Clinical trial networks in orthopaedic surgery

Identifying clinically relevant research questions

Six studies identified in this review discussed the role of networks and societies in fostering collaborations between orthopaedic surgeons as a means to identify and prioritise areas for future research.^5-7,9-11 Rangan et al⁹ suggest that consulting clinicians early in the research design process, for example through research priority-setting exercises, may instil a greater level of ‘ownership’ over research projects. This unified approach to identifying research questions may also help to prevent duplication of effort. In addition, the ability to access expertise from a wider pool of researchers and clinicians may benefit trial design and decision making; for example, Bhandari et al⁵ report the benefits of involving an expert panel in the estimation of recruitment rates for orthopaedic trials. Engagement of clinicians together with researchers, funders, policy makers, and health service users is advocated by the COMET (Core Outcome Measures in Effectiveness Trials) initiative, which was set up in 2010 to develop standardised core outcome sets through agreement and collaboration with a wide range of representatives.¹⁷ In terms of research prioritisation in the field of orthopaedic surgical trials, examples below highlight how clinicians have engaged in discussions either through conferences or using research methods such as a Delphi approach.

Willett et al¹⁰ describe a Delphi approach that was used to develop consensus amongst members of the AOUK (the United Kingdom branch of the Swiss AO Foundation; a group which considers research questions in surgical fracture fixation). This collaborative approach led to the successful identification of ten high priority research questions and methodological discussions about their implementation.¹⁰

Findings from a symposium of the American Academy of Orthopaedic Surgeons (AAOS) and the Orthopaedic Research Society (ORS) in 2009 are presented in three papers included in this review, authored by Katz, Losina and Wright.^6,7,11 To promote the research culture in orthopaedics, Wright et al¹¹ advocate the involvement of leaders in the field to encourage the participation of colleagues in multicentre trials. Katz et al⁶ describe a framework which aims to enable researchers to set priorities for future research by considering aspects such as cost, feasibility and anticipated benefit of conducting a RCT.⁶ This article also presents specific questions for future prioritisation in the field of orthopaedic trials that were considered at this symposium.⁶

Similarly, the International Hip Fracture Research Collaborative (IHFRC), based in Canada and comprised of 310 international members, with expertise in orthopaedics and trial methodology, aims to identify research priority areas and inform the design and co-ordination of large multinational RCTs in the field of hip fractures.⁴ In their overview of the IHFRC collaborative, Bhandari et al⁵ suggest that larger groups such as this may bridge the gap between multiple smaller groups internationally, and act as a single point of reference for researchers and clinicians. A total of two multicentre and multinational trials have since been initiated through the IHFRC group: The FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures: a multicentre randomised trial) and the HEALTH trial (Hip fracture Evaluation with ALternatives of Total Hip arthoplasty versus hemi-arthroplasty: a multicentre trial).⁵

Education and training

The need for greater education and training amongst clinicians has been widely acknowledged, with studies in this review demonstrating the role that research networks can have in implementing these improvements in the field of orthopaedics. In the United Kingdom, the Department of Health’s commitment of ‘Best Research for Best Health’ in 2006,¹⁸ led to the development of the United Kingdom Clinical Research Network (UKCRN) and 25 Comprehensive Local Research Networks (CLRNs) with the aim of supporting researchers running or co-ordinating studies throughout the network. As part of the UKCRN, national Specialty Groups exist in a range of areas, of which two groups are of relevance to orthopaedic research: the ‘Musculoskeletal’ and ‘Injuries and Emergencies’ groups.¹⁹ These networks offer a number of functions that promote good research practice in the United Kingdom by facilitating the successful completion of ongoing trials and fostering collaborations with clinicians and researchers with similar research interests. For ongoing trials, recruitment is monitored monthly for the networks’ ‘portfolio’ of studies, with independent peer support and guidance offered to trials to ensure they deliver research in time and on target.¹⁹ Meanwhile, for those wishing to develop research ideas or collaborate as principal investigators in current national trials, these specialty groups provide local and national contact details of clinicians with research interests in similar fields, lists of ongoing trials that are currently open to recruitment and support on Patient and Public Involvement in research. In addition, Rangan et al⁹ note that these research networks can now be used to facilitate training in areas such as the International Conference on Harmonisation’s Good Clinical Practice (ICH-GCP), which is a pre-requisite for undertaking RCTs in the United Kingdom as it outlines key aspects of research governance.

Meanwhile, in the United States, Trippel et al¹⁵ have highlighted the importance of orthopaedic specialist societies, such as the Clinical Trials Network, established in the United States by the Paediatric Orthopaedic Society of North America, which builds research infrastructure through the development of guidelines and training for investigators. Wright et al¹¹ also stress the importance of greater training provision for clinicians in their summary report from the AAOS and ORS symposium.

Through greater involvement in trials and collaboration with more experienced lead clinicians, it is hoped that the infrastructure and research culture may improve in orthopaedics. For example, international fellowships such as the American British Canadian (ABC) travelling fellowship, have been successfully used to promote international collaboration.⁹ Yeung and Bhandari¹² urge that orthopaedic surgeons in countries proficient in undertaking trials should foster collaborations with colleagues internationally in order to promote the research culture and provide necessary training, but also to improve the external validity of trials to specific settings. Through exploring the rates of RCTs published on hip fractures internationally, this article demonstrates high levels of variance across countries in terms of their contributions in this area. Trials were most common in the United Kingdom and Scandinavian countries, with Canada and the US contributing only one tenth of the number of trials conducted in Europe.¹²

Conduct of multicentre RCTs

Studies included in this review suggest a number of ways through which trial networks and societies can aid the conduct of multicentre RCTs in orthopaedics, such as the identification of and co-ordination between skilled research staff. Their role may be even more important where multinational trials are concerned, with localised systems of gaining research approvals and language and communication barriers creating difficulties. The IHFRC collaboration based in Canada have a central ‘Methods Centre’ where experienced trial methodologists co-ordinate the FAITH and HEALTH trials, with specific ‘Country Offices’ responsible for the day-to-day liaison with centres.⁵

Research networks can be used to develop links between research communities, which may be vitally important, as effective liaison between clinical, academic and regulatory roles in trials is crucial to their success. In an abstract presented at the British Society of Rheumatology, Scott¹⁴ made recommendations for a ‘National Arthritis Research Network’ to facilitate the recruitment of patients and participation of rheumatology and orthopaedic clinicians in trials in this field. This paper suggests a specific network such as this could act as a point of liaison with researchers, clinicians, Research and Development departments and local Clinical Research Networks, to overcome regulatory issues associated with implementing research studies, as well as providing advice and training for clinicians wishing to participate in research.¹⁴

In Germany, Otto et al⁸ have advocated the use of research networks on a central and regional basis to generate support and links between researchers in orthopaedic trials.⁸ This article draws upon the authors’ experiences of setting up a Clinical Trials Unit for trauma and orthopaedic surgery, and highlights the role that networks can play in obtaining skilled project staff.⁸ This point is also raised by Carr and Cooper¹³ in their presentation of recruitment data from a multicentre RCT of treatments for rotator cuff injuries, the UKUFF trial. This paper suggests a beneficial effect on recruitment was obtained when sites were supported through the local research network (i.e. through research nurse provision), with supported sites recruiting almost twice as many patients over the course of the trial.¹³ Rangan et al⁹ have also described how the ProFHER trial, a multicentre RCT of surgical versus non-surgical intervention for fractures of the proximal humerus,²⁰ has benefited from the support of the CLRNs in the UK, which were able to allocate research nurse or physiotherapist support to the study through either service support costs or research capability funding.

Aside from the practical assistance that networks may provide in the day-to-day running of trials, Vitale et al¹⁶ describe the involvement of a clinical research network, launched in 1999 by the Paediatric Orthopaedic Society of North America, in developing a trauma registry to record and manage clinical outcome data in paediatric musculoskeletal trauma across five centres. The authors, however, acknowledge that the usefulness of such registers to promote multicentre research activity, may be limited by regulatory challenges associated with storing patient-identifiable data.¹⁶

Dissemination and adoption of trial results

The active promotion of trials amongst the medical community is important not only during the early phases of design and eventual conduct of the trial, but also crucially when disseminating trial results, in order for them to be adopted into medical practice. Larger multicentre RCTs with wider participation improves generalisability and facilitates adoption of trial findings into clinical practice. In the United Kingdom, Clinical Commissioning Groups and bodies such as National Institute for Health and Care Excellence (NICE)²¹ use trial findings to inform healthcare commissioning, thus facilitating adoption into clinical practice. Rangan et al⁹ have described the importance of this at a national and international level, and suggest specialist societies, such as the British Elbow and Shoulder Society (BESS) can be used to provide this interface between researchers and the medical community. Furthermore, these societies may produce guidelines for best practice for their members based upon the reports of RCTs in the field.⁹

Trainee-led research collaboratives

Current United Kingdom health research policy, based on the Cooksey report,²² encourages collaborative research, with the National Health Service (NHS) becoming a partner as opposed to a mere receptacle in research. This in turn has led to development of trainee research collaboratives, which empower trainees in these roles.^23,24 They offer an environment in which trainees can support each other, develop research ideas and attain the necessary skills to remain research active beyond completion of their higher surgical training.

In 2007, general surgical trainees in the West Midlands set up the first trainee-led research collaborative in the United Kingdom.²⁵ The West Midlands Research Collaborative (WMRC) aimed to use the natural network formed by surgical trainees to run multicentre RCTs. Their initial success encouraged other regions to develop like-minded research groups. With over 15 active research groups covering England, Scotland and Wales, the general surgical trainees now have an effective research network, which has enabled them to complete a range of prospective clinical trials and co-ordinated audit projects.^26-29 Clinical audits, in addition to a variety of surveys,^29-31 systematic reviews/meta-analyses,^32,33 and cohort studies²⁸ have helped to identify gaps in current knowledge and highlight variations in clinical practice. Such information has been successfully used to generate hypotheses and research questions, and provides the background and justification for subsequent prospective randomised trials.²⁷

The general surgical model has subsequently been adopted by a number of other surgical specialties including neurosurgery, urology, paediatric surgery, ENT, cardiothoracic surgery, plastic/reconstructive surgery and orthopaedics.³⁴ The importance of effective communication, interaction and information-sharing, both within and between groups, is recognised and encouraged and is supported by national events such as the National Research Collaborative Meeting.³⁵

To date, trainee-led research groups in surgical specialties have attracted almost £2 million in research funding, mainly from the National Institute for Health Research (NIHR) for trials like ROSSINI (ISRCTN40402832), DREAMS (ISRCTN21973627) and Hughes Abdominal Repair Trial (HART) (ISRCTN25616490).

Trainees in orthopaedic surgery have established similar clinical research networks. The Collaborative Orthopaedic Research NETwork (CORNET), set up by trainees in the Northern Deanery³⁶ and the South Yorkshire Trainees’ Orthopaedic Research Collaborative (STORC) in the Yorkshire Deanery are examples of regional collaboratives. To supplement the work of these regional groups, the British Orthopaedic Trainees Association (BOTA) recently announced the launch of the British Orthopaedic Network Environment (BONE). This trainee-led initiative aims to provide a platform for nationally co-ordinated research and audit while also supporting orthopaedic leadership and education.