Computable phenotypes for cohort identification: core content for a new class of FAIR Digital Objects
Authors: Conte Marisa , Flynn Allen , Boisvert Peter , Landis-Lewis Zach , Richesson Rachel , Friedman Charles 
Published: October 2022

Introduction

We present current work to develop and define a class of digital objects that facilitates patient cohort identification for clinical studies, such that these objects are Findable, Accessible, Interoperable, and Reusable (FAIR) (Wilkinson et al. 2016). Developing this class of FAIR Digital Objects (FDOs) builds on the work of several years to develop the Knowledge Grid (https://kgrid.org/), which facilitates the development, description and implementation of biomedical knowledge packaged in machine-readable and machine-executable formats (Flynn et al. 2018). Additionally, this work aligns with the goals of the Mobilizing Computable Biomedical Knowledge (MCBK) community (https://mobilizecbk.med.umich.edu/) (Mobilizing Computable Biomedical Knowledge 2018). In this abstract, we describe our work to develop a FDO carrying a computable phenotype.

Defining computable phenotypes

In biomedical informatics, 'phenotyping' describes a data-driven approach to identifying a group of individuals sharing observable characteristics of interest, generally related to a disease or condition, and a 'computable phenotype' (CP) is a machine-processable expression of a phenotypic pattern of these characteristics (Hripcsak and Albers 2018).

For the purposes of this work, we are interested in CPs derived from data contained in electronic health record (EHR) systems. This includes both structured data, e.g. codes for diseases, diagnoses, procedures, or laboratory tests, and unstructured data, e.g. free text including patient histories, clinical observations, discharge summaries, and reports. Thus, we define computable phenotype FDOs (CP-FDOs) as a class of FDO that packages an executable EHR-derived CP together with documentation needed to implement and use it effectively for creating cohorts of individuals with similar observable characteristics from EHR data sets.

Importance of portable and FAIR CPs

There is tremendous excitement for using real-world EHR data to discover important findings about human health and well-being. However, for discovery to happen, researchers need mechanisms like CPs to identify study cohorts for analysis. Beginning in the early 2010s, a growing literature explores various methods for the secondary use of EHR data for patient phenotyping to arrive at consistent study cohorts (Shivade et al. 2014, Banda et al. 2018). The heterogeneous nature of EHR data has inspired a wide variety of phenotyping methods, from those which rely solely on documented codes linked to terms in existing vocabularies to those which combine such codes with other concepts extracted from free text using natural language processing.

Our current focus is on packaging CPs inside FDOs for classifying patients as having or not having a phenotype of interest. This can be done within an individual health system, or at scale across a clinical data research network. Using CPs for cohort identification can reduce the time and expense of traditional data set building and clincal trial recruitment, and expand the potential scope of a study population(Boland et al. 2013).

Creating and validating CPs requires time, resources, and both clinical and technical expertise. One estimate is that it can take 6-10 months to develop and validate a CP (Shang et al. 2019). And, as there is no standard data model within EHRs in the United States, many CPs are designed for performance at a single site, rather than for portability, which is understood as the ability to implement a phenotype at a different site with similar performance (Shang et al. 2019). While portability is increasingly recognized as an important element of phenotyping, and there have been recent efforts to develop more portable CPs, many of these processes still require significant technical expertise at the implementation site to adapt the phenotype for use on local data.

There may also be significant advantages to making CPs FAIR. These include transparency in cohort selection, and better generalizability of results. FAIR CPs may also increase the potential for robust comparisons of data from related studies, leading to better evidence synthesis to improve delivery of care and ultimately human health.

Defining a new class of FDOs to hold and convey CPs

We believe that packaging validated CPs inside digital objects may alleviate many of the pressures mentioned above, and contributes to making both the processes and products of clinical research more FAIR. To this end, our current work focuses on packaging a validated CP inside a machine-processable FDO. The phenotype of interest identifies pediatric and adult patients with a rare disease (Oliverio et al. 2021), and has several features which make it ideal for transformation to an executable FDO. First, the phenotype utilizes standards to define the clinical characteristics of interest, and is based on a common data model; these features increase the potential for both interoperability and reuse. Additionally, because the phenotype has been validated across three sites, its portability has already been demonstrated. Finally, the full computable phenotype has been shared as a series of SQL queries, including scripts for patient identification, deriving statistics, and validation, which have been annotated with instructions for implementation at other sites.

The goals of this work are:

To develop CPs as executable DOs, leveraging previous work to develop executable Knowledge Objects (KO) (Flynn et al. 2018)

To advance our understanding of how to define computable phenotypes as a class of FDO, including what is needed to meet the requirements of binding, abstraction, and encapsulation (Wittenburg et al. 2019)

To develop CPs as executable DOs, leveraging previous work to develop executable Knowledge Objects (KO) (Flynn et al. 2018)

To advance our understanding of how to define computable phenotypes as a class of FDO, including what is needed to meet the requirements of binding, abstraction, and encapsulation (Wittenburg et al. 2019)

Conclusion

Computable phenotypes, packaged as FDOs, may increase the potential both for the portability of a phenotype and the reusability of data resulting from its implementation. Providing CPs as executable FDOs may also reduce barriers to portability and local implementation. In this presentation, we describe our work to develop a FDO computable phenotype from an existing validated phenotype. Lessons learned from this process will increase our understanding of both the technical requirements, and how to address necessary components of abstraction, binding, and encapsulation so that these can function as FAIR Digital Objects.