Expectations, needs and mid-term outcomes in people accessing to secondary findings from ES: 1st French mixed study (FIND Study)

Abstract

Generation and subsequently accessibility of secondary findings (SF) in diagnostic practice is a subject of debate around the world and particularly in Europe. The French FIND study has been set up to assess patient/parent expectations regarding SF from exome sequencing (ES) and to collect their real-life experience until 1 year after the delivery of results. 340 patients who had ES for undiagnosed developmental disorders were included in this multicenter mixed study (quantitative N = 340; qualitative N = 26). Three groups of actionable SF were rendered: predisposition to late-onset actionable diseases; genetic counseling; pharmacogenomics. Participants expressed strong interest in obtaining SF and a high satisfaction level when a SF is reported. The medical actionability of the SF reinforced parents' sense of taking action for their child and was seen as an opportunity. While we observed no serious psychological concerns, we showed that these results could have psychological consequences, in particular for late-onset actionable diseases SF, within families already dealing with rare diseases. This study shows that participants remain in favor of accessing SF despite the potential psychological, care, and lifestyle impacts, which are difficult to anticipate. The establishment of a management protocol, including the support of a multidisciplinary team, would be necessary if national policy allows the reporting of these data.

Fig. 1. Expected study design of the FIND study.

A mixed methodology was proposed, including both a quantitative and qualitative study. For the quantitative study, all participants had to fill in specific and standardized questionnaires at inclusion (QT0). In order to have 250 respondents, with a 25–30% risk of being lost to follow-up, the number of subjects to include was 330. They also had to fill in questionnaires at time of results (QTR), 6 months after results (QT6), and 12 months after results (QT12). QT0: study data concerning the perception of the interest of SF, the needs and expectations regarding the information given about SF, the selected SF category, as well as the reasons for these choices. QTR - QT6 – QT12: The self-administered questionnaire consisted of closed multiple-choice questions and visual analog scales (VAS) that ranged from 0 (lowest agreement or satisfaction score) to 100 (highest agreement or satisfaction score). Standardized scale: anxiety (STAI-Y A and B), depression (CES-D), and quality of life (QoL; SF12 mental and physical). For the qualitative study, the same 30 participants with SF+ were asked to participate at TR, T6, T12, and 10 participants with negative results were planned to be interviewed at TR. Participants also filled in the questionnaires.

Fig. 2. Flow chart of patients and participants.

A This figure shows the number of patients eligible for the study and the number of people who wished to access their SF results. For people with SF, the SF category is specified; B Number of completed questionnaires and interviews (results of questionnaires and interviews with parents without SF are presented in Supplementary Table 3).

Fig. 3. Evolution of psychological aspects based on the analysis of interviews according to the type of SF and the time of results.

A Worry and anxiety; B Feeling at risk for participants or their family members.