Practical Aspects of Recruitment and Retention in Clinical Trials of Rare Genetic Diseases: The Phenylketonuria (PKU) Experience

Bringing treatments for rare genetic diseases to patients requires clinical research. Despite increasing activism from patient support and advocacy groups to increase access to clinical research studies, connecting rare disease patients with the clinical research opportunities that may help them has proven challenging. Chief among these challenges are the low incidence of these diseases resulting in a very small pool of known patients with a particular disease, difficulty of diagnosing rare genetic diseases, logistical issues such as long distances to the nearest treatment center, and substantial disease burden leading to loss of independence. Using clinical studies of phenylketonuria as an example, this paper discusses how, based on the authors’ collective experience, partnership among clinicians, patients, study coordinators, genetic counselors, dietitians, industry, patient support groups, and families can help overcome the challenges of recruiting and retaining patients in rare disease clinical trials. We discuss specific methods of collaboration, communication, and education as part of a long-term effort to build a community committed to advancing the medical care of patients with rare genetic diseases. By talking to patients and families regularly about research initiatives and taking steps to make study participation as easy as possible, rare disease clinic staff can help ensure adequate study enrollment and successful study completion.     

Linking Genetic Counseling Content to Short-Term Outcomes in Individuals at Elevated Breast Cancer Risk

Few studies have linked actual genetic counseling content to short-term outcomes. Using the Self-regulation Model, the impact of cognitive and affective content in genetic counseling on short-term outcomes was studied in individuals at elevated risk of familial breast-ovarian cancer. Surveys assessed dependent variables: distress, perceived risk, and 6 knowledge measures (Meaning of Positive Test; Meaning of Negative Test; Personal Behavior; Practitioner Knowledge; Mechanisms of Cancer Inheritance; Frequency of Inherited Cancer) measured at pre- and post-counseling. Proportion of participant cognitive and affective and counselor cognitive and affective content during sessions (using LIWC software) were predictors in regressions. Knowledge increased for 5 measures and decreased for Personal Behavior, Distress and Perceived Risk. Controlling for age and education, results were significant/marginally significant for three measures. More counselor content was associated with decreases in knowledge of Personal Behavior. More participant and less counselor affective content was associated with gains in Practitioner Knowledge. More counselor cognitive, and interaction of counselor cognitive and affective content, were associated with higher perceived risk. Genetic counselors dominate the content of counseling sessions. Therefore, their content is tied more closely to short term outcomes than participant content. A lack of patient communication in sessions may pose problems for understanding of complex concepts.     

Stress and worry: examining intolerance of uncertainty's moderating effect

Intolerance of uncertainty (IU), or the way an individual perceives, interprets, and reacts to uncertainty in life, has been frequently investigated in relation to anxiety and worry. While a substantial body of research suggests that individual differences in IU foster stress and anxiety, IU's involvement as a potential moderator in the relation between stressful events and worry has only recently been investigated. Therefore, the present study examined the moderating effect of IU on the relation between daily hassles and worry as well as major life events and worry in a sample of 1092 young adults. Results revealed that IU showed a significant moderation effect in the relation between daily stress and worry. More specifically, when the two factors were examined individually only inhibitory IU served as a moderator between daily stress and worry. While major life events significantly predicted worry, no moderation effect was found for this relation. These findings highlight the need to better understand the mechanisms through which IU impacts worry and contributes to anxiety.     

The Impact of Supervision Training on Genetic Counselor Supervisory Identity Development

Supervision is critical to the training of genetic counselors. Limited research exists on the influence of supervision training and experience on the development of genetic counseling supervisors. The purpose of this study was to investigate the impact of supervision training in addition to supervisory and clinical experience on supervisory identity development, and the perceived confidence and competence supervisors have in their own supervisory skills. In addition, we explored genetic counselors’ (N?=?291) interest in and barriers to training as well as perspectives on requirements for supervisors. Results indicated clinical experience, supervision experience, and formal supervision training are positively associated with genetic counselors’ supervisory identity development as measured by the Psychotherapy Supervisory Development Scale (PSDS) (p?ρ?=?0.42, p?p?相似文献   

Teachers as therapeutic agents: perceptions of a school-based mental health initiative

Teacher–child relationship building (TCRB) is a play-based professional development programme adapted from kinder training and filial therapy. Intended for early education teachers and students, TCRB is designed to strengthen the teacher–child relationship, improve student behaviour, enhance academic involvement and develop teachers' classroom management skills. In the current study, we utilised a phenomenological approach to examine teachers' perceptions of the initial implementation of TCRB through identifying individual and collective perspectives in the summation of themes. Findings indicated that the teachers perceived the TCRB model to be informative, well organised, appropriately structured and effective in enhancing teacher–child relationships, improving classroom management skills and reducing behavioural problems among child participants. Limitations of the study, implications and suggestions for future research are discussed.     

Females in the forefront: time-based intervention effects on impulsive choice and interval timing in female rats

Impulsive choice has been implicated in substance abuse, gambling, obesity, and other maladaptive behaviors. Deficits in interval timing may increase impulsive choices, and therefore, could serve as an avenue through which suboptimal impulsive choices can be moderated. Temporal interventions have successfully attenuated impulsive choices in male rats, but the efficacy of a temporal intervention has yet to be assessed in female rats. As such, this experiment examined timing and choice behavior in female rats, and evaluated the ability of a temporal intervention to mitigate impulsive choice behavior. The temporal intervention administered in this study was successful in reducing impulsive choices compared to a control group. Results of a temporal bisection task indicated that the temporal intervention increased long responses at the shorter durations. Further, results from the peak trials within the choice task combined with the progressive interval task suggest that the intervention increased sensitivity to delay and enhanced timing confidence. Overall, these results indicate that a temporal intervention can be a successful avenue for reducing impulsive choice behavior in female rats, and could contribute to the development of behavioral interventions to prevent impulsive choice and maladaptive behaviors that can be applied to both sexes.     

An investigation of intra-individual variability in children with fetal alcohol spectrum disorder (FASD)

Intra-individual variability (IIV) is defined as systematic within-person variation in performance either across test sessions (e.g., test/retest performance on the same task) or in one session (e.g., variations in performance on multiple trials of a single task). Higher levels of IIV have been noted as a characteristic of neurodevelopmental disorders such as attention deficit/hyperactivity disorder? (ADHD), but IIV is yet to be investigated in fetal alcohol spectrum disorder (FASD). FASD is a term used to describe a range of conditions resulting from prenatal exposure to alcohol. As part of a comprehensive neuropsychological battery, four study groups (1. fetal alcohol syndrome/partial fetal alcohol syndrome; 2. static encephalopathy/alcohol exposed; 3. neurobehavioral disorder/alcohol exposed as diagnosed using the University of Washington FASD 4-Digit Code; 4. typically-developing (TD) age-matched children with no prenatal alcohol exposure) were administered measures of motor response and inhibitory control, attention, and adaptive behavior. The results indicate increased levels of IIV in those with FASD compared to the TD controls. It was found that IIV uniquely contributes to predicting adaptive behavior above and beyond attention, while attention partially mediates the relationship between IIV and adaptive behavior. This is the first study to the authors’ knowledge to show the presence of increased IIV in children with FASD. It additionally provides evidence that IIV measures some inherent variability in performance independent of poor attention in children with FASD.     

Understanding Adult Participant and Parent Empowerment Prior to Evaluation in the Undiagnosed Diseases Network

The burden of living with an undiagnosed condition is high and includes physical and emotional suffering, frustrations, and uncertainty. For patients and families experiencing these stressors, higher levels of empowerment may be associated with better outcomes. Thus, it is important to understand the experiences of patients with undiagnosed conditions and their families affected by undiagnosed conditions in order to identify strategies for fostering empowerment. In this study, we used the Genetic Counseling Outcome Scale (GCOS-24) to assess levels of empowerment and support group participation in 35 adult participants and 67 parents of child participants in the Undiagnosed Diseases Network (UDN) prior to their UDN in-person evaluation. Our results revealed significantly lower empowerment scores on the GCOS-24 in adult participants compared to parents of child participants [t(100)?=???3.01, p?=?0.003, average difference?=???11.12, 95% CI (??3.78, ??18.46)] and no significant association between support group participation and empowerment scores. The majority of participants (84.3%, 86/102) are not currently participating in any support groups, and participation rates were not significantly different for adult participants and parents of child participants (11.4 vs. 19.7%, respectively, FE p?=?0.40). Open-ended responses provided additional insight into support group participation, the challenges of living with undiagnosed conditions, and positive coping strategies. Future research will evaluate the extent to which empowerment scores change as participation in the UDN unfolds.