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Introduction

Cohorts are a fundamental building block for studies that use the OMOP CDM, identifying people who satisfy one or more inclusion criteria for a duration of time based on their clinical records. Currently cohorts are typically built using CIRCE which allows complex cohorts to be represented using JSON. This JSON is then converted to SQL for execution against a database containing data mapped to the OMOP CDM. CIRCE JSON can be created via the ATLAS GUI or programmatically via the Capr R package. However, although a powerful tool for expressing and operationalising cohort definitions, the SQL generated can be cumbersome especially for complex cohort definitions, moreover cohorts are instantiated independently, leading to duplicated work.

The CohortConstructor package offers an alternative approach, emphasizing cohort building in a pipeline format. It first creates base cohorts and then applies specific inclusion criteria. Unlike the “by definition” approach, where::here cohorts are built independently, CohortConstructor follows a “by domain” approach, which minimizes redundant queries to large OMOP tables. More details on this approach can be found in the Introduction vignette.

We benchmarked this package using nine phenotypes from the OHDSI Phenotype library that cover a range of concept domains, entry and inclusion criteria, and cohort exit options. We replicated these cohorts using CodelistGenerator and CohortConstructor to assess computational time and agreement between CIRCE and CohortConstructor.

Code and collaboration

The benchmarking code is available on the BenchmarkCohortConstructor repository on GitHub.

If you are interested in running the code on your database, feel free to reach out to us for assistance, and we can also update the vignette with your results! :)

The benchmark script was executed against the following four databases:

  • CPRD Gold: A primary care database from the UK, capturing data mostly from Northern Ireland, Wales, and Scotland clinics. The benchmark utilized a 100,000-person sample from this dataset, which is managed using PostgreSQL.

  • CPRD Aurum: Another UK primary care database, primarily covering clinics in England. This database is managed on SQL Server.

  • Coriva: A sample of approximately 400,000 patients from the Estonia National Health Insurance database, managed on PostgreSQL.

  • OHDSI SQL Server: A mock OMOP CDM dataset provided by OHDSI, hosted on SQL Server.

The table below presents the number of records in the OMOP tables used in the benchmark script for each of the participating databases.

OMOP table
Database
CPRD Aurum CORIVA-Estonia CPRD Gold 100k OHDSI Postgres server OHDSI redshift OHDSI snowflake OHDSI SQL server
person 47,193,158 438,433 100,000 1,000 1,000 116,352 1,000
observation_period 47,193,158 438,433 100,000 1,048 1,000 104,891 1,048
drug_exposure 3,256,609,138 31,265,445 12,403,195 49,542 57,095 6,303,388 49,542
condition_occurrence 2,110,992,846 40,957,155 3,191,739 160,322 147,186 14,455,993 160,322
procedure_occurrence 2,267,113,392 14,545,615 1,914,271 62,189 137,522 13,926,771 62,189
visit_occurrence 7,091,248,835 38,037,330 9,183,206 47,457 55,261 5,579,542 47,457
measurement 8,255,241,316 39,378,570 10,913,588 2,858 34,556 3,704,839 2,858
observation 16,425,069,199 37,010,044 11,107,039 13,481 19,339 1,876,834 13,481

Cohorts

We replicated the following cohorts from the OHDSI phenotype library: COVID-19 (ID 56), inpatient hospitalisation (23), new users of beta blockers nested in essential hypertension (1049), transverse myelitis (63), major non cardiac surgery (1289), asthma without COPD (27), endometriosis procedure (722), new fluoroquinolone users (1043), acquired neutropenia or unspecified leukopenia (213).

The COVID-19 cohort was used to evaluate the performance of common cohort stratifications. To compare the package with CIRCE, we created definitions in Atlas, stratified by age groups and sex, which are available in the benchmark GitHub repository with the benchmark code.

Cohort counts and overlap

The following table displays the number of records and subjects for each cohort across the participating databases:

Tool
Cohort name
CIRCE
CohortConstructor
Number records Number subjects Number records Number subjects
CPRD Aurum
Acquired neutropenia or unspecified leukopenia 1,429,966 632,966 1,302,498 633,030
Asthma without COPD 4,009,925 4,009,925 3,934,106 3,934,106
COVID-19 5,600,429 4,452,410 6,206,907 4,452,196
COVID-19: female 3,111,643 2,434,062 3,452,138 2,438,759
COVID-19: female, 0 to 50 2,172,113 1,730,180 2,382,039 1,730,116
COVID-19: female, 51 to 150 939,818 708,838 1,070,099 708,643
COVID-19: male 2,488,786 2,018,348 2,754,769 2,020,625
COVID-19: male, 0 to 50 1,709,375 1,422,999 1,862,219 1,422,962
COVID-19: male, 51 to 150 779,629 597,804 892,550 597,663
Endometriosis procedure 139 108 77 77
Inpatient hospitalisation 0 0 0 0
Major non cardiac surgery 1,932,745 1,932,745 1,932,745 1,932,745
New fluoroquinolone users 1,765,274 1,765,274 1,817,439 1,817,439
New users of beta blockers nested in essential hypertension 98,592 98,592 102,589 102,589
Transverse myelitis 11,930 4,040 5,818 4,119
CORIVA-Estonia
Acquired neutropenia or unspecified leukopenia 2,231 634 2,188 634
Asthma without COPD 25,867 25,867 25,867 25,867
COVID-19 421,053 193,435 435,059 193,435
COVID-19: female 235,740 105,849 243,773 106,322
COVID-19: female, 0 to 50 150,121 69,168 155,256 69,168
COVID-19: female, 51 to 150 85,620 37,154 88,517 37,154
COVID-19: male 185,313 87,586 191,286 87,891
COVID-19: male, 0 to 50 130,252 63,558 134,415 63,558
COVID-19: male, 51 to 150 55,062 24,333 56,871 24,333
Endometriosis procedure 0 0 0 0
Inpatient hospitalisation 267,010 133,705 267,010 133,705
Major non cardiac surgery 4,025 4,025 4,025 4,025
New fluoroquinolone users 39,712 39,712 39,712 39,712
New users of beta blockers nested in essential hypertension 18,967 18,967 18,967 18,967
Transverse myelitis 27 10 12 10
CPRD Gold 100k
Acquired neutropenia or unspecified leukopenia 2,719 1,167 2,675 1,167
Asthma without COPD 8,808 8,808 8,741 8,741
COVID-19 3,231 2,881 3,275 2,881
COVID-19: female 1,748 1,543 1,771 1,543
COVID-19: female, 0 to 50 1,271 1,125 1,291 1,125
COVID-19: female, 51 to 150 477 418 480 418
COVID-19: male 1,483 1,338 1,504 1,341
COVID-19: male, 0 to 50 1,054 960 1,072 960
COVID-19: male, 51 to 150 429 381 432 381
Endometriosis procedure 0 0 0 0
Inpatient hospitalisation 0 0 0 0
Major non cardiac surgery 4,146 4,146 4,146 4,146
New fluoroquinolone users 5,412 5,412 5,412 5,412
New users of beta blockers nested in essential hypertension 1,723 1,723 1,723 1,723
Transverse myelitis 31 11 15 11
OHDSI Postgres server
Acquired neutropenia or unspecified leukopenia 151 86 106 86
Asthma without COPD 126 126 126 126
COVID-19 0 0 0 0
COVID-19: female 0 0 0 0
COVID-19: female, 0 to 50 0 0 0 0
COVID-19: female, 51 to 150 0 0 0 0
COVID-19: male 0 0 0 0
COVID-19: male, 0 to 50 0 0 0 0
COVID-19: male, 51 to 150 0 0 0 0
Endometriosis procedure 0 0 0 0
Inpatient hospitalisation 522 321 522 321
Major non cardiac surgery 88 88 92 92
New fluoroquinolone users 145 145 145 145
New users of beta blockers nested in essential hypertension 112 112 112 112
Transverse myelitis 0 0 0 0
OHDSI redshift
Acquired neutropenia or unspecified leukopenia 155 88 108 88
Asthma without COPD 228 228 228 228
COVID-19 0 0 0 0
COVID-19: female 0 0 0 0
COVID-19: female, 0 to 50 0 0 0 0
COVID-19: female, 51 to 150 0 0 0 0
COVID-19: male 0 0 0 0
COVID-19: male, 0 to 50 0 0 0 0
COVID-19: male, 51 to 150 0 0 0 0
Endometriosis procedure 0 0 0 0
Inpatient hospitalisation 612 365 612 365
Major non cardiac surgery 616 616 613 613
New fluoroquinolone users 109 109 109 109
New users of beta blockers nested in essential hypertension 25 25 25 25
Transverse myelitis - - - -
OHDSI snowflake
Acquired neutropenia or unspecified leukopenia 13,960 8,525 10,147 8,525
Asthma without COPD 24,288 24,288 24,291 24,291
COVID-19 0 0 0 0
COVID-19: female 0 0 0 0
COVID-19: female, 0 to 50 0 0 0 0
COVID-19: female, 51 to 150 0 0 0 0
COVID-19: male 0 0 0 0
COVID-19: male, 0 to 50 0 0 0 0
COVID-19: male, 51 to 150 0 0 0 0
Endometriosis procedure - - 0 0
Inpatient hospitalisation 64,275 37,780 64,275 37,780
Major non cardiac surgery 66,171 66,171 66,034 66,034
New fluoroquinolone users 14,203 14,203 13,398 13,398
New users of beta blockers nested in essential hypertension 2,022 2,022 2,028 2,028
Transverse myelitis 102 43 42 42
OHDSI SQL server
Acquired neutropenia or unspecified leukopenia 151 86 106 86
Asthma without COPD 126 126 126 126
COVID-19 0 0 0 0
COVID-19: female 0 0 0 0
COVID-19: female, 0 to 50 0 0 0 0
COVID-19: female, 51 to 150 0 0 0 0
COVID-19: male 0 0 0 0
COVID-19: male, 0 to 50 0 0 0 0
COVID-19: male, 51 to 150 0 0 0 0
Endometriosis procedure 0 0 0 0
Inpatient hospitalisation 522 321 522 321
Major non cardiac surgery 88 88 92 92
New fluoroquinolone users 145 145 145 145
New users of beta blockers nested in essential hypertension 112 112 112 112
Transverse myelitis 0 0 0 0

We also computed the overlap between patients in CIRCE and CohortConstructor cohorts, with results shown in the plot below:

Performance

To evaluate CohortConstructor performance we generated each of the CIRCE cohorts using functionalities provided by both CodelistGenerator and CohortConstructor, and measured the computational time taken.

Two different approaches with CohortConstructor were tested:

  • By definition: we created each of the cohorts seprately.

  • By domain: All nine targeted cohorts were created together in a set, following the by domain approach described in the Introduction vignette. Briefly, this approach involves creating all base cohorts at once, requiring only one call to each involved OMOP table.

By definition

The following plot shows the times taken to create each cohort using CIRCE and CohortConstructor when each cohorts were created separately.

By domain

The table below depicts the total time it took to create the nine cohorts when using the by domain approach for CohortConstructor.

Database_name
Time (minutes)
CIRCE CohortConstructor
CORIVA-Estonia 9.51 9.95
CPRD Aurum 3,288.11 109.08
CPRD Gold 100k 73.41 7.85
OHDSI Postgres server 4.32 29.20
OHDSI SQL server 2.89 18.56
OHDSI redshift 5.44 34.05
OHDSI snowflake 11.40 84.56

Cohort stratification

Cohorts are often stratified in studies. With Atlas cohort definitions, each stratum requires a new CIRCE JSON to be instantiated, while CohortConstructor allows stratifications to be generated from an overall cohort. The following table shows the time taken to create age and sex stratifications for the COVID-19 cohort with both CIRCE and CohortConstructor.

Database
Time (minutes)
CIRCE CohortConstructor
CORIVA-Estonia 14.38 23.51
CPRD Aurum 3,300.18 241.81
CPRD Gold 100k 166.66 19.52
OHDSI Postgres server 6.75 73.24
OHDSI SQL server 4.56 46.64
OHDSI redshift 8.32 84.79
OHDSI snowflake 17.04 202.95

Use of SQL indexes

For Postgres SQL databases, the package uses indexes in conceptCohort by default. To evaluate how much these indexes reduce computation time, we instantiated a subset of concept sets from the benchmark, both with and without indexes.

Four calls were made to conceptCohort, each involving a different number of OMOP tables. The combinations were:

  1. Drug exposure

  2. Drug exposure + condition occurrence

  3. Drug exposure + condition occurrence + procedure occurrence

  4. Drug exposure + condition occurrence + procedure occurrence + measurement

The plot below shows the computation time with and without SQL indexes for each scenario: