score is further based on e) a reliability of the involved sources of the predictive rules. 
     
     
         12 . The method of  claim 1 , wherein the score is further based on
 f) a reliability of measurement of the biomarkers.   
     
     
         13 . The method of  claim 12 , wherein a value for the reliability of measurement of the biomarkers comprises a value for a reliability of the detection of the biomarkers and a value representing the abundance of the biomarkers in the patient. 
     
     
         14 . The method of  claim 1 , wherein the score is further based on one or more of the following:
 g) whether the treatments are recommended in a standard treatment guideline,   h) an availability of the treatments, and   i) a past treatment history of the patient.   
     
     
         15 . The method of  claim 1 , further comprising retrieving an identification of an indication of the patient and identifying one or more treatments associated with the indication of the patient and not associated with any of the set of one or more biomarkers of the patient and generating a score for the identified treatments associated with the indication, and wherein the treatment option or treatment contraindication prioritization list comprises both treatments associated with any of the set of one or more biomarkers and treatments associated with the indication. 
     
     
         16 . The method of  claim 15 , wherein generating a score for each of the identified treatments associated with the indication and not associated with any of the set of one or more biomarkers of the patient comprises extracting background knowledge on response, resistance, and/or risk. 
     
     
         17 . The method of  claim 1 , further comprising outputting the treatment option prioritization to a user as a list comprising one or more of the highest ordered treatments and/or comprising outputting the treatment contraindication prioritization to a user as a list comprising one or more of the lowest ordered treatments. 
     
     
         18 . A method, comprising:
 retrieving, by an analysis engine executed by a computing device, an identification of an indication of a patient and the results of measurements of a set of one or more biomarkers in the patient;   identifying, by the analysis engine, a plurality of treatments associated with the indication, the patient, or any of the set of one or more biomarkers in a treatment information database;   generating, by the analysis engine, a score for each of the identified plurality of treatments, the score being based on:
 clinical validation levels of predictive rules for each of the one or more biomarkers; 
   whether predictive rules for each of the one or more biomarkers are associated with response to the treatment, resistance to the treatment, or risk of adverse effects from the treatment, and
 a reliability of measurement of each of the one or more biomarkers; and 
   ordering at least a portion of the identified plurality of treatments according to the generated score to provide a treatment option or treatment contraindication prioritization for the patient.   
     
     
         19 . A device for prioritization of patient treatment options based on an analysis of biomarker information, comprising:
 one or more processors, in communication with one or more storage devices storing a curated database comprising information prepared for being used for generating a score for a treatment to be prioritized, and instructions for performing a method for providing a prioritization of patient treatment options that, when executed by the one or more processors, cause the device to:   retrieve the results of measurements of a set of one or more biomarkers of the patient,   identify a plurality of treatments associated with any of the set of one or more biomarkers in a database,   generate a score for each of the identified plurality of treatments, the score being based on:
 a) whether predictive rules for each of the one or more biomarkers are associated with response to the treatment, resistance to the treatment, or risk of adverse effects from the treatment, and 
   order at least a portion of the identified plurality of treatments according to the generated score to provide a treatment option or treatment contraindication prioritization for the patient.   
     
     
         20 . The device of  claim 19 , wherein the curated database further comprises one or more of the following:
 data extracted from other databases,   information extracted from text documents via text mining,   measurement data or processed measurement data from appropriate assays,   manually entered data, and   sign-offs and/or changes by curators.   
     
     
         21 . (canceled) 
     
     
         22 . The device of  claim 19 , wherein execution of the instructions further causes the one or more processors to instantiate a data mining module.