Primary care providers' role in newborn screening result notification for cystic fibrosis.

OBJECTIVE: To explore primary care providers' (PCPs') role in result notification for newborn screening (NBS) for cystic fibrosis (CF), given that expanded NBS has increased the number of positive screening test results, drawing attention to the role of PCPs in supporting families. DESIGN: Cross-sectional survey and qualitative interviews. SETTING: Ontario. PARTICIPANTS: Primary care providers (FPs, pediatricians, and midwives) who received a positive CF NBS result for an infant in their practice in the 6 months before the study. MAIN OUTCOME MEASURES: Whether the PCP notified the family of the initial positive CF screening result. RESULTS: Data from 321 PCP surveys (response rate of 51%) are reported, including 208 FPs, 68 pediatricians, and 45 midwives. Interviews were completed with 34 PCPs. Most (65%) surveyed PCPs reported notifying the infant's family of the initial positive screening result; 81% agreed that they have an important role to play in NBS; and 88% said it was important for PCPs, rather than the NBS centre, to notify families of initial positive results. With support and information from NBS centres, 68% would be extremely or very confident in doing so; this dropped to 54% when reflecting on their recent reporting experience. More than half (58%) of all PCPs said written point-of-care information from the NBS centre was the most helpful format. Adjusted for relevant factors, written educational information was associated with a lower rate of notifying families than written plus verbal information (risk ratio of 0.79; 95% CI 0.69 to 0.92). In the interviews, PCPs emphasized the challenge of balancing required content knowledge with the desire for the news to come from a familiar provider. CONCLUSION: Most PCPs notify families of NBS results and value this role. These data are relevant as NBS programs and other genomic services expand and consider ways of keeping PCPs confident and actively involved.

Newborn screening for cystic fibrosis: Role of primary care providers in caring for infants with positive screening results.

OBJECTIVE: To explore primary care providers' (PCPs') preferred roles and confidence in caring for infants receiving a positive cystic fibrosis (CF) newborn screening (NBS) result, as well as management of CF family planning issues, given that expanded NBS has resulted in an increase in positive results. DESIGN: Mailed questionnaire. SETTING: Ontario. PARTICIPANTS: Ontario FPs, pediatricians, and midwives identified by Newborn Screening Ontario as having had an infant with a positive CF NBS result in their practice in the previous 6 months. MAIN OUTCOME MEASURE: Primary care providers' preferred roles in providing well-baby care for infants with positive CF screening results. RESULTS: Overall, 321 of 628 (51%) completed surveys (208 FPs, 68 pediatricians, 45 midwives). For well-baby care for infants confirmed to have CF, 77% of PCPs indicated they would not provide total care (ie, 68% would share care with other specialists and 9% would refer to specialists completely); for infants with an inconclusive CF diagnosis, 50% of PCPs would provide total care, 45% would provide shared care, and 5% would refer to a specialist; for CF carriers, 89% of PCPs would provide total care, 9% would provide shared care, and 2% would refer. Half (54%) of PCPs were extremely or very confident in providing reassurance about CF carriers' health. Only 25% knew how to order parents' CF carrier testing; 67% knew how to refer for prenatal diagnosis. Confidence in reassuring parents about the health of CF carrier children was associated with providing total well-baby care for CF carriers (risk ratio of 1.50; 95% CI 1.14 to 1.97) and infants with an inconclusive diagnosis (risk ratio of 3.30; 95% CI 1.34 to 8.16). CONCLUSION: Most PCPs indicated willingness to treat infants with a range of CF NBS results in some capacity. It is concerning that some indicated CF carriers should have specialist involvement and only half were extremely or very confident about reassuring families about carrier status. This raises issues about possible medicalization of those with carrier status, prompting the need for PCP education about genetic disorders and the meaning of genetic test results.

Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis.

OBJECTIVE: To explore the psychosocial implications of diagnostic uncertainty that result from inconclusive results generated by newborn bloodspot screening (NBS) for cystic fibrosis (CF). STUDY DESIGN: Using a mixed methods prospective cohort study of children who received NBS for CF, we compared psychosocial outcomes of parents whose children who received persistently inconclusive results with those whose children received true positive or screen-negative results. RESULTS: Mothers of infants who received inconclusive results (n = 17), diagnoses of CF (n = 15), and screen-negative results (n = 411) were surveyed; 23 parent interviews were completed. Compared with mothers of infants with true positive/screen-negative results, mothers of infants with inconclusive results reported greater perceived uncertainty (P < .006) but no differences in anxiety or vulnerability (P > .05). Qualitatively, parents valued being connected to experts but struggled with the meaning of an uncertain diagnosis, worried about their infant's health-related vulnerability, and had mixed views about surveillance. CONCLUSION: Inconclusive CF NBS results were not associated with anxiety or vulnerability but led to health-related uncertainty and qualitative concerns. Findings should be considered alongside efforts to optimize protocols for CF screening and surveillance. Educational and psychosocial supports are warranted for these families.

Parent Experience With False-Positive Newborn Screening Results for Cystic Fibrosis.

BACKGROUND: The risk of psychosocial harm in families of infants with false-positive (FP) newborn bloodspot screening (NBS) results for cystic fibrosis (CF) is a longstanding concern. Whether well designed retrieval and confirmatory testing systems can mitigate risks remains unknown. METHODS: Using a mixed-methods cohort design, we obtained prospective self-report data from mothers of infants with FP CF NBS results 2 to 3 months after confirmatory testing at Ontario's largest follow-up center, and from a randomly selected control sample of mothers of screen negative infants from the same region. Mothers completed a questionnaire assessing experience and psychosocial response. A sample of mothers of FP infants completed qualitative interviews. RESULTS: One hundred thirty-four mothers of FP infants (response rate, 55%) and 411 controls (response rate, 47%) completed questionnaires; 54 mothers of FP infants were interviewed. Selected psychosocial response measures did not detect psychosocial distress in newborns or 1 year later (P > .05). Mothers recalled distress during notification of the positive result and in the follow-up testing period related to fear of chronic illness, but valued the screening system of care in mitigating concerns. CONCLUSIONS: Although immediate distress was reported among mothers of FP infants, selected psychometric tools did not detect these concerns. The NBS center from which mothers were recruited minimizes delay between notification and confirmatory testing and ensures trained professionals are communicating results and facilitating follow-up. These factors may explain the presence of minimal psychosocial burden. The screening system reflected herein may be a model for NBS programs working to minimize FP-related psychosocial harm.

Accountability in the ontario cancer services system: a qualitative study of system leaders' perspectives.

Cancer Care Ontario (CCO), the provincial cancer agency, operates under a model of accountable governance that has been hailed as exemplary. We explored cancer system leaders' views on the balance and perceived efficacy of approaches to accountability in this context. Semi-structured interviews were conducted with 19 participants (MOHLTC=5, CCO=14). Adopting a qualitative descriptive approach, we coded data for four policy instruments used in approaches to accountability. Financial incentives are a key lever used by both parties to effect change. Cancer-specific regulations were somewhat weak, but agency-wide directives were a necessary nuisance that had great force. The effect of public reporting on mobilizing consumer sovereignty was questioned; however, transparency for its own sake was highly valued. Professionalism and stewardship, with an emphasis on trust-based partnerships and clinical engagement, were critical to CCO's success. These approaches were seen to work together, but what made each have force was reliance on professionalism and stewardship.

Genomic testing in cancer: patient knowledge, attitudes, and expectations.

BACKGROUND: Genomic testing in cancer (GTC) characterizes genes that play an important role in the development and growth of a patient's cancer. This form of DNA testing is currently being studied for its ability to guide cancer therapy. The objective of the current study was to describe patients' knowledge, attitudes, and expectations toward GTC. METHODS: A 42-item self-administered GTC questionnaire was developed by a multidisciplinary group and patient pretesting. The questionnaire was distributed to patients with advanced cancer who were referred to the Princess Margaret Cancer Center for a phase 1 clinical trial or GTC testing. RESULTS: Results were reported from 98 patients with advanced cancer, representing 66% of the patients surveyed. Seventy-six percent of patients were interested in learning more about GTC, and 64% reported that GTC would significantly improve their cancer care. The median score on a 12-item questionnaire to assess knowledge of cancer genomics was 8 of 12 items correct (67%; interquartile range, 7-9 of 12 items correct [58%-75%]). Scores were associated significantly with patients' education level (P < .0001). Sixty-six percent of patients would consent to a needle biopsy, and 39% would consent to an invasive surgical biopsy if required for GTC. Only 48% of patients reported having sufficient knowledge to make an informed decision to pursue GTC whereas 34% of patients indicated a need for formal genetic counseling. CONCLUSIONS: Patients with advanced cancer are motivated to participate in GTC. Patients require further education to understand the difference between somatic and germline mutations in the context of GTC. Educational programs are needed to support patients interested in pursuing GTC.

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.

One thing leads to another: the cascade of obligations when researchers report genetic research results to study participants.

Even as debate continues about the putative obligation to proactively report genetic research results to study participants, there is an increasing need to attend to the obligations that might cascade from any initial report. We conducted an international, quasi-experimental survey of researchers involved in autism spectrum disorders (ASD) and cystic fibrosis (CF) genetics to explore perceived obligations to ensure updated information or relevant clinical care subsequent to any initial communication of research results, and factors influencing these attitudes. 5-point Likert scales of dis/agreement were analyzed using descriptive and multivariate statistics. Of the 343 respondents (44% response rate), large majorities agreed that in general and in a variety of hypothetical research contexts, research teams that report results should ensure that participants gain subsequent access to updated information (74-83%) and implicated clinical services (79-87%). At the same time, researchers perceived barriers restricting access to relevant clinical care, though this was significantly more pronounced (P<0.001) for ASD (64%) than CF (34%). In the multivariate model, endorsement of cascading obligations was positively associated with researcher characteristics (eg, clinical role/training) and attitudes (eg, perceived initial reporting obligation), and negatively associated with the initial report of less scientifically robust hypothetical results, but unaffected by perceived or hypothetical barriers to care. These results suggest that researchers strongly endorse information and care-based obligations that cascade from the initial report of research results to study participants. In addition, they raise challenging questions about how any cascading obligations are to be met, especially where access challenges are already prevalent.

What does 'respect for persons' require? Attitudes and reported practices of genetics researchers in informing research participants about research.

BACKGROUND: It has been suggested that researchers are obliged to offer summary findings to research participants to demonstrate respect for persons, and that this may increase public trust in, and awareness of, the research enterprise. Yet little research explores researchers' attitudes and practices regarding the range of initiatives that might serve these ends. METHODS: Results of an international survey of 785 eligible authors of genetics research studies in autism or cystic fibrosis are reported. RESULTS: Of 343 researchers who completed the survey (44% response rate), the majority agreed that their team should (i) inform participants of summary findings (90.7%) and (ii) ensure they gain an awareness of developments in the field (86.9%). Additionally, the majority reported that in practice, their team (i) informs participants of summary findings (69.4%) and (ii) provides other types of relevant non-results information (eg, state of science in the field, opportunities for research participation) (67.9%). CONCLUSION: Researchers endorsed the obligation of communicating with research participants by providing summary findings and other research-related information in equal measure. In light of these findings, it is suggested that while the provision of summary results may contribute to efforts to discharge the obligation of respect for persons, it may be neither a necessary nor a sufficient means to this end.

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.

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.