HCLSIG/PharmaOntology/Roles

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Roles

1. Typical Questions Based Upon Roles

The "views" below are based on the contents of the Parkinson's Use Case by Don Doherty. (see resources page)

Strategic/Portfolio Manager View

Focus: Market Opportunities.
Concepts of interest: Competitors, Drugs, Diseases, Regulators, Payers, Patents, Market, Outcomes @@@
Potential ontologies: Human disease ontology, GO, Pathway Ontology, GAZ, UMLS (need to identify vocabulary needed), Prous, IDDB3, EPOC Patient ontology, CDISC, HL7, CPR, Semantic Network@@@

  • Given Company Name get MOA’s that this company is working on.
  • What other companies have drugs that are similar to ours in terms of compound similarity of therapeutic focus?
  • Where is there unmet need?
  • Which diseases are increasing in the population?
  • How is this therapy/compound different from existing therapies/compounds?
  • What therapies for the disease would be valued by payers?
  • What subpopulation demographics are associated with this disease?
  • What patents exist for this pathway/target?
  • Provide a list of drugs approved by the FDA, EMEA and/or Japan for disease x.
  • How does the price of this drug compare to other drugs?
  • What are our patients saying about our drugs?
  • Are some physicians getting much better results for disease X? Why?
  • Is this course of treatment economical?
  • Of drugs from either the same or different company for the same indication, are they approved in the same target region of interest – US or Global?
  • What is the share of voice in the literature for the drug? Depending on how soon past launch, may need to take into account the company drug compound name if only recently trademarked.
  • When does the drug go off patent?
  • What is the target audience for the drug, based on journals with drug mentioned in literature search?
  • Who are the key opinion leaders for the therapeutic area?
  • What are potential publication topics based on current or recently completed clinical trials?
  • What is the delivery method and dosing of the drug?
  • What generic drugs exist for the same indication?
  • How does the price of this drug compare to other drugs?
  • What subset of the population is most likely to have a success outcome from this medication based on gene expression and other molecular profiles?
  • What subset of the population is most likely to have an adverse event from this medication based on gene expression and other molecular profiles?
  • Who are the opinion leaders for a therapeutic area/drug/pathway based on literature and presentations?
  • @@@


Project Manager

Focus: Prioritizing activities and resources
Concepts of interest: People, Projects, Resource
Potential ontologies: SK2 (Projects), Lilly PR&D ontology

  • Which projects should have priority
  • What resources are required for this project?
  • Who is working on this project?
  • When do we need the next step completed?
  • @@@


Immunology

Focus: Developing large compounds
Concepts of interest: Antibodies, immune response
Potential ontologies: OBI/EFO, IEDB (OBI - antibodies, not an ontology)

  • Which immunisation regime delivers the most antibodies?
  • What process delivers the greatest diversity of antibodies?
  • which immunization regime produces antibodies with the right properties?
  • Which project is generating antibodies with the right properties
  • What were the immunisation conditions that led to this positive test result?
  • Where else does this sample appear on the Assay Plates?
  • @@@


Cheminformaticians View

Focus: Analyzing data and making predictions; relating bioinformatics and cheminformatics information
Concepts of interest: Molecular Structure (parts: pharmacophore, scaffold), Target, Pathway, Assay @@@
Potential ontologies: PubChem (not an ontology, but a source), ChEBI for molstruct, PRO for target, BIOPAX for pathway, OBI/EFO for assay? @@@

  • What patterns are in the data?
  • What is the diversity of molecules that have been active against this target? Can you infer other things from that?
  • Given a set of molecules that are active vs. inactive, can you develop a model that will predict whether a given molecule is active? How accurate is that?
  • Can one take the available actives and develop a 3D docking model that explains the data?
  • Is there any information available for related targets that will help us understand the current target and select molecules for screening?
  • What can we learn from previous targets/diseases?
  • Can you identify a set of compounds that are related to currently active compounds?
  • What are the opportunities for scaffold hopping? Can one identify a three, four, or five part pharmacophore that explains the known activities? Can one then design or find other molecules that would have a different scaffold (may be scaffold hop) that are likely to be active?
  • Is there any information available to help with multi-parameter optimization? (e.g. ADME, efficacy)
  • What predictive liabilities are associated with compounds that we are thinking about making?
  • @@@


Systems Physiologist View

Focus: Understanding the Biological System.
Concepts of interest: Receptors, Proteins, Genomic Sequences, Pathway @@@
Potential ontologies: GO for receptor activity, PRO for targets, Sequence Ontology, BioPax, SBO, GFF3 (not an ontology but format for genomic data), OMIM (also not an ontology) for phenotype, FMA for tissues, PATO for phenotypes, Human Phenotype Ontolgy (OBO) @@@

  • Retrieve the antibodies that have been used to assess the X pathway activity in X
  • Exon Descriptors - If we could 'semantically' describe all the exons on a genome and relate transcription and SNPs to other functional consequences, we could reason across the genome (Sequence Ontology!)
  • Tell me everything we know about a gene?
  • What is the function of this target (gene/protein/phenotype)?
  • What are the gene regulatory regions for this target?
  • What articles are available for this target?
  • Where is this gene expressed?
  • How are the gene and target correlated?
  • Given this hypothesis, does the ontology support it?
  • What can we infer about the gene?
  • Who are the experts on this topic in our company, within our collaboration network, and worldwide?
  • What's the statistical evidence of the association?
  • Gene expression profiles + proteomic profiles and metabolic profiles + imaging + genomic data (SNPs and epigenetics), + clinical data (treatments, family history, demographics, environmental) -> integrated model -> Predictions (risk, individual prognosis and response, drug response, environment (diet) response)
  • What are the changes in the sequence of a miRNA and / or variationsin the miRNA target region of a transcript?
  • How are miRNAs and alternate splicing differentially controlling genes?
  • Do patients have variations in the drug target itself?
  • Given a tissue, how do we model the pathway?
  • What hypotheses have been made about this gene?
  • What is the gene expression in this tissue?
  • @@@


Cellular and Molecular Biologist View

Focus: Understanding the Proteins/Genes Associated with Disease.
Concepts of interest: Disease, Pathway @@@
Potential ontologies: Human Disease Ontology (DO), BIOPAX, OMIM/PATO for phenotypes, GO for cellular components, SO for sequence variation/splice variants, Lilly experiment ontology, NCI thesaurus, MedDRA, Snomed @@@

  • Have we worked on this target in the past? If so, what happened? Why did we continue (or discontinue) work on this target?
  • Get all the interactions for X enzymes that are involved in Colon cancer. For all these genes, get the expression and aCGH values for all colon cancer samples
  • High Content Imaging Data - If we could 'semantically' describe cellular localization with other properties, we could discover novel indicators (e.g. cell size relates to expression)
  • What is the right target and pathway - How do variations in the sequences of genes in the pathway X correlate with the extent of disease severity, vulnerability and familial predisposition to Disease Q?
  • Who is the right patient - Are there genetic variations in the X pathway that predispose patients against response to Competitor Y but towards response to our X?
  • What targets are associated with this disease?
  • What experiments have been conducted on this target (gene/protein/phenotype)?
  • What experiments have altered the same pathway as this gene?
  • What active compounds or structures affect this target?
  • What epigenic regulators exist for this target?
  • What subpopulation demographics are associated with this disease?
  • How does the gene variant affect patient survival for this disease?
  • Provide a list of drugs approved by the FDA, EMEA and/or Japan for disease x.
  • Has a similar compound to ours been approved previously, and what were the side effects?
  • Are there outcomes data on the effectiveness of each of these drugs?
  • What are the current hot research topic areas for disease x?
  • What is the standard disease progression?
  • Is this a new phenotype for disease x?
  • How is the disease state correlated with genes, translated proteins, and post translational modifications and splice variants, and small molecule metabolites?
  • Do proteomic assays of tumor material and serum samples identify patterns reflecting outcomes?
  • What markers for predictions should be used in research discovery?
  • What is the underlying aspect of the profile that distinguishes high and low risk patients (pathway)?
  • What is the disease phenotype?
  • What variations are there in disease tissue versus germ line genes?
  • @@@


Medicinal Chemist View

Focus: @@@
Concepts of interest: Assay, Activity, Fragment, Synthesis, 'Lipinski'-type chemical properties, Polypharmacology @@@
Potential ontologies: Activity can be xp with GO, Lilly experiment ontology @@@

  • What is the history of what has been tested and shown active?
  • Are there similar themes/patterns that are apparent?
  • What classes of compounds appear to have activity?
  • What is the patent landscape?
  • What are the opportunities in this space?
  • How does the current activity space overlap with internal efforts?
  • What are the chemical properties? Given the IP landscape and the target, are there challenges that we would have to circumvent? (e.g. off-target effects, ADME)
  • Does the project lend itself to a fragment-based approach? A combinatorial chemistry approach?
  • Are there any particular challenges with the structure?(e.g. chirality)
  • Is there polypharmacology of target effect already ?


In-Vitro Biologist View

Focus: @@@
Concepts of interest: Bioassay, pathway @@@
Potential ontologies: OBI/EFO, BIOPAX, Lilly PR&D ontology, Lilly experiment ontology, ATCC, @@@

  • Find all the experiments that were done using my sample
  • Find cell lines in which RNAi data has been generated using X reagents
  • Find all samples which are grade III colorectal cancer. For these sample, retrieve the expression, mutation and aCGH data
  • How similar is the biological impact of closely related drugs?
  • What experiments have been conducted on this target (gene/protein/phenotype)?
  • What experiments have altered the same pathway as this gene?
  • What active compounds or structures affect this target?
  • How is this therapy/compound different from existing therapies/compounds?
  • What issues have been seen in this type of formulation in this drug class?
  • What side effects are seen in therapies that affect this target?
  • How do the pathways, receptors and the drug response genes from the 5 different schizophrenia drugs compare?
  • Do proteomic assays of tumor material and serum samples identify patterns reflecting outcomes?
  • What markers for predictions should be used in research discovery?
  • @@@


In-Vivo Biologist View

Focus: Toxicology or efficacy animal studies, preparation for first human dose @@@
Concepts of interest: @@@
Potential ontologies: Lilly PR&D ontology, OBI, Lilly experiment ontology, GMODs (mouse:MGD,rat:RGD), Entrez Genes database,

                     OMIA (Online Mendelian Inheritance in Animals) @@@ 
  • Find all the experiments that were done using my sample
  • What is the right compound and dose - What variations in metabolites correlate with the efficacy of compounds against Targets X, Y and Z?
  • How similar is the biological impact of closely related drugs?
  • What experiments have been conducted on this target (gene/protein/phenotype)?
  • How is this therapy/compound different from existing therapies/compounds?
  • What issues have been seen in this type of formulation in this drug class?
  • What side effects are seen in therapies that affect this target?
  • Which animal species has the closest genome for the pathway/target of this disease?
  • Are there any on-target safety concerns for this compound?
  • Might I be able to learn from some one else's study design?
  • Should my study compare my drug to vehicle or an existing drug?
  • What subset of the population is most likely to have a success outcome from this medication based on gene expression and other molecular profiles?
  • What subset of the population is most likely to have an adverse event from this medication based on gene expression and other molecular profiles?
  • What would be the best study design?
  • How might we adapt our study design?
  • What markers for predictions should be used in clinical assays?
  • @@@


Clinical Trial Formulator/Lead Physician View

Focus: Clinical Trials, Interventions
Concepts of interest: @@@
Potential ontologies: Sequence Ontology, OMIM/PATO, HPO (human phenotype ontology), DO: Disease Ontology, EPOC @@@

  • What is our research hypothesis?
  • Who are the experts on this topic in our company, within our collaboration network, and worldwide?
  • What's the statistical evidence of the association?
  • Gene expression profiles + (proteomic profiles and metabolic profiles) + imaging + genomic data (SNPs and epigenetics), + clinical data (treatments, family history, demographics, environmental) -> integrated model -> Predictions (risk, individual prognosis and response, drug response, environment (diet) response)
  • What is the disease phenotype?
  • Do patients have variations in the drug target itself?
  • Patient Stratification - If we could 'semantically' describe a patient with biomarker/genomic properties, we could 'semantically' compare them.
  • Who is the right patient - Are there genetic variations in the X pathway that predispose patients against response to Competitor Y but towards response to our X?
  • Which patients are most likely to respond in a clinical trial?
  • What other companies are running clinical trials in the same therapeutic area as us?
  • What issues have been seen in this type of formulation in this drug class?
  • What subpopulation demographics are associated with this disease?
  • Which population is most likely to respond to this therapy?
  • What side effects are seen in therapies that affect this target?
  • Has a similar compound to ours been approved previously, and what were the side effects?
  • Are there outcomes data on the effectiveness of each of these drugs?
  • Are there risk factors associated with the drug that should be taken into consideration (genetic, environmental)?
  • Might I be able to learn from some one else's clinical trial design?
  • Should my trial compare my drug to placebo or an existing drug?
  • What is the treatment regime for this drug?
  • What are the clinical care guidelines for this drug?
  • What subset of the population is most likely to have a success outcome from this medication based on gene expression and other molecular profiles?
  • What subset of the population is most likely to have an adverse event from this medication based on gene expression and other molecular profiles?
  • What clinical endpoints would be appropriate to measure for x clinical trial?
  • What would be the best study design?
  • How might we adapt our study design?
  • Careful phenotypic quality control and statistical considerations consisting of power, detection of population stratification and corrective measures, proper modeling of covariants and genetic variants, validation of results using independent data sets, and phenotypic and genotyping quality data itself.
  • What is the standard disease progression?
  • What is the likely disease progression for this patient?
  • What is the predicted outcome for the patient?
  • How quickly will this patient metabolize the drug?
  • Why did x respond to a trial but y didn't?
  • Is hypothesis x the reason why population y didn't respond in a trial?
  • Are there longitudinal studies available?
  • Where on the high-dimensional risk spectrum is the patient, based on the aggregate of environmental, life style, genetic, and other factors?
  • What discrete subset of the disease does this patient have?
  • How is the drug response state correlated with genes, translated proteins, and post translational modifications and splice variants, and small molecule metabolites?
  • Which drug metabolizing enzymes does the patient have?
  • Do patients have variations in the drug target itself?
  • Where is a patient on a complex, multi-dimensional risk spectrum based on detailed, individual molecular characteristics at genomics scale?
  • What markers for predictions should be used in clinical assays?
  • @@@


Clinical Decision Support System Implementer View

Focus: Clinicians, Diagnoses, Therapies
Concepts of interest: @@@
Potential ontologies: Sequence Ontology, OMIM/PATO, HPO (human phenotype ontology), DO: Disease Ontology, EPOC @@@

  • How is this therapy/compound different from existing therapies/compounds?
  • What issues have been seen in this type of formulation in this drug class?
  • What subpopulation demographics are associated with this disease?
  • Which population is most likely to respond to this therapy?
  • What side effects are seen in therapies that affect this target?
  • Are there any on-target safety concerns for this compound?
  • Are there risk factors associated with the drug that should be taken into consideration (genetic, environmental)?
  • What are our patients saying about our drugs?
  • What are the clinical care guidelines for this drug?
  • Are there tests that will need to be performed before prescribing this drug?
  • What subset of the population is most likely to have a success outcome from this medication based on gene expression and other molecular profiles?
  • What subset of the population is most likely to have an adverse event from this medication based on gene expression and other molecular profiles?
  • What's the statistical evidence of the association?
  • How quickly will this patient metabolize the drug?
  • Why did x respond to a trial but y didn't?
  • Is hypothesis x the reason why population y didn't respond in a trial?
  • Is this a new phenotype for disease x?
  • What discrete subset of the disease does this patient have?
  • How is the drug response state correlated with genes, translated proteins, and post translational modifications and splice variants, and small molecule metabolites?
  • How is the clinical outcome state correlated with genes, translated proteins, and post translational modifications and splice variants, and small molecule metabolites?
  • Which drug metabolizing enzymes does the patient have?
  • Do patients have variations in the drug target itself?
  • Is it likely that the patient will experience a recurrence?
  • Where is a patient on a complex, multi-dimensional risk spectrum based on detailed, individual molecular characteristics at genomics scale?
  • What was the strength of validation of genomic/integrated predictions?
  • Is this course of treatment economical?
  • What is the underlying aspect of the profile that distinguishes high and low risk patients (pathway)?
  • @@@


Statistician View

Focus: @@@
Concepts of interest: @@@
Potential ontologies: OBI, PATO, Sequence Ontology @@@

  • What statistical models are best for analyzing these data?
  • Careful phenotypic quality control and statistical considerations consisting of power, detection of population stratification and corrective measures, proper modeling of covariants and genetic variants, validation of results using independent data sets, and phenotypic and genotyping quality data itself.
  • @@@


Sales and Marketing View

Focus: @@@
Concepts of interest: @@@
Potential ontologies: @@@

  • Who are the opinion leaders I need to influence?
  • What physicians should I visit?
  • What media should we use for advertising?
  • Should we target internet based advertising?
  • Are we in compliance with the regulatory authorities and local laws?
  • @@@


Primary Care Clinician View

Focus: Patient, Patient Diagnosis, Disease Symptoms, Referral, Treatment/Management Plan
Concepts of interest: @@@
Potential ontologies: Human disease ontology (DO), Human Phenotype Ontology, Symptom Ontology, Chebi, PATO, IDO (Infectious Disease Ontology)

  • What are the alternative names for the disease/condition?
  • What are the diagnostic criteria for the disease?
  • What symptoms or test (finding) would show that the patient does not have the disease/condition?
  • What are the alternative names for the symptom?
  • What are the most recent treatments?
  • What are the previous treatments?
  • How do the most recent treatments differ from previous treatments?
  • How is this therapy/compound different from existing therapies/compounds?
  • What issues have been seen in this type of formulation in this drug class?
  • What subpopulation demographics are associated with this disease?
  • Which population is most likely to respond to this therapy?
  • Are there risk factors associated with the drug that should be taken into consideration (genetic, environmental)?
  • What are the current hot research topic areas for disease x?
  • What are our patients saying about the drug?
  • What is the treatment regime for this drug?
  • Are some physicians getting much better results for disease X? Why?
  • What are the clinical care guidelines for this drug?
  • Are there tests I need to perform before prescribing this drug?
  • What is the most appropriate therapeutic for this patient?
  • What is the standard disease progression?
  • What is the likely disease progression for this patient?
  • What is the predicted outcome for the patient?
  • How quickly will this patient metabolize the drug?
  • Is this a new phenotype for disease x?
  • Where on the high-dimensional risk spectrum is the patient, based on the aggregate of environmental, life style, genetic, and other factors?
  • What is the disease phenotype?
  • What discrete subset of the disease does this patient have?
  • Is it likely that the patient will experience a recurrence?
  • Where is a patient on a complex, multi-dimensional risk spectrum based on detailed, individual molecular characteristics at genomics scale?
  • Is this course of treatment economical?
  • What treatments are available for high risk patients?
  • What treatments are available for low risk patients?
  • What is the underlying aspect of the profile that distinguishes high and low risk patients (pathway)?
  • Are there natural alternatives to this drug?
  • Are there interferences between the drugs your taking and anything else (drugs, food, lifestyle) ?
  • @@@


Specialty Medical Provider View (e.g. Neurologist)

Focus: Cost/benefit of Therapy, Differential Diagnosis, Prognosis for Patient
Concepts of interest: @@@
Potential ontologies: OMIM, Human disease ontology (DO), Human Phenotype Ontology, Symptom Ontology, Chebi, PATO, IDO (Infectious Disease Ontology) @@@

  • What are the diagnostic criteria for the disease?
  • What symptoms or test would show that the patient does not have the disease/condition?
  • What are the most recent treatments?
  • How do the most recent treatments differ from previous treatments?
  • How is this therapy/compound different from existing therapies/compounds?
  • What issues have been seen in this type of formulation in this drug class?
  • Which population is most likely to respond to this therapy?
  • Are there risk factors associated with the drug that should be taken into consideration (genetic, environmental)?
  • What are the current hot research topic areas for disease x?
  • What are our patients saying about the drug?
  • What is the treatment regime for this drug?
  • Are some physicians getting much better results for disease X? Why?
  • What are the clinical care guidelines for this drug?
  • Are there tests I need to perform before prescribing this drug?
  • What is the most appropriate therapeutic for this patient?
  • What is the standard disease progression?
  • What is the likely disease progression for this patient?
  • What is the predicted outcome for the patient?
  • How quickly will this patient metabolize the drug?
  • Is this a new phenotype for disease x?
  • Where on the high-dimensional risk spectrum is the patient, based on the aggregate of environmental, life style, genetic, and other factors?
  • What is the disease phenotype?
  • What discrete subset of the disease does this patient have?
  • Is it likely that the patient will experience a recurrence?
  • Where is a patient on a complex, multi-dimensional risk spectrum based on detailed, individual molecular characteristics at genomics scale?
  • Is this course of treatment economical?
  • What treatments are available for high risk patients?
  • What treatments are available for low risk patients?
  • What is the underlying aspect of the profile that distinguishes high and low risk patients (pathway)?
  • Are there ongoing clinical trials for this disease?
  • Is the patient suitable for the clinical trial in terms of location, ethnic background, and other inclusion criteria?
  • Are there contraindications between the drug and others the patient is taking (including alcohol, food, heavy equipment)?
  • What side effects are there for this drug, especially those not on the label?
  • What lifestyle changes should I recommend?
  • How does the drug interact with the disease?
  • Is there interesting research or research results in this area (presented as a summary)?
  • Is there a combination of drugs that would work best?
  • @@@


Health Plan Provider View

Focus: @@@
Concepts of interest: @@@
Potential ontologies: Health Plan Model, @@@

  • How is this therapy/compound different from existing therapies/compounds?
  • How does the price of this drug compare to other drugs?
  • What are the clinical care guidelines for this drug?
  • Is this course of treatment economical?
  • @@@


Legal View

Focus: @@@
Concepts of interest: @@@
Potential ontologies: @@@