Direct Information to At-risk Relatives

NCT ID: NCT04197856

Last Updated: 2024-07-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 490 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-06
• Study Completion Date: 2025-07-01

Brief Summary

This study evaluates if uptake of genetic counselling in high-risk families is increased when patients at cancer genetics clinics are being offered healthcare-assisted disclosure to at-risk relatives compared to current standard care (with family-mediated disclosure).

Patients/families who have undergone a cancer genetic investigation will be invited to participate in the study. All participants will receive standard care. Half of them will in addition be offered a healthcare-assisted disclosure with the service of direct letters to identified at-risk relatives distributed by the healthcare provider. After a year we will compare the proportion of at-risk relatives who have contacted a cancer genetic clinics in each study arm.

Detailed Description

(When the formal study protocol is published, this section will instead refer to the published study protocol).

This study is a multi-centre open label, prospective, randomized controlled superiority trial comparing an intervention of healthcare-assisted disclosure with standard care of family-mediated disclosure of hereditary cancer risk information in high-risk families in Sweden.

SUBJECTS AND METHODS

Patients/families will be enrolled and allocated in parallel to intervention or standard care.

All participants receive standard genetic counseling and information summarizing the results of their family investigation. They are informed about preventive measures when applicable, and are encouraged to inform their at-risk relatives (t=0 months).

The intervention component is the addition of a healthcare-assisted disclosure procedure. Participants in the intervention arm will be offered the service of sending letters directly to their at-risk relatives.

If the participant approves the offer, letters will be sent to eligible at-risk relatives deemed to be recommended genetic counseling within a year.

The direct letter will inform the at-risk relative that a cancer genetic investigation has been conducted in the family and the implications for him or her, and their blood relatives.

To facilitate access to further information, contact details to the closest cancer genetics unit are included in the letter. The letters are sent with registered mail in neutral envelopes which means that recipients will have to show proof of identity to retrieve the letter from their local delivery service provider.

METHODS FOR ASSESSMENT OF STUDY OUTCOMES

For participants in both study arms, contact details of the at-risk relatives are identified in collaboration between health care provider and the participant. The health care provider records the name, approximate or exact year of birth and postal address of each at-risk relative for follow-up.

At the time of follow-up (t=12 months) the research nurse will check whether the relatives, listed one year before, have contacted a Swedish cancer genetic unit. Primary outcome data is retrieved from the patient data registries at each clinic. The research nurse will also record additional data points from CRFs, enabling analysis of the other pre-specified outcome measures in the intervention arm.

The outcome data are reported back to the national study secretariat as plain numbers without any personal details of the at-risk relatives.

SAMPLE SIZE AND STATISTICAL METHODS

For sample size calculation and statistical methods, see attached documents.

INTERNAL PILOT, AUDIT and PROGRESS CRITERIA

As this protocol has never been tested in Swedish clinical practice an internal pilot phase is included in the outline of the project.

Progress criteria at each study site are evaluated at internal pilot point and thereafter at formal audit at least yearly. Internal pilot point is set to the time when 20 individuals in total (across the 3 pilot study sites) have been included and treated according to protocol.

Continuation of the full-powered study at the specific study site will be determined by considering the criteria filled, the potentially necessary amendments, and the degree of which the amendments deviate from the original piloted study protocol.

The outcomes and process criteria are found in the attached document.

Conditions

Familial Breast Cancer; Familial Colorectal Cancer; Hereditary Breast and Ovarian Cancer Syndrome; Hereditary Breast Cancer; Lynch Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Control / Family-mediated disclosure (standard care)

Genetic counseling according to current clinical practice

Group Type: ACTIVE_COMPARATOR

Standard care encouraging family-mediated disclosure of hereditary cancer risk

Intervention Type: OTHER

At counseling, eligible at-risk relatives (who may benefit from disclosure of risk information) are listed on a specified protocol in collaboration between health care provider and the participant.

Intervention / Health-care assisted disclosure

Genetic counseling according to current clinical practice with the addition of an offer from health care provider to mail letters directly to eligible at-risk relatives.

Group Type: EXPERIMENTAL

Standard care encouraging family-mediated disclosure of hereditary cancer risk

Intervention Type: OTHER

At counseling, eligible at-risk relatives (who may benefit from disclosure of risk information) are listed on a specified protocol in collaboration between health care provider and the participant.

Offer of health-care assisted disclosure by sending direct letters to at-risk relatives

Intervention Type: OTHER

The participant is offered that the health care provider at the cancer genetic unit mail a direct letter with personalized family risk information to all at-risk relatives that participant approve contact with.

Interventions

Standard care encouraging family-mediated disclosure of hereditary cancer risk

At counseling, eligible at-risk relatives (who may benefit from disclosure of risk information) are listed on a specified protocol in collaboration between health care provider and the participant.

Intervention Type: OTHER

Offer of health-care assisted disclosure by sending direct letters to at-risk relatives

The participant is offered that the health care provider at the cancer genetic unit mail a direct letter with personalized family risk information to all at-risk relatives that participant approve contact with.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Patient being offered a cancer genetic investigation for hereditary breast, ovarian or colorectal cancer.

2. Written consent to participate the study,

3. Belonging to a family with; a) familial breast cancer, b) familial colorectal cancer, c) pathogenic variant in PALB2, BRCA1/2 (Hereditary breast cancer, hereditary breast and ovarian cancer), MLH1, MSH2, MSH6, PMS2 (Lynch syndrome) and

4. Having at least one eligible at-risk relative (family member deemed to be an ARR recommended genetic counseling within a year).

Exclusion Criteria

1. Cannot convey personal opinions and preferences by themselves.

2. No eligible at-risk relatives living in Sweden.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Göteborg University

OTHER

Sponsor Role: collaborator

Lund University

OTHER

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: collaborator

Umeå University

OTHER

Sponsor Role: lead

Responsible Party

Anna Rosen

Principal investigator, MD, PhD, Specialist in Clinical genetics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Cancergenetisk mottagning

Umeå, , Sweden

Countries

Sweden

References

Hawranek C, Ehrencrona H, Ofverholm A, Hellquist BN, Rosen A. Direct letters to relatives at risk of hereditary cancer-study protocol for a multi-center randomized controlled trial of healthcare-assisted versus family-mediated risk disclosure at Swedish cancer genetics clinics (DIRECT-study). Trials. 2023 Dec 17;24(1):810. doi: 10.1186/s13063-023-07829-5.

Reference Type: DERIVED

PMID: 38105176 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2018-00964

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2020-1107

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2022-02226

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

86719

Identifier Type: REGISTRY

Identifier Source: secondary_id

The Swedish DIRECT study

Identifier Type: -

Identifier Source: org_study_id