Journal of Medical Imaging and Radiation Oncology 56 (2012) 449451

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R ADIOLO GYPO I N T O F VI E W

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The controversy over vertebroplasty: An analysis of the debate and proposals for a way forward
Jane Johnson,1 Wendy Rogers1,2 and Rosalind L Jeffree2
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Department of Philosophy, and 2Australian School of Advanced Medicine, Macquarie University, North Ryde, New South Wales, Australia

J Johnson PhD; W Rogers PhD MRCGP FRACGP; RL Jeffree MBBS MSc FRACS. Correspondence Dr Jane Johnson, Department of Philosophy, Macquarie University, North Ryde, NSW 2109, Australia. Email: jane.johnson@mq.edu.au Conict of interest: None. Submitted 17 February 2012; accepted 19 March 2012. doi:10.1111/j.1754-9485.2012.02409.x

Summary
This paper examines the ongoing and often heated debate about the merits or otherwise of percutaneous vertebroplasty as a treatment for painful osteoporotic vertebral fractures. In spite of the proliferation of research on this topic there is no agreement over its indications, safety or efcacy. We discuss the ethical issues which arise when new medical interventions such as vertebroplasty are introduced and make suggestions of relevance not just to the case of vertebroplasty, but to the introduction of innovative procedures generally. Key words: ethics; new intervention; vertebroplasty.

Despite recent research, the efcacy of percutaneous vertebroplasty as a treatment for painful osteoporotic vertebral fracture remains hotly contested, with disagreement over indications, safety and efcacy. In this paper we identify central disagreements in the debate; argue why these are ethically important; and suggest potential ways forward. While our focus is on vertebroplasty, the issues raised are relevant to the introduction of other procedural interventions.

The dispute over vertebroplasty

Since it was rst described in 1987, vertebroplasty has been widely used to treat osteoporotic vertebral fracture, a painful and disabling condition. Yet two randomized controlled trials (RCTs) published in 2009 raised questions about the efcacy and safety of vertebroplasty. It was claimed that the procedure was no more effective than placebo, and had the potential to generate harm through cement leakage, infection and spinal cord injury.1 The current debate revolves around three main issues: what constitutes appropriate evidence for or against the procedure; which patients may benet; and what is the best method for vertebroplasty? First, there is fundamental disagreement over the evidence required to substantiate the efcacy and safety

of vertebroplasty. Initial uptake was based upon case studies and clinical experience; however, this is not widely accepted as evidence of efcacy. Formal trials have adopted a variety of methodologies including RCTs, with14 and without randomization.5 Blinding is a key method of reducing bias, yet large unblinded trials have been undertaken, with researchers arguing that blinding is not possible when investigating an intervention like vertebroplasty.2 Trials have compared vertebroplasty to a sham procedure on the grounds that a sham arm will control for the enhanced placebo effect likely for invasive procedures;1 while other trials used standard management on the grounds that this is the critical comparator to establish whether or not vertebroplasty is superior to standard management.6 Of note, there is disagreement over the best conservative management for these fractures, further complicating claims about comparative efcacy.7 Second, there is lack of agreement over who should be recruited into research. Some commentators suggest two groups are likely to benet from vertebroplasty those with acute pain and those with severe pain. For instance Clark et al. maintain that vertebroplasty should be undertaken in the acute phase because it works by stabilizing and helping repair complex fractures. They claim that the patients enrolled by Buchbinder et al. (up

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to 1 year post fracture) would therefore not be expected to benet from the procedure.8 Given neither of the 2009 trials had sufcient statistical power to make denitive claims about patient subgroups with either acute or severe pain, a meta-analysis was undertaken pooling data from these trials. The meta-analysis found no advantage to patients in the acute phase or those with severe pain.9 Clark and colleagues have argued, however, that the patient cohort in this meta-analysis included almost no inpatients, and yet inpatients constitute the main acute fracture cohort treated in Australia.10 A nal issue concerns disagreement over the most appropriate method for vertebroplasty. Clark and colleagues argue, for example, that the amount of cement used in the Buchbinder trial is insufcient to properly stabilize the lumbar fractures being treated.8,10

broplasty, we lack evidence of its superiority compared with less costly interventions, and of its long-term effectiveness in the Australian context. Thus until recently, when Medicare funding was withdrawn, Australian patients were provided with an intervention funded by the Australian community, whose safety, efcacy and effectiveness were in dispute.

Ways of progressing the debate

Evidence is clearly crucial in resolving questions about vertebroplasty, but more research in the pattern of previous trials is unlikely to resolve these issues, as these are talking past each other. We argue that future research should be directed towards resolving the main outstanding points of disagreement. First, we need some consensus on the indications and methods for vertebroplasty. This is not solely a scientic matter, as it requires judgment about such issues as: acceptable healing times for vertebral fractures; levels of pain considered normal for healing versus pathological pain; and the goals of treatment (to decrease duration and/or intensity of pain, to increase mobility as rapidly as possible, to reduce costs to the health care system, etc.). Once the questions are settled, it will be relatively simple to match research methods to the questions; however, reaching agreement on the questions is the critical matter. One possible way of managing the development of research questions for emerging interventions is by dedicated groups similar to guideline development groups. These would need to have relevant expertise including that of patient and community members. Research would then proceed based on agreed research questions, matched to appropriate trial method and design, including monitoring of long-term outcomes via mechanisms such as registers. This proposal relies upon ideal notions of professional cooperation and coordinated research efforts. While the latter is unlikely to be possible given diverse sources of research funding, it is possible to set up research question development groups, and for these to endorse research that addresses identied questions. Professional cooperation should be possible, based upon the duty of doctors to act for the good of patients. We note that interventions like vertebroplasty which rely upon the skill of individual operators raise challenges for evaluation, partly because of the learning curves associated with practitioners performing new procedures. Data about practitioner expertise should therefore be collected as part of any research. Well designed research that addresses the efcacy and safety of vertebroplasty can meet some of the ethical issues described above, but may introduce further concerns. For instance use of a sham arm in which patients receive no treatment (merely a placebo) can be justied only if the research question is

Ethical issues
The introduction of any new medical intervention raises ethical concerns. As with vertebroplasty, these may relate to uncertainty about the safety, efcacy and effectiveness of the intervention; questions that may be resolved by appropriate trials. New interventions also raise broader questions about their value and cost to the health care system where they are introduced. To minimize patient harm, new interventions such as vertebroplasty require evidence of short-term safety and efcacy, as well as research which tracks mediumand long-term outcomes. While RCTs are the most robust method for establishing efcacy, safety may be established with evidence from clinical practice. Despite being widely performed since the late 1980s, there are lingering questions over vertebroplastys safety, and as noted, little consensus within the medical community about its efcacy. This latter point raises ethical issues in relation to recruiting patients into trials; randomization of participants to different arms of a trial is ethical only in the presence of equipoise. This principle requires that there be uncertainty over the merits of the procedure being tested. While there is clearly equipoise across the broader medical community, practitioners who are skilled in vertebroplasty maintain it is safe and effective, and may therefore nd it ethically troubling to participate in RCTs in which some of the patients will not receive what they regard as the best possible treatment. The broader ethical issue of whether or not a publicly funded health care system should fund new interventions such as vertebroplasty requires taking account of two types of cost the cost of performing the intervention, and the opportunity costs associated with funding vertebroplasty, rather than other treatments for painful osteoporotic vertebral fracture, or of funding treatments for other diseases and conditions. Research therefore needs to demonstrate proof of effectiveness, as well as compare vertebroplasty with other treatment options for vertebral fractures. In spite of public funding for verte-

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Controversy over vertebroplasty

sufciently important, equipoise holds and the harms to patients are minimized. Currently trials in the Netherlands and Australia are recruiting to address questions of efcacy,11,12 safety and cost-effectiveness of vertebroplasty for patients with acute fractures.12 Both trials employ a sham arm which we argue is ethically justied given the importance of the issues being addressed and the ongoing uncertainty surrounding vertebroplasty. While the focus of this paper has been vertebroplasty, the issues we raise are relevant to the introduction of other procedural interventions. Setting up research question development groups and enrolling all patients for data collection may seem bureaucratic and cumbersome. However, the costs of this approach may be considerably less than the current costs of multiple yet apparently inconclusive trials; lack of evidence for patients, practitioners and funding bodies; and the expense of funding interventions that may be no better than placebo. Restricting procedural funding to patients enrolled in appropriate clinical trials would not only remove some of the practical difculties, but also several of the ethical problems that arise when interventions are introduced in advance of robust evidence.

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Acknowledgements
Jane Johnson and Wendy Rogers are members of the INCISIVE Research Team based at Macquarie University, Sydney, Australia. Research towards this paper was partly supported by an Australian Research Council Linkage Grant (LP110200217 On the cutting edge: promoting best practice in surgical innovation).
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References
1. Buchbinder R, Osborne R, Ebeling P et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med 2009; 361: 55768. 2. Klazen CAH, Lohle PNM, de Vries J et al. Vertebroplasty versus conservative treatment in 12.

acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial. Lancet 2010; 376: 108592. Rousing R, Hansen KL, Anderson MO et al. Twelve-months follow-up in forty-nine patients with acute/semiacute osteoporotic vertebral fractures treated conservatively or with percutaneous vertebroplasty. Spine 2010; 35: 47882. Kallmes DF, Comstock BA, Heagerty PJ et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009; 361: 56979. Diamond TH, Bryant C, Browne L et al. Clinical outcomes after acute osteoporotic vertebral fractures: a 2-year non-randomised trial comparing vertebroplasty with conservative therapy. Med J Aust 2006; 184: 11317. Klazen CAH, Mali WPTM, Lohle PNM et al. Authors reply. Lancet 2010; 376: 20712. Denaro V, Longo UG, Denaro L. Correspondence. Lancet 2010; 376: 2071. Clark WA, Diamond TH, McNeil HP et al. Vertebroplasty for painful acute osteoporotic vertebral fractures: recent Medical Journal of Australia editorial is not relevant to the patient group that we treat with vertebroplasty. Med J Aust 2010; 192: 3347. Staples MP, Kallmes DF, Comstock BA et al. Effectiveness of vertebroplasty using individual patient data from two randomized placebo controlled trials: meta-analysis. BMJ 2011; 343: d3952. Clark WA, Burnes JP, Lyon SM. Vertebroplasty for acute osteoporotic fractures position statement from the Interventional Radiology Society of Australasia (editorial). J Med Imaging Radiat Oncol 2011; 55: 13. van Rooij WJ, Lohle PN, De Vries J (Investigators). A Randomised sham controlled trial of vertebroplasty for painful acute osteoporotic vertebral fractures. 2010. [updated 1 Aug 2011; Cited 7 Mar 2012.] Available from URL: http://www.clinicaltrials.gov Clark W (Principal Investigator). A Controlled trial of vertebroplasty for acute painful osteoporotic fractures. 2011. [updated 30 Nov 2011; Cited 7 Mar 2012.] Available from URL: http://www. clinicaltrials.gov

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