A qualitative study exploring stakeholders’ perceptions of registry-based randomised controlled trials capacity and capability in Australia

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RCTs however are complex, expensive and have low external validity. Registry-based randomised controlled trials (RRCTs) are an emerging alternative approach that integrate the internal validity of an RCT with the external validity of a clinical registry by recruiting more real-world patients and leveraging an existing registry platform for data collection. As RRCTs are a novel research design, there is limited understanding of the RRCT landscape in Australia. This qualitative study aims to explore the RRCT landscape in Australia including current capacity and capabilities, and to identify challenges and opportunities for conducting RRCTs. Methods We conducted 30 semi-structured interviews with 18 Clinician researchers, 6 Research Administrators, and 6 Research Governance Officers. Interviews were audio-recorded and transcribed verbatim. We analysed the data using thematic analysis. Results We identified four overarching themes: 1) Understanding of the RRCT methodology concept and knowledge of Australian clinical registries and RRCT landscape; 2) Enablers and barriers in the uptake and conduct of RRCTs; 3) Ethics and governance requirements impacting the conduct of RRCTs and 4) Recommendations for the promotion, support and implementation of RRCTs. Understanding of and ability to define an RRCT varied considerably amongst participants, as did their appreciation of the role the registry should play in supporting these trials. Lack of ongoing funding to support both registries and RRCTs, along with low awareness and minimal education around this methodology, were identified as the predominant barriers to the uptake of RRCTs in Australia. The simplicity of RRCTs, specifically their pragmatic nature and lower costs were identified as one of their best attributes. There was consensus that inadequate funding, onerous research governance requirements and poor awareness of this methodology were currently prohibitive in enticing clinicians and researchers to conduct RRCTs. Recommendations to improve the uptake of RRCTs included establishing a sustainable funding model for both registries and RRCTs, harmonising governance requirements across jurisdictions and increasing awareness of RRCTs through education initiatives. Conclusions RRCTs in Australia are an evolving methodology with slow but steady uptake across a number of clinical disciplines. Whilst RRCTs are increasingly identified as a beneficial alternative methodology to evaluate and improve current standards of care, several barriers to effective RRCT implementation were identified. Creating greater awareness of the benefits of RRCTs across a number of stakeholders to help secure ongoing funding, and addressing both registry and RRCT governance challenges are two essential steps in enhancing the uptake of RRCTs in Australia and internationally. registry-based randomised controlled trials registry qualitative study Introduction Randomised controlled trials (RCTs) are considered the gold standard for evaluating the effectiveness of interventions in clinical research ( 1 , 2 ). Traditional RCTs are expensive and complex to perform. They enrol a highly selected population through strict inclusion criteria, impacting their generalisability with a high proportion of trials failing to meet recruitment goals ( 3 , 4 ). Alternative research methodologies have been developed in pursuit of more affordable and generalisable high-quality clinical evidence ( 3 , 5 ). One such alternative methodology is the registry-based randomised controlled trial (RRCT). RRCTs encompass a broad and varied definition whereby data is obtained from or collected into a registry. A registry is defined as “an organised system that uses observational study methods to collect uniform data to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure”( 6 ). A registry can support an RRCT in various ways, including by facilitating participant identification, participant recruitment, or capture of patient detail and outcome measures in the registry. Participant randomisation can occur either within or outside the registry. RRCTs share a number of common features with RCTs such as patient stratification and randomisation ( 7 ), but depending on what role the registry plays, they are usually best suited for testing hypotheses involving approved clinical interventions for which there are uncertainties about the optimal sequence, duration or combination of standard-of-care treatment, or where multiple standard-of-care options exist that have not previously been compared head to head ( 2 ). All RRCTs in Australia must be ethically and scientifically reviewed, and approved by a Human Research Ethics Committee (HREC) under the National Statement on Ethical Conduct in Human Research ( 8 ). They also need to fulfil institutional site specific governance requirements to be granted authorization to be conducted at that institution ( 9 ). Governance requirements predominantly involve research agreements between institutions, study related budgets and approvals from various levels of management. It is a requirement that the registry to support the RRCT has the appropriate ethics approvals and that permission to access the data for research purposes is in accordance with the registry ethics approval and the registry data access governance requirements ( 10 ). The potential benefits that RRCTs offer have been well documented across a number of reviews that have been conducted on RRCT implementation ( 11 , 12 ). These include: ease of recruitment, broad inclusion criteria, large sample size, long term follow up, generalizability of findings, and cost effectiveness ( 2 , 13 ). One study that demonstrated the true potential of RRCTs is the Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction (TASTE ) study ( 14 ). TASTE involved 7,400 patients and cost 10% of the budget of an equivalent conventional RCT. Such significant cost savings can be attributed to data collection and operational infrastructure already in place through existing registries. Further TASTE study cost savings, in comparison to conventional RCTs, are attributed to reduced trial-specific visits, site start-up expenses and trial monitoring requirements ( 11 ). RRCTs have the potential to inform and change clinical practice as demonstrated by the TASTE trial which resulted in a rapid decrease in the use of Thrombus Aspiration in STEMI patients undergoing Percutaneous Coronary Intervention(PCI) in Sweden ( 15 ). The Validate Swedeheart trial also demonstrated similar findings confirming that the efficacy of certain treatment choices were equal to their more expensive alternative ( 16 ). Despite their advantages, RRCTs have a number of limitations that are predominantly underpinned around the robustness of the registry and the registry data supporting them. The most commonly reported limitations are: insufficient or incomplete registry data, non uniformity of data collection ( 2 , 17 ) and access to registry data due to privacy issues ( 17 ). Previous reviews ( 2 , 13 , 18 ) found that a large number of RRCTs are being conducted in Scandinavian and North American countries where their research infrastructure and well established national registries with strong data linkage capabilities with external data sources are best suited to support such studies. In Australia, RRCTs represent less than one percent of the total RCTs registered on the Australian New Zealand Clinical Trial Register (ANZCTR) and this substantiates the findings by Ahern ( 18 ) and Yan et al. ( 19 ) that RRCTs are an emerging methodology and predominantly confined to non-commercial investigator or collaborative group led studies. In 2022, Ahern et al. searched the ANZCTR by using the search term “registry” and study type “interventional” and identified 20 trials using a registry to support the RCT in some capacity ( 18 ). Of these 20 trials, we ascertained that 16 would meet the broader criteria of an RRCT whereby the registry is used for either identifying, recruiting, randomizing or collecting trial outcomes ( 20 ). Studies that only used the registry for post trial follow up or confirmation of disease or treatment status were excluded. We conducted an updated search on ANZCTR in 2024 using the search term and variation of ‘ Registry Randomized Clinical Trials ’ and yielded 52 results. When each trial was further assessed against the RRCT definition above, only 11 trials met the criteria (Table 1 ). Some RRCT eligible studies that were captured in Ahern et al. ( 18 ) were not captured under our search terms and vice versa. Table 1 RRCT Registered on ANZCTR Discipline Study name Registry Use Sponsor/Funding Orthopaedic RASKAL ACTRN12621000205831 Study data collected in registry Philantropic Funds Orthopaedic Acronym not provided ACTRN12620001251910 Patients identified from registry Self Funded Nephrology SWIFT ACTRN12620001061921; ACTRN12618001976279 Patient feedback captured in registry Government Funded (NHMRC) Oncology PROpatient ACTRN12619001126101 Study data collected in registry Government Funded Neurology-stroke STELAR ACTRN12619001072101 Study data collected in registry Charity Funding Oncology-Upper GI ALLTRAC ACTRN12618001480279 Study Data collected in registry Collaborative Group Cardiology FAN Trial ACTRN12618001124224 Patients identified from registry Charity Funding Neurology-Stroke Prevent Second Stroke (P2S) ACTRN12617001205325 Patients recruited from registry Government Emergency Department RAPID-TnT ACTRN12615001379505 Study data collected in registry Collaborative Groups NHMRC Commercial Sponsor Support Urology No Acronym ACTRN12615001369516 PROMS collected in registry Government Funded Cardiac Surgery PORTICO-IDE Registered on clinicaltrials.gov NCT02000115 Patients identified from registry Commercially sponsored Ten RRCTs were non-commercially funded studies, predominantly being funded by the National Health and Medical Research Council (NHMRC) grants or by other government or philanthropic funds. The role of the registry was variable with patient identification, participant recruitment and study data collection being the prevalent use of the registry. Capturing all studies that may fall under the definition of an RRCT presents a number of challenges as not all RRCTs are registered under the banner of an RRCT or easily searchable by using commonly used search definitions for RRCTs. This is further compounded by the fact that not all studies are registered on ANZCTR. As such it is difficult to accurately estimate the number of RRCTs currently being conducted in Australia and more broadly internationally and does highlight the need for a more prescribed definition of what characteristics should attach to an RRCT, particularly around how a resgistry is employed. Objectives of study As RRCT is a relatively new clinical trial methodology, the need to gain greater understanding of the RRCT landscape in Australia is important in an effort to identify what is limiting uptake of this methodology. Given that RRCTs are governed by the same regulatory requirements of conventional RCTs which comprises ethical, governance and legal considerations, it is important to get the perspectives of a broad range of stakeholders to understand how this impacts RRCT uptake and implementation. The focus of our study is on stakeholders rather than on end-users acceptance and participation in RRCTs as this has been previously explored ( 21 ). Using a qualitative approach, this study aims to explore the RRCT landscape in Australia including current capacity and capabilities, and to identify challenges and opportunities for conducting RRCTs from the perspectives of clinicians, research administrators and research governance officers. This understanding will inform strategies that help to create greater awareness of RRCTs and to enhance RRCT acceptability and uptake in Australia and internationally. Methods Study design This study used a qualitative approach to capture the experience and attitudes of clinicians, research administrators and research governance officers in relation to RRCTs, considering their role at their respective hospital or academic institution. Semi-structured interviews with participants were conducted using an interview guide. The interview guide was designed to elicit an understanding of awareness, feasibility and acceptability of conducting RRCTs in Australia including potential barriers and enablers to effective RRCT implementation. Participants were invited to make additional comments to ensure that all topics they wished to discuss were covered. The qualitative study is reported in line with guidelines set out in consolidated criteria for reporting qualitative research (COREQ) ( 22 )(Appendix 1). Recruitment of participants Maximum variation sampling and snowballing were employed to identify and select eligible participants ( 23 ). This is a type of purposive sampling technique that aims to explore a wide range of perspectives. All participants were eligible for interview if they were involved in the conduct or support of clinical trials within a healthcare setting in Australia and internationally without the prerequisite of any current or prior direct experience with RRCTs. However, prior experience or association with supporting or administering clinical trials or a registry was considered essential to ensure that perspectives could be meaningful and informative. The eligible participants were defined by the nature of their association in supporting clinical trials or a registry at their respective institution as either a clinician researcher, research governance officer, registry/data custodian or research program manager. Hereafter the latter two profession classifications are broadly referred to as ‘research administrators’ . Australian participants were recruited from five major Melbourne Metropolitan Hospitals and two regional hospitals using well established clinician, governance officer and research administrator networks in place to identify eligible participants. International participants were identified through their publication output on RRCTs and were included to get an international perspective against the study aims and to ascertain degree of alignment with Australian perspectives. A total of 32 participants from Australia and 4 internationally were ultimately invited to participate via email, of which six did not respond despite follow up invites. Data collection Thirty interviews were undertaken between October 2020 and March 2023 by one researcher (BK) (BAppSc Hons in Medical Laboratory Science) who is a health research ethics and governance administrator undertaking their PhD investigating the Australian RRCT and registry landscape, including identifying the barriers and enablers for the uptake and implementation of RRCTs. Due to COVID-19 related social distancing requirements, most of the participants were interviewed via zoom with only eight interviews conducted face to face at a venue of their choice. Interviews averaged 35 minutes (range 15 to 85 mins) in length. All interviews were audio-recorded with the participant's consent. Interview recordings were transcribed verbatim by a professional transcription service and imported into QSR NVivo 12 coding and storing. Data analysis Participants were grouped into five categories as either RRCT Practitioners, RRCT Proficient, RRCT Aware, RRCT Beginner or RRCT Novice based on their understanding of the RRCT methodology concept, how they defined an RRCT and how a registry is able to support an RRCT (Table 2 ). This categorisation across all participant group helps capture their level of understanding, awareness and overall competency of this methodology and helps identify any variability across and within the participant groups. Table 2 RRCT competency categories Category Definition RRCT Practitioner Participants who were directly involved in the conduct of an RRCT or who currently or previously supported an RRCT through their role of employment and who could clearly articulate the concept and the various ways the registry could support an RRCT. They could name RRCTs that they were involved with. RRCT Proficient Participants who may have supported an RRCT through their role of employment and who articulated the various ways a registry could support an RRCT and could name a registry that has supported an RRCT. RRCT Aware Participants who were familiar with the concept and were able to articulate some of the aspects of how a registry can support an RRCT. No prior involvement with RRCTs. RRCT Beginner Participants who had some idea of what an RRCT was but were unable to clearly articulate the various ways a registry could be used to support an RRCT. They could not name any RRCTs. RRCT Novice Participants who had no awareness of RRCT methodology Themes were identified, analysed and reported within the data and across participant groups, using a combination of inductive and deductive coding as part of our thematic analysis ( 24 , 25 ). Two researchers (BK and KP) independently analysed five interview transcripts using a coding tree developed from the structure of the interview questions. The researchers’ resulting coding trees (theme lists) were compared and through further discussion between the researchers amended accordingly until consensus on an agreed coding tree was reached. The remaining interview transcripts were then coded by one researcher (BK), and emergent themes added as needed. Codes that were similar were clustered together and subsequently collapsed into emergent themes as part of the theme development and revision process and were only accepted once consensus was reached. Ethical considerations Ethical approval for this study was granted by the University of Melbourne, Medicine and Dentistry Human Research Ethics Sub-Committee (Ethics ID 1954874). Written consent was obtained from all participants prior to data collection to record and use their interview data. Results Participants Thirty (83%) of the 36 participants invited were interviewed. Table 3 shows the demographic characteristics of the participants. This included 18 clinicians across several specialties (two of which were also registry custodians and one part-time Chief Informatics Officer); six research administrators (two of which manage national data platforms); and six research governance officers within the Office for Research in a public health service overseeing ethics and governance of research at their respective institutions (one also administered registries). Participants exhibited varied levels of understanding around the RRCT methodology with clinicians showing the greatest RRCT awareness and research governance officers the least. Table 3 Participant Professional Classification and Competency Profession Gender Sub-speciality RRCT Competency 18 clinicians 12 Male, 6 Female 5 medical oncology 5 Practitioners 3 surgeons 3 Aware 10 others a 5 Practitioners, 2 Proficient, 3 Aware 6 research governance officers 2 Male, 4 Female 5 ethics/governance 2 Aware, 2 Minimal, 1 Novice 1 dual role (governance and research administrator) 1 Practitioner 6 research administrators 4 Male, 2 Female 4 Research Program Managers 2 Practitioner, 1 Proficient, 1 Aware 2 Data Managers 1 Aware, 1 Minimal a epidemiology, cardiology, neurology, intensive care, primary care, nephrology, health administration and paediatrics Themes Four overarching themes were identified from participant interview responses regarding their knowledge and awareness of: 1) the current registry and RRCT landscape in Australia; 2) enablers and barriers in the conduct of RRCTs; 3) ethical and governance issues impacting the conduct of RRCTs and; 4) strategies for the promotion, support and implementation of RRCTs in the future. The overarching themes and sub themes by registry and RRCT are presented separately in Table 4 . Table 4: Overarching themes and sub-themes Overarching themes Sub-themes Australian clinical registries and RRCT Landscape Registry RRCT Registry Funding Registries are not well supported or funded Registry data quality dependent on funding RRCT Awareness Variable awareness of RRCTs being conducted Awareness of RRCTs confined to within area of expertise Greatest awareness held by trialists and registry custodians Registry Type Most registries are clinical registries RRCT Definition RRCT Definition provided was broad and varied Consensus not to restrict RRCTs to a single definition RRCTs can be supported by a registry in many different ways Electronic Medical Records (EMR) EMR not suited to replace registries in near future Enablers Registry supporting RRCT Patient Identification and recruitment Collection of baseline and outcome data Facilitate long term follow up RRCT Benefits More efficient, simple and cost effective Greater external validity of trial outcomes Help answer questions of public health interest Barriers Registry Cost/Funding Registries expensive to establish and maintain Registries not adequately resourced or financed Predominanceof clinical registries RRCT Funding Not adequately funded Competing for participants by well-funded commercially sponsored RCTs Registry Limitations Registry data quality Lack of value proposition for all contributing to the registry Do not capture SAEs Not suitable end points collected RRCT Awareness Unknown methodology Registry Environment Registry steering committees not having a research focus Federated system RRCT Scope Not suited for novel/early phase clinical studies Ethics and Governance of Registries and RRCTs Registry Consent Opt out consent acceptable RRCT Consent Participant consent required due to randomization Registry Governance Cross jurisdictional registry governance requirements challenging-including access to registry data RRCT Governance Research governance bureaucracy prohibitive Burdensome research governance requirements for level of funding and trial risk profile Registry Ethics Current ethical review arrangements not a concern RRCT Ethical Review Current ethics requirements deemed appropriate Opportunity however to explore lesser review pathways based on trial risk profile Recommendations Education Educate registry steering committees to facilitate better access to registries for research purposes Education/ Awareness RRCT education and training to increase methodology understanding and awareness Government Support Government to prioritise funding and support for registries Government to guide a registry funding model involving all potential registry users/stakeholders Government support Government to prioritise funding and support for RRCTs Streamline ethical review of RRCTs based on risk profile Reduce governance administrative burden Harmonise jurisdictional research governance requirement RRCT activity as quality indicator for health services Institutional Support Embed RRCTs at an organizational level Theme 1: Understanding of the RRCT methodology and concept, and knowledge of the Australian clinical registry and RRCT landscape RRCT Definition The definition of an RRCT varied amongst all participants interviewed and was predominantly underpinned around the role of the registry in supporting the RRCT. Practitioner or Proficient level RRCT participants were more likely to define an RRCT as a trial that is supported by a robust registry that facilitates patient identification, recruitment or a collection of basic clinical and trial outcome data or a combination thereof. Randomisation could occur within or outside the registry. “I would describe them [RRCT] as, innovative, and pragmatic way of ensuring data from each patient is used wisely. I would say that to me, the gold standard for a registry-based trial would be a very clear, comprehensive, prospective registry that's already been built, already has the IT system, already has key players in the hospital system, involved and interested. And then from there to build a trial- a randomized trial into the registry allowing patients on the trial to be compared to patients that are already existing on the registry.” (Clinician 1) Aware and Beginner practitioners provided a broader definition of what an RRCT could be and were more likely to limit the role of the registry to either one of only identifying patients, recruiting patients or collecting an outcome(s) in the registry. Some participants declared complete ignorance. Overall, there was consensus that a registry can support an RRCT in many different ways and applying a strict definition could be counterproductive, and could potentially “cause trouble” because it would limit the scope of an RRCT. RRCT Awareness Awareness of what RRCTs were being conducted was variable amongst participants, with greater awareness held for trials that were conducted within their discipline of practice or where there was a close association with an institute or colleagues who were actively involved in conducting RRCTs. Even RRCT practitioners were relatively unfamiliar with Australian RRCTs outside of their own clinical discipline. Both research administrators (RA) and research governance officers (RGO) had “little knowledge” of RRCTs and were less likely to name an RRCT given their indirect involvement in supporting RRCTs. Clinicians that had an affiliation with a State or national registry were more likely to declare a greater level of RRCT awareness. Some participants across all stakeholder categories stated they had awareness of RRCTs being conducted but could not name a specific RRCT. Australian Registry landscape There was general consensus amongst the participants that clinical registries in Australia overall are not well organized and there are only a limited number of disease or procedure specific registries that are well funded and supported. These registries tend to be national registries that have been in place for many years. Most participants acknowledged that registry data quality was associated with the amount of funding and resourcing made available to a registry. Australia’s Federated system with its cross-jurisdictional regulatory variability was attributed by some as a significant reason why Australian registries are generally not well organized and supported. It was also noted that this is further compounded by the public-private health system divide and the overall data flow disconnect with primary care providers. “Yes, I would say so [level of maturity of Australian registries]. I don’t think that we’re as mature as some of those countries. We’ve certainly got a way to go. There are some great registries, but not many, and I think it’s still difficult to undertake for a lot of areas” (RGO: 1) Whereby it was acknowledged that Electronic Medical Records (EMR) could play a pivotal role in supporting RRCTs, the current state of play and variability in how EMRs are configured, implemented, supported and utilised across health services makes this a distant proposition. This will required a “major cultural change” and “many, many, many years to get there”. Theme 2: Enablers and barriers in the uptake and conduct of RRCTs Five enablers and six barriers were identified. RRCTs present a number of benefits predominantly around: being simple and efficient to conduct, have reduced trial related costs, provide generalisability of findings which is somewhat lacking in conventional RCTs and help answer questions of public health interest. However, RRCTs present a number of barriers which are associated with: inadequate funding and support for registries and RRCTs, recruitment challenges against novel trials, lack of awareness of methodology, not being suitable for early phase trials and burdensome governance processes. Enablers The majority of participants appreciated that RRCTs provide a number of advantages over conventional RCTs. Most participants see the simplicity, efficiency and cost effectiveness of RRCTs over conventional RCTs as one of their greatest attractions. They appreciated that RRCTs predominantly compare two standards of care, greatly enhance the generalizability of the trial findings, and offer public interest benefit unlike commercially sponsored RCTs as they are not underpinned around commercial imperatives. They acknowledged that well established registries should be able to accommodate patient identification, recruitment and collection of baseline and trial outcome data therefore negating further data collection forms and administrative workload. Participants also noted that the registry will provide more accurate participant numbers to assist with performing feasibility estimates. “You should run everything within the registry because the whole point of the registry is that you don't have to do anything extra, you can just simply use the patient's existing [data] collection within the registry to answer standard of care questions that would otherwise take a lot of effort to set up outside the registry” (Clinician 2) Barriers The majority of participants identified the lack of financial support to accommodate staffing and other resources for both registries and RRCTs as one of the biggest barriers in the conduct of RRCTs. Although RRCTs are considered to be more efficient to conduct than conventional RCTs, this was prefaced around an already existing and well supported registry being in place to support the RRCT. Furthermore, as most Australian registries are Clinical Quality Registries that support quality and safety initiatives, it was recognized that the data points they collect may not always be suitable to support an RRCT. Therefore the funding and resources required to establish and maintain a suitable high quality registry was recognized as one of the biggest challenges for RRCTs. The lack of substantive commercial sponsorship or a clear government funding agenda for registries and RRCTs more broadly was identified as contributing significantly to this. Lack of awareness and education around this methodology was identified by many participants as a limiting factor to the uptake of RRCTs. This was further compounded by the perception that an institution contributing to a multisite registry may not necessarily receive any direct benefit such as being part of a registry trial or being informed early on of RRCT outputs to help guide local clinical practice. It was well acknowledged that registries play a critical role in supporting an RRCT and can directly impact their uptake and how RRCTs are perceived. Given that the majority of registries are not built to capture and report on Serious Adverse Events it was acknowledged by most that RRCTs are not well suited to test novel therapies in early phases of clinical trial studies. This was identified as a potential deterrent for some clinicians who may only be interested in working with new drugs or devices. It was noted that this may influence clinicians in giving preference to a commercial RCT if an RRCT was also on offer therefore impacting RRCT recruitment capability. “I think that registries would be more appropriate for interventions that already have some reasonable phase one phase two data. […..] I think the amount of oversight you need to do for these first-in-man studies is probably over and above what a registry would provide.”(Clinician 3) The above limitations have the potential to relegate RRCTs predominantly to regional centres where there are fewer commercially sponsored RCTs being offered and where RRCTs are confined to a select group of clinicians who appreciate what they can offer. Theme 3: Ethical and governance requirements impacting the conduct of RRCTs Registry governance requirements associated with establishing a registry and collecting data, or seeking permission for access to registry data was identified as a significant barrier to the conduct of RRCTs. Opt out consent for participation in a registry was considered appropriate by most participants and this is consistent with current practice of participant enrolment in a registry. Registry and RRCT governance requirements were identified as being highly bureaucratic potentially discouraging clinicians from conducting RRCTs. Many participants felt that the governance burden associated with conducting RRCTs was disproportionate to the level of risk they presented. Some felt that the lack of national harmonization of the governance process for both registries and RRCTs further compounded the situation. Whilst there was collective agreement around the burden imposed by governance bureaucracy, the issue of ethics review of RRCTs provided a mixed response. A number of participants felt that current RRCT ethics review requirements were appropriate given that the methodology randomised patients across two intervention arms. Others felt that given that RRCTs were predominantly used to compare two standards of care, the risk profile of RRCTs could justify their review under a less rigorous review pathway such as the Low Risk Ethics Panel (LREP) process. Responses around participant consent did not change much even when a distinction between randomising participants or cluster randomisation was discussed. There was general consensus that some form of consent to participate in the RRCT was required due to the introduction of randomisation. Overall current ethics requirements were not identified as onerous or overly prohibitive but responses did highlight the opportunity to pursue a more simplified review pathway commensurate to the RRCT risk profile. “ So the question I would have is, is that truly an intervention? I would argue it's not, and if it's not, then I don't think it would have to go through high-risk ethics. That would be my feeling about them ”(Clinician 4) Theme 4: Recommendations for the promotion, support and implementation of RRCTs Participants acknowledged that RRCTs both globally and in Australia are an emerging methodology and provided the following suggestions that could help promote and increase the uptake of RRCTs in Australia: education and awareness, broad stakeholder engagement, government funding support and advocacy. Raising awareness and providing education opportunities would help advance the profile of RRCTs. This could be achieved in part by conducting and publishing further landmark studies and also leveraging off the validation provided by prior landmark studies like TASTE ( 14 ). As it is important to demonstrate that RRCTs can be impactful, an integral part of the education process would be to emphasise the importance that the research question and design of the RRCT must be simple and that the outcomes collected in the registry will help answer the research question and provide a clear health outcome. RRCTs that are too ambitious, complex or are not designed with due consideration to the registry limitations are set up to fail unless other workarounds are put in place. Education would be integral in ensuring that this research methodology is utilized in the best possible way in order to be impactful and to continue providing the methodology validation. It was also proposed that education would need to extend to registry steering committees which currently do not have a “research focus” and may therefore make accessing registry data for research purposes more difficult. Participants broadly acknowledged that RRCTs involve many and varied stakeholders that needed to be actively engaged. Ultimately RRCTs need to not only be embedded in the culture of a department but the institution as a whole and ultimately more broadly across the healthcare system. A national approach would be the ultimate goal. This will help address certain challenges around registry data quality, access to registry data, governance processes and consenting of patients into an RRCT. “The most important aspect of an embedded trial is it's one thing to embed it into the record, but you need to then embed it into the culture of the department. If you're going to rely on the clinician to consent, then all the clinicians have to agree that it's a worthwhile thing to do. It has to be embedded into the workflow, has to be embedded into the psyche of the clinicians, and it has to be embedded in the record. The embedding in the record is the easiest.” (Clinician 5) Participants proposed that Governments can assist with this by providing infrastructure support and funding of registries and RRCTs as a healthcare priority. It was acknowledged that in parts this was now been fulfilled through the Medical Research Future Fund (MRFF) offering grant opportunities to support RRCTs ( 26 ). Most participants noted that there is a role for government in helping develop a registry funding model that could seek contribution from the various public and private sector stakeholders toward sustainable registries that are well suited to support RRCTs. Discussion In this qualitative study, we explored the awareness, perceptions and understanding of the RRCT landscape in Australia, and perceived RRCT barriers and enablers across a range of stakeholders including clinicians, research governance officers and research administrators engaged either in the conduct or support of RRCTs. Our findings around RRCT recruitment challenges and barriers aligned with the findings from a qualitative study ( 21 ) exploring the feasibility and acceptability of RRCTs among cancer patients and clinicians. We identified that RRCT awareness and activity was widely variable and dependent on the institution the participants belonged to and their respective role. Clinicians from institutions with high clinical trial activities where more likely to define what an RRCT is correctly and to be aware of at least one RRCT being conducted in Australia. Research governance officers and research administrators were less likely to be able to define what an RRCT is and exhibited the least amount of RRCT awareness. They were more likely to provide non-specific responses to the questions asked, such as being able to name an RRCT or a registry that was used to support it. There was greater alignment amongst the participants in relation to RRCT barriers and enablers and potential strategies to address them. Promotion of RRCTs through education materials and workshops will help to inform and demonstrate the benefits of this methodology. The participants were not explicitly asked as to which entity should assume the role of education provider. However, entities that are well advanced in the conduct of RRCTs are possibly best placed to facilitate education and training around this methodology. In Australia, the Victorian Comprehensive Cancer Centre (VCCC) Alliance-Centre for Cancer Education has developed education materials on Registry Based Trials ( 27 ). Similarly, the Australian Clinical Trials Alliance (ACTA) has been promoting education workshops and forums around registry based trials ( 28 ). There was overall consensus that RRCTs are a valuable methodology in need of greater promotion and support as they help answer simple but important public health questions. This is underpinned by RRCTs, by recruiting real-world patients, having the benefit of integrating the internal validity of an RCT with the external validity of a clinical registry. This is consistent with findings from a number of publications promoting the ‘real world’ benefits of pragmatic trials, which are underpinned on the enhanced generalizability of their outcomes. ( 5 , 29 ) Inadequate funding and resources to support registries and RRCTs was one of the biggest barriers identified as impacting their uptake. As RRCTs are largely investigator initiated studies and are predominantly funded by non-commercial means, the role of government in establishing a funding model to ensure the sustainability of registries and RRCTs is important. As commercially sponsored RCTs are adequately funded, the lack of sustainable funding for registries and RRCTs can create reluctance by clinicians to commit to this new methodology. RRCTs registered on the ANZCTR (Table 1 ) confirm that ultimately RRCTs are initiated and conducted by clinicians and trialists who are truly committed to RRCTs and who are willing to expend the time and energy to pursue highly competitive grants, provide their own funds or pursue other non-commercial funding options to support them. This in turn creates the risk whereby RRCTs may be confined to a smaller number of trialists, therefore maintaining the status quo in relation to their uptake and accessibility. It was beyond the scope of the interviews to identify suitable funding models but this should be an area for further exploration. Government prioritising support for registries and RRCTs as part of the healthcare agenda would be a requisite step in facilitating their greater uptake. The Australian Government’s announcement of the Medical Research Future Fund (MRFF) 2023 Innovative Trials Guidelines which will provide $ 23.7 million Australian dollars toward innovative trials including RRCTs is a step in the right direction ( 26 ). This should provide the support needed to initiate a number of important and potentially landmark RRCTs that may further validate this methodology in Australia. There were some concerns expressed with current ethical review requirements for RRCTs. As RRCTs compare two accepted standards of care they could be considered for review by a Low Risk Ethics Panel rather than High Risk Ethics Panel, but consent for participation remains. This risk benefit approach is also consistent with what is being proposed by Andersen et al. ( 30 ), particularly where standard of care and already approved interventions are trialed. Califf et al. argued for the need to re-examine the regulatory and ethical landscape in which pragmatic trials are conducted in order to help facilitate their uptake ( 31 ). In Australia, the single ethical review process streamlines ethics review of trials and to some extent ameliorates potential cross jurisdictional discrepancies as single ethics review by any accredited HREC can be accepted across jurisdictions. Allocation of low risk RRCTs for review by LREPs will help expedite review of trials by institutions that only have a LREP and no HREC but may be best suited for single site studies at those sites as not all LREPs are adequately constituted to facilitate ethical review for multisite studies in the manner accredited HRECs currently do. This is an area that requires further exploration under the auspices of the NHMRC. Although ethical review of RRCTs presents no major concern, a significant challenge pertains to governance authorization and the bureaucracy associated with accessing registries, and the institutional governance authorisation requirements for approving the conduct of RRCTs at individual sites. The Australian research landscape is somewhat hindered by the Federation system under which certain aspects of research are governed by either Federal or State legislation creating governance process variability across jurisdictions resulting in an increased bureaucracy. Yan et al found that jurisdictional boundaries place limitations on RRCTs around data sharing and create the need for multiple approvals ( 19 ). The manner in which EMRs have been implemented across Australia is another prime example of the variability of a Federated system presents cross jurisdictions. Where EMRs could potentially one day in part assume the role of a registry this is inhibited to some extent by the variable EMR systems across the public health care sector. The role of Federal government in establishing a funding model for registries and RRCTs, and legislation/policies that provide provisions for addressing the governance challenges that arise from current arrangements would be highly welcomed and would help reduce the administrative burden for clinicians and trialists wanting to access registry data and initiate a multisite RRCT. The benefits gained from the streamlined single ethical review process are somewhat eroded by the persisting and mounting research governance challenges that need urgent attention, but should be used as an example of what can be achieved through good will, appropriate legislation and cooperation across all levels of government. Limitations One of the limitations of this study was the potential for selection bias as those interviewed were participants who were known to the author to be active in the clinical trial and registry environment. As we employed maximum variation sampling and snowballing to identify and select eligible participants we ran the risk of not including an adequate number of participants who were RRCT naïve. We were only able to interview one participant from a rural/regional setting and therefore findings from our metropolitan participants may not be representative of what is occurring in the regional centres. A follow up survey to a large and diverse clinical trial active workforce should provide good representativeness in this regard and help determine RRCT awareness and understanding across a number of cohorts and locations. We did not interview a number of other stakeholders that would support RRCTs, such as study coordinators and pharmacists. Conclusions RRCTs are an emerging methodology in Australia as awareness of the benefits they provide are progressively appreciated by clinicians and other stakeholders. Increasing awareness and providing education on this methodology are essential elements in ensuring that RRCTs capture the interest of clinicians and trialists and are therefore a consideration as the alternative methodology to the conventional RCT. Government support and prioritisation of establishing a sustainable funding model for both registries and RRCTs would greatly bridge the current gap. Abbreviations ACTA Australian Clinical Trials Alliance ANZCTR Australian and New Zealand Clinical Trial registry EMR Electronic Medical Record HREC Human Research Ethics Committee LREP Low Risk Ethics Panel MRFF Medical Research Future Fund NHMRC National Health and Medical Research Council PCI Percutaneous Coronary Intervention RA Research Administrator RCT Randomised Controlled Trial RGO Research Governance Officer RRCT Registry-based Randomised Controlled Trial STEMI ST-Elevation Myocardial Infarction TASTE Thrombus Aspiration in ST-Elevation VCCC Victorian Comprehensive Cancer Centre Declarations Ethics approval and consent to participate Ethical approval was granted by the Melbourne Health Human Research Ethics Committee Consent for publication Written informed consent, including the publication of anonymised quotes, were obtained from all participants prior to data collection. Availability of data and materials The datasets generated and analysed during the current study are not publicly available due to participants’ confidentiality. Competing interests The authors declare that they have no competing interests. Authors’ contributions BK developed interview questions and conducted all interviews BK collected the data. BK and KP analysed and interpreted the data. BK and KP drated the manuscript. All authors reviewed and approved final manuscript. Acknowledgements We wish to thank all the participants for generously sharing their experiences with us. References Tang M, Schaffer A, Pearson SA. Embracing the full spectrum of real-world data for cancer medicines research in Australia. Asia Pac J Clin Oncol. 2019;15(3):186-7. Karanatsios B, Prang KH, Verbunt E, Yeung JM, Kelaher M, Gibbs P. Defining key design elements of registry-based randomised controlled trials: a scoping review. Trials. 2020;21(1):552. Bergqvist D, Björck M, Säwe J, Troëng T. Randomized trials or population-based registries. Eur J Vasc Endovasc Surg. 2007;34(3):253-6. Califf RM, Sugarman J. Exploring the ethical and regulatory issues in pragmatic clinical trials. Clinical Trials. 2015;12(5):436-41. Barnish MS, Turner S. The value of pragmatic and observational studies in health care and public health. Pragmat Obs Res. 2017;8:49-55. Aljurf M, Rizzo JD, Mohty M, Hussain F, Madrigal A, Pasquini MC, et al. Challenges and opportunities for HSCT outcome registries: perspective from international HSCT registries experts. Bone Marrow Transplant. 2014;49(8):1016-21. Foroughi S, Wong HL, Gately L, Lee M, Simons K, Tie J, et al. Re-inventing the randomized controlled trial in medical oncology: The registry-based trial. Asia Pac J Clin Oncol. 2018;14(6):365-73. Human Research Ethics Committees (HRECs) review research proposals involving human participants to ensure that they are ethically acceptable: National Health and Medical Research Council; 2022 [Available from: https://www.nhmrc.gov.au/research-policy/ethics/human-research-ethics-committees. Research Governance and Site Specific Assessment: Victorian Department of Health; 2024 [Available from: https://www.clinicaltrialsandresearch.vic.gov.au/__data/assets/pdf_file/0020/171146/Research-Governance-SSA-Process-and-Practice.-March-2024.pdf. Purple Translational Registry: WEHI; 2024 [Available from: https://purplepancreas.pixo.com.au/page/83/registry-data-projects. James S, Rao SV, Granger CB. Registry-based randomized clinical trials--a new clinical trial paradigm. Nat Rev Cardiol. 2015;12(5):312-6. Lauer MS, D'Agostino RB, Sr. The randomized registry trial--the next disruptive technology in clinical research? N Engl J Med. 2013;369(17):1579-81. Baba A, Tay J, Sammy A, Douglas WA, Goren K, Krause KR, et al. Paper I: Heterogeneous use of registry data for participant identification and primary outcome ascertainment is found in registry-based randomized controlled trials: A scoping review. J Clin Epidemiol. 2023;159:289-99. Frobert O, Lagerqvist B, Olivecrona GK, Omerovic E, Gudnason T, Maeng M, et al. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med. 2013;369(17):1587-97. Buccheri S, Sarno G, Fröbert O, Gudnason T, Lagerqvist B, Lindholm D, et al. Assessing the Nationwide Impact of a Registry-Based Randomized Clinical Trial on Cardiovascular Practice. Circ Cardiovasc Interv. 2019;12(3):e007381. Erlinge D, Koul S, Eriksson P, Scherstén F, Omerovic E, Linder R, et al. Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial). Am Heart J. 2016;175:36-46. Krause KR, Tay J, Douglas WA, Sammy A, Baba A, Goren K, et al. Paper II: thematic framework analysis of registry-based randomized controlled trials provided insights for designing trial ready registries. J Clin Epidemiol. 2023;159:330-43. Ahern S, Gabbe BJ, Green S, Hodgson CL, Wood EM, Zalcberg Oam JR, et al. Realising the potential: leveraging clinical quality registries for real world clinical research. Med J Aust. 2022;216(6):273-7. Yan MK, Adler NR, Heriot N, Shang C, Zalcberg JR, Evans S, et al. Opportunities and barriers for the use of Australian cancer registries as platforms for randomized clinical trials. Asia Pac J Clin Oncol. 2022;18(4):344-52. Li G, Sajobi TT, Menon BK, Korngut L, Lowerison M, James M, et al. Registry-based randomized controlled trials- what are the advantages, challenges, and areas for future research? J Clin Epidemiol. 2016;80:16-24. Prang KH, Karanatsios B, Zhang A, Verbunt E, Wong HL, Wong V, et al. "Nothing to lose and the possibility of gaining": a qualitative study on the feasibility and acceptability of registry-based randomised controlled trials among cancer patients and clinicians. Trials. 2023;24(1):92. Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. International Journal for Quality in Health Care. 2007;19(6):349-57. Nyimbili F, Nyimbili L. Types of Purposive Sampling Techniques with Their Examples and Application in Qualitative Research Studies. British Journal of Multidisciplinary and Advanced Studies. 2024;5(1):90-9. Braun V CV. Using thematic analysis in psychology. . Qual Res Psychol. 2006;3(2):77-101. Fereday J M-CE. Demonstrating rigor usimg thematic analysis: A hybrid approach of inductive and deductive coding and theme development. Int J Qual Methods. 2006;5(1):80-9. National Critical Research Infrastructure Initiative-2023 Innovative Trials: Australian Government-Medical Research Future Fund; 2023 [Available from: https://www.grants.gov.au/Fo/Show?FoUuid=f54f2ea2-3a5d-48f0-84c9-8e23862f004a. Registry Based Trials: Victorian Comprehensive Cancer Centre Alliance (VCCC); 2023 [Available from: https://vcccalliance.org.au/research/clinical-trial-innovations/registry-trials/. Registry Randomised Trials Workshop: Australian Clinical Trials Alliance(ACTA) 2020 [Available from: https://clinicaltrialsalliance.org.au/?s=registry+trials. Newman AB, Avilés-Santa ML, Anderson G, Heiss G, Howard WJ, Krucoff M, et al. Embedding clinical interventions into observational studies. Contemp Clin Trials. 2016;46:100-5. Anderson ML, Califf RM, Sugarman J. Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems. Clin Trials. 2015;12(3):276-86. Califf RM, Sugarman J. Exploring the ethical and regulatory issues in pragmatic clinical trials. Clin Trials. 2015;12(5):436-41. Supplementary Files Appendix1ISSMCOREQChecklist.pdf Cite Share Download PDF Status: Published Journal Publication published 18 Dec, 2024 Read the published version in Trials → Version 1 posted Editorial decision: Minor revision 17 Oct, 2024 Reviewers agreed at journal 26 Jun, 2024 Reviewers invited by journal 24 Jun, 2024 Editor assigned by journal 24 Jun, 2024 First submitted to journal 20 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4614839","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":318373002,"identity":"8a4dde86-2b22-4ccb-a16d-230e4d26639a","order_by":0,"name":"Bill Karanatsios","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEUlEQVRIie2Rv0rEQBCHZ0m7sK0i5F5hlgNBOMyr5BC8Jv6r1TNH4GzyAAt5iVRWFnssXJp7gAUF10YbC9OluEJ39SpzCXYi+1UzO3zM/FgAj+cPEgXBTJL5pkUABrRb4RlJJcldTVKr7KY9CkqriI3iXvq23FqlPDxjRfb63JyPoqE+kVDfXwMT8ZYsVjFHB+JxyTOKx+M7fRoT8VLBjm5XvrKYAEHHPANU8f5DggGVS4AtCip32A0O9KSeNaiiYfGtDDoVoRB1wlP62ZZ7TrkC7DpsnFfIdXJR2Czi6Q0XQkrKV6Y9PlMLU88vMdSTsm7Wo4jlK27e5TQMq/Ytjh8jCaB6fqeF6a8Nj8fj+bd8AKQdaQFnKjg3AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0681-5986","institution":"Western Health","correspondingAuthor":true,"prefix":"","firstName":"Bill","middleName":"","lastName":"Karanatsios","suffix":""},{"id":318373003,"identity":"877afc74-e5d0-4713-9c52-536b4bc5d336","order_by":1,"name":"Khic-Houy Prang","email":"","orcid":"","institution":"University of Melbourne School of Population Health: The University of Melbourne School of Population and Global Health","correspondingAuthor":false,"prefix":"","firstName":"Khic-Houy","middleName":"","lastName":"Prang","suffix":""},{"id":318373004,"identity":"5d54d2c7-aae2-4ac3-afad-ce7c021d287a","order_by":2,"name":"Peter Gibbs","email":"","orcid":"","institution":"Walter and Eliza Hall Institute of Medical Research","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Gibbs","suffix":""},{"id":318373005,"identity":"362e36ca-a5e8-4318-b642-f0586c1ed31a","order_by":3,"name":"Justin Yeung","email":"","orcid":"","institution":"The University of Melbourne Faculty of Medicine Dentistry and Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Justin","middleName":"","lastName":"Yeung","suffix":""}],"badges":[],"createdAt":"2024-06-21 04:35:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4614839/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4614839/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13063-024-08668-8","type":"published","date":"2024-12-18T15:57:48+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":72202409,"identity":"b7b58798-b070-4563-b183-8a66e8061ec1","added_by":"auto","created_at":"2024-12-23 16:14:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":704445,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4614839/v1/c6af5b66-d858-46c3-b976-60ec53e9a0ac.pdf"},{"id":60382525,"identity":"cc313d42-01ad-4662-9a19-ba57692f7c68","added_by":"auto","created_at":"2024-07-16 07:28:27","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":425935,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix1ISSMCOREQChecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4614839/v1/874a7dcb2b20a7b8f1367deb.pdf"}],"financialInterests":"","formattedTitle":"A qualitative study exploring stakeholders’ perceptions of registry-based randomised controlled trials capacity and capability in Australia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRandomised controlled trials (RCTs) are considered the gold standard for evaluating the effectiveness of interventions in clinical research (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Traditional RCTs are expensive and complex to perform. They enrol a highly selected population through strict inclusion criteria, impacting their generalisability with a high proportion of trials failing to meet recruitment goals (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlternative research methodologies have been developed in pursuit of more affordable and generalisable high-quality clinical evidence (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). One such alternative methodology is the registry-based randomised controlled trial (RRCT). RRCTs encompass a broad and varied definition whereby data is obtained from or collected into a registry. A registry is defined as \u0026ldquo;an organised system that uses observational study methods to collect uniform data to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure\u0026rdquo;(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). A registry can support an RRCT in various ways, including by facilitating participant identification, participant recruitment, or capture of patient detail and outcome measures in the registry. Participant randomisation can occur either within or outside the registry. RRCTs share a number of common features with RCTs such as patient stratification and randomisation (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), but depending on what role the registry plays, they are usually best suited for testing hypotheses involving approved clinical interventions for which there are uncertainties about the optimal sequence, duration or combination of standard-of-care treatment, or where multiple standard-of-care options exist that have not previously been compared head to head (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAll RRCTs in Australia must be ethically and scientifically reviewed, and approved by a Human Research Ethics Committee (HREC) under the National Statement on Ethical Conduct in Human Research (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). They also need to fulfil institutional site specific governance requirements to be granted authorization to be conducted at that institution (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Governance requirements predominantly involve research agreements between institutions, study related budgets and approvals from various levels of management. It is a requirement that the registry to support the RRCT has the appropriate ethics approvals and that permission to access the data for research purposes is in accordance with the registry ethics approval and the registry data access governance requirements (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe potential benefits that RRCTs offer have been well documented across a number of reviews that have been conducted on RRCT implementation (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). These include: ease of recruitment, broad inclusion criteria, large sample size, long term follow up, generalizability of findings, and cost effectiveness (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). One study that demonstrated the true potential of RRCTs is the \u003cem\u003eThrombus Aspiration during ST-Segment Elevation Myocardial Infarction (TASTE\u003c/em\u003e) study (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). TASTE involved 7,400 patients and cost 10% of the budget of an equivalent conventional RCT. Such significant cost savings can be attributed to data collection and operational infrastructure already in place through existing registries. Further TASTE study cost savings, in comparison to conventional RCTs, are attributed to reduced trial-specific visits, site start-up expenses and trial monitoring requirements (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). RRCTs have the potential to inform and change clinical practice as demonstrated by the TASTE trial which resulted in a rapid decrease in the use of Thrombus Aspiration in STEMI patients undergoing Percutaneous Coronary Intervention(PCI) in Sweden (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The Validate Swedeheart trial also demonstrated similar findings confirming that the efficacy of certain treatment choices were equal to their more expensive alternative (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite their advantages, RRCTs have a number of limitations that are predominantly underpinned around the robustness of the registry and the registry data supporting them. The most commonly reported limitations are: insufficient or incomplete registry data, non uniformity of data collection (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) and access to registry data due to privacy issues (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Previous reviews (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) found that a large number of RRCTs are being conducted in Scandinavian and North American countries where their research infrastructure and well established national registries with strong data linkage capabilities with external data sources are best suited to support such studies.\u003c/p\u003e \u003cp\u003eIn Australia, RRCTs represent less than one percent of the total RCTs registered on the Australian New Zealand Clinical Trial Register (ANZCTR) and this substantiates the findings by Ahern (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) and Yan et al. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) that RRCTs are an emerging methodology and predominantly confined to non-commercial investigator or collaborative group led studies. In 2022, Ahern et al. searched the ANZCTR by using the search term \u0026ldquo;registry\u0026rdquo; and study type \u0026ldquo;interventional\u0026rdquo; and identified 20 trials using a registry to support the RCT in some capacity (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Of these 20 trials, we ascertained that 16 would meet the broader criteria of an RRCT whereby the registry is used for either identifying, recruiting, randomizing or collecting trial outcomes (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Studies that only used the registry for post trial follow up or confirmation of disease or treatment status were excluded. We conducted an updated search on ANZCTR in 2024 using the search term and variation of \u0026lsquo;\u003cem\u003eRegistry Randomized Clinical Trials\u003c/em\u003e\u0026rsquo; and yielded 52 results. When each trial was further assessed against the RRCT definition above, only 11 trials met the criteria (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Some RRCT eligible studies that were captured in Ahern et al. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) were not captured under our search terms and vice versa.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRRCT Registered on ANZCTR\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiscipline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudy name\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRegistry Use\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSponsor/Funding\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrthopaedic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRASKAL\u003c/p\u003e \u003cp\u003eACTRN12621000205831\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy data collected in registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePhilantropic Funds\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrthopaedic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcronym not provided\u003c/p\u003e \u003cp\u003eACTRN12620001251910\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients identified from registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSelf Funded\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNephrology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSWIFT\u003c/p\u003e \u003cp\u003eACTRN12620001061921;\u003c/p\u003e \u003cp\u003eACTRN12618001976279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient feedback captured in registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGovernment Funded (NHMRC)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOncology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePROpatient\u003c/p\u003e \u003cp\u003eACTRN12619001126101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy data collected in registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGovernment Funded\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurology-stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSTELAR\u003c/p\u003e \u003cp\u003eACTRN12619001072101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy data collected in registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCharity Funding\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOncology-Upper GI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALLTRAC\u003c/p\u003e \u003cp\u003eACTRN12618001480279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy Data collected in registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCollaborative Group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFAN Trial\u003c/p\u003e \u003cp\u003eACTRN12618001124224\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients identified from registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCharity Funding\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurology-Stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrevent Second Stroke (P2S)\u003c/p\u003e \u003cp\u003eACTRN12617001205325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients recruited from registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGovernment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmergency Department\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRAPID-TnT\u003c/p\u003e \u003cp\u003eACTRN12615001379505\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy data collected in registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCollaborative Groups\u003c/p\u003e \u003cp\u003eNHMRC\u003c/p\u003e \u003cp\u003eCommercial Sponsor Support\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo Acronym\u003c/p\u003e \u003cp\u003eACTRN12615001369516\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePROMS collected in registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGovernment Funded\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac Surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePORTICO-IDE\u003c/p\u003e \u003cp\u003eRegistered on clinicaltrials.gov\u003c/p\u003e \u003cp\u003eNCT02000115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients identified from registry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommercially sponsored\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTen RRCTs were non-commercially funded studies, predominantly being funded by the National Health and Medical Research Council (NHMRC) grants or by other government or philanthropic funds. The role of the registry was variable with patient identification, participant recruitment and study data collection being the prevalent use of the registry. Capturing all studies that may fall under the definition of an RRCT presents a number of challenges as not all RRCTs are registered under the banner of an RRCT or easily searchable by using commonly used search definitions for RRCTs. This is further compounded by the fact that not all studies are registered on ANZCTR. As such it is difficult to accurately estimate the number of RRCTs currently being conducted in Australia and more broadly internationally and does highlight the need for a more prescribed definition of what characteristics should attach to an RRCT, particularly around how a resgistry is employed.\u003c/p\u003e \u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003eObjectives of study\u003c/h2\u003e \u003cp\u003eAs RRCT is a relatively new clinical trial methodology, the need to gain greater understanding of the RRCT landscape in Australia is important in an effort to identify what is limiting uptake of this methodology. Given that RRCTs are governed by the same regulatory requirements of conventional RCTs which comprises ethical, governance and legal considerations, it is important to get the perspectives of a broad range of stakeholders to understand how this impacts RRCT uptake and implementation. The focus of our study is on stakeholders rather than on end-users acceptance and participation in RRCTs as this has been previously explored (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eUsing a qualitative approach, this study aims to explore the RRCT landscape in Australia including current capacity and capabilities, and to identify challenges and opportunities for conducting RRCTs from the perspectives of clinicians, research administrators and research governance officers. This understanding will inform strategies that help to create greater awareness of RRCTs and to enhance RRCT acceptability and uptake in Australia and internationally.\u003c/p\u003e \u003c/div\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis study used a qualitative approach to capture the experience and attitudes of clinicians, research administrators and research governance officers in relation to RRCTs, considering their role at their respective hospital or academic institution. Semi-structured interviews with participants were conducted using an interview guide. The interview guide was designed to elicit an understanding of awareness, feasibility and acceptability of conducting RRCTs in Australia including potential barriers and enablers to effective RRCT implementation. Participants were invited to make additional comments to ensure that all topics they wished to discuss were covered. The qualitative study is reported in line with guidelines set out in consolidated criteria for reporting qualitative research (COREQ) (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)(Appendix 1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eRecruitment of participants\u003c/h2\u003e \u003cp\u003eMaximum variation sampling and snowballing were employed to identify and select eligible participants (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). This is a type of purposive sampling technique that aims to explore a wide range of perspectives. All participants were eligible for interview if they were involved in the conduct or support of clinical trials within a healthcare setting in Australia and internationally without the prerequisite of any current or prior direct experience with RRCTs. However, prior experience or association with supporting or administering clinical trials or a registry was considered essential to ensure that perspectives could be meaningful and informative. The eligible participants were defined by the nature of their association in supporting clinical trials or a registry at their respective institution as either a clinician researcher, research governance officer, registry/data custodian or research program manager. Hereafter the latter two profession classifications are broadly referred to as \u003cem\u003e\u0026lsquo;research administrators\u0026rsquo;\u003c/em\u003e. Australian participants were recruited from five major Melbourne Metropolitan Hospitals and two regional hospitals using well established clinician, governance officer and research administrator networks in place to identify eligible participants. International participants were identified through their publication output on RRCTs and were included to get an international perspective against the study aims and to ascertain degree of alignment with Australian perspectives. A total of 32 participants from Australia and 4 internationally were ultimately invited to participate via email, of which six did not respond despite follow up invites.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eThirty interviews were undertaken between October 2020 and March 2023 by one researcher (BK) (BAppSc Hons in Medical Laboratory Science) who is a health research ethics and governance administrator undertaking their PhD investigating the Australian RRCT and registry landscape, including identifying the barriers and enablers for the uptake and implementation of RRCTs. Due to COVID-19 related social distancing requirements, most of the participants were interviewed via zoom with only eight interviews conducted face to face at a venue of their choice. Interviews averaged 35 minutes (range 15 to 85 mins) in length. All interviews were audio-recorded with the participant's consent. Interview recordings were transcribed verbatim by a professional transcription service and imported into QSR NVivo 12 coding and storing.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eParticipants were grouped into five categories as either RRCT Practitioners, RRCT Proficient, RRCT Aware, RRCT Beginner or RRCT Novice based on their understanding of the RRCT methodology concept, how they defined an RRCT and how a registry is able to support an RRCT (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This categorisation across all participant group helps capture their level of understanding, awareness and overall competency of this methodology and helps identify any variability across and within the participant groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRRCT competency categories\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDefinition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRRCT Practitioner\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParticipants who were directly involved in the conduct of an RRCT or who currently or previously supported an RRCT through their role of employment and who could clearly articulate the concept and the various ways the registry could support an RRCT. They could name RRCTs that they were involved with.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRRCT Proficient\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParticipants who may have supported an RRCT through their role of employment and who articulated the various ways a registry could support an RRCT and could name a registry that has supported an RRCT.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRRCT Aware\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParticipants who were familiar with the concept and were able to articulate some of the aspects of how a registry can support an RRCT. No prior involvement with RRCTs.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRRCT Beginner\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParticipants who had some idea of what an RRCT was but were unable to clearly articulate the various ways a registry could be used to support an RRCT. They could not name any RRCTs.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRRCT Novice\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParticipants who had no awareness of RRCT methodology\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThemes were identified, analysed and reported within the data and across participant groups, using a combination of inductive and deductive coding as part of our thematic analysis (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Two researchers (BK and KP) independently analysed five interview transcripts using a coding tree developed from the structure of the interview questions. The researchers\u0026rsquo; resulting coding trees (theme lists) were compared and through further discussion between the researchers amended accordingly until consensus on an agreed coding tree was reached. The remaining interview transcripts were then coded by one researcher (BK), and emergent themes added as needed. Codes that were similar were clustered together and subsequently collapsed into emergent themes as part of the theme development and revision process and were only accepted once consensus was reached.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEthical considerations\u003c/h2\u003e \u003cp\u003eEthical approval for this study was granted by the University of Melbourne, Medicine and Dentistry Human Research Ethics Sub-Committee (Ethics ID 1954874). Written consent was obtained from all participants prior to data collection to record and use their interview data.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eThirty (83%) of the 36 participants invited were interviewed. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the demographic characteristics of the participants. This included 18 clinicians across several specialties (two of which were also registry custodians and one part-time Chief Informatics Officer); six research administrators (two of which manage national data platforms); and six research governance officers within the Office for Research in a public health service overseeing ethics and governance of research at their respective institutions (one also administered registries). Participants exhibited varied levels of understanding around the RRCT methodology with clinicians showing the greatest RRCT awareness and research governance officers the least.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eParticipant Professional Classification and Competency\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProfession\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSub-speciality\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRRCT Competency\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003e18 clinicians\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e12 Male,\u003c/p\u003e \u003cp\u003e6 Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 medical oncology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 Practitioners\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 surgeons\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 Aware\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 others\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 Practitioners, 2 Proficient, 3 Aware\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e6 research governance officers\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2 Male,\u003c/p\u003e \u003cp\u003e4 Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 ethics/governance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 Aware, 2 Minimal, 1 Novice\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 dual role (governance and research administrator)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 Practitioner\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e6 research administrators\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e4 Male,\u003c/p\u003e \u003cp\u003e2 Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 Research Program Managers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 Practitioner, 1 Proficient, 1 Aware\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 Data Managers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 Aware, 1 Minimal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003ea\u003c/sup\u003e epidemiology, cardiology, neurology, intensive care, primary care, nephrology, health administration and paediatrics\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eThemes\u003c/h2\u003e \u003cp\u003eFour overarching themes were identified from participant interview responses regarding their knowledge and awareness of: 1) the current registry and RRCT landscape in Australia; 2) enablers and barriers in the conduct of RRCTs; 3) ethical and governance issues impacting the conduct of RRCTs and; 4) strategies for the promotion, support and implementation of RRCTs in the future. The overarching themes and sub themes by registry and RRCT are presented separately in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eTable 4: Overarching themes and sub-themes\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverarching themes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"80.8080808080808%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSub-themes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.19191919191919%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAustralian clinical registries and RRCT Landscape\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"40.4040404040404%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegistry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"40.4040404040404%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRRCT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.050632911392405%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegistry Funding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.31645569620253%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eRegistries are not well supported or funded\u003c/li\u003e\n \u003cli\u003eRegistry data quality dependent on funding\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.31645569620253%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRRCT Awareness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.31645569620253%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eVariable awareness of RRCTs being conducted\u003c/li\u003e\n \u003cli\u003eAwareness of RRCTs confined to within area of expertise\u003c/li\u003e\n \u003cli\u003eGreatest awareness held by trialists and registry custodians\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.050632911392405%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegistry Type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.31645569620253%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eMost registries are clinical registries\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.31645569620253%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRRCT Definition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.31645569620253%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eRRCT Definition provided was broad and varied\u003c/li\u003e\n \u003cli\u003eConsensus not to restrict RRCTs to a single definition\u003c/li\u003e\n \u003cli\u003eRRCTs can be supported by a registry in many different ways\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.050632911392405%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eElectronic Medical Records (EMR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.31645569620253%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eEMR not suited to replace registries in near future\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.31645569620253%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.31645569620253%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.19191919191919%\" valign=\"top\"\u003e\n \u003cp\u003eEnablers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegistry supporting RRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003ePatient Identification and recruitment\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCollection of baseline and outcome data\u003c/li\u003e\n \u003cli\u003eFacilitate long term follow up\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRRCT Benefits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eMore efficient, simple and cost effective\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGreater external validity of trial outcomes\u003c/li\u003e\n \u003cli\u003eHelp answer questions of public health interest\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.19191919191919%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eBarriers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegistry Cost/Funding\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eRegistries expensive to establish and maintain\u003c/li\u003e\n \u003cli\u003eRegistries not adequately resourced or financed\u003c/li\u003e\n \u003cli\u003ePredominanceof clinical registries\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRRCT Funding\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eNot adequately funded\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCompeting for participants by well-funded commercially sponsored RCTs\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegistry Limitations\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eRegistry data quality\u003c/li\u003e\n \u003cli\u003eLack of value proposition for all contributing to the registry\u003c/li\u003e\n \u003cli\u003eDo not capture SAEs\u003c/li\u003e\n \u003cli\u003eNot suitable end points collected\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRRCT Awareness\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eUnknown methodology\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegistry Environment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eRegistry steering committees not having a research focus\u003c/li\u003e\n \u003cli\u003eFederated system\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRRCT Scope\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eNot suited for novel/early phase clinical studies\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.19191919191919%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eEthics and Governance of Registries and RRCTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegistry Consent\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eOpt out consent acceptable\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRRCT Consent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eParticipant consent required due to randomization\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegistry Governance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eCross jurisdictional registry governance requirements challenging-including access to registry data\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRRCT Governance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eResearch governance bureaucracy prohibitive\u003c/li\u003e\n \u003cli\u003eBurdensome research governance requirements for level of funding and trial risk profile\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegistry Ethics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eCurrent ethical review arrangements not a concern\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRRCT Ethical Review\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eCurrent ethics requirements deemed appropriate\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOpportunity however to explore lesser review pathways based on trial risk profile\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.19191919191919%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eRecommendations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eEducation\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eEducate registry steering committees to facilitate better access to registries for research purposes\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eEducation/ Awareness\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2020202020202%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eRRCT education and training to increase methodology understanding and awareness\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGovernment Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eGovernment to prioritise funding and support for registries\u003c/li\u003e\n \u003cli\u003eGovernment to guide a registry funding model involving all potential registry users/stakeholders\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGovernment support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eGovernment to prioritise funding and support for RRCTs\u003c/li\u003e\n \u003cli\u003eStreamline ethical review of RRCTs based on risk profile\u003c/li\u003e\n \u003cli\u003eReduce governance administrative burden\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHarmonise jurisdictional research governance requirement\u003c/li\u003e\n \u003cli\u003eRRCT activity as quality indicator for health services\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eInstitutional Support\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eEmbed RRCTs at an organizational level\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cp\u003e \u003cem\u003eTheme 1: Understanding of the RRCT methodology and concept, and knowledge of the Australian clinical registry and RRCT landscape\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eRRCT Definition\u003c/h2\u003e \u003cp\u003eThe definition of an RRCT varied amongst all participants interviewed and was predominantly underpinned around the role of the registry in supporting the RRCT. \u003cem\u003ePractitioner\u003c/em\u003e or \u003cem\u003eProficient\u003c/em\u003e level RRCT participants were more likely to define an RRCT as a trial that is supported by a robust registry that facilitates patient identification, recruitment or a collection of basic clinical and trial outcome data or a combination thereof. Randomisation could occur within or outside the registry.\u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;I would describe them [RRCT] as, innovative, and pragmatic way of ensuring data from each patient is used wisely. I would say that to me, the gold standard for a registry-based trial would be a very clear, comprehensive, prospective registry that's already been built, already has the IT system, already has key players in the hospital system, involved and interested. And then from there to build a trial- a randomized trial into the registry allowing patients on the trial to be compared to patients that are already existing on the registry.\u0026rdquo; (Clinician 1)\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eAware\u003c/em\u003e and \u003cem\u003eBeginner\u003c/em\u003e practitioners provided a broader definition of what an RRCT could be and were more likely to limit the role of the registry to either one of only identifying patients, recruiting patients or collecting an outcome(s) in the registry. Some participants declared complete ignorance. Overall, there was consensus that a registry can support an RRCT in many different ways and applying a strict definition could be counterproductive, and could potentially \u0026ldquo;cause trouble\u0026rdquo; because it would limit the scope of an RRCT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eRRCT Awareness\u003c/h2\u003e \u003cp\u003eAwareness of what RRCTs were being conducted was variable amongst participants, with greater awareness held for trials that were conducted within their discipline of practice or where there was a close association with an institute or colleagues who were actively involved in conducting RRCTs. Even RRCT practitioners were relatively unfamiliar with Australian RRCTs outside of their own clinical discipline. Both research administrators (RA) and research governance officers (RGO) had \u0026ldquo;little knowledge\u0026rdquo; of RRCTs and were less likely to name an RRCT given their indirect involvement in supporting RRCTs. Clinicians that had an affiliation with a State or national registry were more likely to declare a greater level of RRCT awareness. Some participants across all stakeholder categories stated they had awareness of RRCTs being conducted but could not name a specific RRCT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eAustralian Registry landscape\u003c/h2\u003e \u003cp\u003eThere was general consensus amongst the participants that clinical registries in Australia overall are not well organized and there are only a limited number of disease or procedure specific registries that are well funded and supported. These registries tend to be national registries that have been in place for many years. Most participants acknowledged that registry data quality was associated with the amount of funding and resourcing made available to a registry. Australia\u0026rsquo;s Federated system with its cross-jurisdictional regulatory variability was attributed by some as a significant reason why Australian registries are generally not well organized and supported. It was also noted that this is further compounded by the public-private health system divide and the overall data flow disconnect with primary care providers.\u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;Yes, I would say so [level of maturity of Australian registries]. I don\u0026rsquo;t think that we\u0026rsquo;re as mature as some of those countries. We\u0026rsquo;ve certainly got a way to go. There are some great registries, but not many, and I think it\u0026rsquo;s still difficult to undertake for a lot of areas\u0026rdquo; (RGO: 1)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eWhereby it was acknowledged that Electronic Medical Records (EMR) could play a pivotal role in supporting RRCTs, the current state of play and variability in how EMRs are configured, implemented, supported and utilised across health services makes this a distant proposition. This will required a \u0026ldquo;major cultural change\u0026rdquo; and \u0026ldquo;many, many, many years to get there\u0026rdquo;.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eTheme 2: Enablers and barriers in the uptake and conduct of RRCTs\u003c/h2\u003e \u003cp\u003eFive enablers and six barriers were identified. RRCTs present a number of benefits predominantly around: being simple and efficient to conduct, have reduced trial related costs, provide generalisability of findings which is somewhat lacking in conventional RCTs and help answer questions of public health interest. However, RRCTs present a number of barriers which are associated with: inadequate funding and support for registries and RRCTs, recruitment challenges against novel trials, lack of awareness of methodology, not being suitable for early phase trials and burdensome governance processes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eEnablers\u003c/h2\u003e \u003cp\u003eThe majority of participants appreciated that RRCTs provide a number of advantages over conventional RCTs. Most participants see the simplicity, efficiency and cost effectiveness of RRCTs over conventional RCTs as one of their greatest attractions. They appreciated that RRCTs predominantly compare two standards of care, greatly enhance the generalizability of the trial findings, and offer public interest benefit unlike commercially sponsored RCTs as they are not underpinned around commercial imperatives. They acknowledged that well established registries should be able to accommodate patient identification, recruitment and collection of baseline and trial outcome data therefore negating further data collection forms and administrative workload. Participants also noted that the registry will provide more accurate participant numbers to assist with performing feasibility estimates.\u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;You should run everything within the registry because the whole point of the registry is that you don't have to do anything extra, you can just simply use the patient's existing [data] collection within the registry to answer standard of care questions that would otherwise take a lot of effort to set up outside the registry\u0026rdquo; (Clinician 2)\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eBarriers\u003c/h2\u003e \u003cp\u003eThe majority of participants identified the lack of financial support to accommodate staffing and other resources for both registries and RRCTs as one of the biggest barriers in the conduct of RRCTs. Although RRCTs are considered to be more efficient to conduct than conventional RCTs, this was prefaced around an already existing and well supported registry being in place to support the RRCT. Furthermore, as most Australian registries are Clinical Quality Registries that support quality and safety initiatives, it was recognized that the data points they collect may not always be suitable to support an RRCT. Therefore the funding and resources required to establish and maintain a suitable high quality registry was recognized as one of the biggest challenges for RRCTs. The lack of substantive commercial sponsorship or a clear government funding agenda for registries and RRCTs more broadly was identified as contributing significantly to this.\u003c/p\u003e \u003cp\u003eLack of awareness and education around this methodology was identified by many participants as a limiting factor to the uptake of RRCTs. This was further compounded by the perception that an institution contributing to a multisite registry may not necessarily receive any direct benefit such as being part of a registry trial or being informed early on of RRCT outputs to help guide local clinical practice.\u003c/p\u003e \u003cp\u003eIt was well acknowledged that registries play a critical role in supporting an RRCT and can directly impact their uptake and how RRCTs are perceived. Given that the majority of registries are not built to capture and report on Serious Adverse Events it was acknowledged by most that RRCTs are not well suited to test novel therapies in early phases of clinical trial studies. This was identified as a potential deterrent for some clinicians who may only be interested in working with new drugs or devices. It was noted that this may influence clinicians in giving preference to a commercial RCT if an RRCT was also on offer therefore impacting RRCT recruitment capability.\u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;I think that registries would be more appropriate for interventions that already have some reasonable phase one phase two data. [\u0026hellip;..] I think the amount of oversight you need to do for these first-in-man studies is probably over and above what a registry would provide.\u0026rdquo;(Clinician 3)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe above limitations have the potential to relegate RRCTs predominantly to regional centres where there are fewer commercially sponsored RCTs being offered and where RRCTs are confined to a select group of clinicians who appreciate what they can offer.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eTheme 3: Ethical and governance requirements impacting the conduct of RRCTs\u003c/h2\u003e \u003cp\u003eRegistry governance requirements associated with establishing a registry and collecting data, or seeking permission for access to registry data was identified as a significant barrier to the conduct of RRCTs. Opt out consent for participation in a registry was considered appropriate by most participants and this is consistent with current practice of participant enrolment in a registry.\u003c/p\u003e \u003cp\u003eRegistry and RRCT governance requirements were identified as being highly bureaucratic potentially discouraging clinicians from conducting RRCTs. Many participants felt that the governance burden associated with conducting RRCTs was disproportionate to the level of risk they presented. Some felt that the lack of national harmonization of the governance process for both registries and RRCTs further compounded the situation. Whilst there was collective agreement around the burden imposed by governance bureaucracy, the issue of ethics review of RRCTs provided a mixed response. A number of participants felt that current RRCT ethics review requirements were appropriate given that the methodology randomised patients across two intervention arms. Others felt that given that RRCTs were predominantly used to compare two standards of care, the risk profile of RRCTs could justify their review under a less rigorous review pathway such as the Low Risk Ethics Panel (LREP) process. Responses around participant consent did not change much even when a distinction between randomising participants or cluster randomisation was discussed. There was general consensus that some form of consent to participate in the RRCT was required due to the introduction of randomisation. Overall current ethics requirements were not identified as onerous or overly prohibitive but responses did highlight the opportunity to pursue a more simplified review pathway commensurate to the RRCT risk profile.\u003c/p\u003e \u003cp\u003e\u0026ldquo;\u003cem\u003eSo the question I would have is, is that truly an intervention? I would argue it's not, and if it's not, then I don't think it would have to go through high-risk ethics. That would be my feeling about them\u003c/em\u003e\u0026rdquo;(Clinician 4)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eTheme 4: Recommendations for the promotion, support and implementation of RRCTs\u003c/h2\u003e \u003cp\u003e Participants acknowledged that RRCTs both globally and in Australia are an emerging methodology and provided the following suggestions that could help promote and increase the uptake of RRCTs in Australia: education and awareness, broad stakeholder engagement, government funding support and advocacy.\u003c/p\u003e \u003cp\u003eRaising awareness and providing education opportunities would help advance the profile of RRCTs. This could be achieved in part by conducting and publishing further landmark studies and also leveraging off the validation provided by prior landmark studies like TASTE (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs it is important to demonstrate that RRCTs can be impactful, an integral part of the education process would be to emphasise the importance that the research question and design of the RRCT must be simple and that the outcomes collected in the registry will help answer the research question and provide a clear health outcome. RRCTs that are too ambitious, complex or are not designed with due consideration to the registry limitations are set up to fail unless other workarounds are put in place. Education would be integral in ensuring that this research methodology is utilized in the best possible way in order to be impactful and to continue providing the methodology validation. It was also proposed that education would need to extend to registry steering committees which currently do not have a \u0026ldquo;research focus\u0026rdquo; and may therefore make accessing registry data for research purposes more difficult.\u003c/p\u003e \u003cp\u003eParticipants broadly acknowledged that RRCTs involve many and varied stakeholders that needed to be actively engaged. Ultimately RRCTs need to not only be embedded in the culture of a department but the institution as a whole and ultimately more broadly across the healthcare system. A national approach would be the ultimate goal. This will help address certain challenges around registry data quality, access to registry data, governance processes and consenting of patients into an RRCT.\u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;The most important aspect of an embedded trial is it's one thing to embed it into the record, but you need to then embed it into the culture of the department. If you're going to rely on the clinician to consent, then all the clinicians have to agree that it's a worthwhile thing to do. It has to be embedded into the workflow, has to be embedded into the psyche of the clinicians, and it has to be embedded in the record. The embedding in the record is the easiest.\u0026rdquo; (Clinician 5)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eParticipants proposed that Governments can assist with this by providing infrastructure support and funding of registries and RRCTs as a healthcare priority. It was acknowledged that in parts this was now been fulfilled through the Medical Research Future Fund (MRFF) offering grant opportunities to support RRCTs (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Most participants noted that there is a role for government in helping develop a registry funding model that could seek contribution from the various public and private sector stakeholders toward sustainable registries that are well suited to support RRCTs.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this qualitative study, we explored the awareness, perceptions and understanding of the RRCT landscape in Australia, and perceived RRCT barriers and enablers across a range of stakeholders including clinicians, research governance officers and research administrators engaged either in the conduct or support of RRCTs. Our findings around RRCT recruitment challenges and barriers aligned with the findings from a qualitative study (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) exploring the feasibility and acceptability of RRCTs among cancer patients and clinicians.\u003c/p\u003e \u003cp\u003eWe identified that RRCT awareness and activity was widely variable and dependent on the institution the participants belonged to and their respective role. Clinicians from institutions with high clinical trial activities where more likely to define what an RRCT is correctly and to be aware of at least one RRCT being conducted in Australia. Research governance officers and research administrators were less likely to be able to define what an RRCT is and exhibited the least amount of RRCT awareness. They were more likely to provide non-specific responses to the questions asked, such as being able to name an RRCT or a registry that was used to support it.\u003c/p\u003e \u003cp\u003eThere was greater alignment amongst the participants in relation to RRCT barriers and enablers and potential strategies to address them. Promotion of RRCTs through education materials and workshops will help to inform and demonstrate the benefits of this methodology. The participants were not explicitly asked as to which entity should assume the role of education provider. However, entities that are well advanced in the conduct of RRCTs are possibly best placed to facilitate education and training around this methodology. In Australia, the Victorian Comprehensive Cancer Centre (VCCC) Alliance-Centre for Cancer Education has developed education materials on Registry Based Trials (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Similarly, the Australian Clinical Trials Alliance (ACTA) has been promoting education workshops and forums around registry based trials (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere was overall consensus that RRCTs are a valuable methodology in need of greater promotion and support as they help answer simple but important public health questions. This is underpinned by RRCTs, by recruiting real-world patients, having the benefit of integrating the internal validity of an RCT with the external validity of a clinical registry. This is consistent with findings from a number of publications promoting the \u0026lsquo;real world\u0026rsquo; benefits of pragmatic trials, which are underpinned on the enhanced generalizability of their outcomes. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eInadequate funding and resources to support registries and RRCTs was one of the biggest barriers identified as impacting their uptake. As RRCTs are largely investigator initiated studies and are predominantly funded by non-commercial means, the role of government in establishing a funding model to ensure the sustainability of registries and RRCTs is important. As commercially sponsored RCTs are adequately funded, the lack of sustainable funding for registries and RRCTs can create reluctance by clinicians to commit to this new methodology. RRCTs registered on the ANZCTR (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) confirm that ultimately RRCTs are initiated and conducted by clinicians and trialists who are truly committed to RRCTs and who are willing to expend the time and energy to pursue highly competitive grants, provide their own funds or pursue other non-commercial funding options to support them. This in turn creates the risk whereby RRCTs may be confined to a smaller number of trialists, therefore maintaining the status quo in relation to their uptake and accessibility. It was beyond the scope of the interviews to identify suitable funding models but this should be an area for further exploration. Government prioritising support for registries and RRCTs as part of the healthcare agenda would be a requisite step in facilitating their greater uptake. The Australian Government\u0026rsquo;s announcement of the \u003cem\u003eMedical Research Future Fund (MRFF) 2023 Innovative Trials Guidelines\u003c/em\u003e which will provide \u003cspan\u003e$\u003c/span\u003e23.7\u0026nbsp;million Australian dollars toward innovative trials including RRCTs is a step in the right direction (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). This should provide the support needed to initiate a number of important and potentially landmark RRCTs that may further validate this methodology in Australia.\u003c/p\u003e \u003cp\u003eThere were some concerns expressed with current ethical review requirements for RRCTs. As RRCTs compare two accepted standards of care they could be considered for review by a Low Risk Ethics Panel rather than High Risk Ethics Panel, but consent for participation remains. This risk benefit approach is also consistent with what is being proposed by Andersen et al. (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e), particularly where standard of care and already approved interventions are trialed. Califf et al. argued for the need to re-examine the regulatory and ethical landscape in which pragmatic trials are conducted in order to help facilitate their uptake (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). In Australia, the single ethical review process streamlines ethics review of trials and to some extent ameliorates potential cross jurisdictional discrepancies as single ethics review by any accredited HREC can be accepted across jurisdictions. Allocation of low risk RRCTs for review by LREPs will help expedite review of trials by institutions that only have a LREP and no HREC but may be best suited for single site studies at those sites as not all LREPs are adequately constituted to facilitate ethical review for multisite studies in the manner accredited HRECs currently do. This is an area that requires further exploration under the auspices of the NHMRC.\u003c/p\u003e \u003cp\u003eAlthough ethical review of RRCTs presents no major concern, a significant challenge pertains to governance authorization and the bureaucracy associated with accessing registries, and the institutional governance authorisation requirements for approving the conduct of RRCTs at individual sites. The Australian research landscape is somewhat hindered by the Federation system under which certain aspects of research are governed by either Federal or State legislation creating governance process variability across jurisdictions resulting in an increased bureaucracy. Yan et al found that jurisdictional boundaries place limitations on RRCTs around data sharing and create the need for multiple approvals (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The manner in which EMRs have been implemented across Australia is another prime example of the variability of a Federated system presents cross jurisdictions. Where EMRs could potentially one day in part assume the role of a registry this is inhibited to some extent by the variable EMR systems across the public health care sector. The role of Federal government in establishing a funding model for registries and RRCTs, and legislation/policies that provide provisions for addressing the governance challenges that arise from current arrangements would be highly welcomed and would help reduce the administrative burden for clinicians and trialists wanting to access registry data and initiate a multisite RRCT. The benefits gained from the streamlined single ethical review process are somewhat eroded by the persisting and mounting research governance challenges that need urgent attention, but should be used as an example of what can be achieved through good will, appropriate legislation and cooperation across all levels of government.\u003c/p\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eOne of the limitations of this study was the potential for selection bias as those interviewed were participants who were known to the author to be active in the clinical trial and registry environment. As we employed maximum variation sampling and snowballing to identify and select eligible participants we ran the risk of not including an adequate number of participants who were RRCT na\u0026iuml;ve. We were only able to interview one participant from a rural/regional setting and therefore findings from our metropolitan participants may not be representative of what is occurring in the regional centres. A follow up survey to a large and diverse clinical trial active workforce should provide good representativeness in this regard and help determine RRCT awareness and understanding across a number of cohorts and locations. We did not interview a number of other stakeholders that would support RRCTs, such as study coordinators and pharmacists.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eRRCTs are an emerging methodology in Australia as awareness of the benefits they provide are progressively appreciated by clinicians and other stakeholders. Increasing awareness and providing education on this methodology are essential elements in ensuring that RRCTs capture the interest of clinicians and trialists and are therefore a consideration as the alternative methodology to the conventional RCT. Government support and prioritisation of establishing a sustainable funding model for both registries and RRCTs would greatly bridge the current gap.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACTA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Australian Clinical Trials Alliance\u003c/p\u003e\n\u003cp\u003eANZCTR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Australian and New Zealand Clinical Trial registry\u003c/p\u003e\n\u003cp\u003eEMR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Electronic Medical Record\u003c/p\u003e\n\u003cp\u003eHREC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Human Research Ethics Committee\u003c/p\u003e\n\u003cp\u003eLREP\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Low Risk Ethics Panel\u003c/p\u003e\n\u003cp\u003eMRFF\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Medical Research Future Fund\u003c/p\u003e\n\u003cp\u003eNHMRC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;National Health and Medical Research Council\u003c/p\u003e\n\u003cp\u003ePCI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Percutaneous Coronary Intervention\u003c/p\u003e\n\u003cp\u003eRA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Research Administrator\u003c/p\u003e\n\u003cp\u003eRCT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Randomised Controlled Trial\u003c/p\u003e\n\u003cp\u003eRGO\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Research Governance Officer\u003c/p\u003e\n\u003cp\u003eRRCT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Registry-based Randomised Controlled Trial\u003c/p\u003e\n\u003cp\u003eSTEMI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;ST-Elevation Myocardial Infarction\u003c/p\u003e\n\u003cp\u003eTASTE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Thrombus Aspiration in ST-Elevation\u003c/p\u003e\n\u003cp\u003eVCCC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Victorian Comprehensive Cancer Centre\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was granted by the Melbourne Health Human Research Ethics Committee\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent, including the publication of anonymised quotes, were obtained from all participants prior to data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are not publicly available due to participants\u0026rsquo; confidentiality.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBK developed interview questions and conducted all interviews\u003c/p\u003e\n\u003cp\u003eBK collected the data. BK and KP analysed \u0026nbsp;and interpreted the data. BK and KP drated the manuscript. \u0026nbsp; All authors reviewed and approved final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe wish to thank all the participants for generously sharing their experiences with us.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTang M, Schaffer A, Pearson SA. Embracing the full spectrum of real-world data for cancer medicines research in Australia. Asia Pac J Clin Oncol. 2019;15(3):186-7.\u003c/li\u003e\n\u003cli\u003eKaranatsios B, Prang KH, Verbunt E, Yeung JM, Kelaher M, Gibbs P. Defining key design elements of registry-based randomised controlled trials: a scoping review. Trials. 2020;21(1):552.\u003c/li\u003e\n\u003cli\u003eBergqvist D, Bj\u0026ouml;rck M, S\u0026auml;we J, Tro\u0026euml;ng T. Randomized trials or population-based registries. 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International Journal for Quality in Health Care. 2007;19(6):349-57.\u003c/li\u003e\n\u003cli\u003eNyimbili F, Nyimbili L. Types of Purposive Sampling Techniques with Their Examples and Application in Qualitative Research Studies. British Journal of Multidisciplinary and Advanced Studies. 2024;5(1):90-9.\u003c/li\u003e\n\u003cli\u003eBraun V CV. Using thematic analysis in psychology. . Qual Res Psychol. 2006;3(2):77-101.\u003c/li\u003e\n\u003cli\u003eFereday J M-CE. Demonstrating rigor usimg thematic analysis: A hybrid approach of inductive and deductive coding and theme development. Int J Qual Methods. 2006;5(1):80-9.\u003c/li\u003e\n\u003cli\u003eNational Critical Research Infrastructure Initiative-2023 Innovative Trials: Australian Government-Medical Research Future Fund; 2023 [Available from: https://www.grants.gov.au/Fo/Show?FoUuid=f54f2ea2-3a5d-48f0-84c9-8e23862f004a.\u003c/li\u003e\n\u003cli\u003eRegistry Based Trials: Victorian Comprehensive Cancer Centre Alliance (VCCC); 2023 [Available from: https://vcccalliance.org.au/research/clinical-trial-innovations/registry-trials/.\u003c/li\u003e\n\u003cli\u003eRegistry Randomised Trials Workshop: Australian Clinical Trials Alliance(ACTA) 2020 [Available from: https://clinicaltrialsalliance.org.au/?s=registry+trials.\u003c/li\u003e\n\u003cli\u003eNewman AB, Avil\u0026eacute;s-Santa ML, Anderson G, Heiss G, Howard WJ, Krucoff M, et al. Embedding clinical interventions into observational studies. Contemp Clin Trials. 2016;46:100-5.\u003c/li\u003e\n\u003cli\u003eAnderson ML, Califf RM, Sugarman J. Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems. Clin Trials. 2015;12(3):276-86.\u003c/li\u003e\n\u003cli\u003eCaliff RM, Sugarman J. Exploring the ethical and regulatory issues in pragmatic clinical trials. Clin Trials. 2015;12(5):436-41.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"registry-based randomised controlled trials, registry, qualitative study","lastPublishedDoi":"10.21203/rs.3.rs-4614839/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4614839/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRandomised Controlled Trials (RCTs) are the gold standard for evaluating the effectiveness of interventions in clinical research. RCTs however are complex, expensive and have low external validity. Registry-based randomised controlled trials (RRCTs) are an emerging alternative approach that integrate the internal validity of an RCT with the external validity of a clinical registry by recruiting more real-world patients and leveraging an existing registry platform for data collection. As RRCTs are a novel research design, there is limited understanding of the RRCT landscape in Australia. This qualitative study aims to explore the RRCT landscape in Australia including current capacity and capabilities, and to identify challenges and opportunities for conducting RRCTs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted 30 semi-structured interviews with 18 Clinician researchers, 6 Research Administrators, and 6 Research Governance Officers. Interviews were audio-recorded and transcribed verbatim. We analysed the data using thematic analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe identified four overarching themes: 1) Understanding of the RRCT methodology concept and knowledge of Australian clinical registries and RRCT landscape; \u0026nbsp;2) Enablers and barriers in the uptake and conduct of RRCTs; \u0026nbsp;3) Ethics and governance requirements impacting the conduct of RRCTs and 4) Recommendations for the promotion, support and implementation of RRCTs.\u003c/p\u003e\n\u003cp\u003eUnderstanding of and ability to define an RRCT varied considerably amongst participants, as did their appreciation of the role the registry should play in supporting these trials. Lack of ongoing funding to support both registries and RRCTs, along with low awareness and minimal education around this methodology, were identified as the predominant barriers to the uptake of RRCTs in Australia. The simplicity of RRCTs, specifically their pragmatic nature and lower costs were identified as one of their best attributes. There was consensus that inadequate funding, onerous research governance requirements and poor awareness of this methodology were currently prohibitive in enticing clinicians and researchers to conduct RRCTs. Recommendations to improve the uptake of RRCTs included establishing a sustainable funding model for both registries and RRCTs, harmonising governance requirements across jurisdictions and increasing awareness of RRCTs through education initiatives.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRRCTs in Australia are an evolving methodology with slow but steady uptake across a number of clinical disciplines. Whilst RRCTs are increasingly identified as a beneficial alternative methodology to evaluate and improve current standards of care, several barriers to effective RRCT implementation were identified. \u0026nbsp;Creating greater awareness of the benefits of RRCTs across a number of stakeholders to help secure ongoing funding, and addressing both registry and RRCT governance challenges are two essential steps in enhancing the uptake of RRCTs in Australia and internationally.\u003c/p\u003e","manuscriptTitle":"A qualitative study exploring stakeholders’ perceptions of registry-based randomised controlled trials capacity and capability in Australia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-16 07:28:22","doi":"10.21203/rs.3.rs-4614839/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2024-10-17T10:33:14+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-06-26T09:00:49+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-24T14:25:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-24T12:16:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2024-06-21T00:35:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d22141de-e45b-492b-aaf6-bce355bcdfa8","owner":[],"postedDate":"July 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-23T16:08:00+00:00","versionOfRecord":{"articleIdentity":"rs-4614839","link":"https://doi.org/10.1186/s13063-024-08668-8","journal":{"identity":"trials","isVorOnly":false,"title":"Trials"},"publishedOn":"2024-12-18 15:57:48","publishedOnDateReadable":"December 18th, 2024"},"versionCreatedAt":"2024-07-16 07:28:22","video":"","vorDoi":"10.1186/s13063-024-08668-8","vorDoiUrl":"https://doi.org/10.1186/s13063-024-08668-8","workflowStages":[]},"version":"v1","identity":"rs-4614839","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4614839","identity":"rs-4614839","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}