Table 3.

The version of the DIKB’s evidence taxonomy used in the reported study

➢ [EV Clinical Trial] A clinical trial: “a pre-planned clinical study of the safety, efficacy, or optimum dosage schedule of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in humans selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects.”-(Medical Subject Headings (MeSH) [23] version 2008, concept code D016430, Clinical Trial) ➢ [EV CT DDI] A DDI clinical trial: A study designed to quantify the pharmacokinetic and/or pharmacodynamic effects within study participants of a single drug in the presence of a purported precipitant. ➢ [EV PK DDI NR] A non-randomized DDI clinical trial: A pharmacokinetic DDI study where participants receive a drug in the presence of a purported precipitant (experimental group) or not (control group) but participants are not randomly assigned to experiment and control groups. This can include fixed-order studies where all participants are tested with placebo and precipitant after some period of washout - [EV PK DDI Par Grps] A parallel groups DDI clinical trial: A pharmacokinetic DDI study involving two groups of non-randomized participants where both groups receive the purported object drug while only one group receives the purported precipitant ➢ [EV PK DDI RCT] A randomized DDI clinical trial: A randomized, controlled, pharmacokinetic DDI study where participants receive a drug either in the presence of a purported precipitant (experimental group) or not (control group) ➢ [EV CT Pharmacokinetic] A pharmacokinetic clinical trial: ”A study of the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body.” (NCI Thesaurus [28] version 8, concept code C49663, Pharmacokinetic Study) - [EV CT PK Genotype] A genotyped pharmacokinetic clinical trial: A drug pharmacokinetics study whose population consists of at least two groups known to posses distinct forms of some drug-metabolizing enzyme - [EV CT PK Phenotype] A phenotyped pharmacokinetic clinical trial: A drug pharmacokinetics study whose population consists of at least two groups known to posses distinct drug metabolizing phenotypes ➢ [EV Retrospective] A retrospective study: ”Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.” (Medical Subject Headings (MeSH) [23] version 2008, concept code D012189, Retrospective Studies) - [EV PK DDI Retro] A retrospective DDI study: A retrospective study looking at the change in patient exposure of a single drug in the presence of a purported precipitant using a retrospective set of clinical records - [EV Population PK] A retrospective population PK study: a “…study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug in question.” ([48], p.1) ➢ [EV EX Met Enz ID] A drug metabolism identification experiment: An experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to identify the specific enzymes responsible for the metabolism of a drug ([15], p. 25) ➢ [EV EX Met Enz ID Cyp450] A CYP450 drug metabolism identification experiment: A metabolic enzyme identification experiment specifically designed to identify the Cytochrome P-450 enzymes involved in the metabolism of a drug ➢ [EV EX Met Enz ID Cyp450 Hum Recom] A CYP450, recombinant, drug metabolism iden-tification experiment with possibly NO probe enzyme inhibitor(s) - [EV EX Met Enz ID Cyp450 Hum Recom Chem] A CYP450, recombinant, drug metabolism identification experiment using chemical inhibitors - [EV EX Met Enz ID Cyp450 Hum Recom Antibody] A CYP450, recombinant, drug metabolism identification experiment using antibody inhibitors ➢ [EV EX Met Enz ID Cyp450 Hum Microsome] A CYP450, human microsome, drug metabolism identification experiment: A Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity and possibly NO probe enzyme inhibitor(s) - [EV EX Met Enz ID Cyp450 Hum Microsome Chem] A CYP450, human microsome, drug metabolism identification experiment using chemical inhibitors - [EV EX Met Enz ID Cyp450 Hum Microsome Antibody] A CYP450, human micro-some, drug metabolism identification experiment using antibody inhibitors: ➢ [EV EX Met Enz Inhibit] A metabolic enzyme inhibition experiment: An experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to determine whether or not a drug inhibits a specific drug-metabolizing enzyme ➢ [EV EX Met Enz Inhibit Cyp450] A CYP450 metabolic enzyme inhibition experiment: A metabolic inhibition experiment specifically designed to determine whether or not a drug inhibits a specific CYP450 enzyme ➢ [EV EX Met Enz Inhibit Cyp450 Hum Recom] A CYP450, recombinant, metabolic enzyme inhibition experiment: A Cytochrome P-450 inhibition experiment using recombinant human enzymes - [EV EX Met Enz Inhibit Cyp450 Hum Microsome] A CYP450, human microsome, metabolic enzyme inhibition experiment: A Cytochrome P-450 metabolic enzyme inhibition experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity ➢ [EV Observation] An observation-based report: An observation-based report of some occurrence ➢ [EV Obs ADE] An observation-based ADE report: An observation-based report of an adverse drug event - [EV Obs ADE Public Reported] An observation-based ADE report in a public reporting database: An adverse event report on file in a public adverse event reporting database such as the FDA’s Adverse Event Reporting System ➢ [EV Obs DI CR] A published observation-based ADE report: An published observation-based case-report of a drug interaction - [EV Obs DI CR Evaluated] A published and evaluated observation-based ADE report: An observation-based report of a drug interaction that has been evaluated by some assessment tool ➢ [EV Review] A review article: A published analysis of the evidence supporting and/or refuting some topic ➢ [EV Drug Review] A drug review article: A published analysis of research on the efficacy or safety of a drug, family of drugs, or drug therapy. - [EV DrugClinicalReview] An FDA clinical review: An FDA-sponsored review of a drug’s pre-market studies and adverse event reports. ➢ [Statement] A statement: A published artifact that is “…the basis for belief or disbelief; knowledge on which to base belief” see the term “evidence” in Wordnet version 3.0 [27] ➢ [Non Traceable Statement] A non-traceable, but possibly authoritative, statement: A statement that does not explicitly refer to evidence items in justification of its assertion(s) or that refers to an evidence item that is not accessible to the curator (e.g. pre-market drug studies only accessible to drug-company or FDA researchers) - [Non traceable Drug Label Statement] A non-traceable drug-label statement: An assertion found in a drug label that does not provide any traceable citations for its evidence support ➢ [Traceable Statement] A traceable statement: A statement that provides citation to evidence support for justification of its assertion(s) - [Traceable Drug Label Statement] A traceable drug-label statement: An assertion stated in a drug label that provides citations for its evidence support