A Prospective Study of Parental Perceptions of Rapid Whole-Genome and -Exome Sequencing among Seriously Ill Infants.

Rapid diagnostic genomic sequencing recently became feasible for infants in intensive care units (ICUs). However, research regarding parents' perceived utility, adequacy of consent, and potential harms and benefits is lacking. Herein we report results of parental surveys of these domains from the second Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT2) study, a randomized, controlled trial of rapid diagnostic genomic sequencing of infants in regional ICUs. More than 90% of parents reported feeling adequately informed to consent to diagnostic genomic sequencing. Despite only 23% (27) of 117 infants receiving genomic diagnoses, 97% (156) of 161 parents reported that testing was at least somewhat useful and 50.3% (88/161) reported no decisional regret (median 0, mean 10, range 0-100). Five of 117 families (4.3%) reported harm. Upon follow-up, one (1%) confirmed harm to child and parent related to negative results/no diagnosis, two (2%) reported stress or confusion, and two (2%) denied harm. In 81% (89) of 111 infants, families and clinicians agreed that genomic results were useful. Of the families for whom clinicians perceived harm from genomic testing, no parents reported harm. Positive tests/genomic diagnosis were more frequently perceived to be useful by parents, to benefit their infant, and to help manage potential symptoms (p < .05). In summary, the large majority of parents felt that first-tier, rapid, diagnostic genomic sequencing was beneficial for infants lacking etiologic diagnoses in ICUs. Most parents in this study perceived being adequately informed to consent, understood their child's results, and denied regret or harm from undergoing sequencing.

Sexual Health Research With Young Black Men Who Have Sex With Men: Experiences of Benefits and Harms.

Young Black men who have sex with men (YBMSM) are often underrepresented in sexual health research because of concerns about safety, privacy, and the potential for research harms. Empirical data are needed to understand YBMSM experience of participating in research, benefits and harms (discomfort), to inform policy and regulatory decisions. Using qualitative methods, this article examines 50 YBMSM, aged 15-19 years, experiences of benefits/harms, challenges of participating in sexual health research, and contextual factors impacting research experiences. Participants were asked about benefits and harms experienced in answering questions about sexual orientation, first same-sex attraction, and same-sex sexual experiences after completing an in-depth interview. Interviews were transcribed and coded. Inductive open coding was used to identify themes within and between interviews. Participants were able to describe perceived direct benefits resulting from research interview participation, including awareness of risky sexual behaviors, a safe space to share early coming out stories and same-sex sexual experiences, and a sense of empowerment and comfort with one's sexual orientation. Indirect benefits described by participants included perceptions of helping others and the larger gay community. Few participants described harms (discomfort recalling experiences). Our data suggest that participating in qualitative sexual health research focused on sexual orientation, sexual attraction, and early same-sex sexual experiences may result in minimal harms for YBMSM and multiple benefits, including feeling more comfortable than in a general medical visit.

On balance: weighing harms and benefits in fundamental neurological research using nonhuman primates.

One of the most controversial areas of animal research is the use of nonhuman primates for fundamental research. At the centre of the controversy is the question of whether the benefits of research outweigh the harms. We argue that the evaluation of harms and benefits is highly problematic. We describe some common procedures in neurological research using nonhuman primates and the difficulties in evaluating the harm involved. Even if the harm could be quantified, it is unlikely that it could be meaningfully aggregated over different procedures, let alone different animals. A similar problem arises for evaluating benefits. It is not clear how benefits could be quantified, and even if they could be, values for different aspects of expected benefits cannot be simply added up. Sorting harms and benefits in three or four categories cannot avoid the charge of arbitrariness and runs the risk of imposing its structure on the moral decision. The metaphor of weighing or balancing harms and benefits is inappropriate for the moral decision about whether to use nonhuman primates for research. Arguing that the harms and benefits in this context are incommensurable, we suggest describing the moral consideration of harms and benefits as a coherent trade-off. Such a decision does not require commensurability. It must be well-informed about the suffering involved and the potential benefits, it must be consistent with the legal, regulatory and institutional framework within which it is made, and it must cohere with other judgments in relevant areas.

Assessment of harms, benefits, and cost-effectiveness of prostate cancer screening: A micro-simulation study of 230 scenarios.

BACKGROUND: Prostate cancer screening incurs a high risk of overdiagnosis and overtreatment. An organized and age-targeted screening strategy may reduce the associated harms while retaining or enhancing the benefits. METHODS: Using a micro-simulation analysis (MISCAN) model, we assessed the harms, benefits, and cost-effectiveness of 230 prostate-specific antigen (PSA) screening strategies in a Dutch population. Screening strategies were varied by screening start age (50, 51, 52, 53, 54, and 55), stop age (51-69), and intervals (1, 2, 3, 4, 8, and single test). Costs and effects of each screening strategy were compared with a no-screening scenario. RESULTS: The most optimum strategy would be screening with 3-year intervals at ages 55-64 resulting in an incremental cost-effectiveness ratio (ICER) of €19 733 per QALY. This strategy predicted a 27% prostate cancer mortality reduction and 28 life years gained (LYG) per 1000 men; 36% of screen-detected men were overdiagnosed. Sensitivity analyses did not substantially alter the optimal screening strategy. CONCLUSIONS: PSA screening beyond age 64 is not cost-effective and associated with a higher risk of overdiagnosis. Similarly, starting screening before age 55 is not a favored strategy based on our cost-effectiveness analysis.

Assessing the implications of positive genomic screening results.

Aim: Before population screening of 'healthy' individuals is widely adopted, it is important to consider the harms and benefits of receiving positive results and how harms and benefits may differ by age. Subjects & methods: Participants in a preventive genomic screening study were screened for 17 genes associated with 11 conditions. We interviewed 11 participants who received positive results. Results: Interviewees expressed little concern about their positive results in light of their older age, the risk condition for which they tested positive, or other pressing health concerns. Conclusion: Researchers and clinicians should recognize that returning positive results may not have the impact they presume given the diversity of the conditions screened and those who choose to undergo screening.

Individualized Approach to Cancer Screening in Older Adults.

The primary goal of cancer screening is early detection of cancer to reduce cancer-specific mortality and morbidity. The benefits of screening in older adults are uncertain due to paucity of evidence. Extrapolating data from younger populations, evidence suggests that the benefit occurs years later from the time of initial screening and therefore may not be applicable in those older adults with limited life expectancy. Contrast this with the harms of screening, which are more immediate and increase with age and comorbidities. An individualized approach to cancer screening takes these factors into consideration, allowing for thoughtful decision making for older adults.