BJA
Editorial IV
British Journal of Anaesthesia 112 (1): 9–12 (2014) doi:10.1093/bja/aet470
EDITORIAL IV
Managing chronic pain: a clinical challenge: new SIGN guidelines provide a practical evidence-based approach and identify research gaps L. A. Colvin 1*, A. Stein 2 and B. H. Smith 3 on behalf of the SIGN Chronic Pain guideline development group 1
* Corresponding author. E-mail: [email protected]
Chronic pain is common, with around 20% of the adult population suffering from moderate-to-severe chronic pain.1 2 Chronic pain has been recognized as a long-term condition in its own right, rather than just a symptom, with evidence to support this from neuroimaging studies.3 4 Like other longterm conditions, chronic pain has a significant impact on quality of life for sufferers and their families. It also has a much wider impact on society, with financial implications being very much greater than healthcare costs alone.5 6 The majority of patients with chronic pain present are managed outside the specialist setting, mainly in primary care, although patients will make a variety of choices for self-management of their pain.7 There is some evidence that current management is less than optimal, with around 60 –70% of patients being unhappy with their treatment.1 Neuropathic pain can be especially difficult to diagnose, with resultant delay in starting appropriate therapy.8 We need to develop approaches to managing chronic pain that are accessible and underpinned by current evidence and understanding of mechanisms, not just in specialist pain services, where a small minority of patients are seen, but also in the non-specialist and primary care settings.9 10 Particularly for non-specialists, keeping up with the latest evidence in a variety of areas, and having the knowledge to critically assess new findings in specialist areas, such as chronic pain, can be difficult: hence the need for good quality, evidence -based clinical guidelines. There is also an urgent need to ensure that research priorities are directed towards the areas of clinical need where there is a lack of good quality evidence to underpin clinical practice. The Scottish Intercollegiate Guideline Network (SIGN) is a multi-professional organization that aims to produce evidencebased clinical practice guidelines to improve outcomes for patients by delivering healthcare based on the best available evidence, and reducing variations in practice (www.sign.ac .uk). Internationally recognized for their methodology and objectivity, SIGN has produced 134 clinical guidelines to date,
covering a wide range of clinical topics and influencing care in Scotland and worldwide. The methodology used has an approach that is consistent with a number of other national and international groups that produce clinical practice guidelines [such as the National Institute for Health and Care Excellence (NICE) in England and Wales, the Council of Europe, and the World Health Organization]. Key components used by all of these organizations include user involvement, contribution from a multidisciplinary group, systematic review, and critical appraisal of current research evidence.11 It has been shown that evidence synthesized only from expert consensus and narrative-based literature surveys may not accurately reflect the full range and effectiveness of available interventions, and may be open to bias. We therefore need systematic literature reviews, with objective critical appraisal of the published evidence, to form the basis of any valid new guideline.12 Although national and local guidelines have been in existence for some specific chronic pain conditions or management approaches, none had addressed chronic pain as a single clinical entity and addressed management comprehensively. SIGN therefore recognized the need for a new Guideline on Chronic Pain, with establishment of a multidisciplinary development group and publication of these guidelines in December 2013 (freely available at http://www.sign.ac.uk/guidelines/ fulltext/136/index.html). This guideline reviews the evidence for assessment and management of chronic non-malignant pain in the adult population in the non-specialist setting. It is based on the principle that the pathophysiology and psychosocial impact of chronic pain are largely independent of its biological aetiology, and therefore that common approaches to assessment and management are required, irrespective of its underlying cause. It takes a comprehensive approach to chronic pain as a clinical entity (defined as pain lasting longer than 3 months), although it does not cover chronic pain in children, nor specialist interventions.13 Additionally, it does not cover treatment of specific clinical conditions such as
9
Downloaded from http://bja.oxfordjournals.org/ at Belgorod State University on December 6, 2013
Department of Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh, Western General Hospital Crewe Rd, Edinburgh EH4 2XU, UK 2 Scottish Intercollegiate Guidelines Network, Healthcare Improvement Scotland, Gyle Square, 1 South Gyle Crescent, Edinburgh EH12 9EB, UK 3 University of Dundee, Mackenzie Building, Ninewells Hospital and Medical School, Kirsty Semple Way, Dundee DD2 4DB, UK
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Editorial IV
Table 1 Summary of some of the key recommendations for chronic pain management made in the SIGN guideline. Grade A, at least one meta-analysis, systematic review, or RCT rated as 1++ , and directly applicable to the target population; or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results; Grade B, a body of evidence including studies rated as 2++ , directly applicable to the target population, and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 1++ or 1+ ; Grade C, a body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 2++ ; Grade D , evidence level 3 or 4; or extrapolated evidence from studies rated as 2+ ;GPP, good practice point: best practice based on the experience of the guideline development group, in the absence of good quality evidence. For more information on grading, see ref. 17 Summary of key recommendation
Level of evidence
Assessment and planning of care
In order to best direct treatment options, a comprehensive biopsychosocial assessment, including identification of pain type (e.g. neuropathic) should be carried out in any patient with chronic pain
GPP
Supported self-management
Self-management can be used from an early stage in a pain condition, with patients being directed to self-help resources at any stage in the patient journey
GPP
Pharmacological therapies
There should be at least annual assessment of patients on pharmacotherapy for chronic pain
GPP
Strong opioids should be considered for chronic low back pain or osteoarthritis and only continued if there is ongoing pain relief
B
Specialist advice or referral should be considered if there are concerns about rapid opioid dose elevation or if .180 mg per day morphine equivalent dose is needed
D
Consideration should be given for referral to a pain management programme for patients with chronic pain
C
There should be an awareness of the impact of healthcare workers behaviour, and the treatment environment, in reinforcing unhelpful responses
GPP
Any form of exercise or exercise is recommended for patients with chronic pain
B
In addition to exercise therapy, advice to stay active should be given to patients with chronic low back pain. This will improve disability in the long term. Advice alone is insufficient
A
Psychologically based interventions
Physical therapies
rheumatoid disease, nor treatment of patients with headaches (which is covered in a separate guideline).14
What areas are reviewed in the guideline? The guideline development group identified and agreed a series of 17 structured key questions, based on PICO methodology.15 16 The P(Population) for all the key questions was defined as adults suffering from chronic non-malignant pain of more than 3 months duration. Clearly, within this, there is a wide variation: thus, as with any clinical guideline, this must be recognized when applying the evidence base to any individual patient—no one is ‘average’. Following standard SIGN methodology,17 the following areas were addressed with respect to chronic pain: (i) (ii) (iii) (iv) (v) (vi)
Assessment Self-management Pharmacological therapies Psychologically based interventions Physical therapies Complementary therapies
The primary output was a number of key recommendations, relating to the pre-defined key questions, and these were accompanied by consensus statements rooted in the derived evidence. A summary of some of the key recommendations is shown in Table 1.
10
Evidence, research gaps, and limitations Much good quality evidence was found to support the management of chronic pain by non-specialists, particularly allowing strong recommendations to be made on advice for physical activity and on the effectiveness of some physical, psychological, and pharmacological interventions. These are presented in the guideline, along with other recommendations based on weaker evidence. While we identified a considerable literature in chronic pain, we also identified that there is a number of areas where further research is needed, to allow non-specialist clinical practice to be based on the highest quality of evidence (or even any evidence). Some of these areas have already been identified as lacking appropriate evidence and reflecting a significant research gap.18 One of the functions of this guideline was therefore to identify where current practice does not have a good evidence base and to make research recommendations (Table 2). It is hoped that these will be of use to research funders in terms of priority planning. Like all guidelines and systematic reviews, this guideline can only be as good as the published evidence, and the nature of chronic pain and its response to treatment makes this a particular challenge. A recent editorial in the Methodology series in the BJA highlights the role of uncertainty in the evidence on which clinical guidelines are based. It is suggested that research gaps and lack of evidence do not preclude the development of good quality clinical guidelines, but that these issues must be acknowledged in interpretation and application of such guidelines.19
Downloaded from http://bja.oxfordjournals.org/ at Belgorod State University on December 6, 2013
Area addressed by key question
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Editorial IV
Consensus pathways There is a tension between producing a high-quality systematic review of current evidence, where it is difficult to give high grade recommendations about clinical management of
chronic pain patients because of the lack of evidence, and producing a clinically useful resource. This was recognized in the current guideline, so that a number of consensus pathways were developed—based on best available evidence, but also using the combined expertise of the guideline development group and peer reviewers to produce three comprehensive consensus-based pathways for areas that were felt to offer particular challenges for the non-specialist: (i) Pathway for chronic pain assessment, early management, and care planning in non-specialist settings. (ii) Pathway for patients with neuropathic pain. (iii) Pathway for using strong opioids in patients with chronic pain. These are intended to guide the practitioner practically, through a comprehensive biopsychosocial process of assessment and management, recognizing good evidence and other relevant guidelines, and also the need for patient-centredness and safety. The British Pain Society has also developed a number of pathways of care recently, in collaboration with Map of Medicine (and have been the subject of BJA commentaries).27 28 The first two SIGN pathways are complementary to the BPS pathways, while the third area (strong opioid use) was not covered as a focused pathway by the BPS, although a separate BPS guideline exists.29
Dissemination and implementation Once published, guidelines need active dissemination and approaches to ensure that recommendations are embedded into clinical practice. Effective strategies include the development of care pathways, engagement with topic-relevant professionals, local clinical champions, availability in different formats (a patient version, quick reference guide, and an app), and the production of audit support tools, linked to performance indicators. One of the unique aspects of the SIGN process is a link [through NHS Healthcare Improvement Scotland (HIS)] to all NHS Health Boards throughout Scotland, where newly formed chronic pain multidisciplinary groups
Table 2 Some of the identified research gaps and recommendations for further research Area addressed by key question
Research recommendation
Assessment and planning of care
† Examine effect of assessing different components of pain on treatment outcomes † Studies for early identification of patients most at risk of poor outcomes and to assess the effect of early referral † Investigate efficacy of simple approaches to improving professional– patient interaction and impact on outcomes
Pharmacological therapies
† † † †
Psychologically based interventions
† RCTs on acceptance and commitment therapy
Complementary therapies
† Well-designed studies (e.g. RCTs) to assess alternative therapies such as herbal medicines, dietary interventions, music therapy, hypnosis, and acupuncture
Study patterns of opioid prescribing and factors to optimize good practice use of opioids Studies of long-term effects of opioids on pain and adverse effects Studies on combination pharmacotherapy Studies on factors contributing to interindividual variation in treatment responses and possible clinical biomarkers of response
11
Downloaded from http://bja.oxfordjournals.org/ at Belgorod State University on December 6, 2013
Particularly for pharmacotherapy, there are a number of issues that must be considered when interpreting the evidence. It has been highlighted previously that even good quality double-blind randomized controlled trials (RCTs)— considered to form the basis of the strongest clinical evidence—may not be the best way of assessing chronic pain treatments.20 One potential problem is that the apparent effectiveness of specific treatments in trials may be diluted by including subgroups of patients that will have no chance of responding to that treatment (e.g. due to the underlying neurobiological changes in that patient).21 While clinical trial evidence may not translate well into individual patient response, many will respond to at least one of the available drugs.22 23 At the opposite end of the spectrum, another problem is that of overestimating the effectiveness of a treatment, depending on the type of analysis used—in particular, the way in which missing data are handled. If there is an assumption that drop-outs in either arm are random, but the treatment being studied is effective, but poorly tolerated, then using Last Observation Carried Forward (LOCF) will overestimate the treatment effect. More recent good quality RCTs specifically state the type of analysis used and treatment of missing data.24 An additional challenge in chronic pain trials is the duration of the trial—ideally long duration studies are needed, but this is balanced by the challenges of patients lost to follow-up. For example, with strong opioids, used for an increasing number of patients, there is a significant need for, but definite lack of, good quality long-term studies, where the method of dealing with drop-outs has been pre-defined.25 26 There has been considerable discussion about how to address these problems and how to best design chronic pain clinical trials in the future (see www.immpact.org).
BJA
Declaration of interest All authors contributed to the design and writing of this paper, without any financial or other assistance. B.H.S. has received an unrestricted educational grant and consultancy fees from Pfizer; L.A.C. is an Editor of the British Journal of Anaesthesia; A.S. is employed by SIGN.
References 1 Breivik H, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 2006; 10: 287– 333 2 Harker J, Reid KJ, Bekkering GE, et al. Epidemiology of chronic pain in Denmark and Sweden. Pain Res Treat 2012; 2012: 30 3 Wartolowska K, Hough MG, Jenkinson M, et al. Structural changes of the brain in rheumatoid arthritis. Arthritis Rheum 2012; 64: 371–9 4 Tracey I, Bushnell M. How neuroimaging studies have challenged us to rethink: is chronic pain a disease? J Pain 2009; 10: 1113– 20 5 Reid KJ, Harker J, Bala MM, et al. Epidemiology of chronic non-cancer pain in Europe: narrative review of prevalence, pain treatments and pain impact. Curr Med Res Opin 2011; 27: 449– 62 6 Maniadakis N. The economic burden of back pain in the UK. Pain 2000; 84: 95– 103 7 Elliot A, Smith BH, Hannaford PC, Smith W, Chambers WA. The course of chronic pain in the community: results of a 4-year followup study. Pain 2002; 99: 299– 307 8 Hall GC, Carroll D, McQuay HJ. Primary care incidence and treatment of four neuropathic pain conditions: a descriptive study, 2002– 2005. BMC Fam Pract 2008; 9: 26 9 van HO, Torrance N, Smith BH. Chronic pain epidemiology and its clinical relevance. Br J Anaesth 2013; 111: 13– 8
12
10 Colvin LA, Rowbotham DJ. I. Managing pain: recent advances and new challenges. Br J Anaesth 2013; 111: 1– 3 11 Turner T, Misso M, Harris C, Green S. Development of evidence-based clinical practice guidelines (CPGs): comparing approaches. Implement Sci 2008; 3: 45 12 Antman E, Lau J, Kupelnick B, Mosteller F, Chalmers T. A comparison of results of meta-analyses of randomized controlled trials and recommendations of clinical experts. Treatments for myocardial infarction. J Am Med Assoc 1992; 268: 240– 8 13 Merskey H, Bogduk N. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. IASP, Seattle, WA, 1994 14 Scottish Intercollegiate Guideline Network. Diagnosis and Management of Headache in Adults. Edinburgh: SIGN, 2008 15 Counsell C. Formulating questions and locating primary studies for inclusion in systematic reviews. Ann Intern Med 1997; 127: 380– 7 16 Schardt C, Adams MB, Owens T, Keitz S, Fontelo P. Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Medical Inform Decis Mak 2007; 7: 16 17 Scottish Intercollegiate Guideline Network. SIGN 50: A Guideline Developer’s Handbook, revised Edn. Edinburgh: SIGN, 2011 18 Chapman CR, Lipschitz DL, Angst MS, et al. Opioid pharmacotherapy for chronic non-cancer pain in the United States: a research guideline for developing an evidence-base. J Pain 2010; 11: 807–29 19 Imberger G. Clinical guidelines and the question of uncertainty. Br J Anaesth 2013; 111: 700–2 20 McQuay HJ, Derry S, Moore RA, Poulain P, Legout V. Enriched enrolment with randomised withdrawal (EERW): time for a new look at clinical trial design in chronic pain. Pain 2008; 135: 217– 20 21 Attal N, Bouhassira D, Baron R, et al. Assessing symptom profiles in neuropathic pain clinical trials: can it improve outcome? Eur J Pain 2011; 15: 441–3 22 Moore RA, Derry S, Wiffen PJ. Challenges in design and interpretation of chronic pain trials. Br J Anaesth 2013; 111: 38– 45 23 Moore A, Derry S, Eccleston C, Kalso E. Expect analgesic failure; pursue analgesic success. Br Med J 2013; 346: f2690 24 Moore RA, Straube S, Eccleston C, et al. Estimate at your peril: imputation methods for patient withdrawal can bias efficacy outcomes in chronic pain trials using responder analyses. Pain 2012; 153: 265– 8 25 Dworkin RH, Turk DC, Peirce-Sandner S, et al. Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations. Pain 2010; 149: 177– 93 26 Dworkin RH, Turk DC, Katz NP, et al. Evidence-based clinical trial design for chronic pain pharmacotherapy: a blueprint for ACTION. Pain 2011; 152: S107 –15 27 Smith BH, Lee J, Price C, Baranowski AP. Neuropathic pain: a pathway for care developed by the British Pain Society. [Erratum appears in Br J Anaesth 2013; 111: 522.] Br J Anaesth 2013; 111: 73–9 28 Lee J, Gupta S, Price C, Baranowski AP. British Pain Society. Low back and radicular pain: a pathway for care developed by the British Pain Society. Br J Anaesth 2013; 111: 112–20 29 The British Pain Society’s: Opioids for Persistent Pain: Good Practice, 2nd Edn. London: The British Pain Society, 2010 30 El-Ghorr A, James R, Twaddle S. SIGN is customising implementation support to every guideline. Guidelines Pract 2011; 14: 40– 6
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(Service Improvement Groups) will have local implementation of this new guideline as part of their defined remit. The patient version provides evidence-based information about options for pain management, distilled from the full version, so that patients can engage actively and effectively with their treatment plan, allowing informed involvement of service users. There is recognition and support from NHS HIS that a variety of approaches will be needed to overcome barriers and to change practice at a local level. There is now an opportunity to measure how implementation of an evidence guideline can impact on patient outcomes.30 In summary, SIGN has produced the first national evidencebased guideline for the management of chronic pain by nonspecialists, with practical methods for its dissemination and implementation. This has the potential to both raise awareness and improve the management of this common and disabling condition. Importantly, it also highlights the relative lack of good quality evidence to guide management, and indicates key areas for further, urgent research. The guideline is now freely available for use by patients, clinicians, policy-makers, and researchers to guide current and future practice. We look forward to reviewing it when more and better evidence becomes available.
Editorial IV
Editorial IV
British Journal of Anaesthesia 112 (1): 9–12 (2014) doi:10.1093/bja/aet470
EDITORIAL IV
Managing chronic pain: a clinical challenge: new SIGN guidelines provide a practical evidence-based approach and identify research gaps L. A. Colvin 1*, A. Stein 2 and B. H. Smith 3 on behalf of the SIGN Chronic Pain guideline development group 1
* Corresponding author. E-mail: [email protected]
Chronic pain is common, with around 20% of the adult population suffering from moderate-to-severe chronic pain.1 2 Chronic pain has been recognized as a long-term condition in its own right, rather than just a symptom, with evidence to support this from neuroimaging studies.3 4 Like other longterm conditions, chronic pain has a significant impact on quality of life for sufferers and their families. It also has a much wider impact on society, with financial implications being very much greater than healthcare costs alone.5 6 The majority of patients with chronic pain present are managed outside the specialist setting, mainly in primary care, although patients will make a variety of choices for self-management of their pain.7 There is some evidence that current management is less than optimal, with around 60 –70% of patients being unhappy with their treatment.1 Neuropathic pain can be especially difficult to diagnose, with resultant delay in starting appropriate therapy.8 We need to develop approaches to managing chronic pain that are accessible and underpinned by current evidence and understanding of mechanisms, not just in specialist pain services, where a small minority of patients are seen, but also in the non-specialist and primary care settings.9 10 Particularly for non-specialists, keeping up with the latest evidence in a variety of areas, and having the knowledge to critically assess new findings in specialist areas, such as chronic pain, can be difficult: hence the need for good quality, evidence -based clinical guidelines. There is also an urgent need to ensure that research priorities are directed towards the areas of clinical need where there is a lack of good quality evidence to underpin clinical practice. The Scottish Intercollegiate Guideline Network (SIGN) is a multi-professional organization that aims to produce evidencebased clinical practice guidelines to improve outcomes for patients by delivering healthcare based on the best available evidence, and reducing variations in practice (www.sign.ac .uk). Internationally recognized for their methodology and objectivity, SIGN has produced 134 clinical guidelines to date,
covering a wide range of clinical topics and influencing care in Scotland and worldwide. The methodology used has an approach that is consistent with a number of other national and international groups that produce clinical practice guidelines [such as the National Institute for Health and Care Excellence (NICE) in England and Wales, the Council of Europe, and the World Health Organization]. Key components used by all of these organizations include user involvement, contribution from a multidisciplinary group, systematic review, and critical appraisal of current research evidence.11 It has been shown that evidence synthesized only from expert consensus and narrative-based literature surveys may not accurately reflect the full range and effectiveness of available interventions, and may be open to bias. We therefore need systematic literature reviews, with objective critical appraisal of the published evidence, to form the basis of any valid new guideline.12 Although national and local guidelines have been in existence for some specific chronic pain conditions or management approaches, none had addressed chronic pain as a single clinical entity and addressed management comprehensively. SIGN therefore recognized the need for a new Guideline on Chronic Pain, with establishment of a multidisciplinary development group and publication of these guidelines in December 2013 (freely available at http://www.sign.ac.uk/guidelines/ fulltext/136/index.html). This guideline reviews the evidence for assessment and management of chronic non-malignant pain in the adult population in the non-specialist setting. It is based on the principle that the pathophysiology and psychosocial impact of chronic pain are largely independent of its biological aetiology, and therefore that common approaches to assessment and management are required, irrespective of its underlying cause. It takes a comprehensive approach to chronic pain as a clinical entity (defined as pain lasting longer than 3 months), although it does not cover chronic pain in children, nor specialist interventions.13 Additionally, it does not cover treatment of specific clinical conditions such as
9
Downloaded from http://bja.oxfordjournals.org/ at Belgorod State University on December 6, 2013
Department of Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh, Western General Hospital Crewe Rd, Edinburgh EH4 2XU, UK 2 Scottish Intercollegiate Guidelines Network, Healthcare Improvement Scotland, Gyle Square, 1 South Gyle Crescent, Edinburgh EH12 9EB, UK 3 University of Dundee, Mackenzie Building, Ninewells Hospital and Medical School, Kirsty Semple Way, Dundee DD2 4DB, UK
BJA
Editorial IV
Table 1 Summary of some of the key recommendations for chronic pain management made in the SIGN guideline. Grade A, at least one meta-analysis, systematic review, or RCT rated as 1++ , and directly applicable to the target population; or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results; Grade B, a body of evidence including studies rated as 2++ , directly applicable to the target population, and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 1++ or 1+ ; Grade C, a body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 2++ ; Grade D , evidence level 3 or 4; or extrapolated evidence from studies rated as 2+ ;GPP, good practice point: best practice based on the experience of the guideline development group, in the absence of good quality evidence. For more information on grading, see ref. 17 Summary of key recommendation
Level of evidence
Assessment and planning of care
In order to best direct treatment options, a comprehensive biopsychosocial assessment, including identification of pain type (e.g. neuropathic) should be carried out in any patient with chronic pain
GPP
Supported self-management
Self-management can be used from an early stage in a pain condition, with patients being directed to self-help resources at any stage in the patient journey
GPP
Pharmacological therapies
There should be at least annual assessment of patients on pharmacotherapy for chronic pain
GPP
Strong opioids should be considered for chronic low back pain or osteoarthritis and only continued if there is ongoing pain relief
B
Specialist advice or referral should be considered if there are concerns about rapid opioid dose elevation or if .180 mg per day morphine equivalent dose is needed
D
Consideration should be given for referral to a pain management programme for patients with chronic pain
C
There should be an awareness of the impact of healthcare workers behaviour, and the treatment environment, in reinforcing unhelpful responses
GPP
Any form of exercise or exercise is recommended for patients with chronic pain
B
In addition to exercise therapy, advice to stay active should be given to patients with chronic low back pain. This will improve disability in the long term. Advice alone is insufficient
A
Psychologically based interventions
Physical therapies
rheumatoid disease, nor treatment of patients with headaches (which is covered in a separate guideline).14
What areas are reviewed in the guideline? The guideline development group identified and agreed a series of 17 structured key questions, based on PICO methodology.15 16 The P(Population) for all the key questions was defined as adults suffering from chronic non-malignant pain of more than 3 months duration. Clearly, within this, there is a wide variation: thus, as with any clinical guideline, this must be recognized when applying the evidence base to any individual patient—no one is ‘average’. Following standard SIGN methodology,17 the following areas were addressed with respect to chronic pain: (i) (ii) (iii) (iv) (v) (vi)
Assessment Self-management Pharmacological therapies Psychologically based interventions Physical therapies Complementary therapies
The primary output was a number of key recommendations, relating to the pre-defined key questions, and these were accompanied by consensus statements rooted in the derived evidence. A summary of some of the key recommendations is shown in Table 1.
10
Evidence, research gaps, and limitations Much good quality evidence was found to support the management of chronic pain by non-specialists, particularly allowing strong recommendations to be made on advice for physical activity and on the effectiveness of some physical, psychological, and pharmacological interventions. These are presented in the guideline, along with other recommendations based on weaker evidence. While we identified a considerable literature in chronic pain, we also identified that there is a number of areas where further research is needed, to allow non-specialist clinical practice to be based on the highest quality of evidence (or even any evidence). Some of these areas have already been identified as lacking appropriate evidence and reflecting a significant research gap.18 One of the functions of this guideline was therefore to identify where current practice does not have a good evidence base and to make research recommendations (Table 2). It is hoped that these will be of use to research funders in terms of priority planning. Like all guidelines and systematic reviews, this guideline can only be as good as the published evidence, and the nature of chronic pain and its response to treatment makes this a particular challenge. A recent editorial in the Methodology series in the BJA highlights the role of uncertainty in the evidence on which clinical guidelines are based. It is suggested that research gaps and lack of evidence do not preclude the development of good quality clinical guidelines, but that these issues must be acknowledged in interpretation and application of such guidelines.19
Downloaded from http://bja.oxfordjournals.org/ at Belgorod State University on December 6, 2013
Area addressed by key question
BJA
Editorial IV
Consensus pathways There is a tension between producing a high-quality systematic review of current evidence, where it is difficult to give high grade recommendations about clinical management of
chronic pain patients because of the lack of evidence, and producing a clinically useful resource. This was recognized in the current guideline, so that a number of consensus pathways were developed—based on best available evidence, but also using the combined expertise of the guideline development group and peer reviewers to produce three comprehensive consensus-based pathways for areas that were felt to offer particular challenges for the non-specialist: (i) Pathway for chronic pain assessment, early management, and care planning in non-specialist settings. (ii) Pathway for patients with neuropathic pain. (iii) Pathway for using strong opioids in patients with chronic pain. These are intended to guide the practitioner practically, through a comprehensive biopsychosocial process of assessment and management, recognizing good evidence and other relevant guidelines, and also the need for patient-centredness and safety. The British Pain Society has also developed a number of pathways of care recently, in collaboration with Map of Medicine (and have been the subject of BJA commentaries).27 28 The first two SIGN pathways are complementary to the BPS pathways, while the third area (strong opioid use) was not covered as a focused pathway by the BPS, although a separate BPS guideline exists.29
Dissemination and implementation Once published, guidelines need active dissemination and approaches to ensure that recommendations are embedded into clinical practice. Effective strategies include the development of care pathways, engagement with topic-relevant professionals, local clinical champions, availability in different formats (a patient version, quick reference guide, and an app), and the production of audit support tools, linked to performance indicators. One of the unique aspects of the SIGN process is a link [through NHS Healthcare Improvement Scotland (HIS)] to all NHS Health Boards throughout Scotland, where newly formed chronic pain multidisciplinary groups
Table 2 Some of the identified research gaps and recommendations for further research Area addressed by key question
Research recommendation
Assessment and planning of care
† Examine effect of assessing different components of pain on treatment outcomes † Studies for early identification of patients most at risk of poor outcomes and to assess the effect of early referral † Investigate efficacy of simple approaches to improving professional– patient interaction and impact on outcomes
Pharmacological therapies
† † † †
Psychologically based interventions
† RCTs on acceptance and commitment therapy
Complementary therapies
† Well-designed studies (e.g. RCTs) to assess alternative therapies such as herbal medicines, dietary interventions, music therapy, hypnosis, and acupuncture
Study patterns of opioid prescribing and factors to optimize good practice use of opioids Studies of long-term effects of opioids on pain and adverse effects Studies on combination pharmacotherapy Studies on factors contributing to interindividual variation in treatment responses and possible clinical biomarkers of response
11
Downloaded from http://bja.oxfordjournals.org/ at Belgorod State University on December 6, 2013
Particularly for pharmacotherapy, there are a number of issues that must be considered when interpreting the evidence. It has been highlighted previously that even good quality double-blind randomized controlled trials (RCTs)— considered to form the basis of the strongest clinical evidence—may not be the best way of assessing chronic pain treatments.20 One potential problem is that the apparent effectiveness of specific treatments in trials may be diluted by including subgroups of patients that will have no chance of responding to that treatment (e.g. due to the underlying neurobiological changes in that patient).21 While clinical trial evidence may not translate well into individual patient response, many will respond to at least one of the available drugs.22 23 At the opposite end of the spectrum, another problem is that of overestimating the effectiveness of a treatment, depending on the type of analysis used—in particular, the way in which missing data are handled. If there is an assumption that drop-outs in either arm are random, but the treatment being studied is effective, but poorly tolerated, then using Last Observation Carried Forward (LOCF) will overestimate the treatment effect. More recent good quality RCTs specifically state the type of analysis used and treatment of missing data.24 An additional challenge in chronic pain trials is the duration of the trial—ideally long duration studies are needed, but this is balanced by the challenges of patients lost to follow-up. For example, with strong opioids, used for an increasing number of patients, there is a significant need for, but definite lack of, good quality long-term studies, where the method of dealing with drop-outs has been pre-defined.25 26 There has been considerable discussion about how to address these problems and how to best design chronic pain clinical trials in the future (see www.immpact.org).
BJA
Declaration of interest All authors contributed to the design and writing of this paper, without any financial or other assistance. B.H.S. has received an unrestricted educational grant and consultancy fees from Pfizer; L.A.C. is an Editor of the British Journal of Anaesthesia; A.S. is employed by SIGN.
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10 Colvin LA, Rowbotham DJ. I. Managing pain: recent advances and new challenges. Br J Anaesth 2013; 111: 1– 3 11 Turner T, Misso M, Harris C, Green S. Development of evidence-based clinical practice guidelines (CPGs): comparing approaches. Implement Sci 2008; 3: 45 12 Antman E, Lau J, Kupelnick B, Mosteller F, Chalmers T. A comparison of results of meta-analyses of randomized controlled trials and recommendations of clinical experts. Treatments for myocardial infarction. J Am Med Assoc 1992; 268: 240– 8 13 Merskey H, Bogduk N. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. IASP, Seattle, WA, 1994 14 Scottish Intercollegiate Guideline Network. Diagnosis and Management of Headache in Adults. Edinburgh: SIGN, 2008 15 Counsell C. Formulating questions and locating primary studies for inclusion in systematic reviews. Ann Intern Med 1997; 127: 380– 7 16 Schardt C, Adams MB, Owens T, Keitz S, Fontelo P. Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Medical Inform Decis Mak 2007; 7: 16 17 Scottish Intercollegiate Guideline Network. SIGN 50: A Guideline Developer’s Handbook, revised Edn. Edinburgh: SIGN, 2011 18 Chapman CR, Lipschitz DL, Angst MS, et al. Opioid pharmacotherapy for chronic non-cancer pain in the United States: a research guideline for developing an evidence-base. J Pain 2010; 11: 807–29 19 Imberger G. Clinical guidelines and the question of uncertainty. Br J Anaesth 2013; 111: 700–2 20 McQuay HJ, Derry S, Moore RA, Poulain P, Legout V. Enriched enrolment with randomised withdrawal (EERW): time for a new look at clinical trial design in chronic pain. Pain 2008; 135: 217– 20 21 Attal N, Bouhassira D, Baron R, et al. Assessing symptom profiles in neuropathic pain clinical trials: can it improve outcome? Eur J Pain 2011; 15: 441–3 22 Moore RA, Derry S, Wiffen PJ. Challenges in design and interpretation of chronic pain trials. Br J Anaesth 2013; 111: 38– 45 23 Moore A, Derry S, Eccleston C, Kalso E. Expect analgesic failure; pursue analgesic success. Br Med J 2013; 346: f2690 24 Moore RA, Straube S, Eccleston C, et al. Estimate at your peril: imputation methods for patient withdrawal can bias efficacy outcomes in chronic pain trials using responder analyses. Pain 2012; 153: 265– 8 25 Dworkin RH, Turk DC, Peirce-Sandner S, et al. Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations. Pain 2010; 149: 177– 93 26 Dworkin RH, Turk DC, Katz NP, et al. Evidence-based clinical trial design for chronic pain pharmacotherapy: a blueprint for ACTION. Pain 2011; 152: S107 –15 27 Smith BH, Lee J, Price C, Baranowski AP. Neuropathic pain: a pathway for care developed by the British Pain Society. [Erratum appears in Br J Anaesth 2013; 111: 522.] Br J Anaesth 2013; 111: 73–9 28 Lee J, Gupta S, Price C, Baranowski AP. British Pain Society. Low back and radicular pain: a pathway for care developed by the British Pain Society. Br J Anaesth 2013; 111: 112–20 29 The British Pain Society’s: Opioids for Persistent Pain: Good Practice, 2nd Edn. London: The British Pain Society, 2010 30 El-Ghorr A, James R, Twaddle S. SIGN is customising implementation support to every guideline. Guidelines Pract 2011; 14: 40– 6
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(Service Improvement Groups) will have local implementation of this new guideline as part of their defined remit. The patient version provides evidence-based information about options for pain management, distilled from the full version, so that patients can engage actively and effectively with their treatment plan, allowing informed involvement of service users. There is recognition and support from NHS HIS that a variety of approaches will be needed to overcome barriers and to change practice at a local level. There is now an opportunity to measure how implementation of an evidence guideline can impact on patient outcomes.30 In summary, SIGN has produced the first national evidencebased guideline for the management of chronic pain by nonspecialists, with practical methods for its dissemination and implementation. This has the potential to both raise awareness and improve the management of this common and disabling condition. Importantly, it also highlights the relative lack of good quality evidence to guide management, and indicates key areas for further, urgent research. The guideline is now freely available for use by patients, clinicians, policy-makers, and researchers to guide current and future practice. We look forward to reviewing it when more and better evidence becomes available.
Editorial IV
