The 2008/01/29 OCRe Ontology
- Updated categories in Statistical_concept, characterizing distributional metrics in terms of central tendency, dispersion, and exponential, and added top-level terms in Statistical_method
- Extracted study design descriptors and study categorization into a study_design module imported by the research module
- Deleted the criterion module that contains the ERGO terms and relationships.
- Removed the dependency of study protocol module on the clinical module
- Imported the bfo-mapping module to Start-Here
- Updated mgPerDL to be instance of ComplexDerivedUnit
- Updated OCRe.doc document

The 2008/01/15 OCRe Ontology
- Added UCUM ontology created by MyMobileWeb project, 2008 (Based on the UCM data (c) Gunther Schadow, Clement J. McDonald, 2005"
- Added Time_to_event as a compositional variable type
- Renamed "descriptive statistics" to "Distributional_metric
- Added Distribution_metric as a parent of Proportion

The 2008/12/12 OCRe Ontology
- Updated ocre:Study_characteristics to conform to Ida Sim's StudyDesignClassificaiton.10.ppt
- updated ocre:Statistical_datatype

The20081124 OCRe Ontology
- Updated ocre:Study_characteristics to conform to Ida Sim's StudyDesignClassificaiton.6.ppt
- Updated ocre:Outcome_entity so that they conform the the following conception of Outcome
Outcomes are informational entities specified in a study protocol. It can be divided into two types: Subject_Outcome and Study_Outcome. 
A subject outcome is a description of an outcome for a particular subject participating in the study. An outcome has the following properties:
 
1.	Outcome phenomenon: A description of the phenomenon (e.g., clinical phenotype such as high blood pressure) being assessed, and the method of assessment. An outcome may involve the assessment of multiple phenomena (e.g., stroke, death, and MI) and define an outcome variable based on all phenomena assessed for the outcome. An Assessment_Method has some coded annotation (e.g., Hamilton scale), a text description, and one or more assessment_characteristics (reliability, reproducibility, inter-rater variability, etc.; subclasses of ocre:Performance_characteristics).  How to deal with cost of treating MI (is the phenomenum 'cost'? or 'treating MI' or 'MI? 
2.	Assessment time: The time points at which the outcome phenomena should be assessed
3.	Subject outcome variable: An Outcome_variable has an expression that specifies how the value of outcome should be computed from the assessed outcome phenomena (e.g., the presence of "first event of either death, stroke, MI within 6 months after index MI") and a set of outcome variable characteristics such as descriptive statistics (e.g., mean) and datatype (e.g., continous).
4.	Outcome  characteristics: A characterization of the outcome.  Possible outcome characteristics include Blinding_type
5.	has_analysis_method 0 or more Statistical method
6.	has result (0 or more) a standard term (e.g., slope) that is_result_of some  Statistical method (e.g., linear regression).
A Study outcome is the outcome aggregated over the subject outcomes. 
1.	Statistical method used to analyze the outcome
2.	Study outcome measure: outcome aggregated over all subjects (e.g.,   count of subject outcome of specific kind, average of subject   outcome), and possibly aggregated over other study outcome measures (e.g., proportional hazard model, really any multivariable analysis)
A study may distinguish between primary and secondary outcomes or characterize adverse events as a kind of outcome.

The 20081014 OCRe Ontology
- Updated ocre:Study_characteristics to conform to Ida Sim's StudyDesignClassificaiton.ppt
- Added definitions for "Prospective matched cohort study", "Matched cohort study" and a bunch of Intervention study types.
The 20081009 OCRe Ontology
- Separate out Study_Outcome and Subject_outcome in the "research" module.
  - A subject outcome is assessed at some time points relative to some anchor time. A subject outcome measure is an expression involving assessed values. The outcome measure has some outcome type (e.g., categorical, ratio, etc.)
  - A study outcome is aggregated from other subject or study outcomes. It is analyzed using some statistical method.
- Created separate Study_outcome_type and Subject_outcome_type hierarchies. Right now they differ only in that "Scored_instrument" is not a Study_outcome_type.
- Modeled "Cost" as having a monetary amount (value and currency), base year, and discount rate.
- Added Monetary_amount and Relative_time_point to the "clinical" module.
- Added "factors" of study design as Study characteristics (See FactorsFlowChart.1.ppt). Study types (e.g., Prospective cohort study)  can be dissected using these study design factors. 

**** The 20080722 OCRe Ontology
- General clean up of name spaces and instances
- Added some comment annotations
- Updated ERGO classes to be consistent with Frame version
**** The 20080623 OCRe Ontology
- Added subproperty of study_design_object_property
  - has_baseline_characteristics object property  
    The range of the property is expected to be Outcome.
  - Added/organized subproperties of has_outcome object property
    - has_adverse_event/is_adverse_event_of
    - has_primary_outcome/is_primary_outcome_of
    - has_secondary_outcome/is_secondary_outcome_of
- Added subproperties of administrative_object_property: 
  - executes/executed_by (A StudySite executes some StudyProtocol 
    (from BRIDG 1.1.1)
  - function_as/is represented by: A healthcare organization functions 
    as a study site (from BRIDG 1).1.1
- Added subproperties of the outcome_property
  - is_analyzed_using/is_used_to_analyze (an outcome is analyzed 
    using some statistical method)
- Added StudySite class
- Added Outcome_type (with Continuous, Categorical, Proportion, Rate, Count, Cost, Life-Years, Scored_Instrument as subclasses)
- Added Statistical_method (as a Standard_term??) as a stub for some external classification of statistical methods



**** The 20080603 OCRe ontology
- Cleaned up ontologies so that they are loadable into Protege 3.4 beta, removed redundant properties
-  Added some TGN1412 instances corresponding a part of the Arm SOA. 

**** The 20080519 OCRe ontology
- Re-organized the upper level of OCRe ontology to be Entity, Event, Role, Research_Concept, and Standard_term_interface. 
- Added allocation type, blinding type, randomization method, and allocation concealment type from Igor's earlier ontology. 
- Created tentative mapping of OCRe terms to BFO (see bfo-mapping file)

****The 20080514 OCRe ontology
Added study_protocol module that includes BRIDG StudyProtocol and planned study classes. Clarified mapping between OCRe Observation (previously called Assessment) class and BRIDG PerformedObservation, PerformedObservationResult, and Assessment classes.


****The 20080502 OCRe ontology
Added terminology codes for some Study Characteristics

****The 20080415 revised OCRe ontology

This version of the OCRe adds a number of object properties that are
inverses of existing properties. These inverse properties are created
to facilitate queries.

****The 20080407 revised OCRe ontology models the following:

This version of the OCRe incorporates an experimental specification of
trial outcome defined as follows:

Outcome has the following properties
1. event_type (e.g., MI, death, stroke): classes and/or codes

2. outcome_event (MI, death, or stroke events 6 months after index
   MI): can be specified using SWRL or ERGO. In the current version,
   for the example protocol, outcome_event is an instance of ERGO
   Query for such events

3. subject_outcome_measure: the outcome measure for a particular
   subject, e.g, presence of "first event of either death, stroke, MI
   within 6 months after index MI"). In the current version, for the
   example protocol, the subject_outcome_event is modeled as an ERGO
   Query.

4. trial outcome measure: outcome aggregated over all subjects (e.g.,
   count of subject outcome of specific kind, average of subject
   outcome). In the current version, for the example protocol, trial
   outcome measure is modeled as an ERGO Aggregate_Subject_Query.

See ERGO.zip (linked on the wiki page) for the detailed specification
of ERGO queries.


**** The 20080328 revised OCRe ontology models the following:

1. A Study has instances Tango_study, NeoTango_study, and Thrombolytic_therapy_versus_Primary_Percutaneious_Intervention
2. Thrombolytic_therapy_versus_Primary_Percutaneious_Intervention has
    - a number of study_characterisitcs (clinical trial, Ramdomized, Completed, Treatment)
    - health_condition_studied some acute_MI and value acute_MI_code (acute_MI is a concept from SNOMEDCT, is annotated with acute_MI_code (which is_a_code_for some acute_MI).
    - therapy some Thrombolytic_therapy and value Thrombolytic_therapy_code
    - therapy some percutaneious_coronary_intervention and value percutaneious_coronary_intervention_code
    - eligibility_criteria instances of "ERGO" templates for "Creatinine < 1.5 mg/dL" and "Assessment acute MI"
    - target_subject subjects that has some Acute_MI_Assessment (Assessment has_finding some AcuteMI, has_value some present)
    - NCT Number some string
    - Date of First Enrollment: some date
    - Recruitment status: completed
    - Planned sample size: some number
    - Principle Investigator: a Clinician Role played by an individual Personscientific title some string
3. The instances Tango_study, NeoTango_study have study_event Tango_event and NeoTango_event, study_subject Tango_subject and NeoTango_subject, and study_population Tango_population and NeoTango_population.

I have simple sample interfaces to NCI Thesaurus and SNOMEDCT where we
import parts of the hierarchies from the terminology sources and the
corresponding dodes. As in the acute_MI and acute_MI_code example, we
overload the property (e.g., health_condition_studies) with
restriction based on the concept (acute_MI) and also assert property
value (acute_MI_code). The code is related to the concept through the
is_code_for property and has_code annotation on the concept.

In this ontology, a randomized_clinical_trial is defined, not through
the events it has, but through the study_characteristics of Randomized
and clinical_trial that have been asserted about individual trials. I
see the clinical events in the Dec 31 OCRe model as records of events
that happens in the world. Classes such as NeoTango_events are
constraints on those events that complies with requirements of
NeoTango protocol. Eligibility criteria are instances of ERGO
templates (something else that UCSF and Stanford have been working
on). Instead, we define "target_subject" as members of the study
population from which subjects will be recruited.

Right now there is no notion of trial protocol or planned event in the
ontology.

One thing we have to decide is whether we want to optimize the model
for querying or for having precise semantics. For example, one of the
items in Ida's Research Characterization Use Cases for OCRe document
is "Identify age range of study participants." We can write an
expression for age as an Assessment with finding equals age and value
>= 18 years, or we can put in an instance of Time Interval with lower
bound = 18 years.  The first representation allows us to compute
whether a patient satisfies the criterion, the second allows easier
query for all trials that have 18 years as lowerbound of age
restriction.

We have to do the same thing when it comes to outcomes. The
thrombolytic therapy versus CPI trial's primary outcome is "incident 6
months after index MI of the first occurrence of death, recurrent MI,
or stroke." We can't model this complex outcome precisely in OWL. We
need some discussion on the use cases for outcomes.
