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Pain Medicine 2014; 15: 1811–1819 Wiley Periodicals, Inc.
LETTERS TO THE EDITOR Reply to “A Response to Two Recent Reviews of Epidural Steroid Injections” Funding source: None. Disclosure: None. Dear Editor,
Nampiaparampil and Engel criticized our methods for pooling across all ESI approaches, but failed to mention that we provided separate data for treatment effects for each approach. Appendix Figure 3 in our publication shows a significant short-term relief of leg pain (weighted mean difference = −6.1 [95% confidence interval −11.3 to −0.9]), favoring the transforaminal ESI over the placebo [2]. This pooled effect, similar to the pooled effects found for other ESI approaches, is probably not sufficiently large to be judged clinically meaningful by patients and clinicians. Nampiaparampil and Engel also argued that our analyses included studies using “blind” non-fluoroscopyguided injections. We would like to clarify that all five trials [3–7] included in this subgroup analysis reported the use of fluoroscopy, so this criticism is unwarranted. In addition, the presence of clinical symptoms with concordant evidence from magnetic resonance imaging (MRI) was an inclusion criterion in four trials [3,4,6,7], and MRI scans were used as part of the baseline clinical assessment in one trial [5]. Hence, in our opinion, there is no reason to believe that injections were not performed at the appropriate clinical level as suggested by these authors. Nampiaparampil and Engel also criticized our review for only including randomized controlled trials and excluding observational studies. It is well accepted that the preferred and most valid design to evaluate the effect of therapy is a randomized controlled trial so this criticism has no basis and conflicts with contemporary approaches to medical research. Nampiaparampil and Engel criticized our approach to meta-analysis as we used group level data, and they suggested that analysis of individual patient data may reveal subgroups of patients who do respond to epidural injections. We were unable to conduct such an analysis
Nampiaparampil and Engel state that “most practitioners who perform interventional procedures recognize the clinical benefits of ESI. Therefore, the high-quality research performed often compares different procedural approaches to one another.” This statement fails to consider that observed benefits in patients may well occur due to factors other than the interventional procedures, such as the natural course of the disease, placebo effects, or measurement error. This is why clinical trials comparing interventional procedures to placebo (or no treatment) are needed in order to control for these variables. According to Nampiaparampil and Engel, studies that compare ESI with control injections only assess the incremental effect of the injected steroid, suggesting that the volume of injectate may be a factor in the treatment outcomes. This is probably counterintuitive and questions the pharmacological rationale of using corticosteroid to treat this condition. Clearly, more research is needed to better understand the mechanism of action of such an invasive procedure before it can be widely recommended. Our view is that conclusions drawn from systematic reviews that evaluated evidence from different research designs and methods are, not surprisingly, very likely to differ. We state that our review was conducted by a multidisciplinary group of independent researchers, included the relevant literature in this topic, and used the appropriate methods to analyze the available literature. Readers need to be aware that the critical appraisal presented by Nampiaparampil and Engel has several limitations before making their own judgments. RAFAEL Z. PINTO, PhD,*† CHRIS G. MAHER, PhD,‡§ and BART KOES, PhD¶ *Honorary Fellow, The George Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia and † Research Manager, Pain Management Research Institute, University of Sydney at Royal North Shore 1811
Downloaded from http://painmedicine.oxfordjournals.org/ by guest on June 6, 2016
The letter published by Nampiaparampil and Engel, both members of the International Spine Intervention Society, in the June issue of Pain Medicine considered the conflicting conclusions of two recent reviews of epidural steroid injections (ESIs) for sciatica [1]. They applaud the authors of the positive review and dismiss our review that came to a different conclusion as flawed. In this letter, we argue why their critical appraisal of our review is itself flawed and misleading.
as we did not have access to the individual patient data from each trial. While they hypothesize that there is a subgroup that experience great benefit, they fail to appreciate the ramifications of that suggestion. As the mean group effect of treatment was close to zero, the only way a subgroup of patients would experience great benefit from ESI would be if another subgroup experienced great harm from ESI (as compared with a control injection). That is a fairly depressing scenario and probably not a great argument in favor of epidural injections.
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Bogduk Hospital, Sydney, New South Wales, Australia; Professor, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia and ‡ Director, The George Institute for Global Health, Sydney, New South Wales, Australia; ¶ Professor, Department of General Practice, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands §
References 1 Nampiaparampil DE, Engel AJ. A response to two recent reviews of epidural steroid injections. Pain Med 2013;14:954–5.
3 Cohen SP, White RL, Kurihara C, et al. Epidural steroids, etanercept, or saline in subacute sciatica a
trial.
Ann
Intern
Med
4 Ghahreman A, Ferch R, Bogduk N. The efficacy of transforaminal injection of steroids for the treatment of lumbar radicular pain. Pain Med 2010;11:1149– 68. 5 Karppinen J, Malmivaara A, Kurunlahti M, et al. Periradicular infiltration for sciatica: A randomized controlled trial. Spine (Phila Pa 1976) 2001;26:1059–67. 6 Ng L, Chaudhary N, Sell P. The efficacy of corticosteroids in periradicular infiltration for chronic radicular pain: A randomized, double-blind, controlled trial. Spine (Phila Pa 1976) 2005;30:857–62. 7 Tafazal S, Ng L, Chaudhary N, Sell P. Corticosteroids in peri-radicular infiltration for radicular pain: A randomised double blind controlled trial. One year results and subgroup analysis. Eur Spine J 2009;18: 1220–5.
Editor’s Response: Group vs Categorical Data in Epidural Studies Dear Editor, In their letter, Nampiaparampil and Engel raise a number of concerns about the study of Pinto et al. [1], and their exchange provides us a valuable opportunity to discuss study design and interpretation. Some of their concerns can be questioned, but they do reflect the irritation felt by practitioners who find their procedures being assaulted, seemingly unfairly, by academics who do not practice in the field under review. The concern that studies differed in the doses used are not fair criticisms of a review, because in practice there is no uniformity of dose for epidural injections. Nor is it a fair criticism that studies may have been compromised because the injection was at the wrong level, for there is no evidence that epidural injections have to be that target-specific. Of some relevance is the criticism that blind injections should not be lumped with fluoroscopically guided injections, for it has been shown that blind injections often miss the epidural space completely. In their letter of response, Pinto et al. retort that they did perform a subgroup analysis of fluoroscopically guided injections; but here the arguments get confused. The subgroup in question was not studies of fluoroscopically guided epidural injections but studies of transforaminal injections, which is a different procedure from interlaminar injections, either blind or fluoroscopically guided. The review in question repeats the same error as past reviews, of lumping all procedures as alike, when they are not, either with respect to technique or the associated evidence. 1812
Nampiaparampil and Engel raised one, serious and valid criticism that I would like to rearticulate. They stated that the review of Pinto et al. [1], like previous reviews, drew their conclusions on the basis of group data, i.e., mean values (and standard deviations). This emerges as an important point and happens to underlie another concern of Nampiaparampil and Engel, namely that practitioners “recognize the clinical benefits of ESI.” Group data do not reflect reality. Practitioners do not encounter “mean” patients or “mean” responses. Reality is measured by success or failure, and this is what practitioners encounter. The liability, however, is that practitioners are likely to remember their successes but forget their failures and, therefore, exaggerate the apparent success of their interventions. This is why documentation of success rates are the gold standard in both observational studies or randomized controlled trials. In responding to this point, Pinto et al. use eminencebased medicine, rather than data. In an authoritative manner they write dismissively that “the only way a subgroup of patients would experience great benefit from ESI would be if another subgroup experienced great harm . . .”. The available data refute this dismissal. Ghahreman et al. [2] showed and emphasized that group data camouflage outcomes. Upon analysis, their own group data showed no statistically significant change in pain scores after transforaminal injection of steroids; however, their categorical data were strongly significant.
Downloaded from http://painmedicine.oxfordjournals.org/ by guest on June 6, 2016
2 Pinto RZ, Maher CG, Ferreira ML, et al. Epidural corticosteroid injections in the management of sciatica: A systematic review and meta-analysis. Ann Intern Med 2012;157:865–77.
multicenter, randomized 2012;156:551–9.
Pain Medicine 2014; 15: 1811–1819 Wiley Periodicals, Inc.
LETTERS TO THE EDITOR Reply to “A Response to Two Recent Reviews of Epidural Steroid Injections” Funding source: None. Disclosure: None. Dear Editor,
Nampiaparampil and Engel criticized our methods for pooling across all ESI approaches, but failed to mention that we provided separate data for treatment effects for each approach. Appendix Figure 3 in our publication shows a significant short-term relief of leg pain (weighted mean difference = −6.1 [95% confidence interval −11.3 to −0.9]), favoring the transforaminal ESI over the placebo [2]. This pooled effect, similar to the pooled effects found for other ESI approaches, is probably not sufficiently large to be judged clinically meaningful by patients and clinicians. Nampiaparampil and Engel also argued that our analyses included studies using “blind” non-fluoroscopyguided injections. We would like to clarify that all five trials [3–7] included in this subgroup analysis reported the use of fluoroscopy, so this criticism is unwarranted. In addition, the presence of clinical symptoms with concordant evidence from magnetic resonance imaging (MRI) was an inclusion criterion in four trials [3,4,6,7], and MRI scans were used as part of the baseline clinical assessment in one trial [5]. Hence, in our opinion, there is no reason to believe that injections were not performed at the appropriate clinical level as suggested by these authors. Nampiaparampil and Engel also criticized our review for only including randomized controlled trials and excluding observational studies. It is well accepted that the preferred and most valid design to evaluate the effect of therapy is a randomized controlled trial so this criticism has no basis and conflicts with contemporary approaches to medical research. Nampiaparampil and Engel criticized our approach to meta-analysis as we used group level data, and they suggested that analysis of individual patient data may reveal subgroups of patients who do respond to epidural injections. We were unable to conduct such an analysis
Nampiaparampil and Engel state that “most practitioners who perform interventional procedures recognize the clinical benefits of ESI. Therefore, the high-quality research performed often compares different procedural approaches to one another.” This statement fails to consider that observed benefits in patients may well occur due to factors other than the interventional procedures, such as the natural course of the disease, placebo effects, or measurement error. This is why clinical trials comparing interventional procedures to placebo (or no treatment) are needed in order to control for these variables. According to Nampiaparampil and Engel, studies that compare ESI with control injections only assess the incremental effect of the injected steroid, suggesting that the volume of injectate may be a factor in the treatment outcomes. This is probably counterintuitive and questions the pharmacological rationale of using corticosteroid to treat this condition. Clearly, more research is needed to better understand the mechanism of action of such an invasive procedure before it can be widely recommended. Our view is that conclusions drawn from systematic reviews that evaluated evidence from different research designs and methods are, not surprisingly, very likely to differ. We state that our review was conducted by a multidisciplinary group of independent researchers, included the relevant literature in this topic, and used the appropriate methods to analyze the available literature. Readers need to be aware that the critical appraisal presented by Nampiaparampil and Engel has several limitations before making their own judgments. RAFAEL Z. PINTO, PhD,*† CHRIS G. MAHER, PhD,‡§ and BART KOES, PhD¶ *Honorary Fellow, The George Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia and † Research Manager, Pain Management Research Institute, University of Sydney at Royal North Shore 1811
Downloaded from http://painmedicine.oxfordjournals.org/ by guest on June 6, 2016
The letter published by Nampiaparampil and Engel, both members of the International Spine Intervention Society, in the June issue of Pain Medicine considered the conflicting conclusions of two recent reviews of epidural steroid injections (ESIs) for sciatica [1]. They applaud the authors of the positive review and dismiss our review that came to a different conclusion as flawed. In this letter, we argue why their critical appraisal of our review is itself flawed and misleading.
as we did not have access to the individual patient data from each trial. While they hypothesize that there is a subgroup that experience great benefit, they fail to appreciate the ramifications of that suggestion. As the mean group effect of treatment was close to zero, the only way a subgroup of patients would experience great benefit from ESI would be if another subgroup experienced great harm from ESI (as compared with a control injection). That is a fairly depressing scenario and probably not a great argument in favor of epidural injections.
bs_bs_banner
Bogduk Hospital, Sydney, New South Wales, Australia; Professor, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia and ‡ Director, The George Institute for Global Health, Sydney, New South Wales, Australia; ¶ Professor, Department of General Practice, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands §
References 1 Nampiaparampil DE, Engel AJ. A response to two recent reviews of epidural steroid injections. Pain Med 2013;14:954–5.
3 Cohen SP, White RL, Kurihara C, et al. Epidural steroids, etanercept, or saline in subacute sciatica a
trial.
Ann
Intern
Med
4 Ghahreman A, Ferch R, Bogduk N. The efficacy of transforaminal injection of steroids for the treatment of lumbar radicular pain. Pain Med 2010;11:1149– 68. 5 Karppinen J, Malmivaara A, Kurunlahti M, et al. Periradicular infiltration for sciatica: A randomized controlled trial. Spine (Phila Pa 1976) 2001;26:1059–67. 6 Ng L, Chaudhary N, Sell P. The efficacy of corticosteroids in periradicular infiltration for chronic radicular pain: A randomized, double-blind, controlled trial. Spine (Phila Pa 1976) 2005;30:857–62. 7 Tafazal S, Ng L, Chaudhary N, Sell P. Corticosteroids in peri-radicular infiltration for radicular pain: A randomised double blind controlled trial. One year results and subgroup analysis. Eur Spine J 2009;18: 1220–5.
Editor’s Response: Group vs Categorical Data in Epidural Studies Dear Editor, In their letter, Nampiaparampil and Engel raise a number of concerns about the study of Pinto et al. [1], and their exchange provides us a valuable opportunity to discuss study design and interpretation. Some of their concerns can be questioned, but they do reflect the irritation felt by practitioners who find their procedures being assaulted, seemingly unfairly, by academics who do not practice in the field under review. The concern that studies differed in the doses used are not fair criticisms of a review, because in practice there is no uniformity of dose for epidural injections. Nor is it a fair criticism that studies may have been compromised because the injection was at the wrong level, for there is no evidence that epidural injections have to be that target-specific. Of some relevance is the criticism that blind injections should not be lumped with fluoroscopically guided injections, for it has been shown that blind injections often miss the epidural space completely. In their letter of response, Pinto et al. retort that they did perform a subgroup analysis of fluoroscopically guided injections; but here the arguments get confused. The subgroup in question was not studies of fluoroscopically guided epidural injections but studies of transforaminal injections, which is a different procedure from interlaminar injections, either blind or fluoroscopically guided. The review in question repeats the same error as past reviews, of lumping all procedures as alike, when they are not, either with respect to technique or the associated evidence. 1812
Nampiaparampil and Engel raised one, serious and valid criticism that I would like to rearticulate. They stated that the review of Pinto et al. [1], like previous reviews, drew their conclusions on the basis of group data, i.e., mean values (and standard deviations). This emerges as an important point and happens to underlie another concern of Nampiaparampil and Engel, namely that practitioners “recognize the clinical benefits of ESI.” Group data do not reflect reality. Practitioners do not encounter “mean” patients or “mean” responses. Reality is measured by success or failure, and this is what practitioners encounter. The liability, however, is that practitioners are likely to remember their successes but forget their failures and, therefore, exaggerate the apparent success of their interventions. This is why documentation of success rates are the gold standard in both observational studies or randomized controlled trials. In responding to this point, Pinto et al. use eminencebased medicine, rather than data. In an authoritative manner they write dismissively that “the only way a subgroup of patients would experience great benefit from ESI would be if another subgroup experienced great harm . . .”. The available data refute this dismissal. Ghahreman et al. [2] showed and emphasized that group data camouflage outcomes. Upon analysis, their own group data showed no statistically significant change in pain scores after transforaminal injection of steroids; however, their categorical data were strongly significant.
Downloaded from http://painmedicine.oxfordjournals.org/ by guest on June 6, 2016
2 Pinto RZ, Maher CG, Ferreira ML, et al. Epidural corticosteroid injections in the management of sciatica: A systematic review and meta-analysis. Ann Intern Med 2012;157:865–77.
multicenter, randomized 2012;156:551–9.
