Jessica P. Bytautas

What is a Meaningful Result? Disclosing the Results of Genomic Research in Autism to Research Participants

Developments in genomics research have been accompanied by a controversial ethical injunction: that researchers disclose individually relevant research results to research participants. With the explosion of genomic research on complex psychiatric conditions such as autism, researchers must increasingly contend with whether – and which results – to report. We conducted a qualitative study with researchers and participants involved in autism genomics research, including 4 focus groups and 23 interviews with parents of autistic children, and 23 interviews with researchers. Respondents considered genomic research results ‘reportable’ when results were perceived to explain cause, and answer the question ‘why;’ that is, respondents set a standard for reporting individually relevant genetic research results to individual participants that is specific to autism, reflecting the metaphysical value that genetic information is seen to offer in this context. In addition to this standard of meaning, respondents required that results be deemed ‘true.’ Here, respondents referenced standards of validity that were context nonspecific. Yet in practice, what qualified as ‘true’ depended on evidentiary standards within specific research disciplines as well as fundamental, and contested, theories about how autism is ‘genetic.’ For research ethics, these finding suggest that uniform and context-free obligations regarding result disclosure cannot readily be specified. For researchers, they suggest that result disclosure to individuals should be justified not only by perceived meaning but also by clarity regarding appropriate evidentiary standards, and attention to the status of epistemological debates regarding the nature and cause of disorders.

Testing personalized medicine: patient and physician expectations of next-generation genomic sequencing in late-stage cancer care

Developments in genomics, including next-generation sequencing technologies, are expected to enable a more personalized approach to clinical care, with improved risk stratification and treatment selection. In oncology, personalized medicine is particularly advanced and increasingly used to identify oncogenic variants in tumor tissue that predict responsiveness to specific drugs. Yet, the translational research needed to validate these technologies will be conducted in patients with late-stage cancer and is expected to produce results of variable clinical significance and incidentally identify genetic risks. To explore the experiential context in which much of personalized cancer care will be developed and evaluated, we conducted a qualitative interview study alongside a pilot feasibility study of targeted DNA sequencing of metastatic tumor biopsies in adult patients with advanced solid malignancies. We recruited 29/73 patients and 14/17 physicians; transcripts from semi-structured interviews were analyzed for thematic patterns using an interpretive descriptive approach. Patient hopes of benefit from research participation were enhanced by the promise of novel and targeted treatment but challenged by non-findings or by limited access to relevant trials. Family obligations informed a willingness to receive genetic information, which was perceived as burdensome given disease stage or as inconsequential given faced challenges. Physicians were optimistic about long-term potential but conservative about immediate benefits and mindful of elevated patient expectations; consent and counseling processes were expected to mitigate challenges from incidental findings. These findings suggest the need for information and decision tools to support physicians in communicating realistic prospects of benefit, and for cautious approaches to the generation of incidental genetic information.

Citizens’ Values Regarding Research With Stored Samples From Newborn Screening in Canada

OBJECTIVES: Newborn screening (NBS) programs may store bloodspot samples and use them for secondary purposes. Recent public controversies and lawsuits over storage and secondary uses underscore the need to engage the public on these issues. We explored Canadian values regarding storage and use of NBS samples for various purposes and the forms of parental choice for anonymous research with NBS samples. METHODS: We conducted a mixed-methods, public engagement study comprising 8 focus groups (n = 60), an educational component, deliberative discussion, and pre- and post-questionnaires assessing knowledge and values toward storage and parental choice. RESULTS: Canadian citizens supported the storage of NBS samples for quality control, confirmatory diagnosis, and future anonymous research (>90%). There was broad support for use of NBS samples for anonymous research; however, opinions were split about the extent of parental decision-making. Support for a “routinized” approach rested on trust in authorities, lack of concern for harms, and an assertion that the population’s interest took priority over the interests of individuals. Discomfort stemmed from distrust in authorities, concern for harms, and prioritizing individual interests, which supported more substantive parental choice. Consensus emerged regarding the need for greater transparency about the storage and secondary use of samples. CONCLUSIONS: Our study provides novel insights into the values that underpin citizens’ acceptance and discomfort with routine storage of NBS samples for research, and supports the need to develop well-designed methods of public education and civic discourse on the risks and benefits of the retention and secondary use of NBS samples.

A Systematic Review of the Effects of Disclosing Carrier Results Generated Through Newborn Screening

Evidence on the effects of disclosing carrier results identified through newborn screening (NBS) is needed to develop effective strategies for managing these results, and to inform debate about contradictory policies governing genetic testing in minors in the context of NBS relative to clinical care. This is likely to be even more important as technological opportunities for carrier identification through NBS increase. We report the results of a systematic review of evidence related to the generation of carrier results through NBS to summarize what is known about: (1) the outcomes associated with these results; (2) the best strategies for providing information and follow-up care to parents; and (3) the impact they have on reproductive decision-making. Our study expands the existing body of knowledge and identifies gaps in the evidence base. As key players in the management of carrier results clinically, genetic counselors are well positioned to engage in formative research and policy development in this area.

The primary care physician role in cancer genetics: a qualitative study of patient experience

BACKGROUND Increased availability of genetic testing is changing the primary care role in cancer genetics. The perspective of primary care physicians (PCPs) regarding their role in support of genetic testing has been explored, but little is known about the expectations of patients or the PCP role once genetic test results are received. METHODS Two sets of open-ended semi-structured interviews were completed with patients (N=25) in a cancer genetic programme in Ontario, Canada, within 4 months of receiving genetic test results and 1 year later; written reports of test results were collected. RESULTS Patients expected PCPs to play a role in referral for genetic testing; they hoped that PCPs would have sufficient knowledge to appreciate familial risk and supportive attitudes towards genetic testing. Patients had more difficulty in identifying a PCP role following receipt of genetic test results; cancer patients in particular emphasized this as a role for cancer specialists. Still, some patients anticipated an ongoing PCP role comprising risk-appropriate surveillance or reassurance, especially as specialist care diminished. These expectations were complicated by occasional confusion regarding the ongoing care appropriate to genetic test results. CONCLUSIONS The potential PCP role in cancer genetics is quite broad. Patients expect PCPs to play a role in risk identification and genetics referral. In addition, some patients anticipated an ongoing role for their PCPs after receiving genetic test results. Sustained efforts will be needed to support PCPs in this expansive role if best use is to be made of investments in cancer genetic services.

Not so simple: a quasi-experimental study of how researchers adjudicate genetic research results

Ethicists contend that researchers are obliged to report genetic research findings to individual study participants when they are clinically significant, that is, when they are clinically useful or personally meaningful to participants. Yet whether such standards are well understood and can be consistently applied remains unknown. We conducted an international, cross-sectional survey of cystic fibrosis (CF) and autism genetics researchers using a quasi-experimental design to explore factors influencing researchers’ judgments. Eighty percent of researchers agreed, in principle, that clinically significant findings should be reported to individual participants. Yet judgments about when a specific finding was considered clinically significant or warranted reporting varied by scientific factors (replication, robustness, intentionality, and disease context), capacity of the research team to explain the results, and type of research ethics guidance. Further, judgments were influenced by the researchers’ disease community (autism or CF), their primary role (clinical, molecular, statistical) and their beliefs regarding a general reporting obligation. In sum, judgments about the clinical significance of genetic research results, and about whether they should be reported, are influenced by scientific parameters as well as contextual factors related to the specific research project and the individual researcher. These findings call into question the assumption that the conditions under which an obligation to disclose arises are uniformly understood and actionable. Adjudicating the clinical readiness of provisional data may be a responsibility better suited to evaluative experts at arms’ length of the provisional data in question, rather than a responsibility imposed upon researchers themselves.

Understanding sickle cell carrier status identified through newborn screening: a qualitative study

The expansion of newborn screening (NBS) is increasing the generation of incidental results, notably carrier results. Although carrier status is generally understood to be clinically benign, concerns persist that parents may misunderstand its meaning, with deleterious effects on children and their families. Expansion of the NBS panel in Ontario, Canada in 2006 to include sickle cell disorders drew attention to the policy challenge of incidental carrier results. We conducted a study of consumer and provider attitudes to inform policy on disclosure. In this paper, we report the results of (i) qualitative interviews with health-care providers, advocates and parents of carrier infants and (ii) focus groups with new parents and individuals active with the sickle cell community. Lay and provider participants generally believed that carrier results were clinically insignificant. However, some uncertainty persisted among lay consumers in the form of conjecture or doubt. In addition, consumers and advocates who were most informed about the disease articulated insistent yet dissonant claims of clinical significance. Meanwhile, providers referenced research knowledge to offer an equivocal assessment of the possibility and significance of clinically symptomatic carrier status. We conclude that many interpretations of carrier status are in circulation, failing to fit neatly into the categories of ‘clinically significant’ or ‘benign.’ This creates challenges for communicating clearly with parents – challenges exacerbated by inconsistent messages from screening programs regarding the significance of sickle cell carrier status. Disclosure policy related to incidentally generated infant carrier results needs to account for these complex realities.

Informing Parents About Expanded Newborn Screening: Influences on Provider Involvement

OBJECTIVE: Expanded newborn screening (NBS) identifies some disorders for which clinical benefit is uncertain, as well as “incidental” findings (eg, carrier status), thus enhancing the need to inform parents about NBS before sample collection. METHODS: A self-complete survey was sent to a cross-sectional, stratified, random sample of 5 provider groups in Ontario (obstetricians, midwives, family physicians, pediatricians, and nurses). Univariate and multivariate analyses were used to investigate the effects of core beliefs, perceived barriers, and demographic characteristics on the reported frequency of informing parents about NBS before sample collection. RESULTS: Virtually all of the midwives and almost half of the nurses reported discussing NBS with parents, whereas less than one sixth of the physicians did so. Providers who perceived a responsibility to inform parents were 3 times more likely to report doing so than those who did not perceive this responsibility (odds ratio: 2.9 [95% confidence interval: 2.1–4.1]). Those who lacked confidence to inform parents were 70% less likely to discuss NBS with parents compared with those who did not experience this cognitive barrier (odds ratio: 0.3 [95% confidence interval: 0.2–0.4]). Controlling for these covariates, family physicians and obstetricians were more likely than pediatricians to inform parents. CONCLUSIONS: These results provide guidance for capacity building among providers who are positioned to inform parents about NBS before sample collection. Our findings call for targeted educational interventions that consider patterns of provider practice related to prenatal and NBS care, seek to redress confidence limitations, and engage key provider groups in the importance of this professional responsibility.

Clinical obligations and public health programmes: healthcare provider reasoning about managing the incidental results of newborn screening

Background: Expanded newborn screening generates incidental results, notably carrier results. Yet newborn screening programmes typically restrict parental choice regarding receipt of this non-health serving genetic information. Healthcare providers play a key role in educating families or caring for screened infants and have strong beliefs about the management of incidental results. Methods: To inform policy on disclosure of infant sickle cell disorder (SCD) carrier results, a mixed-methods study of healthcare providers was conducted in Ontario, Canada, to understand attitudes regarding result management using a cross-sectional survey (N  =  1615) and semistructured interviews (N  =  42). Results: Agreement to reasons favouring disclosure of SCD carrier results was high (65.1%–92.7%) and to reasons opposing disclosure was low (4.1%–18.1%). Genetics professionals expressed less support for arguments favouring disclosure (35.3%–78.8%), and more agreement with arguments opposing disclosure (15.7%–51.9%). A slim majority of genetics professionals (51.9%) agreed that a reason to avoid disclosure was the importance of allowing the child to decide to receive results. Qualitatively, there was a perceived “duty” to disclose, that if the clinician possessed the information, the clinician could not withhold it. Discussion: While a majority of respondents perceived a duty to disclose the incidental results of newborn screening, the policy implications of these attitudes are not obvious. In particular, policy must balance descriptive ethics (ie, what providers believe) and normative ethics (ie, what duty-based principles oblige), address dissenting opinion and consider the relevance of moral principles grounded in clinical obligations for public health initiatives.

Consent for Newborn Screening: The Attitudes of Health Care Providers

Background: As newborn screening (NBS) expands to meet a broader definition of benefit, the scope of parental consent warrants reconsideration. Methods: We conducted a mixed methods study of health care provider attitudes toward consent for NBS, including a survey (n = 1,615) and semi-structured interviews (n = 36). Results: Consent practices and attitudes varied by provider but the majority supported mandatory screening (63.4%) and only 36.6% supported some form of parental discretion. Few health care providers (18.6%) supported seeking explicit consent for screening condition-by-condition, but a larger minority (39.6%) supported seeking consent for the disclosure of incidentally generated sickle cell carrier results. Qualitative findings illuminate these preferences: respondents who favored consent emphasized its ease while dissenters saw consent as highly complex. Conclusion: Few providers supported explicit consent for NBS. Further, those who supported consent viewed it as a simple process. Arguably, these attitudes reflect the public health emergency NBS once was, rather than the public health service it has become. The complexity of NBS panels may have to be aligned with providers’ capacity to implement screening appropriately, or providers will need sufficient resources to engage in a more nuanced approach to consent for expanded NBS.