The scope, funding and publication of musculoskeletal clinical trials performed in Australia

According to the recently published 2010 Global Burden of Disease study, musculoskeletal (MSK) conditions have the fourth greatest impact on the health of the world’s population, accounting for 6.8% of the total disease burden.1 In considering disability alone, low back pain has the greatest impact on health, outranking ischaemic heart disease, chronic obstructive pulmonary disease and major depressive illness, with other MSK conditions ranked sixth and osteoarthritis ranked 11th.1

In Australia, MSK conditions are the leading contributor to total disability burden (27.4%), and are second only to cancer (15.3% versus 16.2%) when death is also considered.2 They are the most common reason for accessing health care services,3 and in financial terms, contribute to 7.5% of total health expenditure (costing around $4 billion).4 Given their large burden on the Australian population, osteoarthritis, rheumatoid arthritis and osteoporosis were designated National Health Priority Areas (NHPAs) in 2002.5 Importantly, the burden from MSK conditions is increasing as the population ages. There is therefore an urgent need to prioritise research on the most effective and affordable strategies to deal with these conditions.

High-quality trials to test these strategies should be informed by factors such as burden of disease, greatest needs of the population, evidence syntheses showing that more research is required, and identification of novel or promising interventions. To facilitate the conduct of large, high-quality Australian MSK clinical trials that address the most pertinent questions with an emphasis on improving the translation of research findings into clinical practice, we have formed the Australian Musculoskeletal Clinical Trials Group (AUSMUSC). To determine the current scope of Australian MSK clinical trials, we identified the MSK trials currently being performed in Australia, including their source of funding and where they are being published.

Our data indicate that Australian MSK trialists are productive and internationally competitive. The NHMRC has funded an average of 5.8 new MSK trials per year through the project grant scheme over the past 5 years; 128 Australian-initiated trials were registered in the past 2 years; and about one in 20 MSK RCTs published in leading general medical and MSK-specific journals in the past 2 years was initiated in Australia.

A significant number of Australian-initiated trials were for osteoarthritis. While this is commensurate with its known burden on the population, and its status as an NHPA, there were proportionally fewer trials for osteoporosis and rheumatoid arthritis, both also designated NHPAs. Despite the ranking of back pain as the leading cause of disability worldwide and in Australia, there were also comparatively fewer trials for back pain, and a paucity of trials for other MSK conditions. Integrating other MSK conditions such as back pain into the NHPA framework could increase their profile and result in more systematic development and implementation of programs aimed at promoting best practice treatment of these conditions.8

NHMRC funding for MSK trials was found to be disproportionately low in relation to the size of the burden from MSK conditions in Australia and internationally. A 2000–2008 review of NHMRC funding found that some of Australia’s NHPAs are better funded than others.9 The NHMRC has estimated that more than $216 million has been invested in arthritis and osteoporosis research in the past decade.10 While the data may not be directly comparable, as estimated funding is based on identification of chief investigator-provided keywords and titles contained in the NHMRC research database, this appears to be less than the amount invested in other NHPAs such as diabetes (> $475 million) and cardiovascular disease ($795 million). In contrast to one NHMRC MSK program grant in the past 5 years, three have been awarded for diabetes and eight for cardiovascular clinical research.

We think it is unlikely that we missed any NHMRC-funded MSK trials, although we have no information about unsuccessful grant applications (as this information is not publicly available). However, it is possible that we underestimated the number of other NHMRC-funded trials, as before 2011 there was no specific category for clinical trials and identification was reliant on a key word and title search of the NHMRC database using the terms clinical trial, clinical study, clinical studies, randomised trial or controlled trial. It is also unlikely that we missed relevant registered Australian MSK trials. While most registered MSK trials are likely to denote themselves as MSK, we also searched other potentially relevant categories. It is also unlikely that we missed relevant Australian MSK trials published in the past 2 years. Two independent reviewers used two different but complementary strategies to identify potentially relevant papers. The scope of trials was also broadly similar across all three components of our scoping project, further supporting the validity of our findings.

There was a wide range of interventions under study, most commonly drug treatments or physical therapies. While the range of current Australian MSK trials likely reflects the interests and expertise of Australian MSK trialists, our review suggests that not all Australian MSK trials reflect priorities based on the greatest burden of disease, the most novel and/or promising interventions and the greatest needs of the population. Many trials may be too small to be of value; many appear to be driven (either directly or indirectly) by commercial imperatives rather than genuine clinical novelty or patient-centred research priorities, and most are unlikely to influence clinical practice. While a significant number included a placebo or usual care comparator, there were no placebo-controlled surgical trials and only one comparing surgery with conservative care. In addition, we identified only one multicentre trial (which involved two states).

Identifying and addressing evidence–practice gaps has been identified as a major NHMRC priority,11 yet none of the Australian trials we identified was testing interventions to improve uptake of research findings or guidelines into practice. This is in keeping with a previous study that found scarce high-quality implementation trials addressing nine evidence–practice gaps relating to other conditions, and no indication that this had improved over time.12 The NHMRC has now established a Research Translation Faculty to address the challenge of research translation in Australia.13 As part of this process, steering groups across major health areas have been tasked with identifying major evidence–practice gaps. While the role of each steering group is to develop a single case for action that the NHMRC could address, this process may also serve to identify priorities for MSK trials based on population needs, to complement and enhance current investigator-initiated trials.

More investment to support the conduct of MSK trials in Australia is needed. This includes infrastructure funding in both the public and private sectors, more support for clinical researcher training and supervision and, importantly, greater buy-in from clinicians and patients. Many studies have identified suboptimal clinician buy-in for clinical research, particularly those directed towards closing evidence–practice gaps.12,14,15 The lack of clinician buy-in for clinical research directed specifically at improving care suggests the need for a global culture shift towards clinician (and patient) participation in research as a matter of course.

There is also an onus on MSK trialists to ensure that they ask the most important questions. Evidence suggests that this is not consistently the case.16 In discussing the mismatch between what clinical researchers do and what patients need in oncology, Liberati has suggested that inclusion of patients and patient advocacy groups, who spend much time in raising awareness and money to support research in the hope of improving care, should be at the centre of redefining the research agenda.17 The Arthritis Research UK clinical studies initiative has already taken a strategic approach to prioritising clinical study funding for MSK disorders.18 Consultations with consumer representatives and all relevant health care professionals and scientists have led to nationally agreed priorities for MSK clinical trials. It is time to replicate this approach in Australia to ensure that only worthwhile MSK trials are performed and funded.