Table 1.

Description of interventions and summary of outcomes.

Study (Country) (Citation)	Study Design	Condition	No. of probands/ families	Definition of at-risk relatives	Response rate	Intervention	Comparison/Control	Primary aim	Outcome	Quality Assessment category (%)
Atkan-Collan (Jyväskylä, Finland) [7]	Retrospective cohort study	HNPCC	110 families with known pathogenic variant	Family members at 50% risk of HNPCC	FMA: 90% DCA: 51%	Direct-contact approach (DCA) - clinic sent a direct letter to probands inviting them to the study, including subsequent genetic counselling and testing from the genetic clinic	Family-mediated approach (FMA) - proband informed relatives about genetic counselling and testing	1. Examine attitudes and reactions towards DCA vs FMA 2. Psychosocial responses	•76% (112/247) in the DCA and 86% (333/401) in the FMA study took the test and received results (χ2(1) = 3.58, p = 0.06) • 92% (103/113) approved of DCA by healthcare professionals • DCA group had a higher expectation of a positive future than FMA group (F(1.49) = 5.0, p = 0.03)	Adequate (63%)
Eijzenga (Amsterdam, Netherlands) [17]	RCT	BRCA1, BRCA2, HNPCC	763 probands (1st in family to request counselling with >1 relative at risk)	1st, 2nd	336/763 (44%)	• Additional telephone counselling based on motivational interviewing provided by trained psychosocial workers. • Two-phases (1week and 4 months post), & follow-up questionnaires	No counselling	1. Knowledge of who to inform 2. Motivation and self-efficacy 3. Overall evaluation	• No between-group differences concerning knowledge of who to inform • Generally, participants had better knowledge of which first-degree relatives at risk needed to be notified (ICCs 0.75–0.91) as opposed to second-degree relatives (ICCs 0.06–0.72) • No difference in motivation • 96% (142/148) of participants found telephone counselling helpful	Good (78%)
Forrest (Victoria, Australia) [24]	Retrospective cohort study	Multiple: a balanced reciprocal chromosomal translocation, BRCA1,BRCA2, HNPCC, multiple endocrine neoplasia type 1, Peutz-Jegher syndrome, or an X-linked condition with reproductive implications	19 probands	1st, 2nd, 3rd	Not specified	Specific pedigree discussion, telephone follow-up calls 2–4 weeks post-result disclosure, review of family file and verification of whether at-risk relatives had made contact with the genetic service at 3-4 weeks post-result disclosure, recontacting index patient to document reasons, letter offered to be sent directly or via patient	Standard genetic counselling practices	1. The proportion of at-risk relatives who had made contact with the clinical genetics service within 2 years of the diagnosis of the index patient	• After 2-years, 61% (46/76) of intervention at- risk relatives definitely informed vs 36% (20/55) of control (p = 0.01) • Intervention group participants 2.6 times more likely to contact genetic clinic than control	Adequate (67%)
Garcia (Virginia, USA) [2]	Prospective nonrandomized pre- and post-intervention comparison pilot study	BRCA1, BRCA2	40 probands	1st	Not specified	Facing Our Risk of Cancer Empowered (FORCE) – written education materials provided prior to genetic counselling at oncology clinic visits	Pre-intervention standardised counselling	Determine whether incorporating materials as an adjunct to counselling is: 1. Acceptable to patients 2. Improve Knowledge of HBOC 3. Improve disclosure rates	• Majority found communication aid useful (90%; >4/5 on Likert scale) • Knowledge scores did not improve after use (p = 0.48) • No difference in disclosure rates between pre- and post-intervention cohorts (83% vs 77%, p = 0.26)	Limited (41%)
Hodgson (Victoria, Australia) [18]	RCT	Multiple: BRCA1,BRCA2, HNPCC, inherited cardiac conditions (e.g., long QT syndrome), X-linked conditions (Fragile X syndrome and Duchenne/Becker muscular dystrophy), autosomal recessive conditions (cystic fibrosis, deafness and spinal muscular atrophy)	95 probands	1st	95/167 (56.8%)	Specific genetic counselling using the Reciprocal Engagement Model (REM) and motivational interviewing via telephone at 3, 6 and 12 months from a trained genetic counsellor	Standard genetic counselling practices with no follow up contact	Determine whether the telephone counselling intervention increased frequency of contact with genetic services	• 25.6% (142/554) of the intervention group relatives contacted genetic services, compared with 20.9% (112/536) of the control group relatives (OR = 1.30; 95% CI = 0.70–2.42, p = 0.40) • 63.2% of intervention group high risk offspring made contact, compared with 6.7% of control offspring (OR = 24; 95% CI = 3.42–168.47, p = 0.001)	Good (74%)
Kardashian (California, USA) [25]	Pilot retrospective cohort study	BRCA1,BRCA2	37 probands	1st, 2nd, 3rd	19/37 (51.3%)	Sharing risk information tool (ShaRIT) is used in genetic clinic providing personalised recommendations, letter to family, written fact sheet/ education	Standard genetic counselling	1. Feasibility and acceptability of ShaRIT 2. Reported rates of sharing of results	• All ShaRIT group participants reported it was a useful resource • No difference in sharing rates between ShaRIT group (90%; n = 9) vs. control group (88%; n = 10; p = 1.00)	Adequate (56%)
Montgomery (Philadelphia, USA) [19]	RCT	BRCA1,BRCA2	345	1st	345/446 (77%)	Two sessions of a communication intervention involving the six-step breaking bad news model and education by a trained health educator	Two sessions of a wellness education intervention with general nutrition and exercise information by a trained health educator	1. Percentage of probands who shared genetic test results 2. Variables associated with sharing results	• No difference in sharing rates with all relatives between intervention group (54%; n = 74) vs. control (52.7%; n = 59; p = 0.83) • If the proband perceived that her relative was in favour of hearing her test result, she was more likely to share her test results (OR = 7.20, p < 0.0001; OR = 11.28, p < 0.0001, respectively) • Unambiguous results rather than inconclusive, female rather than male, children more than parents and daughters more than sons are likely to be informed	Strong (89%)
Roshanai (Uppsala, Sweden) [20]	RCT	BRCA1,BRCA2, HNPCC	210 probands	1st	147/210 (72%)	Additional genetic counselling session with a specialist nurse (provided after counselling), pedigree discussion, six-step breaking bad news model presented, written & video aids	Standard genetic counselling with a geneticist, no pedigree	Examine impact of intervention on: 1. Knowledge about genetics 2. Risk perception 3. Informed relatives 4. Satisfaction with counselling	• Increased level of knowledge was observed in the participants over time (F = 18 379, df = 2, p < 0.001), independent of the intervention • Increase in no. of probands who accurately estimated risk over time, significant difference between groups at 2 weeks • Majority of relatives reported receiving sufficient information, (75% intervention vs 67% control, but no difference) • Higher level of satisfaction in intervention group	Strong (81%)
Sermijin (Brussels, Belgium) [22]	Sequential prospective study	BRCA1,BRCA2	20 families	1st, 2nd, 3rd	89/172 (52%)	DCA: Direct-contact approach through letter and a 6-month follow-up phone call (Phase 2)	Family-mediated approach (FMA) with genetic counselling (family pedigree, discussion about barriers to communication, negative reactions, provided contact details of clinic, and 6-month visit to discuss informing relatives) (Phase 1)	1. Feasibility and safety of a stepwise interventional approach 2. Actively inform relatives	• Stepwise approach appeared feasible and nearly all participants that received a direct letter/phone had a positive experience • After DCA, 34% (42/125, 95% CI 26–42) of relatives were additionally reached, compared with the standard procedure	Adequate (59%)

HNPCC Hereditary nonpolyposis colorectal cancer or Lynch Syndrome, BRCA “BReast CAncer gene”—BRCA1 and BRCA2, 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, RCT randomised control trial, Index patient an individual with the first known case of the pathogentic varinat in the family.