Improving Identification of Familial Hypercholesterolaemia in Primary Care (FAMCAT) (FAMCAT)

Improving Identification of Familial Hypercholesterolaemia in Primary Care Using a New Case Ascertainment Tool (FAMCAT)

Multi-centre, non-randomised, non-controlled quasi-experimental study with nested qualitative study and economic appraisal.

Improving the identification of patients at high risk of cardiovascular disease in primary care, caused by conditions such as familial hypercholesterolaemia (FH), is a well-recognised national priority to prevent morbidity and mortality by early effective intervention.

This study will prospectively evaluate the clinical utility of the new primary care FH identification tool (FAMCAT) for identifying undiagnosed FH in routine primary care practice; and to assess its appropriateness, acceptability and cost-effectiveness.

This study will answer the following research questions (RQ):

1. What is the detection rate for new genetically-confirmed FH cases using the FAMCAT algorithm?
2. Is the FAMCAT tool appropriate and acceptable to practitioners and patients?
3. How can the FAMCAT tool be optimised to improve identification of FH?
4. What is the potential cost-effectiveness of the FAMCAT tool compared with current practice to identify patients with FH?
5. Can the FAMCAT intervention be improved?
6. What definitive study design and outcome measures are needed to provide robust evidence on whether to introduce FAMCAT into primary care practice?

RQ(1) & (3) will be answered by a quasi-experimental diagnostic accuracy study; RQ(2) & (5) answered by qualitative study; RQ (4) answered by economic appraisal and RQ(6) informed by all previous studies.

Study Overview

• Status: Unknown
• Conditions: Familial Hypercholesterolemia
• Intervention / Treatment: Other: FAMCAT

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Division of Primary Care, University of Nottingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients - General practices

• Able to give written informed consent
• 18 years of age or over
• Serum cholesterol recorded in General Practice (GP) electronic records
• Registered with a participating GP practice
• Able to complete the self-administered questionnaires in English
• No previous recorded diagnosis of familial hypercholesterolaemia in their GP electronic health records
• Considered by their General Practitioner(s) to be appropriate to recruit to the study.

Patients - Secondary care

• Able to give written informed consent
• 18 years of age or over
• Referred to or under the care of participating Trusts (e.g. lipid clinics)
• Able to understand the study information and consent in English
• Considered by their healthcare professions to be appropriate to recruit to the study.

Staff

• Able to give written informed consent
• 18 years of age or over
• Working at a participating General Practice, Clinical Commissioning Group (CCG) or Secondary Care Trust.

Nominal Group

• Able to give written informed consent
• 18 years of age or over
• A FH stakeholder (including specialists, primary care commissioners, FH patient representative)

Exclusion Criteria:

Patients - General practices

• Unable to give written informed consent
• Under 18 years of age
• Serum cholesterol not recorded in GP electronic records
• Not registered with a participating GP practice
• Unable to complete the self-administered questionnaires in English
• Has a diagnosis of familial hypercholesterolaemia in their GP electronic records
• Unable to have a blood test (for medical or personal reasons)
• Have an opt-out code where patients has declined electronic medical records examined
• Considered by their General Practitioner(s) to be inappropriate to recruit due to psycho-social reasons, participating in another related clinical trial or significant health reasons, e.g. terminal illness/diagnosis.

Patients - Secondary care

• Unable to give written informed consent
• Under 18 years of age
• Not referred to or under the care of participating Trusts (e.g. lipid clinics)
• Unable to understand the study information and consent in English
• Considered by their healthcare professionals to be inappropriate to recruit to the study.

Staff

• Unable to give written informed consent
• Under 18 years of age
• Has not worked at a participating General Practice, CCG or Secondary Care Trust.

Nominal Group

• Unable to give written informed consent
• Under 18 years of age
• Not an FH stakeholder or FH patient representative

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: FAMCAT	Other: FAMCAT; The intervention is a computer-based software algorithm (FAMCAT) for use in general practice with a family history questionnaire.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of genetically confirmed new FH cases using case identification tool (FAMCAT)	Efficacy measure: Proportion (%) of genetically-confirmed FH cases Proportion (%) of genetically-confirmed FH cases	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability of FAMCAT	Efficacy measure: representativeness of qualitative interview sample. Key themes will be identified from qualitative interview transcripts of patient experience of participating in the study, acceptability of the study procedures (ie. location of blood test clinic appointments, waiting time to receive test results) , and appropriateness of methods of contact with study participants (ie. format and content of study materials, communicating test results). Key themes on usability will be identified from qualitative interview transcripts of health care professionals who used the FAMCAT tool clinically (ie. search criteria for clinical records, interpretation of results)	Through study completion, an average of 2 years.
Appropriateness of FAMCAT	Efficacy measure: representativeness of qualitative interview sample. Key themes will be identified from qualitative interview transcripts of patient experience of appropriateness of methods of contact with study participants (ie. format and content of study materials, communicating test results).	Through study completion, an average of 2 years.
Usability of FAMCAT	Efficacy measure: representativeness of qualitative interview sample. Key themes on usability will be identified from qualitative interview transcripts of health care professionals who used the FAMCAT tool clinically (ie. search criteria for clinical records, interpretation of results)	Through study completion, an average of 2 years.
Self-reported anxiety measures for use in a future trial	Anxiety measured using 6 item Spielberger State-Trait Anxiety Inventory (STAI). The total score will be calculated at study entry, after receiving genetic test results and 12- 15 months after genetic tests results received	Baseline to 15 months after genetic test results reported
Self-reported lifestyle change measures for use in a future trial	Stages of change for smoking cessation and physical activity will be measured. The five stages of change will be dichotomised into: (1) pre-contemplation, contemplation and preparation and (2) action/maintenance. The distribution of proportions for each measure will be presented at study entry, after receiving genetic test results and 12- 15 months after genetic tests results received	Baseline to 15 months after genetic test results reported
Beliefs about predisposition to coronary heart disease	Beliefs on causes for heart disease were assessed using 8 items, from a total of 18 items, which comprise the 'Causes of my illness' subscale in the Revised Illness Perception Questionnaire, IPQ-R. The distribution of data for each one of the 8 questions will be presented at study entry, after receiving genetic test results and 12- 15 months after genetic tests results received	Baseline to 15 months after genetic test results reported
Cost-effective FAMCAT threshold to identify genetically confirmed FH	Efficacy measure: Primary analysis: Incremental cost-effectiveness ratio (ICER) of FAMCAT compared to Simon-Broome criteria; Sensitivity analysis: Incremental costeffectiveness ratio (ICER) of FAMCAT at different testing thresholds. Short-term model: 24 Months	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: University College, London; Newcastle University; University of Manchester
• Investigators: Principal Investigator: Nadeem Qureshi, DM, University of Nottingham

Publications and helpful links

General Publications

• Qureshi N, Akyea RK, Dutton B, Leonardi-Bee J, Humphries SE, Weng S, Kai J. Comparing the performance of the novel FAMCAT algorithms and established case-finding criteria for familial hypercholesterolaemia in primary care. Open Heart. 2021 Oct;8(2). pii: e001752. doi: 10.1136/openhrt-2021-001752.
• Qureshi N, Akyea RK, Dutton B, Humphries SE, Abdul Hamid H, Condon L, Weng SF, Kai J; FAMCAT study. Case-finding and genetic testing for familial hypercholesterolaemia in primary care. Heart. 2021 Dec;107(24):1956-1961. doi: 10.1136/heartjnl-2021-319742. Epub 2021 Sep 14.

Helpful Links

• Funder website

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2017
• Primary Completion (Anticipated): July 31, 2020
• Study Completion (Anticipated): July 31, 2020

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: April 30, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): May 1, 2019
• Last Update Submitted That Met QC Criteria: April 30, 2019
• Last Verified: April 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: 16090; 332 (NIHR School for Primary Care Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We do not have consent from participants to share their data for the purposes of future research.

Drug and device information, study documents

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