Background
Hemodialysis (HD) is the commonest treatment for patients with kidney failure worldwide and can only be provided via a functioning vascular access [
1]. Establishing and maintaining a functioning access, however, is one of the greatest challenges in caring for these patients. Vascular access-related complications and interventions are associated with increased patient morbidity and mortality and healthcare costs accounting for 20–25% of annual hospital admissions in patients on HD [
2‐
4]. From a patient’s perspective, the experience and anticipation of vascular access complications are key sources of stress and can lead to anxiety about the potential for vascular access failure [
5]. Improving vascular access outcomes is therefore considered a critical priority not only by patients, but also their caregivers and health professionals [
6‐
8].
Despite increasing numbers of vascular access trials, successful interventions to improve vascular access outcomes have been sparse and compromised by highly variable, often selectively reported outcomes of limited relevance to patients and health professionals [
9,
10]. Based on a systematic review of vascular access outcomes in HD trials, vascular access function was the most frequently reported outcome, yet was described in 489 different ways with “mean access blood flow” and “number of thromboses” being the most frequently used measures. Despite efforts to standardize outcome definitions for vascular access by various working groups [
11‐
14], only a minority of HD trials made use of these standardized definitions. For example, of the 134 patency measures reported across 64 trials, only 13% were consistent with 1 or more of the standardized definitions as proposed by national and international consortiums and societies [
10]. These findings underpin the need for broader implementation of standardized, patient-important outcome measures to enhance the consistency and relevance of outcome reporting in clinical trials in HD. To address this issue, considerable efforts have been made to identify and standardize vascular access outcomes that are important to patients, their caregivers and healthcare professionals that should be reported consistently in clinical research to improve the quality, reliability and relevance of research evidence that guides patient care [
15,
16]. The Standardized Outcomes in Nephrology in HD (SONG-HD) initiative identified vascular access as one of four critically important core outcome domains (along with fatigue, cardiovascular disease and mortality) for clinical trials in HD based on a consensus-based, multiphase, mixed-methods process involving over 1300 patients, caregivers and health professionals from more than 70 countries [
6,
8,
17‐
19]. Based on international contributions of 237 patients and 720 clinicians, researchers, policy makers and industry from 58 different countries, “vascular access function” was deemed the most critically important outcome because of: 1. the broad applicability of function regardless of the vascular access type; 2. the involvement of a multidisciplinary team in achieving a functioning vascular access; and, 3. the impact of vascular access function on quality of life, survival, and other vascular access-related outcomes. “The need for interventions to enable and maintain the use of a vascular access for HD” was considered a simple, pragmatic, and inexpensive measure of vascular access function that was meaningful and relevant to patients [
20]. Stakeholders considered the frequency (rate) of vascular access interventions and the intervention-free time to be key descriptors of a functioning vascular access [
20]. In order to ensure global implementation of this outcome measure across all trials in HD, it needs to be feasible to accurately measure vascular access function as part of routine clinical practice without requiring additional resources or expertise in vascular access [
20,
21].
While vascular access interventions have been reported in HD research and collected by renal registries [
22‐
27] the granularity of data collection (i.e., type of vascular access interventions, date of intervention, and indication of intervention) vary substantially across studies and registries precluding reliable comparisons across trials and countries to inform research and clinical practice. A Canadian experience including five Canadian dialysis programs has shown that granular data collection of all types, dates, and indications of vascular access interventions in patients on HD using the Dialysis Measurement Analysis and Reporting (DMAR) system is feasible and reliable [
22,
27,
28]. However, it remains unknown whether these data can be collected in other countries and different settings (i.e., in-center versus satellite versus home-based HD; rural versus urban; private versus public; small versus large units) by clinical staff without special expertise in vascular access and as part of routine clinical practice. VALID will address this uncertainty by assessing the validity, acceptability and feasibility of measuring vascular access function, defined by the need for interventions to enable and maintain the use of a vascular access for HD, by clinical staff as part of their routine clinical practice in a prospective, multi-center, multinational validation study covering a broad range of HD settings to ensure successful implementation of this core outcome measure in research and clinical practice without the need for additional resources or expertise in vascular access [
21].
Discussion
Vascular access function has been identified as one of the most critically important outcome measures for trials in HD that is pragmatic and meaningful [
20,
35], yet, this outcome has not been reported consistently across clinical trials [
10]. The VALID study will address this issue by assessing the accuracy, acceptability and feasibility of measuring vascular access function, defined by any vascular access intervention required to enable and maintain HD vascular access function, in an international validation study that covers a broad range of different HD settings to ensure successful implementation of this core outcome measure in research and clinical practice without the need for additional resources or expertise in vascular access [
21].
VALID follows the three key strategies for successfully implementing core outcomes in research. Firstly, all relevant stakeholders, including patients, have been engaged in the identification of the core outcome and development process of the study [
6,
8,
14,
17,
19,
20,
35]. Secondly, feasibility and validity of proposed core outcomes will be demonstrated and is the basis for the protocol in this manuscript. Thirdly, the reasons for, and type of core outcomes will be disseminated globally [
33]. Global implementation of a validated outcome measure for vascular access function in HD trials, national kidney registries, and clinical practice would be a major step forward in reporting what is important to patients and will facilitate quality improvement as well as maximize the chances of discovering effective interventions to reduce the burden and cost of vascular access interventions required to maintain the function of the patients’ vascular accesses, their lifelines for HD.
The strength of this research is that it uses a robust, adequately powered methodological approach to evaluate the accuracy and feasibility of measuring vascular access function in various clinical setting and locations. The study has been developed and designed by patients on HD and vascular access experts (nephrologists, nurses and vascular access surgeons), researchers and statisticians with established track records of excellence in the conduct of large-scale clinical trials. The study has considerable buy-in from dialysis units in Australia, Europe, Canada, and Malaysia and will be overseen internationally by the Australasian Kidney Trials Network, which has a strong track record in adopting novel, pragmatic trial designs and generating new knowledge that changes practice in kidney failure care. The broad range of clinical settings in which this study will be conducted, such as small and large centers, rural and urban areas, in-center, satellite and home-dialysis facilities, public and private sectors, will enhance the external validity of this study. Importantly, the study adheres to the STARD diagnostic accuracy tests guidelines. The limitations include the potential for incorrect or missing vascular access data collated by Assessor 2 serving as the reference standard: however, the audit assessor double checking data accuracy should mitigate this risk. Furthermore, the study does not include centers from low- to very-low-income countries thereby limiting the applicability of study findings to these settings. Independence of data acquisition between Assessor 1 and 2 could potentially be breached by assessors thereby impacting the accuracy of study findings. Several risk mitigation strategies have been put in place including enforcement of independence in the trial operations manual and protocol, a special emphasis during the site initiation visit and individual database access with restricted view of the data by assessors.
In summary, the VALID study will evaluate the accuracy, acceptability and feasibility of measuring vascular access function as part of routine clinical practice, as well as determine the frequency of vascular access interventions across different HD settings and countries. This will facilitate global implementation of this patient-important core outcome measure in HD trials to improve the quality and relevance of research to inform patient-centered care and reduce research waste.
Trial status
The current VALID protocol is Version 1.1 dated 5th August 2019. Recruitment commenced on 9th December 2019 and concluded on 30th November 2021. The study including participant follow-up, feasibility assessment and auditing of data accuracy by the Audit assessors is estimated to be completed by December 2022 when the dataset will be locked. The study protocol was submitted after recruitment of all sites was completed due to earlier than anticipated achievement of the target sample size and enrollment of all participants within a site within 4 weeks of site initiation.
Acknowledgements
Project management team
The Australasian Kidney Trials Network, Brisbane, Australia: Carmel M Hawley, David W Johnson, Charani Kiriwandeniya, Alistair Mallard, Donna Reidlinger, Laura Robison, Andrea Valks, Liza A Vergara, Andrea Viecelli and Alyssa Welch.
The Australasian Kidney Trials Network Executive Committee Members
Carmel M Hawley (Chair), Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Australia and Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; David W Johnson (Deputy Chair), Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Australia and Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia and Translational Research Institute, Brisbane, Australia; Sunil V Badve, Department of Renal Medicine, St George Hospital, Sydney, Australia and Renal and Metabolic Division, the George Institute for Global Health, University of New South Wales Medicine, Sydney, Australia; Neil Boudville, Sir Charles Gairdner Hospital, Perth, Australia and Medical School, University of Western Australia, Perth, Australia; Katrina Campbell, Menzies Health Institute, Griffith University, Queensland, Australia and Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland, Australia; Yeoungjee Cho, Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Australia, Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Michael Collins, Auckland City Hospital & University of Auckland, Auckland, New Zealand, Royal Adelaide Hospital and University of Adelaide, Adelaide SA; Magid A Fahim, Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Australia, the Translational Research Institute and Australasian Kidney Trials Network and The University of Queensland, Brisbane, Australia; Meg Jardine, Concord Repatriation and General Hospital, Concord, Australia and NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia; Charani Kiriwandeniya, Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Rathika Krishasamy, Sunshine Coast University Hospital, Queensland, Australia and Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland, Australia; Alistair Mallard, Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Elaine M Pascoe, Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Donna Reidlinger, Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Laura Robison, Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Matthew Roberts, Eastern Health Clinical School, Monash University, Melbourne, Australia; Andrea Viecelli Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Australia, the Translational Research Institute and Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Alyssa Welch, Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia.
Collaborating sites and investigators
Australia: Queensland: Hervey Bay Hospital (Krishan Madhan, Dianne Du Toit, Michelle Mayne and Kim Stevenson); Mackay Base Hospital (Roy Cherian, Rachel James and Quynh Vu); Mater Hospital Brisbane (Richard Baer, Karyn Allen, Leanne Glancy, Jijo Kumbikkal); Princess Alexandra Hospital (Andrea Viecelli, Sharan Burton, Lisa Gordon, Kylee McCarthy and Veronica Oliver).
Canada: University Health Network, Ontario (Charmaine Lok, Cathy Forrester and Sally Lima).
France: Centre Hospitalier Régional Universitaire de Tours (Bénédicte Sautenet, Olivier Bourgault, Claire Drouault, Fanny Teasdale).
Malaysia: Hospital Sultanah Aminah Johor Bahru (Liu Wen Jiun, Jamian Abidin, Cheng Jin Kiang, Lee Soon Leng and Yuana Mohd Yusoff).
The Netherlands: Maastricht University Medical Center (Maarten Snoeijs, Adriana Ciochina, Magda van Loon, Ronald Ophelders and Marie-Jose Vleugels).
Switzerland: Ente Ospedaliero Cantonale, Lugano (Pietro E Cippà, Paolo Ferrari, Marie-Ève Brodeur, Davide Giunzioni and Christine Bressan Molfese).
United Kingdom: Sheffield Teaching Hospitals NHS Foundation Trust (Martin Wilkie, Christopher Blackwell, Louese Dunn, Laura Gillis, Barry Gray and Sarah Jenkins).