Stratifying and annotating a clinical practice guideline

Abstract

Personalized medicine involves the use of a patient's molecular markers to guide treatment regimens for the patient. The scientific literature provides multiple examples of correlations between drug treatment efficacy and the presence or absence of molecular markers in a patient sample. Methods are provided herein that permit efficient dissemination of scientific findings regarding treatment efficacy and molecular markers found in patient tumors to health care providers.

1 .- 75 . (canceled) 
     
     
         76 . A method of determining one or more personalized cancer treatment options for a subject, the method comprising:
 a. obtaining a sample from a subject, wherein the sample comprises molecular markers from a tumor cell;   b. determining a status of the molecular markers;   c. stratifying cancer drug treatment options in a clinical practice guideline for a cancer based on the status of the molecular markers; and   d. annotating the clinical practice guideline with information comprising information regarding one or more additional drug treatment options not listed in the clinical practice guideline for the cancer, wherein the information is included based on the status of the molecular markers.   
     
     
         77 . The method of  claim 76 , wherein the stratifying is based on information in scientific literature. 
     
     
         78 . The method of  claim 76 , wherein the stratifying takes into account the status of one or more molecular markers in drug absorption, distribution, metabolism, or excretion genes in a sample from the subject. 
     
     
         79 . The method of  claim 76 , wherein the stratifying takes into account whether the subject is hypermetabolic. 
     
     
         80 . The method of  claim 76 , wherein the stratifying takes into account the CYP450 status of the subject. 
     
     
         81 . The method of  claim 76 , wherein the stratifying and/or the annotating is further based on clinical information for the subject. 
     
     
         82 . The method of  claim 76 , wherein the stratifying comprises ranking drug treatment options with a higher likelihood of efficacy higher than drug treatment options with a lower likelihood of efficacy or for which no information exists with regard to treating subjects with the determined status of the one or more molecular markers. 
     
     
         83 . The method of  claim 76 , wherein the stratifying comprises indicating on the clinical practice guideline one or more drug treatment options for which scientific information suggests the one or more drug treatment options will be efficacious in a subject, based on the status of one or more molecular markers in the sample from the subject. 
     
     
         84 . The method of  claim 76 , wherein the stratifying comprises indicating on a clinical practice guideline one or more drug treatment options for which some scientific information suggests the one or more drug treatment options will be efficacious in the subject, and some scientific information suggests the one or more drug treatment options will not be efficacious in the subject, based on the status of one or more molecular markers in the sample from the subject. 
     
     
         85 . The method of  claim 76 , wherein the stratifying comprises indicating on a clinical practice guideline one or more drug treatment options for which scientific information indicates the one or more drug treatment options will not be efficacious for the subject, based on the status of one or more molecular markers in the sample from the subject. 
     
     
         86 . The method of  claim 76 , wherein the annotating comprises listing one or more FDA-approved drugs for off-label use, one or more drugs listed in a Centers for Medicare and Medicaid Services (CMS) anti-cancer treatment compendia, and/or one or more experimental drugs found in scientific literature, in the clinical practice guideline. 
     
     
         87 . The method of  claim 76 , wherein the annotating comprises connecting a listed drug treatment option to a reference containing scientific information regarding the drug treatment option. 
     
     
         88 . The method of  claim 87 , wherein the scientific information is from a peer-reviewed article from a medical journal. 
     
     
         89 . The method of  claim 76 , wherein the annotating comprises adding information to the clinical practice guideline selected from the group consisting of one or more drug treatment options, scientific information regarding one or more drug treatment options, one or more links to scientific information regarding one or more drug treatment options, one or more links to citations for scientific information regarding one or more drug treatment options, and clinical trial information regarding one or more drug treatment options. 
     
     
         90 . The method of  claim 76 , wherein the sample comprises a tumor biopsy or a cell-free sample. 
     
     
         91 . The method of  claim 76 , wherein the tumor cell comprises a cell from a colon cancer, a bone cancer, a breast cancer, a central nervous system cancer, a gastric cancer, a cervical cancer, a blood cancer, an esophageal cancer, a head and neck cancer, a kidney cancer, a skin cancer, a lung cancer, or a carcinoma. 
     
     
         92 . The method of  claim 76 , wherein the determining comprises nucleic acid amplification, DNA sequencing, fluorescent in-situ hybridization (FISH), quantitative PCR (qPCR), and/or immunohistochemistry (IHC). 
     
     
         93 . The method of  claim 76 , wherein the determining comprises determining a presence, absence, increase, or decrease of one or more molecular markers. 
     
     
         94 . The method of  claim 76 , wherein the determining comprises determining an absence of one or more mutations or a presence of the one or more mutations in the molecular markers. 
     
     
         95 . The method of  claim 94 , wherein the one or more mutations comprise a de novo mutation, nonsense mutation, missense mutation, silent mutation, frameshift mutation, insertion, substitution, point mutation, single nucleotide polymorphism (SNP), deletion, rearrangement, amplification, chromosomal translocation, interstitial deletion, chromosomal inversion, loss of heterozygosity, loss of function mutation, gain of function mutation, dominant negative mutation, or lethal mutation.