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Identifying the Best Treatment Among Common Nonsurgical Neck Pain Treatments: A Decision Analysis

van der Velde, Gabrielle, DC*†‡§; Hogg-Johnson, Sheilah, PhD; Bayoumi, Ahmed M., MD, MSc†∥**††; Cassidy, J David, PhD, DrMedSc†‡§; Côté, Pierre, DC, PhD*†‡§; Boyle, Eleanor, PhD‡§; Llewellyn-Thomas, Hilary, PhD‡‡; Chan, Stella, MSc*; Subrata, Peter, MSc*; Hoving, Jan Lucas, PhD§§; Hurwitz, Eric, DC, PhD¶¶; Bombardier, Claire, MD, MSc*†∥∥; Krahn, Murray, MD, MSc†∥∥***

doi: 10.1097/BRS.0b013e31816454f8
Supplementary Research Studies
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Study Design. Decision analysis.

Objective. To identify the best treatment for nonspecific neck pain.

Summary of Background Data. In Canada and the United States, the most commonly prescribed neck pain treatments are nonsteroidal anti-inflammatory drugs (NSAIDs), exercise, and manual therapy. Deciding which treatment is best is difficult because of the trade-offs between beneficial and harmful effects, and because of the uncertainty of these effects.

Methods. (Quality-adjusted) life expectancy associated with standard NSAIDs, Cox-2 NSAIDs, exercise, mobilization, and manipulation were compared in a decision-analytic model. Estimates of the course of neck pain, background risk of adverse events in the general population, treatment effectiveness and risk, and patient-preferences were input into the model. Assuming equal effectiveness, we conducted a baseline analysis using risk of harm only. We assessed the stability of the baseline results by conducting a second analysis that incorporated effectiveness data from a high-quality randomized trial.

Results. There were no important differences across treatments. The difference between the highest and lowest ranked treatments predicted by the baseline model was 4.5 days of life expectancy and 3.4 quality-adjusted life-days. The difference between the highest and lowest ranked treatments predicted by the second model was 7.3 quality-adjusted life-days.

Conclusion. When the objective is to maximize life expectancy and quality-adjusted life expectancy, none of the treatments in our analysis were clearly superior.

A decision-analytic model was used to identify the best treatment among common nonsurgical neck pain treatments. With the objective to maximize (quality-adjusted) life expectancy, no treatment was clearly superior.

From the *Institute for Work & Health, Toronto, Canada; †Department of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; ‡Division of Health Care and Outcomes Research, Toronto Western Research Institute, Toronto, Canada; §Centre of Research Expertise in Improved Disability Outcomes, University Health Network Rehabilitation Solutions, Toronto Western Hospital, Toronto, Canada; ¶Department of Public Health Sciences, University of Toronto; ∥Centre for Research on Inner City Health, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital; **Department of Medicine, University of Toronto; ††Division of General Medicine, St. Michael’s Hospital, Toronto, Canada; ‡‡Department of Community and Family Medicine, Dartmouth Medical School, Dartmouth College, Hanover, NH; §§Coronel Institute of Occupational Health and Research Centre for Insurance Medicine, Academic Medical Centre, Universiteit van Amsterdam, Amsterdam, The Netherlands; ¶¶Department of Public Health Sciences, John A. Burns School of Medicine, University of Hawaii at Mᾱnoa, Honolulu, HI; ∥∥Toronto General Research Institute, Division of Clinical Decision Making and Health Care, Toronto, Canada; and ***Faculty of Pharmacy, University of Toronto, Toronto, Canada.

The manuscript submitted does not contain information about medical device(s)/drug(s).

Provincial funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Supported by the Canadian Institutes of Health Research through a Fellowship Award (to G.v.d.V.), Canadian Institutes of Health Research through a New Investigator Award (to P.C.), Canada Research Chair in Knowledge Transfer for Musculoskeletal Care (to C.B.), and F. Norman Hughes Chair in Pharmacoeconomics (to M.K.).

The views expressed in this publication are the views of the authors and do not necessarily reflect the views of the Ontario Ministry of Health and Long-term Care.

Ethics Approval: University of Toronto Ethics Review Board Protocol Reference 18807.

Address correspondence and reprint requests to Gabrielle van der Velde, DC, Toronto Western Hospital, 399 Bathurst Street, Fell Pavilion 4-134, Toronto, ON, Canada M5T 2S8; E-mail: gvdvelde@uhnresearch.ca

In Canada and the United States, persons with neck pain generally visit primary care physicians or chiropractors, and are usually treated with nonsteroidal anti-inflammatory drugs (NSAIDs), exercise, or manual therapy.1–6 Physicians typically prescribe medication (most likely a NSAID) or refer to physical therapists for exercise,5,6 whereas most chiropractors typically administer manual therapy (most likely manipulation or mobilization).4,7

Deciding which treatment is best for neck pain is difficult. Each treatment carries trade-offs between potential beneficial and harmful effects. Furthermore, the probability of these effects is uncertain. For example, the evidence for the effectiveness of NSAIDs for relieving neck pain is scant.8,8a NSAIDs may also increase the risk of cardiovascular or gastrointestinal events, although the estimates of increased risk vary widely.9,10 Similarly, evidence about the effectiveness of manipulation is conflicting,8a and published estimates of the risk of stroke with neck manipulation vary substantially.11

Decision analysis is a method for identifying the best treatment based on (1) the outcome (benefits and harms) of a specific treatment and associated probabilities, and (2) patients’ preferences for these outcomes. This method typically synthesizes evidence from various sources.12 Our objective was to use decision analysis to identify the optimal treatment among commonly-used neck pain treatments using evidence from the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders (Neck Pain Task Force).

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Methods

Decision analysis was used to quantify outcomes associated with 6 weeks of NSAID use, exercise, or manual treatments for nonspecific neck pain neck (i.e., neck pain that is not caused by an identifiable etiological lesion such as a fracture, infection, tumor, inflammatory arthritide, or myelopathy). We assumed the patient’s perspective and quantified beneficial and harmful outcomes in terms of life expectancy and quality-adjusted life expectancy.

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Model Structure and Modeling

We built a decision-analytic Markov model that followed a simulated cohort of neck pain patients (TreeAge, Pro Suite 2007, Williamstown, MA). Five treatments were evaluated, including standard NSAIDs (sNSAIDs), selective Cox-2 inhibiting NSAIDs (Coxibs), exercise, mobilization, and manipulation (Figure 1). Model details are available online in a Supplementary Appendix (available online through Article Plus).

Figure 1

Figure 1

The model consisted of health states that represented the beneficial and harmful outcomes of these treatments, including Troublesome Neck Pain, No Troublesome Neck Pain, Myocardial Infarction, Post-Myocardial Infarction, Heart Failure, Minor Stroke Disability, Major Stroke Disability, Surgery for Upper Gastrointestinal Bleed, and Endoscopy for Upper Gastrointestinal Bleed.13 No Troublesome Neck Pain was defined as a Chronic Pain Score Grade of 0 (no neck pain) or I (pain of low intensity and few activity limitations).14–16 Troublesome Neck Pain was defined as grade II (pain of high intensity, but few activity limitations), III (pain associated with high levels of disability and moderate limitations in activities), or IV (pain with high levels of disability and several activity limitations). The model tracked patients over 13 four-week cycles (total 52 weeks). At baseline, all patients had Troublesome Neck Pain and could transition between health states at each cycle. A 1-year follow-up was modeled due to lack of evidence regarding long-term treatment effects. Projected years of remaining lifetime were modeled by assigning a mean life expectancy to each terminal health state at the end of the 1-year follow-up.13,17 Patients were not modeled to cross-over from one treatment to another, nor treated for recurrent episodes.

We modeled a baseline course of neck pain (without treatment) and then modified this course to reflect treatment effectiveness. We also modeled a background risk of adverse events (drawn from rates in the general population) that were modified with estimates of treatment-related risks of harmful events. Patients who received sNSAIDs or Coxibs were at an increased risk of stroke, myocardial infarction, heart failure, and serious upper gastrointestinal bleed (UGIB).9,18–21 Patients who received neck manipulation were assumed to have an increased risk of stroke.11

Life expectancy (measured in years) and quality-adjusted life expectancy (measured in quality-adjusted life years [QALYs]) were used to measure the impact of beneficial and harmful treatment outcomes. The QALY captures health-related gains or losses from reduced or increased morbidity (quality-of-life) and reduced or increased mortality (quantity-of-life) into a single measure, by assigning a quality-of-life weight to each time-cycle spent in a health state.13,17 The weight is based on a preference score, a quantitative expression of the desirability of a health state,17,22 expressed as a numerical anchored at 0, corresponding to Death (presumed to be the least desirable outcome) and 1, corresponding to Good Health (the most desirable outcome).13,17 QALYs were calculated by multiplying the weight associated with each health state by the duration of time spent in that state, then summing this over 1-year. The long-term impact of outcomes on quality-adjusted life expectancy over the projected years of remaining lifetime was estimated by multiplying the quality-of-life weight of each terminal health state by its mean life expectancy.

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Patient Population

Our target population included persons with neck pain seeking care from a physician, a physical therapist, or a chiropractor. The baseline analysis considered a cohort of 45-year-old individuals from the general population with neck pain of ≥2 weeks duration. We chose these characteristics to mirror the age and duration distribution reported in previous studies.1,5,23-26,26a

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Model Data

We obtained evidence about event probabilities and transition rates between health states from studies accepted by the Neck Pain Task Force that approximated the characteristics of our target population (Table 1). Where such data were not available, we searched the literature for data based on samples that matched our cohort as closely as possible (Table 1). Transition rates from Troublesome Neck Pain and No Troublesome Neck Pain were estimated from a population-based cohort (Table 1).27

Table 1

Table 1

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Background Risk of Adverse Events in the General Population.

The population-based incidence of hospitalization for acute strokes in persons aged 45 years was obtained from data gathered for a Neck Pain Task Force cohort study (Table 1).27a The 1-year incidence of stroke after a myocardial infarction was obtained from a meta-analysis.39 The remaining adverse events were estimated by pooling data identified by systematic searches of Medline. Intercept-only random-effects regression models were used to pool incidence rates and incidence proportions. We calculated the following: (1) rates of hospitalization for acute myocardial infarction,28–33 and for serious UGIB53,54; (2) 28-day and 1-year mortality after hospitalization for the following index events: myocardial infarction,30–32,34–38 heart failure,43,44 serious UGIB,55–61 and stroke45–49; and (3) an estimate of the proportion of strokes that result in major disability50–52; serious UGIBs that are treated with surgery59,62–64; and acute myocardial infarctions that result in heart failure.34,36,40–42

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Treatment Risk.

Pooled estimates of stroke, myocardial infarction, and serious UGIB associated with NSAIDs were identified by a systematic search of meta-analyses of harmful events associated with NSAIDs in Medline (Table 1). Wherever possible, we selected pooled estimates that are based on clinical trials comparing classes of NSAIDs to placebo.9,19–21 Where such estimates were not found, we selected estimates that fulfilled these criteria as closely as possible.

The Neck Pain Task Force provided 2 estimates of the risk of stroke after chiropractic visits.11,54a Both studies reported a positive association between chiropractic visits and posterior circulation stroke in persons aged <45 years and a negative association in persons aged ≥45 years. However, the analysis on patients who visited physicians conducted in one of these studies (which found a positive association between physician visits and stroke) suggests that patients with neck pain and headaches consult a health care provider during the prodromal phase of a stroke.54a We applied a risk estimate for all types of strokes associated with chiropractic visits for persons aged <45 years estimated from the Neck Pain Task Force data (Table 1). This estimate was used because we considered it unlikely that the risk of stroke changes discretely at the age of 45. Given the positive association between chiropractic and physician visits with stroke reported by Cassidy et al54a (2008), we performed a sensitivity analysis in which we assumed no excess risk of stroke with manipulation.

We assumed that (1) “chiropractic visit” was a reasonable proxy for “neck manipulation” based on a study that reported 80.8% of patients receive manipulation4; (2) the risk of harmful events with manipulation and NSAIDs ended 4 and 8 weeks, respectively, after treatment10,11; (3) mortality after harmful events was equivalent in treatment users and nonusers; (4) patients could experience only 1 type of harmful event (cardiovascular, cerebrovascular, gastrointestinal) because the probability of experiencing more than 1 harmful event in a 4-week cycle is exceedingly rare; and (5) there were no risks of harms with exercise and mobilization (Table 2).

Table 2

Table 2

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Treatment Effectiveness.

Effectiveness estimates were derived from data provided by a high-quality randomized trial that compared the care provided by general practitioners, physical therapists, and manual therapists.67–69 These interventions were used as proxies for NSAID, exercise, and manual treatments, respectively. We assumed that (1) sNSAIDs and Coxibs have an equivalent effectiveness70–72; (2) manipulation and mobilization have an equivalent effectiveness8a,24,73; and (3) that any differences in effectiveness ends 52 weeks from the start of treatment (Table 2).67,68,74,75

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Mortality and Life Expectancy.

At each cycle, patients were subject to age-specific mortality due to all causes based on Canadian Life Tables.65 Average health state-specific life expectancies for Major Stroke Disability, Minor Stroke Disability, Post-Myocardial Infarction, and Heart Failure were obtained from the Framingham Heart Study cohort (Table 1).66 We assumed that life expectancies for persons in the Troublesome Neck Pain and No Troublesome Neck Pain health states were equivalent to age-matched persons in the general population (Table 2).65

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Quality-of-Life Weights.

Quality-of-life weights for the health states were obtained from a sample of 220 neck pain patients presenting to clinics in Ontario and California (Table 1). Quality-of-life estimates were elicited with the standard gamble using health state descriptions as stimuli.13 The descriptions were constructed in a standardized manner using a recognized health classification framework.76,77 Variances of the mean quality-of-life estimates were estimated by using a variance estimator method.78

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Analyses

The internal consistency of the model was evaluated according to the method proposed by Philips et al.12

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Expected Value Analyses.

We calculated expected value by multiplying the proportion of the cohort in each health state by the corresponding quality-of-life weight in each cycle and then summing products over all cycles, yielding an estimate of quality-adjusted survival.22

Two expected value analyses were performed: a baseline analysis and a case example. For the baseline analysis, we assumed that all treatments had equivalent effectiveness because the Neck Pain Task Force found no clinically important differences in the effectiveness of NSAID, exercise, and manual treatments.8a,24,71–73,79–82 Treatments were therefore compared by their risks of harmful outcomes only. The case example compared treatments by their risks of harmful events and their effectiveness, to explore the extent to which plausible estimates of effectiveness might change the baseline analysis results.67

We estimated the average gain in quality-adjusted life expectancy for exercise, mobilization, and manipulation compared with NSAIDs (the referent group) by subtracting the expected value of a treatment when only harms were considered from the expected value of the treatment when both benefits and harms were considered. Sensitivity analyses determined whether the rank-order of the best treatment (treatment with the highest expected value) changed when variable estimates were varied over plausible ranges.83 We defined plausible range as the lower and upper 95% confidence limits.

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Results

External Validation

At the end of the 1-year follow-up, 50.6% of the cohort was in the Troublesome Neck Pain state when treatments were assumed to have equivalent effectiveness and have no excess risk of harms. This result is consistent with Hill et al84 and the Neck Pain Task Force.84a

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Expected Value Analyses

Baseline Analysis.

The model predicted a small average loss of life expectancy due to the risk of harms associated with NSAIDs and manipulation (Table 3). The difference between treatments assumed to have no harms (exercise, mobilization) versus manipulation, sNSAIDs, and Coxibs was 0.6, 2.2, and 4.5 days of life expectancy, respectively. Note that a loss of life expectancy does not mean, for example, that a 45-year-old person with a life expectancy of 35 years will live 4.5 fewer days;85 a loss of life expectancy means that the probability of a shorter life span has increased. The model also predicted a small average loss of quality-adjusted life expectancy. The difference between the highest-ranked (exercise, mobilization) and lowest-ranked (Coxibs) treatments was 3.4 quality-adjusted life days.

Table 3

Table 3

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Case Example Based on Randomized Control Trial Effectiveness Data.

The average difference in quality-adjusted life expectancy between the highest-ranked (mobilization) and lowest-ranked (Coxibs) treatment was 7.3 quality-adjusted life days (Table 3). Note that predicted life expectancies for the case example are identical to those of the baseline analysis because neck pain treatment effectiveness influences quality-of-life (morbidity) and not length of life (mortality). The model predicted small gains in quality-adjusted life expectancy due to effectiveness. Average gains for manipulation, mobilization, and exercise were 4.2, 3.9, and 1.1 quality-adjusted life days, respectively, compared to NSAIDs (referent group).

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Sensitivity Analyses

Baseline Analysis.

sNSAIDs was predicted to be the highest-ranked treatment when its risk of myocardial infarction was <0.87 (for life expectancy) and <0.86 (for quality-adjusted life expectancy). However, differences in expected values between sNSAIDs and exercise/mobilization were small. As expected, when neck manipulation was assumed to have no excess risk of stroke, its rank-order was equivalent to that of the best treatments.

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Case Example Based on Randomized Control Trial Effectiveness Data.

Exercise was predicted to be the best treatment when all mean hazard rate ratios for mobilization were minimally varied; however, differences in expected values between these treatments remained small. When manipulation was assumed to have no excess risk of stroke, its rank-order was equivalent to that of the highest-ranked treatment.

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Discussion

We compared the impact of harms associated with sNSAIDS, Coxibs, and manipulation compared with mobilization and exercise on the health of a simulated cohort of neck pain patients. The collective impact of harms with these treatments on life expectancy and quality-adjusted life expectancy was small. Our model also predicted small differences in loss of life expectancy85,86 and quality-adjusted life expectancy across treatments. Evaluating both benefits and harms also yielded minor differences across treatments in quality-adjusted life expectancy.

Our study has strengths. To our knowledge, nonsurgical neck pain treatments have not been previously compared in a decision-analytic Markov model. We synthesized high-quality evidence mainly provided by the Neck Pain Task Force. We quantified the impact of the benefits and harms associated with neck pain treatments on patients’ health on a common yardstick. We performed extensive sensitivity analyses.

Our study has limitations. First, certain background estimates of harmful events in the general population were based on samples that did not match our cohort because estimates from samples comparable to our cohort were not available from the literature. For example, the estimate of mortality after a stroke was based on samples that were older than our cohort. However, this limitation is unlikely to have led to a differential bias across treatments because the same background estimates were applied to all treatments. Furthermore, sensitivity analyses showed that our results were robust to variations in these estimates. Second, patients were not modeled to cross-over treatments. Therefore, the impact of serially-combined treatments was not evaluated. Third, we did not include renal complications associated with NSAIDs.87 This likely resulted in a moderate bias that favored NSAID treatments. Then again, the estimates of harmful events associated with NSAIDs tended to be based on samples of patients with serious health conditions, taking higher doses than we expect for our patient cohort. This likely resulted in a moderate bias against NSAIDs. Finally, we assumed an excess risk of stroke with neck manipulation, yet recent evidence suggests no excess risk.54a

Our study did not find overwhelming evidence to suggest that there is 1 treatment among the compared treatments that is, on average, clearly better. Because our results suggest a toss-up, other elements, such as patients’ preferences for treatment88–91 and their attitudes toward risk, likely play an important role in deciding the best treatment. More studies that consider these decisional elements are needed.

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Conclusion

From the standpoint of health policy, and when the objective is to maximize life expectancy and quality-adjusted life expectancy, there is no single treatment among NSAID, exercise, and manual therapies that is clearly better for neck pain. Therefore, a practitioner’s decision about the best treatment to provide to an individual patient should be based on the patient’s informed treatment preferences and attitudes toward risk.

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Key Points

  • Although a harmful event can have serious consequences for an individual patient, on an average, the overall impact of harms associated with 5 common nonsurgical neck pain treatments on patients’ health seems to be small.
  • When the objective is to maximize (quality-adjusted) life expectancy and only risks of harmful events are considered, differences across 5 common nonsurgical neck pain treatments are too small to establish the best treatment.
  • When the objective is to maximize (quality-adjusted) life expectancy, and both treatment-related harms and benefits are considered, no treatment among the 5 common nonsurgical neck pain treatments is clearly superior.

Appendix available online through Article Plus.

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Acknowledgments

The authors are grateful to George Tomlinson (University Health Network, Toronto) and members of the Measurement Research Unit (Dorcas Beaton, Kim Cullen, Anusha Raj, Peter Smith, and Dwayne van Eerd) (Institute for Work & Health, Toronto), and the Members of the Scientific Secretariat of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders (Eugene Carragee, Linda Carroll, Jaime Guzman, Scott Haldeman, Lena Holm, Margareta Nordin, and Paul Peloso) for the expertise they provided. They are also grateful to Rachel Couban, Emma Irvin, Sigmund Kaw, and Quenby Mahood (Institute for Work & Health, Toronto) for their help with the study. They gratefully acknowledge the financial and material support provided by the Bone and Joint Decade 2000-2010 Task Force On Neck Pain and Its Associated Disorders, Institute for Work & Health, Ontario Ministry of Health and Long-term Care, Ontario Chiropractic Association, and Canadian Memorial Chiropractic College.

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Keywords:

decision analysis; exercise; quality-of-life; neck pain; nonsteroidal anti-inflammatory drug; manual therapy; effectiveness; treatment risk

© 2008 Lippincott Williams & Wilkins, Inc.