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Further studies are needed to assess the competing therapies for neck pain

  • Paul M Peloso
    Correspondence
    Address reprint requests to Paul M. Peloso, MD, MSc, University of Iowa, Department of Internal Medicine, E330 GH, Iowa City, IA 52240, USA.
    Affiliations
    Department of Internal Medicine, Roy and Lucille Carver College of Medicine, University of Iowa Health Care, Iowa City, Iowa, USA
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  • Anita Gross
    Affiliations
    Department of Rehabilitation Medicine, McMaster University , Hamilton, Ontario, Canada

    St Joseph's Centre for Acute Injury Rehabilitation, St Joseph's Healthcare, Hamilton, Ontario, Canada
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      While reading the review by Ernst

      Ernst E. Chiropractic spinal manipulation for neck pain: A systematic review. J Pain 4: 2003

      in this issue of the Journal of Pain, we asked ourselves, “Has this review helped us advance the science around the treatment of neck pain, or not?” The answer is mixed. Although there is a clear need for more randomized trials in neck pain in general, including manipulative techniques, there are methodologic issues in this review and unsupported statements of opinion that give us pause. We would first like to address some the methodologic issues and provide alternate points of view and then address the issue of chiropractic spinal manipulation in the broader context of neck pain management.

      Methodologic issues in systematic reviews

      Although the traditional narrative review has a role in linking together seemingly disparate elements of research and in providing historical perspective, its role in summarizing randomized trials in a specific area is limited. This is because traditional narrative reviews are prone to multiple biases.
      • Cook D.J.
      • Mulrow C.D.
      • Haynes R.B.
      Systematic reviews synthesis of best evidence for clinical decisions.
      There has been a great deal written on the proper conduct of a systematic review during the last 10 years.
      • L'Abbe K.
      • Detsky A.S.
      • O'Rourke K.
      Meta-analysis in clinical research.
      • Oxman A.D.
      • Cook D.J.
      • Guyatt G.H.
      Users' guides to the medical literature. VI. How to use an overview. Evidence-Based Medicine Working Group.
      • Oxman A.D.
      • Guyatt G.H.
      Validation of an index assessing the quality of review articles.
      Systematic reviews are defined by their ability to limit biases such as selection bias, which would include incomplete capture of primary trials and exclusion of relevant trials, as well as careful evaluation of the internal validity of the primary trials, which includes proper randomization (allocation concealment), avoidance of treatment contamination, proper outcome assessment, especially patient blinding, complete reporting outcomes, including adequate follow-up, and use of an intent-to-treat analysis. The Cochrane Back Pain Group has published guidelines on performing systematic reviews in spinal pain and include neck pain in their purview.
      • van Tulder M.W.
      • Assendelft W.J.
      • Koes B.W.
      • Bouter L.M.
      Method guidelines for systemic reviews in the Cochrane Collaboration Back Review Group for Spinal Disorders.
      Their recommendations are relevant here. The following methodologic issues in the Ernst review will be specifically addressed: (1) Was there evidence of selection bias? (2) Was limiting the article to chiropractic spinal manipulation only a reasonable decision? (3) Was there a proper assessment of methodologic quality of the primary studies? (4) Is it acceptable to have only one person perform data extraction? (5) Is pain the only outcome of relevance in neck disorders?

       Was there selection bias?

      Ernst did not search the main chiropractic electronic databases, MANTIS and Chirolars, because of cost concerns and instead asked chiropractors to identify their research. Did this strategy miss any articles? A recently published systematic review on mobilization and manipulation
      • Gross A.
      • Kay T.
      • Hondras M.
      • Goldsmith C.
      • Haines T.
      • Peloso P.
      • Kennedy C.
      • Hoving J.
      Manual therapy for mechanical neck disorders A systematic review.
      identified 173 possibly relevant articles and reviewed 20 articles on mobilization and manipulation, and that search strategy was completed to 1997 only. We have recently performed an updated search to 2002 as part of a National Institutes of Health–Consortial Center for Chiropractic Research funded grant, and we found 33 trials related to the topic of mobilization and manipulation. Some of these articles might well have been excluded from the Ernst review, given the restrictive inclusion of chiropractic interventions only. However, the pool of articles related to manipulation and mobilization is more like 20 to 33 articles, not the 10 or so found by Ernst.
      Prior research has demonstrated that several people need to make decisions about which articles to include.

      Haines T, Kennedy C, Goldsmith C, Gross A, Hondras M, Kay T, Hoving J, Peloso P for the Cervical Overview Working Group: Effect of blinding on selection of articles for relevance (abstract). 5th International Cochrane Colloquium, 1999, Rome, Italy

      The article by Gross et al
      • Gross A.
      • Kay T.
      • Hondras M.
      • Goldsmith C.
      • Haines T.
      • Peloso P.
      • Kennedy C.
      • Hoving J.
      Manual therapy for mechanical neck disorders A systematic review.
      showed that agreement on article selection, performed by 2 people, was good but not perfect (estimated kappa, 0.68; range, 0.53 to 0.8). Haines et al.

      Haines T, Kennedy C, Goldsmith C, Gross A, Hondras M, Kay T, Hoving J, Peloso P for the Cervical Overview Working Group: Effect of blinding on selection of articles for relevance (abstract). 5th International Cochrane Colloquium, 1999, Rome, Italy

      showed that there was good but not perfect agreement on which articles should be included (estimated kappas, 0.67 to 0.75) and that article selection was influenced by several factors, such as familiarity with author and journal as well as perceived influence of the author and the journal. Thus there are several reasons to believe that the Ernst review suffered from selection bias and that these factors artifactually reduced the apparent evidence from which Ernst draws conclusions.

       Why limit the review to chiropractic spinal manipulation?

      Ernst suggests that the articles on spinal manipulation should be limited to chiropractic manipulation. The rationale provided is that chiropractors use different techniques. No supporting references are offered for this statement. He also states that chiropractors have a different philosophical approach to treatment. What he does not mention is that these techniques are practiced by many other practitioner types, including physical therapists
      • Jull G.
      Use of high and low velocity cervical manipulative therapy procedures by Australian manipulative physiotherapists.
      and physicians,
      • Dvorak J.
      • Dvorak V.
      • Schneider W.
      • Tritschler T.
      Manual therapy in lumbo-vertebral syndromes.
      that the first randomized trial of spinal manipulation was performed by a medical doctor,
      • Sloop P.R.
      • Smith D.S.
      • Goldenberg E.
      • Dore C.
      Manipulation for chronic neck pain A double-blind controlled study.
      and that many of the standard textbooks on manipulative techniques used by chiropractors were written by medical doctors, including Cyriax,
      • Cyriax J.
      Mennel,

      Mennell J, Mc M: Joint Pain. Diagnosis and Treatment Using Manipulative Techniques. Boston, MA, Little, Brown and Company, 1964.

      Maigne,
      • Maigne R.
      Orthopedic Medicine: A New Approach to Vertebral Manipulation.
      and Haldeman.
      • Haldeman S.
      It is not clear what the relevance of philosophical differences between spinal manipulators is, and this problem is not unique to chiropractic. For instance, we have several theories but no clear answers on the mechanism of action of methotrexate

      Wienblatt ME: Methotrexate, in Kelley WN, Harris ED, Ruddy S, Sledge CB (eds): Textbook of Rheumatology (5th edition). Toronto, Canada, WB Saunders Company, 1997

      and hydroxychloroquine

      Rynes RI: Antimalarial drugs, in Kelley WN, Harris ED, Ruddy S, Sledge CB (eds): Textbook of Rheumatology (5th edition). Toronto, Canada, WB Saunders Company, 1997

      for rheumatoid arthritis, yet they continue to have clinical relevance to patients. We do not know how acetaminophen works as an analgesic,
      • Raffa R.B.
      • Stone Jr, D.J.
      • Tallarida R.J.
      Discovery of “self-synergistic” spinal/supraspinal antinociception produced by acetaminophen (paracetamol).
      although it is used to treat neck pain. A more convincing argument that technique differences are important might have been based on evidence of differences in efficacy or side effects related to technique differences. There are no randomized trials of “different” techniques in spinal manipulation, suggesting that one is preferred. The studies by Haldeman et al
      • Haldeman S.
      • Kohlbeck F.J.
      • McGregor M.
      Stroke, cerebral artery dissection, and cervical spine manipulation therapy.
      of serious complications of spinal manipulation (stroke and death) found that no technique was safest or riskiest. These complications are not unique to chiropractors, and complications from manipulation have occurred at the hands of physical therapists and physicians.
      • Gross A.R.
      • Kay T.
      • Hurley L.
      • Yardley K.
      • Hendry L.
      • McLaughlin L.
      Clinical practice guidelines on the use of manipulation or mobilization in the treatment of adults with neck disorders.
      Thus the selection of chiropractic spinal manipulation alone seems arbitrary and not based on evidence of differences in benefit or harm.
      It is also not clear why he would have excluded studies of whiplash. For many trials the description of the neck pain population is insufficient, so it is not clear whether patients with whiplash are included or excluded in the primary studies. Another review also found no evidence of systematic differences in treatment approaches used for those with whiplash and no systematic differences in treatment outcomes for patients with whiplash as compared to those with other types of nonpathologic neck pain.
      • Gross A.
      • Kay T.
      • Hondras M.
      • Goldsmith C.
      • Haines T.
      • Peloso P.
      • Kennedy C.
      • Hoving J.
      Manual therapy for mechanical neck disorders A systematic review.
      This arbitrary decision would further serve to artificially reduce the pool of studies for evaluation.

       Was the assessment of study quality adequate?

      Ernst reports that 2 studies were of poor quality and 2 were of moderate quality. This was based on the Jadad scoring system.
      • Jadad A.R.
      • Moore R.A.
      • Carroll D.
      • Jenkinson C.
      • Reynolds D.J.M.
      • David J.
      • Gavaghan D.J.
      • McQuay H.J.
      Assessing the quality of reports of randomized clinical trials Is blinding necessary?.
      What was left unstated was that the Jadad instrument was developed for studies of drugs, in which double blinding is readily accomplished with a matching placebo. In fact, the Jadad scoring system awards 2 points for randomization (1 point for stating it was random and 1 point for describing an acceptable method), 2 points for double-blinding (1 point for stating it was double-blinded and 1 point for describing an acceptable method), and 1 point for describing dropouts and follow-up. For almost all hands-on physical techniques, the person delivering the treatment cannot be blinded. Many of them are hard to blind to patients, if patients have experienced them in the past. This is true for spinal manipulation.
      It is possible to have a blinded outcome assessor for some outcomes. In the case of pain assessment, the best outcome assessor is rightly the patient; therefore it is difficult to blind pain assessment. Thus we point out 2 errors with Ernst's quality assessment of quality. The first is that the Jadad quality scoring system, as he uses it, has a maximum score of 3 not 4 points, because there is no option in the Jadad scoring system, as Jadad described it, for scoring points if a trial uses a blinded outcome assessor (ie, single-blinding). The second is that the review excludes trials of outcome measures, such as range of motion, that can be assessed by a blinded outcome assessor. These issues would artificially reduce the apparent methodologic quality of the trials reported. The Cochrane Back Pain group, recognizing the deficiency of the Jadad system when applied to trials of physically based treatments, recommends the scoring system of van Tulder et al.
      • van Tulder M.W.
      • Assendelft W.J.
      • Koes B.W.
      • Bouter L.M.
      Method guidelines for systemic reviews in the Cochrane Collaboration Back Review Group for Spinal Disorders.
      In the van Tulder scoring system, which is based on 19 methodologic elements that good randomized trials should report, trials score methodologic points for using a blinded outcome assessor.

       Was data extraction adequate?

      Mistakes can easily be made by using a single data extractor. L'Abbe et al,
      • L'Abbe K.
      • Detsky A.S.
      • O'Rourke K.
      Meta-analysis in clinical research.
      in one of the earliest reports on the quality of meta-analysis, suggested that having 2 data extractors was important. To quote the 1987 article, “data extraction can be tedious, subject to error and hence potential bias. We recommend that two persons familiar with the clinical topic do the data extraction independently and cross-check their reports to protect against this form of error.” This is also the view of the Cochrane Back Pain Group and of the Cochrane Collaboration in general, as suggested in their handbook,
      as well as reported in standard texts on systematic reviews and meta-analyses.

       Is pain the only outcome of interest?

      Why limit the data extraction to pain only? Although pain might be the cardinal symptom of neck troubles, neck pain only becomes clinically important when people seek and consume health care (seek out health care providers and use their services), lose function (such as range of motion, strength), lose sleep, lose time from work, and have impairments in their health-related quality of life. It is possible to have high pain levels and little disability and, conversely, lower pain levels and high disability.
      • Cote P.
      • Cassidy J.D.
      • Carroll L.
      Saskatchewan Neck and Back Pain Study The prevalence of neck pain and related disability in Saskatchewan adults.
      It is also possible to have neck pain associated with low back pain and headache, and more than half of individuals with neck pain have associated back pain.
      • Cote P.
      • Cassidy J.D.
      • Carroll L.
      The factors associated with neck pain and its related disability in the Saskatchewan population.
      Other contemporary systematic reviews in neck pain have extracted outcome measures, other than pain, including range of motion, and function,
      • Gross A.
      • Kay T.
      • Hondras M.
      • Goldsmith C.
      • Haines T.
      • Peloso P.
      • Kennedy C.
      • Hoving J.
      Manual therapy for mechanical neck disorders A systematic review.
      and the Cochrane Back Pain group recommends extracting several outcome measures.
      • van Tulder M.W.
      • Assendelft W.J.
      • Koes B.W.
      • Bouter L.M.
      Method guidelines for systemic reviews in the Cochrane Collaboration Back Review Group for Spinal Disorders.

       Chiropractic care in social context

      Meeker and Haldeman
      • Meeker W.C.
      • Haldeman S.
      Chiropractic A profession at the crossroads of mainstream and alternative medicine.
      have recently published a thoughtful review of the history and future challenges of chiropractic care, entitled “Chiropractors: A Profession at the Crossroads.” In this report the authors noted the historical philosophy of chiropractic, as Ernst does, but also described how many chiropractors are moving away from these concepts. It would seem that the chiropractic profession has recognized the need to undertake the science supporting their practices and that the National Institutes of Health is supportive of these endeavors.
      There have recently been several well-conducted, large, randomized trials performed by chiropractors with PhD level research training. One of these trials
      • Bronfort G.
      • Evans R.
      • Nelson B.
      • Aker P.D.
      • Goldsmith C.H.
      • Vernon H.
      A randomized clinical trial of exercise and spinal manipulation for patients with chronic neck pain.
      was discussed by Ernst, whereas a recent publication comparing chiropractic mobilization and manipulation was not.
      • Hurwitz E.L.
      • Morgenstern H.
      • Harber P.
      • Kominski G.F.
      • Yu F.Z.
      • Adams A.H.
      A randomized trial of chiropractic mobilization and manipulation for patients with neck pain Clinical outcomes form the UCLA Neck-Pain study.
      The National Institutes of Health, through their National Center for Complementary and Alternative Medicine, supported the trial by Hurwitz et al.
      • Hurwitz E.L.
      • Morgenstern H.
      • Harber P.
      • Kominski G.F.
      • Yu F.Z.
      • Adams A.H.
      A randomized trial of chiropractic mobilization and manipulation for patients with neck pain Clinical outcomes form the UCLA Neck-Pain study.
      Having discussed the changing face of efficacy data, what are the data for harm? We agree with Ernst that chiropractic care has been a politicized process. However, rather than report some of the recent data on harm, Ernst largely quotes his own studies and an opinion piece from the Medical Letter on Drugs and Therpeutics,

      Medical letter: Spinal manipulation. Med Lett Drugs Ther 44:50-51, 2002

      which quotes one of his letters to the editor of the Canadian Medical Association Journal on chiropractic safety. The “Medical Letter” does not present data on the incidence, prevalence, or risk factors for harm related to spinal manipulation, and Ernst does not in this review. However, there have been studies and reviews on the harm associated with manipulation that are relevant to this discussion, and they will be briefly outlined. The comprehensive review by Assendelft et al

      Assendelft WJ, Bouter LM, Knipschild PG. Complications of spinal manipulation: A comprehensive review of the literature. J Fam Pract 1996;42:475–50.

      reported that the estimates of vertebrobasilar artery complications ranges from 1 in 20,000 to 1 in 1,000,000, although they pointed out the poor quality of this literature. They further suggested that the apparent high proportion of complications related to chiropractic might not relate solely to the use of high-velocity thrust techniques. Alternate explanations offered included selection bias for complications inherent in the use of the English language literature, wherein chiropractors make up a larger proportion of those applying spinal manipulation, and misclassification of injuries.

      Assendelft WJ, Bouter LM, Knipschild PG. Complications of spinal manipulation: A comprehensive review of the literature. J Fam Pract 1996;42:475–50.

      A population-based study of chiropractic manipulation and stroke in the Canadian province of Ontario identified age younger than 45 years and more than 3 visits for chiropractic care in the last week were risk factors for vertebrobasilar events.
      • Rothwell D.M.
      • Bondy S.J.
      • Williams I.J.
      Chiropractic manipulation and stroke A population-based case-control study.
      However, the authors noted that the rarity of these events made the association difficult to study, in spite of high volumes of chiropractic treatments during the 6-year period under review. On the basis of reports to the Canadian malpractice carrier for chiropractors, the suggested incidence of arterial dissections is estimated to be less than 1 in 1,000,000.
      • Haldeman S.
      • Carey P.
      • Townsend M.
      • Papadopoulos C.
      Arterial dissections following cervical manipulation The chiropractic experience.
      A Danish retrospective cohort study also suggested that the occurrence of cerebrovascular accidents after manipulation to the neck was estimated to be 1 in 1,000,000 cervical manipulations.
      • Klougart N.
      • Lebouef-Yde C.
      • Rasmussen L.R.
      Safety in chiropractic practice, part I The occurrence of cerebro-vascular accidents after manipulation to the neck in Denmark from 1978-1988.
      Although severe complications with spinal manipulation are uncommon, short-term side effects to spinal manipulation are not.
      • Leboeuf-Yde C.
      • Hennius B.
      • Rudberg E.
      • Leufvenmark P.
      • Thunman M.
      Side effects of chiropractic treatment A prospective study.
      In contrast to the numerous trials of manipulation for neck pain noted above, the situation for medicinal therapies is humbling. A 1996 review found no placebo-controlled trials on acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), or opioids for neck pain.
      • Aker P.D.
      • Gross A.R.
      • Goldsmith C.H.
      • Peloso P.M.
      Conservative management of mechanical neck pain Systematic overview and meta-analysis.
      A recent update of medications and injections for neck pain also failed to disclose any placebo-controlled trials of acetaminophen, NSAIDs, or opioids specifically with a neck pain population.

      Peloso PM, Haines T, Gross AG, Goldsmith CH., Hondras M for the Cervical Overview Group: Medicinal and injection therapies for neck pain: A systematic review (abstract 1611). Arthritis Rheum 43:S335, 2000.

      Yet acetaminophen and NSAIDs continue to be recommended in standard textbooks

      Borenstein DG, Wiesel SW, Boden SD. Medical therapy, in Neck Pain: Medical Diagnosis and Comprehensive Management. Toronto, Canada, WB Saunders Co, 1996

      and used in practice.
      • Bourghouts J.
      • Janssen H.
      • Koes B.
      • Muris J.
      • Metsemakers J.
      • Bouter L.
      The management of neck pain in primary care A retrospective study.
      • Cote P.
      • Cassidy J.D.
      • Carroll L.
      The treatment of neck and low back pain Who seeks care? Who goes where?.
      Acetaminophen is recommended for neck pain in the absence of evidence of benefit and in the face of harm to the gastrointestinal tract,
      • Gross A.
      • Kay T.
      • Hondras M.
      • Goldsmith C.
      • Haines T.
      • Peloso P.
      • Kennedy C.
      • Hoving J.
      Manual therapy for mechanical neck disorders A systematic review.
      liver,
      • Schiodt F.V.
      • Rochling F.A.
      • Casey D.L.
      • Lee W.M.
      Acetaminophen toxicity in an urban county hospital.
      and kidney.
      • Fored C.M.
      • Ejerblad E.
      • Lindblad P.
      • Fryzek J.P.
      • Dickman P.W.
      • Signorello L.B.
      • Lipworth L.
      • Elinder C.G.
      • Blot W.J.
      • McLaughlin J.K.
      • Zack M.M.
      • Nyren O.
      Acetaminophen, aspirin, and chronic renal failure.
      Likewise, there are no randomized, placebo-controlled trials of NSAIDs in a neck pain population, although the gastrointestinal toxicity of these drugs is well known, with serious toxicity occurring in the order of - persons.

      Garcia Rodriguez LA, Hernandez-Diaz S: Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology :570-576, 2001

      NSAIDS can provoke heart failure in those at risk,
      • Garcia Rodriguez L.A.
      • Hernandez-Diaz S.
      Nonsteroidal antiinflammatory drugs as a trigger of clinical heart failure.
      and the newer cyclooxygenase specific inhibitors are equally likely to cause renal failure compared to the traditional NSAIDs.
      • Ahmad S.R.
      • Kortepeter C.
      • Brinker A.
      • Chen M.
      • Beitz J.
      Renal failure associated with the use of celecoxib and rofecoxib.
      Finally, although it appears that spinal manipulation has no distinct advantages over other therapies from an efficacy point of view, Americans with low back pain are more satisfied with chiropractic care than with medical care,
      • Carey T.S.
      • Garrett J.
      • Jackman A.
      • McLaughlin C.
      • Fryer J.
      • Smucker D.R.
      The outcomes and costs of care for acute low back pain among patients seen by primary care practitioners, chiropractors, and orthopedic surgeons The North Carolina Back Pain Project.
      • Heertzman-Miller R.P.
      • Morgenstern H.
      • Hurwitz E.L.
      • Yu F.
      • Adams A.H.
      • Harber P.
      Comparing satisfaction of low back pain patients randomized to receive medical or chiropractic care Results from the UCLA low-back pain study.
      • Solomon D.H.
      • Bates D.W.
      • Panush R.S.
      • Katz J.N.
      Costs, outcomes, and patient satisfaction by provider type for patients with rheumatic and musculoskeletal conditions A critical review of the literature and proposed methodologic standards.
      even though chiropractors cost more. This appears to be true for patients with neck pain as well, because a Canadian study showed patients were satisfied with chiropractic care, and their satisfaction correlated with pain relief and reduction in pain-related disability.
      • Verhoef M.J.
      • Page S.A.
      • Waddell S.C.
      The Chiropractic Outcome Study Pain, functional ability and satisfaction with care.
      In short, we agree that further studies of all therapies for neck pain are needed and that comparative studies of common treatments for neck pain are especially needed. We are beyond the point of benefiting from interdisciplinary finger pointing, and we suggest that interdisciplinary cooperation is needed to address the pressing scientific issues of assessing benefits and harms of competing therapies for patients with neck pain.

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