Table 4.

Review of other real-life studies.

REFERENCES (Country)	METHODOLOGY			RESULT				CONCLUSIONS
	Study design	Study population and number of participants	Modality to present SF/IF	Choice of access to SF (%, reason and risk)	Type of SF/IF and % of SF/IF identified	Experience of the announcement	Psychological impact
QUANTITATIVE STUDY
Wynn et al. [31] (USA)	Medium-term study; Questionnaires at inclusion and between 1 and 12 months after announcement of results for the ES group.	n = 192: 107 patients with a history of breast cancer or congenital heart defect or developmental disorder (ES group—real life group) and 85 patients awaiting exome (No ES group—hypothetic group).	Recruitment via invitation letter and follow-up phone call	Desire to have the SF: 76% initially, then 65% after the information consultation. Choice based on subjective experiences rather than medical categories.	SF in large list of predisposing genes, including low penetrance genes (Alzheimer, CMT neuropathy, cancer, cardiomyopathy, arrhythmia, hemochromatosis, metabolism, coagulation) 37% (40/107)	High level of satisfaction; feelings of empowerment from having the knowledge.	Anxiety and depression levels similar to the general population in the ES group with or without SF (increased anxiety in the group without ES, not significant) more use of coping methods (based on emotion management and problem management in the ES group with SF)	No differences in psychological and social measures between the beginning and end of the study, or between the ES group (real-life group) and non-ES group (hypothetic group). No regrets about participation
QUALITATIVE STUDIES
Hart et al. [29] (USA)	Medium-term study; Interviews at 4 months after announcement of SF results	n = 6240 exomes in patients with cancer or rare diseases n = 18 interviewed with SF: 10 adult patients, 8 parents of minor patients	NA	NA	SF in ACMG list of 56 genes (V1) 1.7% (74/6240)	Surprise: 15/18; Surprised but not shocked because possibility of finding SF mentioned beforehand Inter-individual variability: some ignored these results; others have described it as a “shock, were scared and have to work hard to avoid thinking about it”.	Minimal psychosocial effect according to authors Modification of the insurance contract: 3/18	Moderation of initial reactions over time Feeling of relief and gratitude for accessing the SF Minimal psychosocial impact No regrets
Ormondroyd et al. [32] (UK)	Medium-term study; Interviews between 6 and 12 months after the announcement of the SF results	n = 7203 genomes in patients with rare diseases. n = 4 interviewed with SF	Invitation by letter, followed by meeting with multidisciplinary team who present study rationale, possible outcomes, consequences of SF and presence of an ICC gene variant for the participant and relatives	Agreeing to participate in the study out of altruism and for family and personal reasons	SF in hereditary heart diseases genes 0.61% (44/7203)	Anxiety for one symptomatic patient with family history. Experience modulated by the history of the primary disease.	Concern about the risk to their already disabled children. Fear of not being able to continue working for a patient. Frustration and anxiety due to the long waiting time for cardiac explorations and because of the refusal of genetic tests by certain family members	Satisfaction of the participants No regrets
Schoot et al. [28] Schoot et al. [43] (The Netherlands)	Medium-term study; Interviews several months after the announcement of results.	16,482 index patients received clinical ES). n = 20 interviewed; 10 parents with oncological IF and 10 with cardiac IF.	Short information in prescription consultation	PF/IF confusion (parents think no test if no IF search)	Medically actionable IFs and carrier status of a recessive disease; all discussed in a multidisciplinary team IF in 0.58% (95/16,482)	Some participants forgot about the possibility of discovering IF Psychological impact emphasized in all cases: “overwhelmed, upset, shocked. (Initial feeling that faded over time when the actionability of IF was better perceived and daily life resumed).	Decreased ability to memorize information due to the emotional dimension Questioning about being sick or healthy.	Relevance of receiving information through in-depth pre-and post-test counseling and medical follow-up consultations. Influencing factor of psychological, physical, and financial consequences: actionability of the IF, understanding, pre-test health status and social context
Cheung et al. [33] (Canada)	Long-term study; Interview at 1.3–3.9 years	500 families of children with undiagnosed suspected genetic conditions n = 12 interviewed parents with IF	Information by a genetic counselor as per the recommendations by the CCMG	IF acceptance by 90% Curiosity, desire to know everything in order to act accordingly Influence of personal beliefs and values + having a child with a disease;	IFs related to highly penetrant conditions, reviewed on a case-by-case basis by a multidisciplinary study team 2.3% (21/901)	Surprise at the announcement, anxiety, worry, and nervousness for some patients, especially if pharmacological, oncological, or cardiac IF	According to personal and family history and health beliefs	Different impacts depending on the type of IF and family history No regrets
MIXED STUDIES
Sapp et al. [30] (USA)	Medium-term study; Interviews and questionnaire at 4 months after announcement of results	n = 1197 exomes in patients with cancer or rare diseases. Interview: n = 13: 10 adults, 3 parents of minor patients with SF Questionnaire: n = 107 patients without SF	NA	Confusion between primary diagnosis and SF = 17%	SF in ACMG list of 56 genes (V1) 1.9% (14/1,197)	With SF: Surprise in 10/13, initial shock and disbelief then relief and gratitude with hindsight Without SF: Reassured but also disappointed when there was familial history of the sought diseases	Concern for themselves or their children = 5/13	Minimal psychosocial impact. 11/13 no regrets

ES exome sequencing, SF secondary finding, IF incidental finding, PF primary finding, TR time of result, T6 time at 6 months of result, T12 time at 12 months of result, NA not available, ICC inherited cardiac conditions, CCMG Canadian College of Medical Geneticists.