Wednesday 10th May 2017 – Thursday 11th May 2017
South Australian Health and Medical Research Institute (SAHMRI) Auditorium, Adelaide, SA
Generously supported by
Cabrini Health and Monash University (Foundation Members)
Goals of the meeting
Following the second successful ANZMUSC meeting in 2016, the 2017 meeting aimed to provide ANZMUSC members with an update on ANZMUSC activities and future goals and provide members the opportunity to discuss research proposals for potential endorsement. The meeting also had sessions on rapidly translating evidence into policy and practice and contained presentations by MSK investigators involved in the conduct of high quality MSK trials recently published in high impact journals.
The 2017 meeting was attended by 62 delegates (click here to view the delegate list) from across Australia and New Zealand representing 36 Universities and research institutes as well as various research institutes, professional associations and consumer organisations. Also in attendance for the first time were members of the ANZMUSC CAG; Ms Suzie Edward May (WA), Ms Charlotte Hewson (NZ), Ms Linda Spurrier (ACT) and Ms Annie McPherson (VIC).
Day 1 Presentations
Session 1: ANZMUSC Clinical Trials Network Update
Dr Sheila Cyril, ANZMUSC EO, provided an overview and update on ANZMUSC activities to date including the finalised ANZMUSC structure and governance policies, the establishment and activities of the Scientific Advisory Committee (SAC), the Consumer Advisory Group (CAG), the administrative office, the External Advisory Group (for the CRE) and the Funders Group. She also updated us on the growth of ANZMUSC with 177 members including 8 consumer advisory (CAG) members from various states in Australia and New Zealand. Other goals set by ANZMUSC at the 2016 meeting including the endorsement of 2 trials and the commencement of the priority setting activities was mentioned along with additional achievements such as the establishment of a Chiropractic Australia and COCA Research Pty Ltd funded PhD scholarship in partnership with ANZMUSC and the Consumer Research Registry,
Dr Allison Bourne, Research Fellow, Monash Department of Clinical Epidemiology, provided an update on the ANZMUSC systematic review of priority settings for Arthritis and MSK conditions currently being undertaken as part of the ANZMUSC priority setting project. The systematic review aims to synthesise existing priority statements for clinical research for arthritis and MSK conditions available in the published literature and summarise the methods used to generate these priorities. The search strategy includes the Ovid Medline database, Cochrane priority setting methods group, the James Lind Alliance website, the Cochrane Musculoskeletal and Cochrane Back Groups review priority list, the US National Guidelines Clearinghouse and the Guidelines International Network. Screening of titles and abstracts of 5000+ articles have been completed. Data extraction of included articles is underway.
Ms Ornella Clavisi, CAG Chair, Research & Knowledge Manager, MOVE muscle bone and joint health, Victoria, summarised the function of the CAG and provided an update on the Consumer Research Registry (CRR). The CAG provides a mechanism for consumer input on ANZMUSC trials by reviewing trial proposals, advising on research priorities, reviewing and informing ANZMUSC policies and procedures and participating in working groups and reviewing participant materials of endorsed trials. The CRR provides an opportunity for consumers to function as research partners and provides a platform for researchers and consumers to communicate effectively. Discussions following her presentation highlighted the importance of education and resources to train consumers in research, clinician involvement in research and the role of qualitative research in ANZMUSC. The ability of the CRR to articulate with Twitter and other social networking platforms, as well as the reporting of clinical trials in a form that consumers could easily understand was also discussed, as was the need for plain language summaries of trial results based on consumer feedback. The audience discussed the possibilities of the CRR to enable consumers’ involvement in the latest research and trials taking place in hospitals. Consumer involvement in ATSI groups and the role of infograms (e.g. informing consumers on prostate cancer) in MSK research was also discussed.
Following this, we heard from two consumer members of the CAG. Ms Suzie Edward May, Director, Giving Voice Australia, Deputy Chair Eastern Metropolitan Health Service, WA, discussed the importance of using qualitative research methods and consumer partnerships to incorporate the “true patient voice” in ANZMUSC research. She described her own experiences around the lack of information for consumers regarding arthritis medications and pregnancy and detailed the qualitative research she conducted across five countries to inform her book ‘Arthritis, pregnancy and the path to parenthood’. The book is now available in 14 countries and is recommended reading for GPs by the RACG http://www.givingvoice.com.au/book. She concluded her presentation by highlighting the need for research findings to be presented in ways that are accessible to consumers at all levels of health literacy and acknowledged the immense collaborative opportunity the partnership between consumers and researchers in musculoskeletal research provides by producing research that is relevant to both consumers and clinicians.
Ms Annie McPherson, President and founding member, Ankylosing Spondylitis Victoria (AS Vic), provided an account of what is needed in the formation of peer support groups and the challenges such groups face. She likened the concept of establishing a peer support group to mixing a large cake, with many layers and ingredients such as skills in internet, email, member subscriptions, banking, newsletter writing, social event coordination and seminar preparation and production. She briefed us on the support provided by MOVE, muscle bone and joint health Victoria, in establishing AS Victoria and providing ongoing education in community support and activities. Currently, AS Victoria members provide support and patient talks in the Physiotherapy based exercise program at Caulfield Community Health in Alfred Health’s Caulfield campus, Victoria. Finally, she discussed the eagerness of consumers to know what research is being conducted and highlighted the ability of patient advocacy groups to be involved in the spreading the word about clinical research.
Session 2: Rapidly translating evidence into policy and practice
Professor Maria Makrides Theme Leader Health Mother, Babies and Children, SAHMRI, discussed the challenges and lessons learned in the STEP trial which aimed to trial whether the incidence of egg allergy is reduced by early, regular egg exposure from 4 – 6.5 months compared with delaying egg introduction. The trial results found no increase in allergy as a result of early introduction and was consistent with other trials (including the STAR, BEAT< EAT and HEAP) investigating food allergy and exposure during infancy. Maria highlighted the challenges with converting research findings such as the STEP trial into practice given the challenges in setting a concrete deadline for the age at which exclusive breast feeding should end given the benefits of breast feeding. To address this issue, Maria described a stakeholder summit that was conducted to produce a harmonised guidance statement and concluded her presentation with a discussion about the infographics information sheet being produced to assist with consumer communication.
Following Maria’s presentation, Professor Steve Wesselingh, Executive Director SAHMRI, gave a presentation about the power of Advanced Health and Research Translation Centres to improve the speed of research translation. He highlighted some of the problems with existing health research models including money and entrenched practice, time poor practitioners, lack of financial incentives and difficulty in behaviour change. He also highlighted the current structural issues including dichotomy of funding streams leading to lack of coordination between research funding and health service delivery and the issue of hospital KPIs being based on procedures not on patient outcomes or whether research has been moved into health care.
To overcome these issues, the NHMRC has accredited 4 Advanced Health Research and Translation Centres (AHRTC); Alfred Health and Monash Health Partners, Melbourne Health Partners, South Australian Health Partners and Sydney Health Partners. These centres have the state-wide involvement of primary care, Aboriginal Health, universities and local health networks. The SA Health Centre is chaired by Prof Steve Wesselingh and focuses on 7 priority areas:
- Aboriginal health
- Colorectal cancer
- Cardiac rehabilitation
- Translation of evidence (arthroscopy, hysterectomy, c-section, diabetic amputation)
- Evidence-based pathways (eg. stroke, diabetes)
- Translation pipeline (clinical trials, commercialisation).
- Data access and delivery
He concluded his presentation by highlighting the major opportunity these centres have to embed evaluation, research and workforce development in health services, and how they will improved health outcomes, evidence-based models of care, evidence-based health promotion and prevention, shared data collection and evaluation and consumer engagement by promoting health services to embrace research and training.
Session 4: Australian MSK trials in high impact journals
Day 1 concluded with a session on recent MSK trials published in high impact journals. The first presentation by Dr Xingzhong Jin described his RCT investigating the effect of Vitamin D supplementation on tibial cartilage volume and knee pain among patients with symptomatic knee osteoarthritis (Xingzhong Jin, MD; Graeme Jones, MD, PhD; Flavia Cicuttini, MD, PhD et al JAMA. 2016;315(10):1005-1013. Doi:10.1001/jama.2016.1961). This double-blind placebo-controlled multi-centre RCT concluded that there were no significant differences in annual change of tibial cartilage volume and WOMAC pain score over 2 years and overall does not support the use of vitamin D supplementation for preventing tibial cartilage loss or decreasing pain in patients with knee osteoarthritis. This result contrasts with other studies that have found a small but significant benefit and a systematic review that suggested Vitamin D may promote structural changes in OA. Dr Jin concluded his presentation by highlighting the difficulties in publishing negative trial results and the need to carefully consider primary and secondary end outcomes to ensure the most relevant outcome is measured.
For the final presentation of day 1, Professor Stephen Nicholls, Heart Disease Research Theme Leader, SAHMRI discussed the strengths and weaknesses of surrogate markers that he’d witnessed in cardiometabolic clinical trials. He outlined the numerous benefits of using surrogate markers in clinical trials including; the ability to perform smaller and faster trials; provide potential mechanistic effects; give early no/no-go signal; inform optimal dosing for larger trials and the potential for inclusion in regulatory filings. He also outlined the risks associated with surrogate markers including; a lack of information on safety and cost-effectiveness and a limited capacity to prove comparative effectiveness. He also discussed the need for any changes in surrogate measures to be predictive of the relevant clinical outcome and for them to capture the effect of the intervention on the clinical outcome. He gave several examples of biomarkers used in cardiovascular and diabetes trials that may be inefficient markers including LDL and Glycated Haemoglobin and concluded with the acknowledgement that although surrogate markers play an important role in testing new therapies, they ultimately cannot replace clinical outcomes.
Day 2 Presentations
Session 1: Australian MSK trials in high impact journals continued
Day 2 began with the presentation of more MSK trials recently published in high impact journals. Associate Professor Christin Lin, Senior Research Fellow, University of Sydney, began the session with a summary of her groups trial about the effectiveness of Pregabalin for acute and chronic sciatica (Mathieson S, Maher CG, McLachlan AJ, Latimer J, Koes BW, Hancock MJ, Harris I, Day RO, Billot L, Pik J, Jan S, Lin CC. N Engl J Med. 2017 Mar 23;376(12):1111-1120. doi: 10.1056/NEJMoa1614292). This randomised, double-blind, placebo-controlled trial found that over a course of 8 weeks, treatment with Pregabalin did not significantly reduce leg pain caused by sciatica or improve any of the secondary outcomes compared to the placebo group. Additionally there was a higher rate of adverse events in the intervention group overall, arguing against the use of Pregabalin for the management of sciatica.
Following this, Professor Rana Hinman, Professor of Physiotherapy, University of Melbourne, presented the results of a clinical trial aiming to test whether using appropriate footwear to reduce knee overload is effective for the self-management of knee osteoarthritis (Hinman RS, Paterson KL, Wrigley TV, Bennell KL. Ann Intern Med. 2017 Feb 21; 166(4):312. Doi: 10.7326/L16-0630). In partnership with a shoe company, the group created a shoe that showed reduction in external knee adduction but failed to find a difference in pain with walking and on other outcomes measured in this randomised control trial. Treatment outcome modifiers and limitations around the ability of improved biomechanics to improve clinical symptoms were raised as potential reasons why no difference was found.
Next Associate Professor Justine Naylor, Senior Principal Research Fellow, Orthopaedics, South Western Sydney Local Health District, presented the outcomes of an RCT evaluating the effect of inpatient rehabilitation vs a monitored home- based program on mobility in patients with total knee arthroplasty (HIHO) recently published in JAMA. (Buhagiar MA, Naylor JM, Harris IA, Xuan W, Kohler F, Wright R, Fortunato R.JAMA. 2017 Mar 14;317(10):1037-1046. doi: 10.1001/jama.2017.1224). Overall the study showed no significant difference between the inpatient and home-based groups across a range of outcomes at 10, 26 and 52 weeks after surgery. Justine also discussed the barriers and enablers to changing practice following this study including geographical barriers to inpatient rehabilitation, variations between clinician and patient preferences for rehabilitation and cost-effectiveness of rehab programs. On a positive note, a newspaper report from The Australian (15/3/2017) stated that private insurers support the conclusions of HIHO and advocated for the need for more transparency around the cost-effectiveness of rehab programs to enable consumers make informed decisions around their healthcare and private hospitals (including Cabrini Health) are discouraging clinicians from using inpatient rehab. The group will be conducting a similar trial following hip arthroplasty.
Session 3: Update from ANZMUSC endorsed clinical trials
In Session 3, we heard an overview and update on the progress on the 2 endorsed ANZMUSC trials. Professor Michele Sterling, Director, NHMRC Centre of Research Excellence in recovery Following Road Traffic Injuries, discussed her study on targeting pro-nociception to prevent chronic pain after whiplash injury. Specifically, this study aims to trial whether early consumption of Pregabalin in acute whiplash, prevents chronic pain that develops in 50% of people after a whiplash injury via a double blind, randomised, placebo-controlled trial to be conducted at 2 centres on the Gold Coast. A study protocol describing the strict inclusion and exclusion criteria has been developed and published for the study. Primary and secondary outcomes have been defined and the group has commenced enrolling participants at the Gold Coast University Hospital and plans to start recruiting at Ipswich Hospital shortly to boost recruitment rates. Other challenges including the cost of after-hour patient consultation for nurses and physiotherapists, and flexibility in RA hours have been identified and are being addressed.
Professor Ian Harris AM, Director, Whitlam Orthopaedic Research Centre, provided an update on the ANZMUSC endorsed study “A Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly – CROSSFIRE”. This multicentre randomised comparative effectiveness trial aims to determine whether surgical intervention (plating) leads to better pain and function and is more cost-effective than closed reduction and casting of displaced distal radius fractures in adults aged 60 years and old. An investigator video has been developed available at youtube.com/watch?v=DBx89JQHvRY&t=4s. Participant video incorporating consumer input is currently underway. Currently, the trial is running in 7 sites including Mackay Base Hospital, Liverpool Hospital, JHH, Canberra Hospital, Nambour Hospital, RAH, POWH, Epworth Healthcare, Townsville Hospital and Wellington Hospital. The trial has been registered on the ANZCTR and 15 participants have been recruited (5 randomised: 10 observational). The protocol has been accepted for publication in BMJ Open.
Session 4: CRE and building and developing capacity in ANZMUSC Network
During the last session of the meeting, we heard from Professor Chris Maher, Director, Musculoskeletal Health Sydney, University of Sydney, on the CRE ANZMUSC submitted late last year in order to help ANZMUSC build a workforce of trained musculoskeletal clinical trialists by providing the infrastructure, financial support, methodological leadership and research outcome incentives to encourage clinicians from different disciplines to become actively involved in research. A number of initiatives were included in the CRE application including clinical research fellowships, research project seed funds, summer research scholarships, consumer training workshops, investment in personnel to coordinate ANZMUSC, recruiting/supporting PhD students, postdoctoral fellows and clinician researchers, and providing expert mentoring for their CRE supervisors. The CRE also aims to develop large-scale project management processes to streamline all aspects of the trial process, reduce duplication of effort, and embed trials in routine care. Discussion following the presentation also raised the possibility of ANZMUSC being involved in a national biobank for Rheumatoid Arthritis which is already in the process of being established.
Following on from this, Associate Professor Will Taylor, University of Otago, NZ, provided an overview and update on the ANZMUSC Priority setting project. The project aims to a) develop a framework to determine the importance of a research question and to generate a set of researchable questions; b) develop a non-exhaustive ranked list of musculoskeletal research questions that will enable ANZMUSC to determine if projects meet the ANZMUSC endorsement criterion 1. ANZMUSC prioritisation will involve creating explicit criteria by which a question is considered important, such that new ideas can be immediately rated. The project will deliver a list of research questions that are ranked by importance by ANZMUSC, and includes the following steps
- Lit review (criteria and methods for prioritisation suggested by others) (underway)
- Delphi survey (on what ANZMUSC members think makes a research question important) (underway)
- Consensus workshop (to agree on a manageable set of the most important questions)
- Weighting workshop (to assign meaningful numeric scores to each question) (via discrete choice experiment)
- Application to initial questions, membership survey, document review
The first Delphi survey has been completed by 66 ANZMUSC members including researchers, clinicians, policymakers and consumers and has generated 5 main themes: potential for impact, population need, nature of the intervention, broad appeal, whether the project is able to be delivered/ implementability.
The final presentation of the meeting was from Professor Sally Green, Co-Director of Cochrane Australia, who presented on promoting effective transfer of research outcomes into health policy and practice. Transferring research findings into policy offers ANZMUSC the opportunity to further the science of research translation of MSK conditions (performing implementation trials to check what works for translation into policy, developing living systematic reviews and living guidelines); and effectively disseminating and translating the results of the CRE through external advisory boards, clinical researchers, media and communications plans. She also discussed the “new evidence ecosystem’ which involves linked data repositories, living systematic reviews and living guidelines to support decision making in health practice and highlighted the challenges in generating evidence (Elliot JH, Turner T, Clavisi O, Thomas J, et al. (2014) PLoS Med 11(2): e1001603) as well as the various challenges in current guideline development.
Sally then went on to talk about projects within the Cochrane group including the Cochrane Crowd who identify RCTs and the Cochrane Evidence pipeline which automatically identifies the study design, review group and PICO. She also talked about living (continuously updated) systematic reviews and noted that nesting living systematic reviews in a trials network is a perfect opportunity to identify important evidence-practice gaps, conduct trials, feed the results into guidelines, and conduct implementation trials (Elliott JH, Turner T, Clavisi O, Thomas J, Higgins JPT, Mavergames C, et al. (2014) Living Systematic Reviews: An Emerging Opportunity to Narrow the Evidence-Practice Gap. PLoS Med 11(2): e1001603 https://doi.org/10.1371/journal.pmed.1001603). It was also noted that guidelines could be more efficient if they were ‘living’ as well.