IN-TANDEM Familial Hypercholesterolemia Pilot Study

INTegrating Active Case-finding With Next-generation Sequencing for Diagnosis Through Electronic Medical Records (IN-TANDEM): Familial Hypercholesterolemia Pilot Study

The purpose of this study is to validate the use of the FH Foundation FIND FH® Algorithm as a clinical decision support tool. FIND FH (Flag/Identify/Network/Engage) is a national initiative that utilizes machine learning and data mining techniques to identify individuals whose profiles are consistent with FH patients. The algorithm will be tested in adults with at least one cardiovascular comorbidity. Study subjects will be asked to provide either a saliva, buccal or venous blood sample for DNA and biomarker analysis

Study Overview

• Status: Completed
• Conditions: Familial Hypercholesterolemia
• Intervention / Treatment: Other: Genetic testing

• Study Type: Observational
• Enrollment (Actual): 378

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17602
      • Lancaster General Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Randomly selected patients from University of Pennsylvania and Lancaster General Hospital with at least 1 cardiovascular comorbidity seen at hospital within the past five years.

Description

Inclusion Criteria:

• Age 18 years or older
• At least one cardiovascular co-morbidity or receiving treatment for a cardiovascular comorbidity
• Algorithm score 0-1
• Most recent encounter with a provider within five years of query date

Exclusion Criteria:

• Any medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study, or confound study data

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Strata 0-0.05; Lowest probability of having familial hypercholesterolemia	Other: Genetic testing; Targeted next-generation sequencing for familial hypercholesterolemia causative mutations
Strata 0.06-0.15; Second lowest probability of having familial hypercholesterolemia	Other: Genetic testing; Targeted next-generation sequencing for familial hypercholesterolemia causative mutations
Strata 0.16-0.19; Moderate probability of having familial hypercholesterolemia	Other: Genetic testing; Targeted next-generation sequencing for familial hypercholesterolemia causative mutations
Strata 0.20-0.34; Second highest probability of having familial hypercholesterolemia	Other: Genetic testing; Targeted next-generation sequencing for familial hypercholesterolemia causative mutations
Strata greater than or equal to 35; Highest probability of having familial hypercholesterolemia	Other: Genetic testing; Targeted next-generation sequencing for familial hypercholesterolemia causative mutations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Likelihood of having FH-causing mutation	Proportion of subjects with causative mutation in higher algorithm score groups	12 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Lancaster General Hospital; The Familial Hypercholesterolemia Foundation

Publications and helpful links

General Publications

• Qureshi N, Da Silva MLR, Abdul-Hamid H, Weng SF, Kai J, Leonardi-Bee J. Strategies for screening for familial hypercholesterolaemia in primary care and other community settings. Cochrane Database Syst Rev. 2021 Oct 7;10(10):CD012985. doi: 10.1002/14651858.CD012985.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2017
• Primary Completion (Actual): November 7, 2018
• Study Completion (Actual): November 7, 2018

Study Registration Dates

• First Submitted: August 15, 2017
• First Submitted That Met QC Criteria: August 15, 2017
• First Posted (Actual): August 17, 2017

Study Record Updates

• Last Update Posted (Actual): February 28, 2019
• Last Update Submitted That Met QC Criteria: February 27, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: 826438

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be shared with other investigators
• IPD Sharing Time Frame: De-identified data will be shared at end of study after database lock
• IPD Sharing Access Criteria: Research team
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No