Health practitioners' perceptions of the barriers and enablers to the implementation of reproductive genetic carrier screening: A systematic review

Abstract Background As interest in reproductive genetic carrier screening rises, with increased availability, the role of healthcare practitioners is central in guiding uptake aligned with a couples' values and beliefs. Therefore, practitioners' views on implementation are critical to the success of any reproductive genetic carrier screening programme. Aim To explore healthcare practitioners' perceptions of the barriers and enablers to implementation. Materials & Methods We undertook a systematic review of the literature searching seven databases using health practitioner, screening and implementation terms returning 490 articles. Results Screening led to the inclusion of 26 articles for full‐text review. We found three interconnected themes relating to reproductive genetic carrier screening: (i) use and impact, (ii) practitioners' beliefs and expectations and (iii) resources. Discussion Barriers and enablers to implementation were present within each theme and grouping these determinants by (a) community for example lack of public interest, (b) practitioner for example lack of practitioner time and (c) organisation for example lack of effective metrics, reveals a preponderance of practitioner barriers and organisational enablers. Linking barriers with potential enablers leaves several barriers unresolved (e.g., costs for couples) implying additional interventions may be required. Conclusion Future research should draw on the findings from this study to develop and test strategies to facilitate appropriate offering of reproductive genetic carrier screening by healthcare practitioners.


| INTRODUCTION
Internationally, the move towards population level reproductive genetic carrier screening (RGCS) of prospective parents to identify their risk of having a child with a genetic condition, is growing.
Technological advances are making the process more feasible and costs are falling. 1 Despite the routine practice of RGCS for ethnically specific conditions, such as thalassaemia or Tay-Sachs disease, or in circumstances where there is a family history of disease, healthcare practitioners' (HCPs) attitudes towards screening in the general 'low-risk' population remain unclear. It is well documented 2 that there is no family history in approximately 88% of carriers, emphasising the importance of offering RGCS to all couples planning for a child and guidelines are evolving to reflect this.
To date, attention in the literature has centred on the attitudes of patients and families of those affected by genetic conditions, [3][4][5] hypothetical views of HCPs on whether screening should be offered 6 and the cost effectiveness of RGCS. 7,8 While these elements are important, they do not inform us about how to implement a RGCS programme. The study of implementation facilitates the focus on the factors associated with the success or failure of a clinical intervention. 9 Fortunately, there is now an emerging evidence base identifying HCPs perceptions of factors influencing the implementation of RGCS.
To the best of our knowledge, a systematic review of the literature in this area has not been undertaken. As many countries are investing in the use of RGCS, 10 it is timely to investigate factors influencing its implementation. As patients should be made aware of RGCS, so that they can use RGCS according to their values and beliefs, 11 this phase is an essential first step to identifying appropriate strategies to support HCPs offering RGCS in their day-to-day practice.

| AIMS AND OBJECTIVES
The aim of this systematic review was to identify barriers and enabling factors associated with the implementation of RGCS particularly in relation to the views of HCPs. The study had the following objectives: � To reveal areas where further primary research is required.

| METHODS
The literature search was registered with PROSPERO (registration number CRD42020150581) and conducted in September 2020.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed 12  Articles were downloaded into Endnote X9, a bibliographic database.
Duplicates and incomplete references were discarded resulting in 490 papers for inclusion. We also used a snowball process for cited articles from the initial search to generate another 28 papers.
Five reviewers (J.C.L., T.T., S.B., R.L. and S.H.) analysed the same 10% of titles and abstracts independently, applying inclusion and exclusion criteria (Table 1). We included empirical, human research and excluded any guidelines, commentaries, opinion pieces and studies using secondary data. Only studies related to HCPs engaged with RGCS during the prepregnancy or prenatal period were included.
General public and target population views were not included.
Results of the title and abstract screening were compared, and the Fleiss' Kappa statistic was determined to measure inter-rater reliability, achieving k = 0.79 which is interpreted as 'substantial agreement'. 13

| Data analysis
We imported the final 26 papers into NVivo 12 15 to facilitate data management. Using Braun and Clarke's 16 approach to thematic analysis, thereby bringing structure to the analysis, two authors (S.B. and J.C.L.) familiarised themselves with the papers before T A B L E 1 Inclusion and exclusion criteria for articles independently assessing eight papers to identify codes in the data.
Through a series of discussions, we developed three themes and one author (S.B.) then completed the coding with ongoing discussion with the team. We further compiled the findings from the themes by barriers and enablers for the community, practitioners and organisations.

| RESULTS
First, we outline the types of papers found from the literature search (Table 2) before sharing the themes and subthemes identified (  (a) Achieving equitable service provision: Inequitable access to RGCS was a concern and seen as a barrier to implementation in several papers, including the cost of the test to individuals. [17][18][19][20] Routes to achieving equitable service provision included offering RGCS alongside other health interventions, to promote a wide uptake of testing, 21 and communication with policy makers and other stakeholders which was seen as essential as the availability of RGCS develops. 22 There was also discussion about the range of diseases screened for with Matar et al. 23 noting that private companies were expanding panels beyond the public offer, suggesting this would either promote inequity or stimulate policy development.  (a) Practitioner attitudes to and beliefs about RGCS: Attitudes and beliefs that can act as a barrier to implementation of RGCS included the lack of a collective sense of urgency (i.e., demand from the population and HCPs). 27 While there was generally a positive attitude towards RGCS 25 this was not always supported in practice by the offer of screening. 26 On the other hand, not all practitioners were interested in RGCS, running the risk of inconsistency in practice as to who was offered screening. 7,29 In addition, there was variability in beliefs about who should be offered testing 19 with client request reported as the most common reason amongst obstetricians and BEST ET AL.  (4) to determine the support needed.

Surveys
Both primary and secondary health care providers Poppelaars et al. 25 The Netherlands CF To explore the possibilities and barriers in the implementation of a nationwide preconceptional CF carrier screening programme in The Netherlands.
Focus groups Both primary and secondary health care providers Poppelaars et al. 35 The Netherlands

CF
To investigate the attitudes of GPs and CHS workers with regard to routinely offering preconceptional CF carrier screening, and to identify variables which were associated with a positive and a negative attitude.

Surveys
Both primary and secondary health care providers (Continues) BEST ET AL.
gynaecologists. 33 The belief that socioeconomic status would influence the offer of RGCS was raised. 34 Many HCPs were aware that offering RGCS as routine would influence clients' decisions to take up RGCS which runs counter to informed consent. 22 for example, GPs were reported to be concerned about their ability to discuss potential worrying, harmful or high risk results and especially the possibility of pregnancy termination when women are in early pregnancy. 22 There was also concern about the concept of risk, 21  HCPs perceived their ability to deliver RGCS was hindered by complex and confusing criteria, 33 a feeling that screening is too hard, and too complicated to answer all patients' questions. 29 In addition, genetic practitioners' ability to interpret results and provide counselling was limited by beliefs about the quality and size of the gene list. 30  offering different panels and the potential impact this may have on provider liability. 30,37 Although an enabler to implementation of RGCS, these mechanisms are defensive rather than guided by the needs of the client. However, different legal frameworks in different countries may influence providers' decisions to offer screening or not. 26,32 There was awareness of multiple stakeholders holding views on the place of RGCS in reproductive care that is constantly being negotiated and renegotiated. 22 Here, professional bodies were identified as a facilitator, though there is concern when conflicting guidance is offered. 30 Potential impact (including the offer) on the client, including concern about client anxiety, informed choice and stigma Archibald (2012) 21  demanding both skills and time 28 and many HCPs were aware genetic counsellors are a limited resource. 20,37 They therefore only make referrals to GCs under specific circumstances. 18 Although much counselling is undertaken by nonspecialist staff 37 there was concern that nonspecialist providers would find discussing the implications for pregnancy planning challenging, 19 The literature also discussed timing of the offer and commonly suggested a preference for offering RGCS prepregnancy to offer clients greater reproductive options, 19,21,25,26 for example through, as yet unrealised, preconception consultation centres. 19 Testing interconception was also identified. 27 (c) Nonclinical resources: The literature noted several resource barriers, for example, time for offering and counselling clients 7,17,22,24,25,27,29,34 and support to overcome language and cultural barriers. 26 The cost to the health system was identified as a potential challenge 22,23,26,28 alongside a lack of public health focus on RGCS 27,28 though acknowledging some countries may have more pressing public health issues or limited resources. 19 An additional challenge for policy makers was that uptake (a traditional measure of success) cannot be used for RGCS as screening should be voluntary. 19 The literature identified the need for additional skills training in talking about the test and understanding results. 22,26,27,31 Furthermore, barriers existed where practitioners lacked incentives to participate and so did not see offering RGCS as part of their role. 28 To facilitate implementation of RGCS additional resources were noted to potentially alleviate the challenge faced by lack of time. 24 In addition, the role of leadership was identified as an essential requirement to implementation of a RGCS programme. 27

| DISCUSSION
The three themes presented in the results (i) the use and potential Identifying the determinants of implementation is an essential first step in designing implementation strategies to overcome barriers. 41 Without acknowledging factors that are acting as obstacles, there is a risk of attempting to put in place strategies that do not respond to clinicians' needs and are therefore unlikely to succeed. When examining the themes from the literature it is the barriers that prevail. This may be due to a tendency to focus on negative aspects instead of adopting an approach that encourages a recognition of the learning value of what is going well. 42 However, there are also enablers in the findings that may inform the development of an implementation strategy.
Barriers to the implementation of RGCS identified from the literature are noted in Figure 3 and hypothetically linked with potential enablers. Our search centred on practitioners' perceptions and there is a predominance of practitioner barriers identified.
However, interestingly, the majority of the enablers are organisational, suggesting some strategies for implementing RGCS lie beyond the frontline clinicians. It should be stressed that the potential connection of a barrier with an enabler does not mean resolution of the barrier, merely that the literature provides some possible avenues for addressing some of the challenges when implementing RGCS. Some barriers do not have an associated enabler, for example; 1) cost, both to the consumer and the organisation. Addressing this barrier will be highly dependent on the healthcare system in which RGCS is implemented and an essential step in providing an equitable service. 43 2) aligning RGCS to organisation targets-this is challenging to address as take-up rates do not directly equate to the successful provision of a RGCS programme. 19 and 3) a lack of practitioner confidence and interestclinician education is clearly an essential first step to overcome these challenges though further interventions may be required for example, peer influence to overcome a lack of interest, 44 especially as this runs counter to the public interests. 45 By applying theoretical implementation science and behaviour change approaches, interventions can be designed to overcome these barriers. 46

| LIMITATIONS
There are limitations with this systematic review. We focused on practitioners' perspectives which, although essential, does not provide the whole picture in regard to implementation, for example, the -717 the literature and will need consideration using implementation science and behaviour change theory to develop potential approaches. To ensure the successful delivery of RGCS programmes the need for an implementation plan and relevant implementation strategies has been noted. 25 Such studies require time, collaboration and funding to have impact. 47 Further research is required to identify and then test evidence-informed implementation strategies.