Radiofrequency neurotomy of the cervical & lumbar medial branches: evidence based review. September 2015

Transcription

1 Radiofrequency neurotomy of the cervical & lumbar medial branches: evidence based review September 2015 Requested by: IPM Expert Group Business group: Clinical Services Directorate Date requested: December 2014 Date completed: October 2015 Author Amanda Bowens Status: Final Version Final

2 Important note The purpose of this report is to outline and interpret the best current evidence for the effectiveness of radiofrequency neurotomy (RFN) of the cervical and lumbar medial branches in the treatment of persistent neck or back pain. It is not intended to replace clinical judgement or be used as a clinical protocol. A reasonable attempt has been made to find and review papers relevant to the focus of this report; however, it does not claim to be exhaustive. This document has been prepared by the staff of the Evidence Based Healthcare Team, ACC Research. The content does not necessarily represent the official view of ACC or represent ACC policy. This report is based upon information supplied up to end September ACC Research: Evidence Based Healthcare Review Page 2 of 42

3 Table of Contents Executive summary Background Objective of this review ACC s current position on RFN Description of RFN Methods Literature search Study selection Inclusion criteria... 7 Exclusion criteria Evidence grading Findings Studies identified Critical appraisal: effectiveness Cervical RFN... 9 Lumbar RFN Critical appraisal: safety Information from other guidelines & sources not meeting the criteria for critical appraisal Cervical RFN Lumbar RFN Overseas insurer policies on funding RFN Discussion Nature and quality of the evidence Cervical RFN Lumbar RFN Safety and adverse events Importance of diagnostic selection criteria and RFN technique Limitations of this review Conclusions Evidence statements Implications for practice and purchasing Purchasing recommendations References Appendices Search Strategy Excluded studies ACC Research: Evidence Based Healthcare Review Page 3 of 42

4 7.3 Systematic reviews & guidelines what studies do they cover? Cervical Systematic reviews & guidelines what studies do they cover? Lumbar Systematic reviews (SRs) & SR-based guidelines evidence tables: cervical Systematic reviews (SRs) & SR-based guidelines evidence tables: lumbar Other clinical practice guidelines summary table: cervical Other clinical practice guidelines summary table: lumbar ACC Research: Evidence Based Healthcare Review Page 4 of 42

5 Executive summary Background This review assesses the evidence for radiofrequency neurotomy (RFN) of the cervical and lumbar medial branches as a treatment for persistent neck and lower back pain in order to update the purchasing recommendations made in 2005 as part of ACC s online interventional Pain Management (IPM) guidance. Methods Systematic reviews identified via a comprehensive database search and selected according to stated criteria were critically appraised using the SIGN levels of evidence model. Findings Ten systematic reviews were included in the critical appraisal. A number of other evidence sources, e.g. clinical guidelines and New Zealand based primary studies, were also considered. Overall the systematic reviews were well conducted and the quality of the primary studies was moderate. Conclusions The evidence base for cervical RFN has not changed significantly since The evidence base for lumbar RFN has increased in terms of numbers of randomised controlled trials, but their quality and findings vary. Careful patient selection based on accurate diagnosis appears central to the success of these interventions. Recommendations It is recommended that ACC continues to purchase these interventions on a case by case basis where stated criteria, including patient selection, are met. ACC Research: Evidence Based Healthcare Review Page 5 of 42

6 1 Background 1.1 Objective of this review The objective is to update ACC s current purchasing recommendations on radiofrequency neurotomy (RFN) of the cervical and lumbar medial branches. The recommendations were released in 2005 as part of the online Interventional Pain Management (IPM) guidance. This review will carry out a pragmatic assessment of the best available recent evidence to determine whether the recommendations need to change. The updated purchasing recommendations will be used to support ACC clinical advisors in making decisions about managing clients with persistent pain. They will also be presented to the ACC Purchasing Guidance Advisory Group (PGAG) in order to develop purchasing guidance for the business. In order to update the purchasing recommendations, this review aims to answer the following research questions: 1. What is the evidence for the effectiveness of RFN in relieving persistent neck or back pain originating from the cervical or lumbar facet joints? 2. What is the evidence for the effects of RFN on functional outcomes (e.g. quality of life, return to work) in people with these types of persistent pain? 3. What is the evidence for the safety of RFN interventions? 1.2 ACC s current position on RFN The full clinical practice and purchasing recommendations are available on the IPM website see the intervention pages for RFN cervical medial branch and RFN lumbar medial branch. They are summarised below. Table 1: ACC s current recommendations on medial branch RFN Clinical practice recommendations Purchasing recommendations RFN cervical medial branch: used to treat persistent neck pain RFN of the cervical medial branch should only be performed in a research setting (grade of recommendation = B, supported by fair evidence). Purchase RF neurotomy of the cervical medial branch on a case by case basis in those centres, with specifically trained personnel, where protocols are currently in place and which collect procedural data that is available to guide ACC in future purchasing decisions. RFN lumbar medial branch: used to treat persistent low back pain The general use of RFN of the lumbar medial branch is not recommended for the treatment of adults with lower back pain. However, the procedure may be considered in the research setting (grade of recommendation = C, supported by expert opinion only). Purchase RF neurotomy of the lumbar medial branch on a case by case basis in those centres, with specifically trained personnel, where protocols are currently in place and which collect procedural data that is available to guide ACC in future purchasing decisions. Good practice points Double-blind, comparative, diagnostic cervical or lumbar medial branch blocks are an essential pre-requisite before these interventions are considered The technique used for cervical RFN should conform with the practice guidelines laid down by the International Spine Intervention Society (ISIS) 1 ACC funding of RFN has now extended beyond the research setting and a number of providers are contracted to offer this service. Since 2008, around 370 clients have received ACC-funded cervical or lumbar medial branch RFN. These procedures currently cost around $5,000 - $5,500 excluding GST. ACC Research: Evidence Based Healthcare Review Page 6 of 42

7 1.3 Description of RFN RFN is an outpatient procedure that can be used to treat persistent neck or back pain. A needle inserted beside a spinal nerve has current passed through it to produce heat and coagulate the nerve proteins. Successful treatment temporarily prevents the nerve from conducting pain impulses. As nerves eventually recover, pain relief following RFN may be time limited and the procedure may need to be repeated. Recovery of the nerve typically takes about a year. There is limited evidence on the duration of pain relief and the outcome of repeat RFN 2. This review focuses on RFN of the medial branches of the cervical and lumbar dorsal rami. These provide the nerve supply to the facet (also known as the zygapophyseal or z-) joints of the cervical and lumbar spine. RFN is applied to the medial branches to treat neck or low back pain originating from cervical or lumbar facet joints. Each facet joint (except C2-3) is supplied by two medial branches and therefore two nerves have to be treated in order to relieve pain originating from one joint. The procedure is performed under X-ray guidance. Before RFN is performed, diagnostic nerve blocks should be carried out to ensure that the facet joints are indeed the source of the pain. Facet joints are a more common source of neck pain than back pain: cervical facet joints have been estimated to be the source of 50-60% of trauma-related chronic neck pain 3 but only 30% of chronic back pain overall; the percentage is lower (about 15%) in young adults, but increases with age 4. 2 Methods 2.1 Literature search A search of the following databases was conducted in December 2014: Cochrane Library Embase Medline & Pre-Medline Trip database Auto alerts were run on Medline and Embase to ensure that studies added to the databases whilst the review was in progress were picked up. See the Appendix (section 7.1) for the search strategy. 2.2 Study selection This review is intended as a pragmatic assessment of the best recent evidence. It therefore has tighter inclusion criteria than those used for the 2005 IPM guidance and focuses on secondary research. Due to the relatively high number of secondary studies identified, the decision was taken to set 2010 as the cut off publication date: Inclusion criteria Study types: systematic reviews (SRs) of randomised controlled trials (RCTs) or other primary studies with or without meta-analysis; health technology assessments (HTAs) or clinical guidelines based on SRs Participants: adults with persistent neck or back pain of cervical or lumbar facet joint origin Intervention: conventional thermal RFN of the cervical or lumbar medial branches Controls: any active treatment or placebo, e.g. sham treatment Outcomes: pain relief (primary) and functional (secondary); also safety and adverse events Publication criteria: published 2010 or later in peer reviewed journals Exclusion criteria Studies only available in abstract form, e.g. conference presentations Grey literature and non-english language material Studies involving healthy volunteers or experimentally induced pain Studies on pain due to malignancy or infection, or on acute resolving pain Studies on interventions not meeting accepted definitions of thermal RFN, e.g. pulsed RFN 5 ACC Research: Evidence Based Healthcare Review Page 7 of 42

8 Only studies meeting the selection criteria were included in the critical appraisal. Sources identified as relevant but not meeting the criteria are discussed in section 3.4. Excluded studies are listed in the Appendix (section 7.2). 2.3 Evidence grading For the 2005 IPM guidance, the evidence appraisal was carried out by external research providers. They adapted evidence grading methods used by the by the New Zealand Guidelines Group see the IPM website for details. This review however follows the ACC Evidence Based Healthcare team s standard approach for evidence based reviews carried out in house. Studies meeting the inclusion criteria were assessed for internal validity using the Scottish Intercollegiate Guideline Network (SIGN) checklist for SRs and meta-analyses. Each study was graded for overall methodological quality using the SIGN levels of evidence model. Table 2: SIGN levels of evidence 1++ High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias 1+ Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias 1- Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias 2++ High quality systematic reviews of case-control or cohort studies. High quality case-control or cohort studies with a very low risk of confounding, bias, or chance and a high probability that the relationship is causal 2+ Well conducted case control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal 2- Case control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal 3 Non-analytic studies, e.g. case reports, case series 4 Expert opinion SIGN checklists and accompanying materials are available from the SIGN website, 3 Findings 3.1 Studies identified The literature search identified 10 SRs, or guidelines explicitly based on SRs, which met our criteria for inclusion in the critical appraisal. Four other clinical practice guidelines were also identified. Table 3: identified RFN studies Systematic reviews and/or meta-analyses Guidelines based on a systematic review Other guidelines RFN cervical medial branch RFN lumbar medial branch Studies covering both ACC Research: Evidence Based Healthcare Review Page 8 of 42

9 Some of the SRs were based entirely on higher quality primary research such as RCTs while others also included lower quality observational studies. The SRs are cross-referenced with the primary studies they cover in the Appendix (see sections 7.3 and 7.4). A search was carried out to identify any additional RCTs not covered by the included SRs, but none were found. SRs and guidelines explicitly based on SRs were included in the critical appraisal. They are summarised below and analysed in greater detail in the evidence tables (see Appendix sections 7.5 and 7.6). Other guidelines are briefly discussed in section 3.4. Their recommendations and reasons for exclusion from the critical appraisal are described in the Appendix (sections 7.7 and 7.2). 3.2 Critical appraisal: effectiveness Cervical RFN Four SRs and one SR-based guideline 17 on cervical RFN were included in the critical appraisal. All five based their conclusions largely on a single study, namely the 1996 RCT by Lord et al 19. They also drew on a range of observational studies (see Appendix, section 7.3). Three SRs came from an associated group of authors The 2015 SR by Manchikanti et al 16 synthesised the best available evidence on facet joint interventions for chronic spinal pain. Lower quality studies were excluded and observational studies were only included if fewer than five RCTs were available. Evidence on cervical RFN was drawn from one RCT and three observational studies. The SR concluded that the evidence for long term pain relief following cervical RFN was Level II (i.e. based on one high quality RCT or multiple lower quality RCTs ). This was a well conducted SR, graded SIGN level 1+. The 2013 SR-based guideline by Manchikanti et al 17 updated a previous (2009) version of the American Society of Interventional Pain Physicians (ASIPP) guideline on interventions for chronic spinal pain. Evidence on cervical RFN was provided by one RCT and five observational studies. The SR concluded that there was Fair evidence for cervical RFN (i.e. evidence is sufficient to determine effects on health outcomes, but its strength is limited by the number, size, quality or consistency of included studies; at least one higher quality RCT with sufficient sample size ). This was a well conducted SR, graded SIGN level 1+. On the basis of this SR, the updated ASIPP guideline recommended that RFN be used in the management of chronic neck pain following appropriate diagnosis with controlled diagnostic blocks. The 2012 SR by Falco et al 6 was carried out to inform the ASIPP guideline outlined above. It included the same studies and reached the same conclusion (i.e. Fair evidence) on cervical RFN. The SR noted that the evidence appeared to be strongest when patients were selected using controlled local anaesthetic blocks with 80% pain relief as the entry standard. This was a well conducted SR, graded SIGN level 1+. The 2012 SR by Smuck et al 2 examined the duration of pain relief following initial and repeated RFN facet joint procedures. It included one RCT and eight observational studies on cervical RFN; five of these reported data on repeat procedures. This SR found that the average duration of >50% pain relief following initial cervical RFN was months. Repeat procedures were successful 67-95% of the time where they followed a successful first procedure. However, success fell to 0 67% of the time where the first procedure was not successful. Pain relief following successful repeat procedures lasted months. The SR therefore concluded that pain relief after initial cervical RFN generally ends after 7 9 months and that repeat RFN is likely to provide additional pain relief for a similar duration where the initial procedure was successful. The authors noted that the results were similar for lumbar RFN, but the methodological quality of the cervical studies was better. This SR was judged to have a high risk of bias and was graded SIGN level 1-. Shortcomings included a fairly limited literature search and lack of detail on how the quality of individual studies was assessed. The 2010 SR by Teasell et al 7 examined the evidence on surgical and injection-based interventions for chronic whiplash. Evidence on cervical RFN was provided by one RCT and seven observational studies. Due to the limitations of the evidence base, this SR was unable to draw firm conclusions about any of the interventions it examined. However, of all the interventions, RFN appeared to be supported by the strongest evidence. The SR concluded there was moderate evidence for the effectiveness of cervical RFN as a treatment for chronic whiplashrelated pain. As with the SR by Smuck et al 2 outlined above, Teasell noted that pain relief is not permanent and ACC Research: Evidence Based Healthcare Review Page 9 of 42

10 that the procedure may be repeated with a similar probability of success. This well conducted SR was graded SIGN level 1+. The UK Centre for Reviews and Dissemination 20 (CRD) has assessed this SR and concluded that the authors cautious conclusions reflected the limited evidence presented and are probably reliable Lumbar RFN Seven SRs and one SR-based guideline 17 on lumbar RFN were included in the critical appraisal. Compared to cervical RFN, they had a larger number of RCTs on which to base their conclusions; some also drew on a range of observational studies (see Appendix, section 7.4). Four SRs came from an associated group of authors The 2015 SR by Manchikanti et al 16 synthesised the best available evidence on facet joint interventions for chronic spinal pain. Lower quality studies were excluded and observational studies were only included if fewer than five RCTs were available. Evidence on lumbar RFN was therefore taken from nine RCTs alone. The SR scored the RCTs moderate to high quality, but could not perform meta-analysis due to clinical and methodological heterogeneity. All but one of the RCTs reported some degree of effectiveness in terms of short and/or long term pain relief. The SR therefore concluded that the evidence for long term improvement (pain relief) following lumbar RFN was Level II (i.e. based on one high quality RCT or multiple lower quality RCTs ). It also noted that results appeared superior in patients who received RFN after undergoing controlled diagnostic nerve blocks. This was a well conducted SR, graded SIGN level 1+. The 2014 SR by Leggett et al 11 reviewed sham-controlled RCTs of RFN for chronic low back pain, whether discogenic, sacroiliac joint or facet joint related. Evidence for lumbar facet joint RFN came from six RCTs. The SR reported that five of the six had comparable methods, reported statistically significant results and were rated moderate to high quality. The SR therefore concluded that This number of similar, high-quality sham-controlled RCTs on lumbar facet joints provides a robust evidence base that suggests that continuous, conventional RFN is efficacious in reducing lumbar facet joint pain, at least in the short term (up to one year). However, the authors noted that reductions in pain scores tended to be modest, their clinical significance (e.g. in terms of functional improvement or return to work) was not explored and the potential for long term pain relief was unclear. This was a reasonably well conducted SR, graded SIGN level 1+. The 2014 SR by Poetscher et al 13 reviewed RCTs and quasi-rcts on the benefits and harms of lumbar RFN for chronic low back pain. It drew on nine RCTs, seven of which were included in meta-analyses of: (i) RFN versus placebo (five studies), or (ii) RFN versus steroid injections (two studies). The SR reported that most of the included RCTs favoured RFN with regard to pain reduction, but rated the quality of the RCTs as low to moderate. The SR concluded that, up to one year: (i) RFN was more effective than placebo for pain control and functional improvement, and (ii) RFN was more effective than steroid injections for pain control. It notes however that the overall quality of the evidence is low and should be interpreted with caution. This was a reasonably well conducted SR, graded SIGN level 1+. However, the results of the included RCTs could have been reported more clearly and Australian reviewers have identified flaws in the conduct of the meta-analyses The 2013 SR-based guideline by Manchikanti et al 17 updated a previous (2009) version of the American Society of Interventional Pain Physicians (ASIPP) guideline on interventions for chronic spinal pain. Evidence on lumbar RFN was provided by seven RCTs and 11 observational studies. The RCTs were judged to be of moderate to high quality and all but one reported positive results for RFN. Likewise, 10 of the 11 observational studies also reported positive results. The SR concluded that there was Good evidence for lumbar RFN for short and long term pain relief. Good evidence was defined as follows: evidence includes consistent results from well-designed, wellconducted studies in representative populations that directly assess effects on health outcomes (at least 2 consistent, higher-quality RCTs or studies of diagnostic test accuracy ). This was a well conducted SR, graded SIGN level 1+. On the basis of this SR, the updated ASIPP guideline recommended that RFN be used in the management of chronic low back pain following appropriate diagnosis with controlled diagnostic blocks. The 2012 SR by Falco et al 9 was carried out to inform the ASIPP guideline outlined above. It included the same RCTs and eight of the same observational studies (the guideline included a further three more recently published studies). Meta-analysis of the RCTs was not possible due to heterogeneity. The findings and conclusions were similar to those of the guideline, i.e. Good evidence for short and long term pain relief and functional improvement with lumbar RFN. Overall this was a well conducted SR, graded SIGN level 1+. However, CRD reviewers have ACC Research: Evidence Based Healthcare Review Page 10 of 42

11 cautioned that the reliability of its conclusions may be limited due to the relatively low numbers of participants in clinically different studies of lumbar RFN that could not be statistically combined 23. The 2012 SR by Smuck et al 2 examined the duration of pain relief following initial and repeated RFN facet joint procedures. It included one RCT and seven observational studies on lumbar RFN; only two studies reported data on repeat procedures. The SR found that the average duration of >50% pain relief following initial lumbar RFN was 9.0 months. Repeat procedures were successful 33-85% of the time where they followed a successful first procedure. Pain relief following repeat procedures lasted an average 11.6 months. The SR therefore concluded that pain relief after initial lumbar RFN generally ends after 7 9 months and that repeat RFN is likely to provide additional pain relief for a similar duration where the initial procedure is successful. The findings were similar for cervical and lumbar RFN, but the methodological quality of the lumbar studies was poorer. This SR was judged to have a high risk of bias and was graded SIGN level 1-. Shortcomings included a fairly limited literature search and lack of detail on how the quality of individual studies was assessed. The 2010 SR by Henschke et al 10 reviewed RCT evidence on injection and denervation procedures for chronic low back pain. It included six RCTs on lumbar RFN. Five of the RCTs had similar selection criteria and sufficient data to allow pooled analysis. The SR and meta-analyses concluded that there is only low to very low quality evidence to support the use of lumbar RFN over placebo in patients with chronic low back pain; however, in carefully selected patients, RFN procedures may be of benefit. This was a well conducted SR, graded SIGN level 1+. The 2010 SR by Manchikanti et al 12 re-appraised the evidence review on which the 2009 American Pain Society (APS) guideline 26 on interventional therapies for low back pain was based. The 2009 review had found the RCT evidence on lumbar RFN difficult to interpret due to inconsistent results and variations in both the RFN techniques and the nerve block procedures used to select patients. The APS guideline therefore concluded that the RCT evidence available at the time was insufficient to reliably evaluate the benefits of lumbar RFN. However, the Manchikanti SR re-appraised the evidence following the same methodology and found the evidence on lumbar RFN to be Fair (i.e. sufficient to determine effects on health outcomes, but its strength is limited by the number, size, quality or consistency of included studies; at least one higher quality RCT with sufficient sample size ). The evidence on lumbar RFN came from six RCTs. Manchikanti et al concluded that the APS guideline utilised some studies inappropriately and had methodological flaws. This SR appeared to be well conducted and was graded SIGN level 1+. The APS guideline and 2009 evidence review did not meet our criteria for inclusion in the critical appraisal (published prior to 2010), so we did not compare the two reviews. 3.3 Critical appraisal: safety SRs of both cervical and lumbar RFN reported that complications are rare, but can be serious 6 9. One SR of lumbar RFN noted that it appears to be a safe treatment with most reported complications being infrequent and transitory; however, the authors felt that more evidence is needed on safety Information from other guidelines & sources not meeting the criteria for critical appraisal Cervical RFN Other clinical practice guidelines The 2011 American College of Occupational and Environmental Medicine (ACOEM) guideline on cervical and thoracic disorders did not make a recommendation on RFN for chronic cervical pain; the guideline panel reached a consensus that the evidence was insufficient to recommend for or against routinely providing RFN 8. This guideline was not included in the critical appraisal as the full version is only available to subscribers. The 2010 joint American Society of Anesthesiologists (ASA) and American Society of Regional Anesthesia and Pain Medicine (ASRAPM) guideline on chronic pain management recommended that RFN may be performed for neck pain, provided that other treatments have been tried first 18. The recommendation was supported by evidence from the RCT by Lord et al 19 and by expert opinion. This guideline was not included in the critical appraisal as it provided insufficient information about development methods. ACC Research: Evidence Based Healthcare Review Page 11 of 42

12 New Zealand primary study A 2012 prospective case series by MacVicar et al reported on 104 chronic neck pain patients treated with cervical RFN at two clinics in Christchurch 27. Treatment was carried out according to the 2004 ISIS practice guidelines 1. Only patients who experienced complete pain relief following controlled diagnostic blocks were included. Successful outcome was defined as 80% pain relief for at least six months plus complete restoration of daily activities, return to work and no further need for health care. Patients at the two clinics achieved successful outcomes in 74% and 61% of cases respectively, with pain relief lasting months from first RFN and a further 15 months after repeat treatment. Interestingly the clinic with the lower success rate treated a higher proportion of manual workers and patients with work related injuries. The authors concluded that cervical RFN can be a highly effective treatment for chronic neck pain when performed in a rigorous manner in carefully selected patients. They suggested that the failure rate (around 30%) may be related to the limited specificity of cervical medial branch blocks (around 65%) This study was covered by three of the SRs included in our critical appraisal , but was not itself appraised as it didn t meet our criteria. According to the SIGN levels of evidence, it would have been graded 3. However, it is of interest due to the rigour with which it was carried out (in terms of patient selection and treatment technique), the positive outcomes and the fact that many of the participants would have been ACC clients. Australian NTRI/ISCRR evidence review In 2014 the Australian National Trauma Research Institute (NTRI) and the Institute for Safety, Compensation and Recovery Research (ISCRR) released an evidence review of RFN in the management of spinal pain of facet joint origin They were asked to carry out the review by the Victorian Transport Accident Commission (TAC) and Work Safe Victoria. The authors used a two stage systematic review process focusing on studies of higher apparent methodological quality. They concluded that, based on the small 1996 RCT by Lord et al 19, there is moderate level evidence to support the use of cervical RFN for neck pain Lumbar RFN Other clinical practice guidelines The 2011 ACOEM guideline on back disorders did not make a recommendation on lumbar RFN; the guideline panel reached a consensus that the evidence was insufficient to recommend for or against routinely providing RFN 14. This guideline was not included in the critical appraisal as the full version is only available to subscribers. The 2010 joint ASA/ASRAPM guideline on chronic pain management recommended that RFN may be performed for low back pain, following appropriate diagnostic blocks and provided that other treatments have been tried first 18. The recommendation was supported by evidence from multiple RCTs, some of which were included in a metaanalysis. This guideline was not included in the critical appraisal as it provided insufficient information about development methods. The 2011 Toward Optimized Practice guideline on managing low back pain in primary care recommended that RFN may be beneficial for carefully selected patients with pain originating from the lumbar facet joints 15. The recommendation was apparently based on systematic reviews, but these were not identified. This guideline was not included in the critical appraisal as it provided insufficient information about development methods. New Zealand primary studies A 2013 prospective case series by MacVicar et al 28 reports on 106 patients with chronic pain selected, treated and assessed according to the same rigorous protocols as described above in the authors 2012 study on cervical RFN 27. Patients at two community based clinics achieved successful outcomes in 58% and 53% of cases respectively, with pain relief lasting around 15 months from first RFN and a further 13 months after repeat treatment. The authors concluded that lumbar RFN can be a highly effective treatment for chronic back pain when performed in a rigorous manner in carefully selected patients. They suggested a number of reasons for the lower success rate than that observed in their neck pain study, including: (i) the inclusion of some patients whose pain was dramatically, but not completely, relieved by controlled diagnostic lumbar medial branch blocks; (ii) the confounding effects of other sources of pain in some patients; and (iii) false-positive responses to the controlled diagnostic block, which might have been mitigated by using placebo-controlled blocks instead. ACC Research: Evidence Based Healthcare Review Page 12 of 42

13 As with MacVicar s case series on cervical RFN 27 outlined in above, this study was covered by one of the SRs 17 included in our critical appraisal, but was not appraised in its own right as it did not meet our selection criteria. However it is of interest due to its rigour and applicability to ACC back pain clients. Australian NTRI/ISCRR evidence review This 2014 review (described above) concluded that the evidence on lumbar RFN was of low quality and that the studies identified had serious methodological and technical issues that undermined the internal and external validity of their results. The reviewers were therefore unable to draw definitive conclusions on the effectiveness of lumbar RFN. Despite this finding, TAC will fund lumbar RFN for eligible clients see section below Overseas insurer policies on funding RFN We identified policies on funding RFN from several overseas insurers and one Australian accident compensation agency. Their policies are outlined in the table below. Table 4: insurer funding of RFN Insurer TAC Victoria, Australia (2009) Funding criteria TAC funds RFN for clients with persistent spinal pain resulting from transport accident injuries if the following criteria are met 29 : Client has pain of facet joint origin lasting 3 months (pain score 5/10 on visual analog scale) and conservative therapy has failed RFN is performed by registered medical practitioner with sufficient training covering both technical expertise & appropriate patient selection Two positive medial branch blocks have taken place with at least 75% pain relief on standardized outcome measures Repeat procedures may be funded where (i) relief lasts 4 months and (ii) evidence of significant pain relief, functional improvement and/or reduction in healthcare use is submitted Bupa, UK (2012) Bupa will fund one set of lumbar or cervical facet joint RFN where the consultant has carefully considered patient selection and where these criteria are met 30 : Conservative treatment has failed The patient has no psychological distress, e.g. depression or post-traumatic stress disorder RFN forms part of a comprehensive treatment approach by a multidisciplinary team There is evidence of 80% pain relief for an appropriate time period following medial branch block or intra-articular facet joint injection There is ongoing assessment following a trial of RFN to show evidence of a response Pain is localized and pain severity is 4/10 on visual analog scale Appropriate outcome data (e.g. pain diaries) are kept following intervention Aetna, US (2015) Aetna considers outpatient facet joint RFN medically necessary for members with intractable neck or back pain with/without sciatica if all the following criteria are met 31 : Member has had 6 months of severe pain that limits activities of daily living and conservative treatment have failed Member has had no prior spinal fusion surgery, no significant narrowing of the vertebral canal or spinal instability requiring surgery Neurologic studies are negative or fail to confirm disc herniation Facet joint injections have been successful in relieving the pain Repeat procedures: only one treatment per level per side is considered medically necessary in a 6 month period ACC Research: Evidence Based Healthcare Review Page 13 of 42

14 Cigna, US (2015) Cigna covers initial RFN for the treatment of chronic back or neck pain if deemed medically necessary and all of the following criteria are met 32 : Pain is exacerbated by extension and rotation, or is associated with lumbar rigidity There is severe pain unresponsive to 6 months of conservative therapy Facet joint origin of pain is suspected and medial branch block/injection of facet joint with local anesthetic results in elimination or marked decrease in intensity of pain Clinical findings and imaging studies suggest no other obvious cause of the pain Repeat procedures may be funded after 6 months if 50% pain relief, with associated functional improvement, was achieved for at least 10 weeks following the previous treatment United Healthcare, US (2015) United Healthcare considers RFN of facet joint nerves proven and medically necessary for chronic cervical, thoracic or lumbar pain if the following criteria are met 33 : Positive response to medial branch block injection at the side & level of proposed ablation Needle placement is confirmed by fluoroscopic guided imaging There is 50% documented pain reduction for at least 10 weeks Repeat procedures should not be performed more frequently than every 6 months 4 Discussion 4.1 Nature and quality of the evidence Cervical RFN Of the five SRs included in the critical appraisal, four were graded 1+ and one was graded 1-. All five based their conclusions largely on the 2006 RCT by Lord et al 19 and drew on observational studies to varying degrees. On the whole the SRs rated the Lord RCT as high quality, although some commented on its small sample size (n=24). The SRs largely agreed that the evidence base for cervical RFN was of fair, moderate or Level II quality. All the SRs focused on pain rather than functional outcomes. No further RCTs on cervical RFN have been published since the Lord RCT. A recent SR noted that it continues to be the landmark evaluation to show efficacy of radiofrequency neurotomy in the cervical spine 16. The RFN technique used in the Lord RCT is considered optimal for the cervical spine by some reviewers 2. ACC also based its current recommendation largely on the Lord RCT and judged the quality of the evidence available at the time (2005) to be medium. It therefore appears that the quality of the evidence base for cervical RFN has not changed significantly since. In terms of duration of pain relief, recent SRs support ACC s 2005 conclusion that cervical RF is effective for a median period of nine months. Of the three clinical guidelines identified, two recommended that cervical RFN may be used for chronic neck pain following appropriate diagnosis using controlled diagnostic blocks and/or after conservative treatments have failed. A third guideline 8 made no recommendation as the evidence was judged to be insufficient. In addition, a New Zealand based prospective case series 27 provided SIGN level 3 evidence that cervical RFN can deliver long term pain relief and restoration of function when performed in strict accordance with ISIS guidelines 1 with rigorous patient selection criteria (i.e. complete relief of pain following controlled diagnostic medial branch blocks). It is likely that many of the participants would have been ACC clients. The ISIS-recommended RFN techniques used in this case series were similar to those described in the Lord RCT Lumbar RFN Of the eight SRs included in the critical appraisal, seven were graded 1+ and one was graded 1-. The lumbar SRs based their conclusions on a larger evidence base than the cervical SRs; each SR included between one and nine of 12 identified RCTs published and some also drew on observational studies. ACC Research: Evidence Based Healthcare Review Page 14 of 42

15 Conclusions about the quality of evidence for lumbar RFN varied, although all the SRs were positive to at least some extent. Three SRs judged the evidence to be good or robust and two described it as fair or level II One SR noted that the quality of evidence was lower than that for cervical RFN 2 ; however, this SR focused on repeat procedures and only one lumbar RCTs met its inclusion criteria. Two SRs that performed meta-analysis on suitable RCTs were more cautious in their conclusions. Poetscher et al reported that RFN may be superior to placebo and steroid injections, but noted that the quality of evidence is low overall and that the findings should therefore be interpreted with caution 13. The methodology of this SR has been criticised by other reviewers Henschke et al found only low to very low quality evidence to support RFN over placebo, but noted that the intervention may benefit carefully selected patients 10. Overall the lumbar SRs focused on pain outcomes. Leggett et al commented that RCT evidence on the clinical significance of reported reductions in pain (e.g. return to work) is unclear 11. The meta-analyses by Poetscher 13 and Henschke 10 both suggested that RFN may be more effective than placebo for functional outcomes; however, Poetscher s methodology is questionable and Henschke noted that the evidence was of very low quality. ACC s 2005 guidance on lumbar RFN found that the evidence available at the time was conflicting. The size of the evidence base supporting lumbar RFN has increased significantly since then in terms of published RCTs. However, the quality of those RCTs appears to be variable. Some authors have argued that RFN outcomes are better and the evidence is stronger in the cervical spine than the lumbar spine 34. This may reflect the lower prevalence of facet joint pain in the lumbar region, hence greater difficulty in selecting patients likely to respond. Of the four clinical guidelines identified, three recommended that lumbar RFN may be used to treat chronic low back pain following appropriate diagnosis/patient selection with controlled diagnostic blocks and/or after conservative treatments have failed A fourth guideline made no recommendation as it judged the evidence to be insufficient 14. In addition, we identified a New Zealand based case series 28 by the same authors as the cervical RFN study described in section above 27. It provided further (SIGN level 3) evidence that lumbar RFN can deliver long term pain relief and restoration of function when performed to a rigorous protocol with carefully selected patients. However, the authors reported less impressive results with lumbar RFN than with cervical RFN Safety and adverse events SRs included in the critical appraisal reported that medial branch RFN appears to be a safe treatment. Adverse events tended to be minor and temporary. However, some reviewers have called for more evidence on safety 13. A recent article on facet joint RFN noted that serious adverse effects are rare, occurring in 1% of interventions 34. It reported that risks are higher in the cervical compared to the lumbar spine and the majority of adverse events are local and transient, such as numbness or pain at the injection site. There is also the possibility of complications common to all needle procedures in spinal sites, such as infection or dural puncture. In addition, X-ray guidance during the procedure exposes the patient to radiation Importance of diagnostic selection criteria and RFN technique Some of the SRs included in the critical appraisal commented that evidence for RFN appeared to be strongest when patients were selected using controlled anaesthetic blocks with 80% pain relief as the entry criteria. The latest (2013) edition of the influential ISIS practice guideline 5 recommends that complete (or just short of complete to allow for residual needle pain) relief of pain following controlled diagnostic blocks of the target medial branches is the singular indication for cervical RFN. Blocks may be controlled by placebo or by a comparative local anaesthetic. Placebo control is the most rigorous, but comparative blocks give high diagnostic confidence for facet joint-related neck pain and are recommended for routine practice. For lumbar RFN, the ISIS guideline notes that lower pain relief thresholds are often used in practice, but it warns that, due to the lower prevalence of facet joint-related back pain, more false positives may result from using less stringent pain relief criteria. The guideline notes that the best results have been reported using diagnostic criteria of (i) 80% relief after placebo controlled blocks or (ii) complete relief after comparative blocks. ACC Research: Evidence Based Healthcare Review Page 15 of 42

16 ACC s 2005 IPM guidance recommended diagnosis with double blind comparative medial branch blocks as a prerequisite for RFN treatment of facet joint related cervical or low back pain. Similarly, ACC operational guidance developed in 2014 notes that placebo controlled blocks are preferable for selecting which claimants might benefit from RFN, but, as this would require the use of three blocks, the procedures are usually undertaken twice (i.e. on two separate occasions), in a blinded fashion, using either a short acting or a long acting local anaesthetic The operational guidance states that a positive block requires complete relief of pain apart from a small degree (<5/100) of needle pain, i.e. the threshold for RFN should be 95% pain relief. This is a more rigorous than TAC and Bupa, who specify 75% and 80% respectively. It has been argued that many SRs on medial branch RFN focus on the methodological design of included studies rather than on rigorous patient selection and procedural technique 34. It is noteworthy that some of the primary studies that have reported the best results have selected their patients carefully and treated them according to rigorous protocols such as the ISIS practice guidelines 1 5 These studies include the RCTs by Lord 19 (cervical) and Nath 37 (lumbar) and the observational studies by MacVicar (one cervical 27, one lumbar 28 ). A number of international professional associations recommend that medial branch blocks and subsequent progression to RFN are carried out in accordance with the ISIS practice guidelines. These include the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine, the British Pain Society and the UK Royal College of Anaesthetists 38. ACC would normally expect the RFN procedures it funds to be carried out in accordance with the ISIS guidelines Limitations of this review This review took a pragmatic approach, selecting only SRs published since 2010 for critical appraisal. It therefore excluded SRs published between 2005 and 2009 on the assumption that evidence emerging in that period would be picked up by later reviews. During that time there were disagreements between some practitioner organisations over how evidence was interpreted in the development of pain management guidelines 40. This review does not discuss those controversies in detail, although one of the included SRs (Manchikanti et al ) does present one side of the argument. This review did not examine primary studies in detail. Critical appraisal of available RCTs may have been of value in clarifying the evidence, particularly in the case of lumbar RFN. Several of the SRs originated from an associated group of authors, so there is a risk that biases in interpretation of the evidence may have been compounded and carried forward. Only SRs published in peer reviewed journals were included in the critical appraisal; however, other relevant secondary research (e.g. the Australian NTRI/ISCRR review ) was included in the discussion of the evidence see section Conclusions 5.1 Evidence statements Cervical RFN The evidence base for cervical RFN is moderate. It does not appear to have changed significantly since 2005, especially with regard to higher quality evidence. The recent secondary studies are still largely based on the same 1996 RCT by Lord et al 19 that formed the basis for ACC s 2005 recommendations. Lumbar RFN The evidence base for lumbar RFN is low to moderate overall. It has grown since The recent secondary studies contain evidence from at least five new RCTs; however, assessments of their quality vary, as do their conclusions. ACC Research: Evidence Based Healthcare Review Page 16 of 42

17 5.2 Implications for practice and purchasing The evidence suggests that RFN of the cervical or lumbar medial branches may provide pain relief of up to one year s duration to clients with persistent neck or low back pain of facet joint origin. Careful patient selection based on accurate diagnosis appears to be central to the success of these interventions. 5.3 Purchasing recommendations It is suggested that ACC s 2005 purchasing recommendations be slightly updated to reflect (i) the somewhat stronger evidence base for lumbar RFN and (ii) the importance of patient selection: Cervical RFN Recommendation ACC should continue to purchase RFN of the cervical medial branch to treat persistent neck pain on a case by case basis if the following criteria are met: SIGN recommendation grading* Conditional recommendation for There has been a positive response to double-blind, comparative, diagnostic cervical medial branch blocks The provider offers specifically trained personnel and collects procedural data that is available to guide ACC in future purchasing decisions Good practice point: The technique used for cervical RFN should conform with the current practice guidelines laid down by the International Spine Intervention Society (ISIS) Lumbar RFN Recommendation ACC should continue to purchase RFN of the lumbar medial branch to treat persistent low back pain on a case by case basis if the following criteria are met: SIGN recommendation grading Conditional recommendation for There has been a positive response to double-blind, comparative, diagnostic lumbar medial branch blocks The provider offers specifically trained personnel and collects procedural data that is available to guide ACC in future purchasing decisions Good practice point: The technique used for lumbar RFN should conform with the current practice guidelines laid down by the International Spine Intervention Society (ISIS) * Conditional recommendations should be made where the intervention will do more good than harm for most patients, but may include caveats e.g. on the quality or size of the evidence base, or patient preferences. Conditional recommendations should include should be considered or similar in the wording 41 ACC Research: Evidence Based Healthcare Review Page 17 of 42