Fragile X syndrome clinical trials: exploring parental decision-making.

BACKGROUND: The objective of this research was to understand parental proxy decision-making for drug trial participation for children with Fragile X syndrome (FXS). Specifically, we aimed to capture preferences, motivations, influencing factors and barriers related to trial involvement among trial joiners and decliners and describe ease of trial decision-making and decisional regret. METHODS: Interviews were conducted with parents from two groups: those who chose to enrol their child with FXS in a trial (N = 16; Joiners) and those who declined trial participation (N = 15; Decliners). Data were coded and interpreted through inductive content analysis. RESULTS: Prominent decisional factors included attitudes about medicating FXS symptoms, potential for direct benefit (primarily evaluated through the degree of match between target outcomes and child symptomatology and drug mechanism), logistical convenience and perceived risks of side effects. The ultimate motivation for participation was potential for direct benefit. None of the parents reported decisional regret, and ease of decision-making ranged from easy to difficult for our participants. CONCLUSIONS: Therapeutic optimism was high among those who elected participation. Parents may benefit from an explanation of the rationale behind chosen outcome variables and may be more interested in trials that target or measure as an exploratory outcome the symptoms they find most concerning. Our findings reinforce the need for future trials to reduce participant inconvenience. Our results contrast with what has previously been observed in parents of children with life-threatening conditions; parents of children with FXS may be more trial risk averse and find trial decisions to be harder. Parents of children with FXS considering trials may benefit from a decisional intervention aimed at deliberating motivations and barriers.

Defining personal utility in genomics: A Delphi study.

BACKGROUND: Individual genome sequencing results are valued by patients in ways distinct from clinical utility. Such outcomes have been described as components of "personal utility," a concept that broadly encompasses patient-endorsed benefits, that is operationally defined as non-clinical outcomes. No empirical delineation of these outcomes has been reported. AIM: To address this gap, we administered a Delphi survey to adult participants in a National Institute of Health (NIH) clinical exome study to extract the most highly endorsed outcomes constituting personal utility. MATERIALS AND METHODS: Forty research participants responded to a Delphi survey to rate 35 items identified by a systematic literature review of personal utility. RESULTS: Two rounds of ranking resulted in 24 items that represented 14 distinct elements of personal utility. Elements most highly endorsed by participants were: increased self-knowledge, knowledge of "the condition," altruism, and anticipated coping. DISCUSSION: Our findings represent the first systematic effort to delineate elements of personal utility that may be used to anticipate participant expectation and inform genetic counseling prior to sequencing. The 24 items reported need to be studied further in additional clinical genome sequencing studies to assess generalizability in other populations. Further research will help to understand motivations and to predict the meaning and use of results.

Family risk and related education and counseling needs: perceptions of adults with bipolar disorder and siblings of adults with bipolar disorder.

Genetics and mental health professionals increasingly provide education and counseling related to risk for psychiatric illness, but there is insufficient evidence about patient perceptions and needs to guide such interventions. Affected individuals and relatives may perceive increased family risk and have interest in genetic education and counseling. Our objectives were to explore perceptions of family vulnerability, perceived control, and coping strategies related to familial risk and needs from genetic counseling. Our methods included conducting semi-structured interviews (n = 48) with individuals with bipolar disorder (BPD) and unaffected siblings. Content analysis generated descriptive data that provide guidance for clinical interventions and themes to evaluate in future studies. The results showed that participants perceived increased personal and family risk, attributing BPD to genes and family environment. Causal attributions were often uncertain and at times inconsistent. Participants wished to modify psychiatric risk to relatives, but were uncertain how to do so; despite the uncertainty, most parents reported risk-modification efforts. Efforts to cope with family vulnerability included monitoring and cognitive distancing. Participants endorsed the usefulness of education and psychological support, but described more ambivalence about receiving risk assessment. Educational and supportive interventions around family risk for BPD should focus on perceptions of cause and vulnerability, reproductive decision-making, and early intervention and risk modification in young relatives. Psychological support is an important component. Providers should evaluate patient coping strategies, which could facilitate or hinder genetic counseling interventions, and should not assume interest in quantitative risk assessment.

Applications and limitations of empiric data in provision of recurrence risks for schizophrenia: a practical review for healthcare professionals providing clinical psychiatric genetics consultations.

Schizophrenia is a common disorder that may frequently be encountered when taking family histories in the genetics clinic, whether or not the referral is for a psychiatric indication. Like in other common disorders, the provision of recurrence risks for schizophrenia is a complex clinical issue because empiric recurrence risks (while reasonably well established) can rarely be used without individual tailoring. This review seeks to identify and detail some pertinent issues surrounding the clinical utility of empiric recurrence risks for schizophrenia, and to provide an overview of important factors to consider when tailoring empiric risks for individual patients.