Table 4.

Studies reporting about at-risk relative’s genetic testing uptake after the intervention (Outcome 3).

Study	Type of Study	Intervention and control group description	Intervention			Comparison/Control			Statistical significance
			No. of at-risk relatives	Received genetic testing	%	No. of at-risk relatives	Received genetic testing	%
Atkan-Collan	Retrospective cohort study	Intervention: Direct-contact approach (DCA) i) contact letter sent to high-risk subjects ii) pedigree iii) pre-test genetic counselling providing benefits and disadvantages of a predictive gene test were discussed, including psychological reactions and possible difficulties in employment or insurance coverage in the future iv) post-test counselling for subjects who had a positive predictive test v) referred for regular colonoscopies, and women were also referred for gynaecological examinations Comparison: Family-mediated approach (FMA) i) contact letter sent to high-risk subjects but content differs to the DCA according to assumed previous knowledge of cancer (two rounds of reminds were sent) ii) pedigree iii) pre-test genetic counselling providing benefits and disadvantages of a predictive gene test were discussed, including psychological reactions and possible difficulties in employment or insurance coverage in the future iv) post-test counselling for subjects who had a positive predictive test v) referred for regular colonoscopies, and women were also referred for gynaecological examinations	147	112	76.2	401	333	83.0	X2 = 3.58, p = 0.06
Forrest	Retrospective cohort study	Intervention: i) reviewed pedigree ii) in-person specific discussion of pedigree to identify at-risk relatives and importance of disclosure iii) follow-up letter documenting importance of disclosure iv) 2–4 week post-result disclosure: telephone call with specific discussion about disclosure to at-risk relatives v) 3–6 months post-result disclosure: file review of whether at-risk relative have been contacted, if not, proband is recontact. Offer to provide letter explaining the genetic condition either distributed by proband or mailed directly to at-risk relative at the discretion of proband Control: i) reviewed pedigree ii) in-person general discussion of pedigree iii) follow-up letter documenting importance of disclosure iv) 2–4 week post-result disclosure: telephone call with general discussion about personal adjustment	60a	1st - 24 2nd - 5 3rd - 3 Total = 32a	53.3a	47a	1st - 5 2nd - 3 3rd - 4 Total = 12a	25.5a	Pearson chi2(1) = 18.0, p < 0.001a
Garcia	Prospective nonrandomized pre- and post-intervention comparison pilot study	Intervention: i) genetic counselling ii) supplementary written decision aid provided at the time of genetic testing - Facing Our Risk of Cancer Empowered (FORCE) resources: What you should know about genes and cancer brochure’, ‘Worksheet for sharing cancer information with the family’ and a ‘Family letter template’ Pre-intervention: i) genetic counselling	22	1	4.5	6	0	0	Not provided
Hodgson	RCT	Intervention: i) three-generation pedigree obtained at first clinic visit ii) genetic counselling iii) specific telephone genetic counselling aimed to enhance the ability of each individual to identify and overcome existing barriers in communicating with relatives iv) follow-up contact at three time-points (3, 6, 12-month) after diagnosis (number of calls tailored to each individual’s circumstance e.g., once all designated relatives were approached, calls were not required) Control: i) three-generation pedigree obtained at first clinic visit ii) genetic counselling	1st – 24; 2nd – 52; 3rd – 38; Total = 114a	1st – 8; 2nd – 12; 3rd – 6; Total = 26a	1st – 33.3; 2nd – 23.1; 3rd – 15.8; Total = 22.8a	1st – 25; 2nd – 36; 3rd – 40; Total = 101a	1st – 8; 2nd – 6; 3rd – 3; Total = 17a	1st – 32.0; 2nd – 16.7; 3rd – 7.5; Total = 16.8a	chi sq = 1.19, p = 0.27a
Kardashian	Pilot retrospective cohort study	Intervention: i) in-person post-result genetic counselling informing patients of their BRCA result and discussion of implications of result for individual and their relatives ii) personalised medical report and lab results report iii) family pedigree iv) general information and resources e.g., support groups v) (provided in-person) a 3-4 page personalised medical report reviewing genetic testing process and implications of the result vi) a letter to family member notifying him/her of the pathogenic variant identified in relative vii) Fact-sheet FAQ for family members addressing cancer risk, cost of testing, insurance issues viii) contact information for genetic counsellors) nearest to eligible family members Control: i) in-person post-result genetic counselling informing patients of their BRCA result and discussion of implications of result for individual and their relatives ii) personalised medical report and lab results report iii) family pedigree iv) general information and resources e.g., support groups v) (mailed) a 3-4 page personalised medical report reviewing genetic testing process and implications of the result vi) (optional) a letter to family member notifying him/her of the pathogenic variant identified in relative	1st – 17; 2nd – 20; cousins – 27 Total = 65	1st – 3b; 2nd – 3b; cousins – 0; Total = 6b	1st – 17.6b; 2nd – 15.0b; cousins – 0 Total = 9.2b	1st – 36; 2nd – 33; cousins – 64 Total = 133	1st – 9; 2nd – 22; cousins – 0; Total = 32	1st – 25.0; 2nd – 66.7; cousins – 0; Total = 24.1	1st – p = 1.00 2nd – p = 0.10 cousins – p = N/A
Sermijin	Sequential prospective study	Intervention: Direct-contact approach (DCA; Phase 2) using the following: i) letter about familial cancer risk, predictive genetic testing, and optional genetic counselling, sent to at-risk relatives who had not yet come forward in first phase, or could not be contacted by the proband (proband anonymity is preserved) ii) 6-month follow-up phone call with relatives to have a final ascertainment of their wishes Comparison: Family-mediated approach (FMA; Phase 1) using the following: i) discussed in-detail the family pedigree and identifying at-risk relatives ii) discussion about barriers to communication and informed to disclose when the proband feels comfortable iii) provided contact details of clinic to distribute with relatives ii) 6-month second visit to discuss the status of informing relatives and difficulties encountered	47c	46	98	42d	41	97.6	Not reported

Bold relevant for the study.

FMA family-mediated approach—the proband or family member informs their at-risk relative of their genetic risk, DCA direct-contact approach—the genetic clinic makes direct contact with the at-risk relative apart from the proband, 1st first degree relatives, 2nd second degree relatives, 3rd third degree relatives.

^aAuthor re-analysed results to only include BRCA and Lynch syndrome.

^bCalculated from published data.

^cThe 47/89 relatives came forward for predictive genetic counselling (53%; 95% CI 43–63).

^dThe 42/89 relatives came forward for predictive genetic counselling (47%; 95 % CI 37–57).