“It's both a terrifying and a powerful position to be in”: A qualitative study exploring clinician experiences and perspectives on providing publicly funded fetal exome sequencing.

doi:10.21203/rs.3.rs-4960652/v1

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“It's both a terrifying and a powerful position to be in”: A qualitative study exploring clinician experiences and perspectives on providing publicly funded fetal exome sequencing.

https://doi.org/10.21203/rs.3.rs-4960652/v1

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Objective

Genomics has improved etiological diagnosis for fetal structural anomalies. We aimed to explore the experiences and perspectives of clinicians involved with the delivery of a state-wide public fetal exome sequencing (FES) service in Australia.

Method

This qualitative study was developed using a pragmatism framework. A multidisciplinary cohort of clinicians across all tertiary fetal medicine units in Victoria were interviewed. Inductive content analysis was used to understand the experiences, impact, and utility of FES.

Results

Eight clinician interviews were analysed. The impact of FES on clinicians included: increased pressure, higher emotional toll, and balancing the benefits with resource limitations. FES was most useful when it provided prognostic information. The clinicians felt that FES had the most utility for patients when the result informed their decision about whether or not to continue a pregnancy. Clinicians acknowledged their ‘gatekeeper’ role and valued a collaborative, multidisciplinary approach. The main perceived harm for patients was the anxiety associated with waiting times for results.

Conclusion

This study provides insights into the delivery of a publicly funded FES program. Our findings highlight the importance of the multidisciplinary team in the successful implementation of genomic technologies in reproductive health.

Medical Genetics

exome sequencing

prenatal diagnosis

genomics

qualitative research

Fetal exome sequencing is increasingly utilised in health care.

Diagnostic yield is dependent on indication for testing.

What does this study add?

Infrastructure around this testing is important to support both staff and patients.

Personal utility of testing is highly valued in the prenatal setting, including the value of a negative test.

Multi-disciplinary teams are an essential component of providing this complex service.

Figure legend.

Genetic and genomic diagnostic technologies have revolutionized clinical practice in reproductive health, especially in the evaluation of fetal structural anomalies.¹ Fetal structural anomalies are detected by ultrasound in up to five percent of pregnancies², and first-tier genetic tests (karyotyping, Fluorescent In-Situ Hybridisation and chromosomal microarray analysis) reveal a genetic cause in up to 40% of cases.³ Fetal exome sequencing (FES) is indicated when a multidisciplinary team with clinical genetic expertise believes the fetal phenotype has a genetic etiology.⁴ Large cohort studies^{5, 6} investigating fetal structural anomalies in 234 and 610 pregnancies, respectively, found an increased diagnostic yield from FES of ~ 9–10%. Subsequent systematic reviews and meta-analyses reported pooled diagnostic yields for FES of 31%, varying from 2–53% depending on fetal phenotype, study design and type of structural anomalies.³

Increasingly, the importance of personal utility is recognised, particularly in the prenatal setting. This refers to the ‘ability of a test result to be used for decisions, actions or understanding relevant to the patient beyond healthcare-related management, including facilitating future planning and facilitating reproductive planning’.⁷ Studies have found that FES was useful for determining prognoses for pregnancies impacted by fetal structural anomalies and informing prenatal care, neonatal management, delivery plans, and improved recurrence risk calculations and reproductive options.^{8, 9} It helped families prepare for the arrival of a child with additional medical needs¹⁰, and informed prenatal counselling around termination of pregnancy or neonatal palliative care .¹¹ There is also recognised value in negative or uninformative FES results as they can support parents’ decision to continue a pregnancy.^{9, 12, 13} Personal utility needs to be balanced with diagnostic yield when determining when testing is offered or recommended.

Few studies have explored views and experiences of stakeholders directly involved in the provision of FES. The limited literature outlines positive experiences in relation to timely diagnosis and better counselling but also reports challenges, including managing patient anxiety while awaiting results, appropriate case selection, and building a skilled workforce.¹⁴

The state Department of Health in Victoria, Australia, has provided funding for FES since 2019 through tertiary fetal medicine units, with specific eligibility criteria and the requirement for a multidisciplinary team (MDT) discussion. The primary aim of this study was to explore the experiences and perspectives of clinicians involved with the delivery of the Victorian Clinical Sequencing Initiative. The secondary aim was to explore clinicians’ perceptions of the harms and benefits of FES for patients.

This exploratory study adopted a qualitative methodology to ensure a range and depth of clinician experiences and perspectives were captured. This allowed for flexibility in understanding the nuances of responses, factoring in different professions and health services where FES is being delivered. The study was designed using a pragmatism framework, an approach that focuses on ‘practical understandings’ of concrete, real-world issues.¹⁵ The exploration of clinicians’ experiences and perspectives was well served by this approach as pragmatism values various viewpoints and perspectives of stakeholders in developing a deeper understanding of the subject matter.¹⁶ This deeper understanding of experiences and perspectives of FES can inform and refine the delivery of FES both locally and internationally.

Publicly funded FES is available to patients at four metropolitan Melbourne tertiary hospitals (hereafter referred to as ‘Health Services’). To proceed with funding of FES, a minimum of 3 specialist clinicians (clinical geneticists and maternal fetal medicine specialists) must review the case against eligibility criteria. For a case to be eligible for public funding there must be agreement from the clinicians that the diagnosis is likely to be identified using a genomic test and that the condition is severe, involving a complex neurological condition or affecting multiple systems. If a case does not reach consensus from three specialists, then it is not eligible for funding. If there is disagreement, then eligibility for funding can be determined on a case-by-case basis, and the decision is recorded as one made with uncertainty. All cases considered for public funded are recorded with a date of MDT, decision on eligibility and outcome of testing.

There is an expectation that FES would inform current or future reproductive decision making for the patient/couple. Postpartum FES following stillbirth, including terminations of pregnancy, were also eligible if the results would inform future reproductive planning.

Each fetal exome that receives funding is eligible for $AUD2,500 from the Department of Health. All prenatal samples are tested as trios when possible, and rapid turn-around time provides results within 15 days. FES most commonly tests stored DNA samples following first tier chromosomal microarray analysis. Testing is sequential in all but exceptional circumstances (such as very late gestation). Clinicians from the Health Services who were directly involved in managing at least five cases of FES were eligible to participate in the study. Purposive sampling was used to ensure sufficient sampling from each of the three relevant clinical specialties involved in patient management and care: genetic counsellors, clinical geneticists, and maternal fetal medicine specialists.

Coordinators of genetic services at the four Health Services identified eligible participants and distributed the study invitation by email. After informed consent was provided, semi-structured interviews were conducted via Zoom. (Interview Topic Guide - see Appendix A). Interviews were audio- and video- recorded and stored in the Zoom cloud along with the corresponding automated transcripts. The deidentified transcripts were uploaded to NVivo12 software (QSR International Pty Ltd, 2020) on a secure password protected Murdoch Children’s Research Institute server. The profession of each participant was retained to assist with interpretation of findings.

Interview transcripts were analysed using Inductive Content Analysis (ICA). ICA is an iterative method of summarising the content of a data set by identifying codes within the data that represent units of meaning. These codes emerge from the data, rather than being matched to a pre-determined list of content items.¹⁷ All transcripts were coded by SD and two transcripts were co-coded by co-authors (LH and LD) for rigour and consistency.

This study received ethics approval and governance authorisation from the Royal Children’s Hospital Melbourne Human Research Ethics Committee (HREC Reference 90771/RHCM-2023).

Participant characteristics

Eight clinicians participated in the study, including three genetic counsellors (GC), two maternal fetal medicine specialists (MFM), and three clinical geneticists (CG). The interviews were conducted between April 2023 and August 2023; mean duration of interviews was 56 minutes.

Inductive content analysis revealed three main categories of findings, with sub-categories within each category (Fig. 1).

Category 1: The delivery of FES impacts the experiences and perspectives of clinicians.

i. FES improves clinical care by providing more diagnostic information.

Clinicians recognised the value of FES in their clinical practice, providing greater clarity for patients about the prognosis for their developing baby, recurrence risk in future pregnancies or management for the pregnancy, delivery, and neonatal care.

“When we’ve found this major anomaly, or constellation of anomalies, it's like a fog descends. And over time we do more scans, then do an MRI, get the molecular karyotype, and maybe do an exome. It's like the fog gradually clears, and the way forward becomes clearer. I think exomes have been a very valuable contributor to getting rid of some more of that fog…and just makes the pathway forward clearer”. (MFM3)

ii. The multidisciplinary team plays an essential role in the successful provision of FES.

Clinicians identified the MDT as being key to the successful provision of FES. The MDT facilitated the appropriate decisions about patient selection, which was highly valued. The MDT also provided families with consistent information and continuity of care during their complicated pregnancy. Some clinicians recognised that continuity of care is difficult to deliver in the context of workload pressures (see sub-category iv, below).

“And then we have a unified way of counselling where, even if we're not seeing [the family] at the same time, we know what each person is going to say, and we know what, which aspects we need to talk about. Sometimes we do it combined so we'll have a geneticist, genetic counsellor and obstetrician, all in the same room at the same time.” (MFM2)

Some clinicians highlighted the benefits of collaborating with MDTs from other health services to ensure the state-wide delivery of FES was consistent, and to promote learning.

“That [MDT]email dialogue is very helpful, because that's how we learn and kind of develop consensus and formulate ideas and they're very good practice for learning, I would say.” (CG2)

The role of nonmedical staff, namely genetic counsellors, midwives, and social workers was also highly valued for the wrap-around support they provided to patients.

“Our social workers are very good at providing the practical and emotional and logistical support. They’re the things that really make a huge difference. And they're just someone else to listen ... they may have a huge impact on the experience of patients.” (MFM3)

iii. Clinicians must balance the perceived benefits to patients and clinical care with the cost of testing.

Clinicians within the MDT were seen to have a ‘gatekeeper’ function, determining who was appropriate to be offered FES in a resource limited environment.

Part of the gatekeeper role we have is that we want to do good clinical practice, but a lot of it is financially driven and the fact that we can't afford to provide it to everyone. So, then it raises the question: “Well, let’s say it was free, or very, very cheap, how would that change what we would offer?” And clearly, we would offer it a lot more liberally.

(CG2)

iv. FES has created more pressure on the genetics workforce.

Clinicians expressed concerns about the impact of FES on the clinical workforce. These concerns related to the increased administrative burden, and the urgency of pregnancy related testing. This time sensitivity led to personal experiences of stress by some clinicians. There was also worry about the downstream impacts these urgent cases had on waitlists for genetics referrals.

“These are the conversations that we’re having at the moment around resourcing and funding because we're doing more and more [FES], but we don't have any additional resources or funding for it. And they’re the most urgent of the urgent cases. So, it just means that they get seen, and other people don't. And they're so complex that the actual appointment often takes a lot of time. Then prep for it, and the MDT discussion…and looking up all the relevant information. All of that takes a lot of time”.

(GC2)

v. Delivery of FES can elicit challenging emotional experiences for clinicians.

Clinicians revealed challenging emotions associated with delivering FES and their role in supporting families in high stakes decision-making around continuing or terminating pregnancies where fetal structural anomalies had been identified.

“It's both a terrifying and a powerful position to be in, where you realize that what you say is going to make an often, a life-or-death decision, if you will, or life or no life decision, for this family - is somewhat dictated upon what you say”.

(CG1)

This emotional toll was a potential source of burnout for staff and seen as a potential threat to the long-term sustainability of the clinical service.

“That flow on effect [of the increased workload] is burnout for the workforce, and people feeling overloaded and stressed and anxious. And if we're not properly resourced for these things, then it just doesn't work”.

(GC2)

However, staff were resourceful and resilient and accessed support through formal and informal channels.

“We all have individual and or group supervision. So, I think that's really helpful, and we've got an awesome team, and we all debrief amongst each other”. (GC2)

Category 2: The delivery of FES has perceived impacts on pregnant women/couples.

i. FES results can support high stakes decision-making around continuation or termination of pregnancy.

All clinicians acknowledged the benefits of FES for patients and couples who are making decisions about a pregnancy that is complicated by fetal structural anomalies. When FES confirms a genetic diagnosis, this can allow parents to make informed decisions, with greater certainty about what the expected outcomes could be for their unborn child.

“[A benefit of FES is] being able to say to a couple ‘Here is a really devastating diagnosis, this is awful, here’s what it means for your baby’, and them being able to say, ‘That’s really helpful to inform my decision around what I do next’. So, I think for decision making purposes, when you have a diagnosis, it can be really instrumental for families”.

(CG1)

Clinicians referred to the value of uninformative or negative findings from FES as these results can provide parents with reassurance to continue the pregnancy. Clinicians noted the importance of counselling families around negative results insofar as they do not guarantee the absence of a genetic basis for the clinical presentation.

“And negative tests sometimes can be as valuable as a positive test [result] for families because it then confirms their belief that they want to keep going because there's nothing additional: ‘What I dealt with at the beginning, and what I was prepared to continue with in this pregnancy remains the same. You haven't added any additional findings and haven't worsened the prognosis’”. (MFM2)

ii. There is potential harm associated with waiting for results.

Clinicians raised concerns about the potentially harmful impact of FES on the pregnant woman and family by protracting the decision-making process, especially when the results of the FES do not provide additional information to inform decision-making. This delay can create additional anxiety. Clinicians highlighted the importance of providing parents with ongoing support during this period of waiting.

“So [the extra time for testing] does cost a lot of in terms of emotional issues to the family. Especially when the parents are not sure which way they want to go, it can take a bit of an emotional toll in many families. Some families do change their plan while waiting for the results. So once in a while we see families that say “Okay, it's too much for us. We don't want to continue the pregnancy”. (CG3)

iii. Clinical utility is more than finding a causative variant

Clinicians had a broader view of the clinical utility of FES than simply identifying a causative genetic variant. Clinicians recognised that in many cases, a non-diagnostic result can be just as valuable for parents, as this gives some patients more confidence to continue a pregnancy with a structural anomaly.

“Traditionally, there’s been a view in genetics that a high [diagnostic] yield means a higher clinical utility, but that doesn’t necessarily follow in prenatal, particularly when there’s really only one decision to be made and that is whether a couple will continue with a pregnancy or whether they will terminate a pregnancy”.

(CG2)

As well as FES results providing clinical utility in the traditional sense, contributing to decisions regarding obstetric management and neonatal care in the current pregnancy, it also provided information to inform genetic counselling about reproductive risks and options for future pregnancies.

Clinicians were optimistic that clinical utility of FES would improve with further experience and accumulation of knowledge.

As we have more experience about the longer-term impacts (of not only a positive but also a negative exome) and how protective is it to have a negative exome, this will increase the precision of our counselling so that people can then make better informed decisions.

MFM2

This qualitative study provides valuable insights into clinicians’ perspectives and experiences associated with the delivery of publicly funded FES. Participants valued the contribution of FES to their counselling and clinical management, and not surprisingly, clinicians reported that the main benefit of FES was to inform a couple’s decision to terminate or continue the pregnancy.¹⁸

Importantly, clinicians emphasized that a nondiagnostic FES result could also be valuable in providing reassurance to parents to continue their pregnancy. This has parallels in the paediatric literature where parents perceived an uninformative exome result as ‘good news’ and being reassured they had 'done all they could’ to understand their child’s condition.¹⁹ Our results contribute to this understanding, that a negative result can also have significant personal utility.

The main harms that were identified were the additional waiting period associated with FES, as this testing is performed after a nondiagnostic chromosomal microarray result, rather than tested in parallel. Clinicians were concerned that extending this period of waiting of 2–3 weeks for FES results could add to parents’ distress, especially when FES results are uninformative. Clinicians advocated for sufficient support mechanisms for families during this time and stressed the importance of the MDT midwives, social workers, and genetic counsellors in providing this support.

While clinicians shared their concerns for the wellbeing of parents, this study also highlighted areas where clinicians require additional support. The mismatch between the increased workload associated with the provision of FES and the allocation of funding for testing was a concern. Clinicians highlighted the importance of having well established support mechanisms such as professional supervision and clear guidelines for best practice to prevent burnout. Clinicians also expressed concern about potential downstream impacts on patient care and meeting the needs of the growing number of patients referred to genetic services. They advocated for more resources to build the genomics workforce to ensure the sustainability of FES and future advances in care.

While this study provides an insight into the challenges experienced by clinicians, it also describes features of the existing model of care that are positive. Clinicians highly valued the role of the MDT in patient selection and providing continuity and consistency of care. The MDT was also seen a source of continuing education and peer support. Genetic counsellors were seen as central to the successful provision of FES, anchoring the myriad stakeholders involved (MDT members, laboratory staff, parents, and healthcare professionals in the wider community).

This study was only able to report the clinicians’ perspectives on the impact of FES on the experiences of pregnant women/couples. Future research investigating the lived experience of patients would further inform the future delivery of FES. Participants in this study comprised a small, self-selected sample in the Victorian context. A larger sample of healthcare professionals was not feasible given the small number of specialists working in this area. Little is known about experiences and practices of clinicians in other parts of Australia and internationally. Limited previous literature describes a service where abortion laws have a large effect on service pressures and laboratory turn-around time.⁹ Understanding the experiences of other services and stakeholders (such as referring clinicians, medical scientists and policy makers) could assist in shaping future services to maximize the value from the resource limited health sector.

As the cost of sequencing decreases it is likely to be more frequently incorporated into perinatal care.²⁰ It is thus imperative there are sufficient and appropriately experienced staff available to deal with the expanding workload. Our study revealed some of the hidden costs of providing advanced genomic testing, including increased administrative and clinical workload and often, a higher emotional toll and potential for staff burnout.

This study has provided valuable insights into the experiences and perspectives of clinicians involved in a clinical FES service. The clinicians see themselves as ‘gatekeepers’ of this expensive genomic technology, while supporting patients in a time-sensitive, high-stakes decision making environment. The greatest utility of FES (whether diagnostic or uninformative) was in informing patient decisions to continue or terminate a pregnancy. Collaboration and peer support within an MDT, and an adequately funded and resourced genetics workforce, were seen as essential for the successful and sustainable provision of FES within the public hospital system.

Funding

This study was funded by an innovation grant from the Norman Beischer Medical Research Foundation with infrastructure support from University of Melbourne and Murdoch Children’s Research Institute.

Author contributions

SD: Conceptualization, formal analysis, investigation, writing – original draft, writing – review and editing, project administration; LD: Formal analysis, writing – review and editing; MG: Writing – review and editing; LH: Conceptualization, formal analysis, writing – review and editing, project administration, supervision, funding acquisition

Acknowledgements

We thank the genomic co-ordinators of the health services for their assistance with inviting participants, and the clinicians who volunteered their time to share their insights. We also thank Dr Sharon Lewis for her invaluable advice regarding study design and analysis.

Data availability

No data sharing is available.

Conflict of interest

The authors have no conflicts of interest to declare.

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The authors declare no competing interests.

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“It's both a terrifying and a powerful position to be in”: A qualitative study exploring clinician experiences and perspectives on providing publicly funded fetal exome sequencing.

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Abstract

Objective

Method

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Conclusion

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INTRODUCTION

METHOD

RESULTS

Participant characteristics

DISCUSSION

CONCLUSION

Declarations

Funding

Author contributions

Acknowledgements

Data availability

References

Additional Declarations

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