- Email: [email protected]
In evidence-based medicine, more research is not always better…
The Spine Journal 16 (2016) 313–314
Commentary
In evidence-based medicine, more research is not always better… Simon Dagenais, DC, PhD, MSca,*, O’Dane Brady, DC, MSb a Spine Research LLC, 540 Main St #7, Winchester, MA 01890, USA School of Physical Therapy and Rehabilitation Sciences, Morsani College of Medicine, University of South Florida, 13301 Bruce B Downs Blvd, Tampa, FL 33612, USA
b
Received 16 November 2015; accepted 2 December 2015
COMMENTARY ON: Castro-Sánchez AM, Lara-Palomo IC, Matarán-Peñarrocha GA, Fernández-de-las-Peñas C, Saavedra-Hernández M, Cleland J, et al. Short-term effectiveness of spinal manipulative therapy versus functional technique in patients with chronic non-specific low back pain: a pragmatic randomized controlled trial. Spine J 2016:16:302–312 (in this issue).
Stakeholders involved in managing low back pain (LBP), including patients, health-care providers, and third-party payers, often turn to summary conclusions from systematic reviews to determine the level of evidence supporting the efficacy of an intervention. The highest level of evidence (ie, Level 1) can generally be achieved by providing consistent and clinically meaningful results from two randomized controlled trials (RCTs) of sufficient methodological quality. If the first two RCTs to ever evaluate an intervention can fulfill this requirement, the matter may be concluded and researchers can move on to answer other important questions. However, if the first two RCTs assessing the efficacy of an intervention report inconsistent, negative, or mixed findings, or are of insufficient methodology quality, it may be necessary to conduct additional RCTs to clarify the issue. Even in such cases, not all new RCTs will contribute equally to FDA device/drug status: Not applicable. Author disclosures: SD: Royalties: Elsevier (A), outside the submitted work; Private Investments: Palladian Health (<2% of common shares), outside the submitted work; Consulting: University of South Florida (D), NCMIC Foundation (E), Dr Louis Sportelli (B), Pacira Pharmaceuticals (D), NYUMC (C), Palladian Health (F), Emmi Solutions (B), outside the submitted work; Speaking and/or Teaching Arrangements: NCMIC (B), outside the submitted work; Trips/Travel: NCMIC (A), NASS (A), outside the submitted work; Scientific Advisory Board/Other Office: Palladian Health (Included in consulting), outside the submitted work. ODB: Consulting: Palladian Health (C), Pacira Pharmaceuticals (D), outside the submitted work; Trips/Travel: Palladian Health (A), outside the submitted work; Scientific Advisory Board/ Other Office: World Spine Care (B), outside the submitted work. The disclosure key can be found on the Table of Contents and at www.TheSpineJournalOnline.com. * Corresponding author. Spine Research LLC, 540 Main St #7, Winchester, MA 01890, USA. Tel.: 781-460-3002. E-mail address: [email protected] (S. Dagenais) http://dx.doi.org/10.1016/j.spinee.2015.12.002 1529-9430/© 2016 Elsevier Inc. All rights reserved.
addressing unanswered questions, and more research is not always better. In fact, as the number of RCTs assessing the efficacy of an intervention increases, it can become increasingly difficult to draw meaningful conclusions because of the inevitable differences that arise in study design, quality, and findings. Such is the case with spinal manipulation therapy (SMT) for LBP, which has been evaluated in so many RCTs (at least 61 were identified in 2012) that it is now impractical for all but the most patient and well-funded researchers to conduct a thorough systematic review on this topic [1]. Nevertheless, a simple overview of conclusions from previous reviews may be sufficient to provide some insight into the current literature on the efficacy of this intervention. One of the earliest reviews on this topic was published in 1979, which evaluated seven studies on SMT and concluded that “manipulation of the lumbar spine might have an immediate, short-time effect on low back pain in a limited number of patients” [2]. A 1992 review based on 25 RCTs of SMT concluded that “spinal manipulation is of short-term benefit in some patients” [3]. A 2003 review of 26 RCTs for LBP concluded that SMT “has small clinical benefits that are equivalent to those of other commonly used therapies” [4]. In 2013, a review of 20 RCTs on SMT for acute LBP concluded that SMT “seems to be no better than other recommended therapies” [5]. Based on these conclusions, it does not appear as though the 50 or more RCTs reported between 1979 and 2013 materially impacted what was previously known about the efficacy of SMT for LBP. It is against this backdrop that the recent RCT by CastroSánchez et al. will be assessed. The study in question compares three weekly sessions of high-velocity, low-amplitude thrust
314
S. Dagenais and O.D. Brady / The Spine Journal 16 (2016) 313–314
SMT to the lumbar and thoracic spine performed by physical therapists with three weekly sessions of what appears to be a variant of spinal mobilization (ie, “functional technique”) in patients with chronic non-specific LBP. Outcomes, including pain (0–10 numerical rating scale), disability (Oswestry Disability Index and Roland Morris Disability Questionnaire), health-related quality of life [Short Form 36 (SF36)], fear of movement (Tampa Scale for Kinesiophobia), range of motion (finger to floor distance), and trunk muscle endurance (McQuade test), were measured at 1-month followup. The main study findings were that the group receiving SMT had somewhat more favorable outcomes in disability, with no differences in other outcomes. In other words, this RCT largely supports the conclusion from the 1979 review that SMT provides short-term benefit in some patients with LBP. It is, therefore, challenging to identify the unique contributions made by this recent study to the broader literature on the efficacy of SMT for LBP. In fact, it may be worthwhile instead to highlight some of its limitations and discuss how future RCTs evaluating SMT for LBP could overcome them. For example, the current study speculates about why it failed to uncover meaningful differences between groups in most of its outcomes. A good place to start might be the number of participants included in each group. Although a sample size calculation is provided, its suggestion that only 30 participants per group were necessary is questionable, particularly when viewed against a recommendation from a 2012 review on SMT for LBP that future studies enroll a minimum of 65 patients per group to detect smaller but clinically meaningful differences between groups and minimize the possibility of type 2 errors [1]. Similarly, the choice of a relatively unknown intervention (ie, “functional technique”) as a control group makes it challenging for many readers to interpret study findings as this reference point is unknown. Comparing SMT with other, more commonly used interventions for LBP with known efficacy (eg, education, exercise, and analgesics) could reflect more practical decisions that must be made on a routine basis by stakeholders. Measuring the impact of only three weekly treatment sessions of manual therapy is also questionable, as many patients with chronic LBP routinely receive far more treatment over a much longer time period. Having failed to detect differences in all outcomes in both groups, the study is unable to determine if the number of treatment sessions or duration of treatment was insufficient to achieve the desired effect. Furthermore, having a follow-up period of only 1 month seems somewhat futile when treating a condition such as chronic LBP, whose symptoms can wax and wane in severity for many years.
Although this study has other limitations (some of which are openly acknowledged by its authors), the underlying issue may be that having synthesized available evidence from previous RCT on this topic, additional RCTs are unlikely to yield new insight about the efficacy of SMT for LBP. This suggestion was made in a previous commentary in The Spine Journal (TSJ), which provocatively called for a moratorium on such new studies—that advice appears to not have been heeded [6]. In fact, a recent search of the trial registry site clinicaltrials.gov uncovered 24 ongoing studies assessing the efficacy of SMT for LBP. Optimistically, some of these studies will make meaningful contributions to existing scientific knowledge on this topic. Realistically, many of these new studies will likely conclude that SMT offers modest, shortterm improvements in some patient-reported outcomes that are similar to those offered by other efficacious approaches. Nevertheless, given the generally inconsistent or weak evidence supporting most other interventions for LBP, as well other considerations beyond efficacy, including relative safety, availability, cost, and patient satisfaction, SMT will likely remain one of the core options available to provide shortterm symptomatic relief while pursuing other interventions such as exercise, education, activity modification, and cognitive-behavioral therapies that may offer the possibility of longer term improvement. And although a moratorium on new RCTs of SMT for LBP may not be enforceable, it is advisable for researchers proposing new studies on this topic to review all available evidence and determine how the proposed new study will make a meaningful contribution to the literature before investing the resources necessary to conduct yet another RCT. In evidence-based medicine, more research is not always better. References [1] Rubinstein SM, Terwee CB, de Boer MR, van Tulder MW. Is the methodological quality of trials on spinal manipulative therapy for low-back pain improving? Int J Osteopath Med 2012;15:37–52. [2] Moritz U. Evaluation of manipulation and other manual therapy. Criteria for measuring the effect of treatment. Scand J Rehabil Med 1979;11:173– 9. [3] Shekelle PG, Adams AH, Chassin MR, Hurwitz EL, Brook RH. Spinal manipulation for low-back pain. Ann Intern Med 1992;117:590–8. [4] Cherkin DC, Sherman KJ, Deyo RA, Shekelle PG. A review of the evidence for the effectiveness, safety, and cost of acupuncture, massage therapy, and spinal manipulation for back pain. Ann Intern Med 2003;138:898–906. [5] Rubinstein SM, Terwee CB, Assendelft WJ, de Boer MR, van Tulder MW. Spinal manipulative therapy for acute low back pain: an update of the Cochrane review. Spine 2013;38:E158–77. [6] Hurwitz EL. Commentary: exercise and spinal manipulative therapy for chronic low back pain: time to call for a moratorium on future randomized trials? Spine J 2011;11:599–600.
Commentary
In evidence-based medicine, more research is not always better… Simon Dagenais, DC, PhD, MSca,*, O’Dane Brady, DC, MSb a Spine Research LLC, 540 Main St #7, Winchester, MA 01890, USA School of Physical Therapy and Rehabilitation Sciences, Morsani College of Medicine, University of South Florida, 13301 Bruce B Downs Blvd, Tampa, FL 33612, USA
b
Received 16 November 2015; accepted 2 December 2015
COMMENTARY ON: Castro-Sánchez AM, Lara-Palomo IC, Matarán-Peñarrocha GA, Fernández-de-las-Peñas C, Saavedra-Hernández M, Cleland J, et al. Short-term effectiveness of spinal manipulative therapy versus functional technique in patients with chronic non-specific low back pain: a pragmatic randomized controlled trial. Spine J 2016:16:302–312 (in this issue).
Stakeholders involved in managing low back pain (LBP), including patients, health-care providers, and third-party payers, often turn to summary conclusions from systematic reviews to determine the level of evidence supporting the efficacy of an intervention. The highest level of evidence (ie, Level 1) can generally be achieved by providing consistent and clinically meaningful results from two randomized controlled trials (RCTs) of sufficient methodological quality. If the first two RCTs to ever evaluate an intervention can fulfill this requirement, the matter may be concluded and researchers can move on to answer other important questions. However, if the first two RCTs assessing the efficacy of an intervention report inconsistent, negative, or mixed findings, or are of insufficient methodology quality, it may be necessary to conduct additional RCTs to clarify the issue. Even in such cases, not all new RCTs will contribute equally to FDA device/drug status: Not applicable. Author disclosures: SD: Royalties: Elsevier (A), outside the submitted work; Private Investments: Palladian Health (<2% of common shares), outside the submitted work; Consulting: University of South Florida (D), NCMIC Foundation (E), Dr Louis Sportelli (B), Pacira Pharmaceuticals (D), NYUMC (C), Palladian Health (F), Emmi Solutions (B), outside the submitted work; Speaking and/or Teaching Arrangements: NCMIC (B), outside the submitted work; Trips/Travel: NCMIC (A), NASS (A), outside the submitted work; Scientific Advisory Board/Other Office: Palladian Health (Included in consulting), outside the submitted work. ODB: Consulting: Palladian Health (C), Pacira Pharmaceuticals (D), outside the submitted work; Trips/Travel: Palladian Health (A), outside the submitted work; Scientific Advisory Board/ Other Office: World Spine Care (B), outside the submitted work. The disclosure key can be found on the Table of Contents and at www.TheSpineJournalOnline.com. * Corresponding author. Spine Research LLC, 540 Main St #7, Winchester, MA 01890, USA. Tel.: 781-460-3002. E-mail address: [email protected] (S. Dagenais) http://dx.doi.org/10.1016/j.spinee.2015.12.002 1529-9430/© 2016 Elsevier Inc. All rights reserved.
addressing unanswered questions, and more research is not always better. In fact, as the number of RCTs assessing the efficacy of an intervention increases, it can become increasingly difficult to draw meaningful conclusions because of the inevitable differences that arise in study design, quality, and findings. Such is the case with spinal manipulation therapy (SMT) for LBP, which has been evaluated in so many RCTs (at least 61 were identified in 2012) that it is now impractical for all but the most patient and well-funded researchers to conduct a thorough systematic review on this topic [1]. Nevertheless, a simple overview of conclusions from previous reviews may be sufficient to provide some insight into the current literature on the efficacy of this intervention. One of the earliest reviews on this topic was published in 1979, which evaluated seven studies on SMT and concluded that “manipulation of the lumbar spine might have an immediate, short-time effect on low back pain in a limited number of patients” [2]. A 1992 review based on 25 RCTs of SMT concluded that “spinal manipulation is of short-term benefit in some patients” [3]. A 2003 review of 26 RCTs for LBP concluded that SMT “has small clinical benefits that are equivalent to those of other commonly used therapies” [4]. In 2013, a review of 20 RCTs on SMT for acute LBP concluded that SMT “seems to be no better than other recommended therapies” [5]. Based on these conclusions, it does not appear as though the 50 or more RCTs reported between 1979 and 2013 materially impacted what was previously known about the efficacy of SMT for LBP. It is against this backdrop that the recent RCT by CastroSánchez et al. will be assessed. The study in question compares three weekly sessions of high-velocity, low-amplitude thrust
314
S. Dagenais and O.D. Brady / The Spine Journal 16 (2016) 313–314
SMT to the lumbar and thoracic spine performed by physical therapists with three weekly sessions of what appears to be a variant of spinal mobilization (ie, “functional technique”) in patients with chronic non-specific LBP. Outcomes, including pain (0–10 numerical rating scale), disability (Oswestry Disability Index and Roland Morris Disability Questionnaire), health-related quality of life [Short Form 36 (SF36)], fear of movement (Tampa Scale for Kinesiophobia), range of motion (finger to floor distance), and trunk muscle endurance (McQuade test), were measured at 1-month followup. The main study findings were that the group receiving SMT had somewhat more favorable outcomes in disability, with no differences in other outcomes. In other words, this RCT largely supports the conclusion from the 1979 review that SMT provides short-term benefit in some patients with LBP. It is, therefore, challenging to identify the unique contributions made by this recent study to the broader literature on the efficacy of SMT for LBP. In fact, it may be worthwhile instead to highlight some of its limitations and discuss how future RCTs evaluating SMT for LBP could overcome them. For example, the current study speculates about why it failed to uncover meaningful differences between groups in most of its outcomes. A good place to start might be the number of participants included in each group. Although a sample size calculation is provided, its suggestion that only 30 participants per group were necessary is questionable, particularly when viewed against a recommendation from a 2012 review on SMT for LBP that future studies enroll a minimum of 65 patients per group to detect smaller but clinically meaningful differences between groups and minimize the possibility of type 2 errors [1]. Similarly, the choice of a relatively unknown intervention (ie, “functional technique”) as a control group makes it challenging for many readers to interpret study findings as this reference point is unknown. Comparing SMT with other, more commonly used interventions for LBP with known efficacy (eg, education, exercise, and analgesics) could reflect more practical decisions that must be made on a routine basis by stakeholders. Measuring the impact of only three weekly treatment sessions of manual therapy is also questionable, as many patients with chronic LBP routinely receive far more treatment over a much longer time period. Having failed to detect differences in all outcomes in both groups, the study is unable to determine if the number of treatment sessions or duration of treatment was insufficient to achieve the desired effect. Furthermore, having a follow-up period of only 1 month seems somewhat futile when treating a condition such as chronic LBP, whose symptoms can wax and wane in severity for many years.
Although this study has other limitations (some of which are openly acknowledged by its authors), the underlying issue may be that having synthesized available evidence from previous RCT on this topic, additional RCTs are unlikely to yield new insight about the efficacy of SMT for LBP. This suggestion was made in a previous commentary in The Spine Journal (TSJ), which provocatively called for a moratorium on such new studies—that advice appears to not have been heeded [6]. In fact, a recent search of the trial registry site clinicaltrials.gov uncovered 24 ongoing studies assessing the efficacy of SMT for LBP. Optimistically, some of these studies will make meaningful contributions to existing scientific knowledge on this topic. Realistically, many of these new studies will likely conclude that SMT offers modest, shortterm improvements in some patient-reported outcomes that are similar to those offered by other efficacious approaches. Nevertheless, given the generally inconsistent or weak evidence supporting most other interventions for LBP, as well other considerations beyond efficacy, including relative safety, availability, cost, and patient satisfaction, SMT will likely remain one of the core options available to provide shortterm symptomatic relief while pursuing other interventions such as exercise, education, activity modification, and cognitive-behavioral therapies that may offer the possibility of longer term improvement. And although a moratorium on new RCTs of SMT for LBP may not be enforceable, it is advisable for researchers proposing new studies on this topic to review all available evidence and determine how the proposed new study will make a meaningful contribution to the literature before investing the resources necessary to conduct yet another RCT. In evidence-based medicine, more research is not always better. References [1] Rubinstein SM, Terwee CB, de Boer MR, van Tulder MW. Is the methodological quality of trials on spinal manipulative therapy for low-back pain improving? Int J Osteopath Med 2012;15:37–52. [2] Moritz U. Evaluation of manipulation and other manual therapy. Criteria for measuring the effect of treatment. Scand J Rehabil Med 1979;11:173– 9. [3] Shekelle PG, Adams AH, Chassin MR, Hurwitz EL, Brook RH. Spinal manipulation for low-back pain. Ann Intern Med 1992;117:590–8. [4] Cherkin DC, Sherman KJ, Deyo RA, Shekelle PG. A review of the evidence for the effectiveness, safety, and cost of acupuncture, massage therapy, and spinal manipulation for back pain. Ann Intern Med 2003;138:898–906. [5] Rubinstein SM, Terwee CB, Assendelft WJ, de Boer MR, van Tulder MW. Spinal manipulative therapy for acute low back pain: an update of the Cochrane review. Spine 2013;38:E158–77. [6] Hurwitz EL. Commentary: exercise and spinal manipulative therapy for chronic low back pain: time to call for a moratorium on future randomized trials? Spine J 2011;11:599–600.