Relationship Between Patient-Reported Chronic Low Back Pain Severity and Medication Resources

Clinical Therapeutics/Volume 33, Number 11, 2011

Relationship Between Patient-Reported Chronic Low Back Pain Severity and Medication Resources Gavin Taylor-Stokes, MBA1; Steve Lobosco, MA1; James Pike, MPhil1; Alesia B. Sadosky, PhD2; and Edgar Ross, MD3 1

Adelphi Real World, Adelphi Mill, Bollington, Macclesfield, Cheshire, United Kingdom; 2Pfizer Inc, Global Health Economics and Outcomes Research, New York, New York; and 3Pain Management Center, Brigham and Women’s Hospital, Boston, Massachusetts ABSTRACT Background: Characterization of chronic low back pain (CLBP) severity from a patient’s perspective can provide a context within which management strategies may be determined and therapeutic outcomes evaluated. Objective: The aim of our study was to evaluate the association between patient-rated CLBP severity and medication resources. Methods: Data were drawn from the Adelphi CLPB Disease Specific Programmme, a cross-sectional study of patients undertaken between September and November 2009. Patients reported the severity of their CLBP by answering the statement “Please rate how your chronic lower back pain condition is today” with responses of “mild,” “moderate,” or “severe.” Severity was evaluated relative to physician-reported use of medications for the relief of CLBP and patient-reported satisfaction with pain relief and medications. Results: Data from 170 physicians and 1363 patients (mean age 55 years; 52.3% female) were analyzed. CLBP severity was rated as mild, moderate, and severe by 28.3%, 52.8%, and 18.0% of patients, respectively. Physician-reported analgesia requirements increased with CLBP severity (P ⬍ 0.05). Opioids, nonsteroidal antiinflammatory drugs, and muscle relaxants were the most commonly prescribed medications for CLBP. Opioid prescriptions increased with increasing severity (P ⬍ 0.05), and nonsteroidal antiinflammatory drug prescriptions declined. Purchase of over-the-counter medications was similar across severity categories (23%–26% of patients), but the monthly amount spent on over-the-counter drugs was more than twice as high in patients with severe CLBP ($29.90) than in other severity categories. Patient and physician satisfaction with pain-related medication was inversely associated with CLBP severity; inadequate response was the primary reason for physician

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dissatisfaction. Factors limiting generalizability include potential differences between participants and those who refused to participate; potential misdiagnosis of CLBP in a proportion of patients; and an inability for cause-and-effect imputation due to the cross-sectional nature of the study. Conclusions: The relationship between patient-reported CLBP severity and medication prescribing patterns suggests that this rapid assessment may be of value for informing decisions regarding treatment options. The data also suggest that despite greater use of medications at greater CLBP severity, current options remain less than optimal in providing analgesic efficacy. (Clin Ther. 2011;33:1739 –1748) © 2011 Elsevier HS Journals, Inc. All rights reserved. Key words: chronic low back pain, medication use, severity assessment, treatment satisfaction.

INTRODUCTION Chronic low back pain (CLBP), defined as low back pain with a duration ⱖ3 months, results in sustained periods of pain, significant physical limitations, and activity impairment that account for the majority of disability and costs associated with low back pain.1–3 Recommendations for management of CLBP suggest a multidisciplinary approach. This approach includes pharmacologic agents as well as nonpharmacologic therapies such as psychosocial interventions, physical therapy, massage therapy, acupuncture, spinal manipulation, and alternaThis work was presented as a poster at the American Society of Regional Anesthesia and Pain Medicine 2010 Annual Pain Medicine Meeting and Workshops, Phoenix, Arizona, November 18 –21, 2010. Accepted for publication September 23, 2011. doi:10.1016/j.clinthera.2011.09.026 0149-2918/$ - see front matter © 2011 Elsevier HS Journals, Inc. All rights reserved.

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Clinical Therapeutics tive treatments; surgical interventions are generally reserved for cases of intractable pain.4 –7 Among the pharmacologic therapies, acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), opioids, tramadol, and antidepressants are recommended and used to varying degrees. However no single drug has been identified as conveying a clear advantage, and although a recent systematic review8 suggested some benefit of NSAIDs and opioids for pain relief, that review also highlighted the overall poor quality of evidence for pharmacologic therapy for CLBP. In addition, the well-recognized side effects of several of these drug classes complicate the choice of therapy. In particular, opioids present issues of tolerability and potential misuse/abuse;9 –11 there are inadequate data to support the analgesic potential of acetaminophen;12 and the cardiovascular and gastrointestinal side effects of NSAIDs are of significant concern, especially in elderly persons and among those with pre-existing gastrointestinal and cardiovascular conditions.13–15 Nevertheless, choice of therapy should be in part dependent on the severity of CLBP. Consequently, the ability to characterize CLBP severity can be of benefit by providing a context within which management strategies may be determined and therapeutic outcomes evaluated. Although a number of questionnaires have been developed for assessing functional status and levels of disability,16,17 many of these are measures of impact rather than severity, and many present an administrative burden because of multiple questions covering various domains. A simpler approach to establishing CLBP severity in the clinical setting is for patients to self-rate their severity as mild, moderate, or severe. Asking just one question on severity of CLBP needs to go further by ascertaining if such reporting of severity does in fact correlate with (or manifest via) other relevant outcomes. Therefore, the objective of this study was to evaluate the association of patientrated CLBP severity with medication prescribing patterns and satisfaction using the Adelphi Disease Specific Programme for CLBP (CLBP DSP II). It was expected that such an analysis would provide information both on drug use and gaps in therapeutic management, and follows a previous analysis18 suggesting an association between patient-reported CLBP severity and other patient-reported outcomes, including pain severity, health status, functional disability, and work productivity.

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METHODS The CLBP DSP II is a cross-sectional real world survey of doctors and their patients that was conducted in the United States between September and November 2009. A total of 170 physicians participated in the program. These doctors represented the major medical providers of CLBP care (ie, primary care physicians, orthopaedic surgeons, pain specialists [predominantly anaesthesiologists], and neurologists). It was performed according to European Pharmaceutical Market Research Association guidelines, and in full accord with Health Insurance Portability and Accountability Act standards. Each patient provided consent for anonymous and aggregated reporting of research findings as required by the guidelines. All patients with CLBP diagnosed by a physician were eligible for inclusion in the survey. Its real-world design ensured collection only of information available to the physician/patient at the time of consultation. Therefore, no tests or investigations were required or conducted for a patient to be included in the study. Each physician provided detailed records for his or her next 11 patients with CLBP, ensuring that the CLBP DSP II sample was representative of the consulting population. The same patients were invited to provide patient-reported outcomes data using a Patient SelfCompletion Form (PSC) developed specifically for use in patients with CLBP. Participants were instructed by the physician to complete the PSC independently and return it in a sealed envelope. A full description of the methodology is provided in Anderson et al19 Fully deidentified patient and related physician information were provided to and aggregated by Adelphi (Macclesfield, United Kingdom), prior to the initiation of the present analysis and author access to the data set. Severity of CLBP as a condition was self-rated by patients based on the statement, “Please rate how your chronic lower back condition is today” with potential responses of “mild,” “moderate,” and “severe.” For each patient, the participating physician filled out a Patient Record Form that captured information on physician-rated health outcomes such as clinical disease status, medication use, and health care resource use. This analysis focuses on patterns of medication resources, including patient and physician satisfaction with medications, and is not a validation study of selfreported CLBP severity. Although pain is likely to be considered by a patient when rating CLBP severity, and has been shown to be associated with patient-rated

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G. Taylor-Stokes et al. CLBP severity,18 our analysis does not specifically report on pain severity. Medication use was evaluated based on physician’s report of a patient’s current level of analgesia requirement (0 ⫽ no analgesia required to 10 ⫽ strongest possible analgesia required [eg, opioid]). Physicians also objectively reported the number of medications currently prescribed and types of medications categorized by class based on chart review. Overall patient satisfaction with medication, as well as satisfaction with duration and amount of pain relief were self-rated by patients directly on the PSC using a 5-point Likert scale (1 ⫽ not at all satisfied to 5 ⫽ completely satisfied). The proportion of physicians satisfied with their patients’ current control of CLBP with drug therapy was determined, and the reasons for any physician dissatisfaction were also captured. Descriptive analyses, ANOVA, Kruskal-Wallis and ␹2 contingency tables were used to evaluate the relationships between self-reported CLBP severity and other self-reported outcomes to quantify and construe their associated linkages with CLBP severity levels. All analyses were prespecified in a statistical analysis plan and performed using Stata 10.1 (Stata Corp LP, College Station, Texas). Evidence for statistical significance was based on a P value less than 0.05.

RESULTS Data were available from 170 physicians (47% primary care physicians, 24% orthopedic surgeons, 24% pain specialists, and 6% neurologists) who filled out Patient Record Forms for 1860 patients. Demographic characteristics of physicians are shown in Table I and patient demographic data is presented in Table II. Physicians were predominantly male (82.9%), and most had been in practice for 10 to 20 years with practices that were both hospital and office based; few physicians (4.1%) had clinical trial experience. Mean patient age was 55.2 (15.1) years, gender was approximately evenly distributed (47.7% male, 52.3% female), slightly more than half of patients (50.6%) reported being employed at least part time, and 42.5% had a body mass index ⱖ30, indicating obesity. Among these patients 1363 (73.3%) agreed to participate in the study and responded to the patient-completed questionnaire. Severity of CLBP was rated as mild, moderate, and severe by 28.6%, 53.3%, and 18.1% of patients, respectively, and this patient-rated severity was signifi-

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Table I. Participating physician characteristics (N ⫽ 170). Characteristic

%

Specialty Primary care physician Orthopedic surgeon Pain specialist Neurologist

47.1 23.5 23.5 5.9

Gender Male Female

82.9 17.1

Date of qualification 1971–1980 1981–1990 1991–2000 2001–2009

17.1 41.8 34.7 6.5

Work location Hospital only Office only Hospital and office

1.8 47.6 50.6

Clinical trial experience Currently involved Previously involved Never involved

0 4.1 94.7

Geographical region East Midwest South West

30 28 15 27

cantly associated with overall analgesia requirements (Figure 1). As severity of CLBP increased, physicians’ assessment of patients’ level of required analgesia also increased as rated on a 0 to 10 visual analog scale, with higher scores indicating the need for stronger analgesia (P ⬍ 0.0001) (Figure 1A). Similarly, the number of currently prescribed medications increased at greater CLBP severity levels (Figure 1B); all pairwise comparisons were significant (P ⬍ 0.05). There was also a need for greater polypharmacy at higher severity levels; 61.7%, 75.6%, and 83.1% of patients were prescribed combination therapies for mild, moderate, and severe CLBP, respectively, with all pairwise comparisons showing significance (P ⬍ 0.05).

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Table II. Participating (N ⫽ 1860).

patient

characteristics

Characteristic Age, mean (SD), y Gender, % Male Female Duration of chronic low back pain, mean (SD), y Employment status, % Full time Part time Self-employed Homemaker Retired Unemployed Student Body mass index Mean (SD) Percent ⱖ30

Value 55.2 (15.1) 47.7 52.3 4.0 (4.9) 44.2 6.4 2.4 7.0 27.0 13.2 0.9 30.3 (7.4) 42.5

Highest level of formal education, % High school (or less) Some college College degree Graduate degree

37 28 25 10

Total annual household income, % ⬍$30,000 $30,000–$59,999 ⱖ$60,000 Preferred not to answer

19 29 21 31

CLBP was associated with a substantial medication burden across all CLBP severity categories (Figure 2A). Opioids, NSAIDs, and muscle relaxants were the most commonly prescribed medications, and NSAIDs were the primary drugs prescribed as first-line therapy regardless of CLBP severity in 57% to 67% of patients. Whereas total opioid prescriptions excluding tramadol significantly increased from 32% in patients with mild CLBP to 59% and 78% in those with moderate and severe CLBP, respectively (P ⬍ 0.0001 for all comparisons), NSAID prescriptions declined with increasing severity, although significant differences were only observed for comparisons of severe CLBP with the other

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severity categories (P ⬍ 0.05); comparison between mild and moderate CLBP severity was not significant (P ⫽ 0.446). Prescriptions of muscle relaxants, anticonvulsants, and antidepressants all increased at greater levels of CLBP severity, with significance observed across severity groups for each of these drug classes (P ⬍ 0.05) but not for all pairwise comparisons. Prescribing rates of nonopioid analgesics was comparable across patient-rated CLBP severity categories. However, as CLBP severity increased, the proportion of patients receiving a single opioid and opioid plus one nonopioid drug decreased and greater proportions of patients received polypharmacy with 3 and 4 non-opioid drugs in addition to the opioid (Figure 2B). Greater proportions of patients who saw specialists were prescribed weak (33%) and strong (32%) opioids relative to those who saw primary care physicians (25% for each opioid type). Among patients with mild CLBP, there was only a gradual uptake of opioids (Figure 3). In contrast, opioid prescribing increased sharply from second line onward in patients with moderate CLBP, with even quicker uptake among patients with severe CLBP (Figure 3). Among patients prescribed opioids, prescriptions of weak opioids were comparable across severity levels for both short(90%–93%) and long-acting (7%–10%) release forms of the medication. However, prescriptions for longacting strong opioids increased as CLBP severity level increased; 28%, 36%, and 52% for mild, moderate, and severe CLBP, respectively, and was significant (P ⬍ 0.001) for pairwise comparisons except for mild versus moderate CLBP severity. The proportion of patients who reported purchasing over-the-counter (OTC) medications during the prior 6 months for their CLBP was comparable across severity categories (23%–26%) (Figure 4A). However, there was a significant increase in the mean monthly cost of OTC medications as patients transitioned from moderate to severe CLBP (P ⬍ 0.05) (Figure 4B). Patients with severe CLBP reported spending more than twice as much for OTC drugs ($29.92; 95% CI, $9.36 –$50.47) than patients with mild ($12.12; 95% CI, $9.36 –$14.87) and moderate CLBP ($13.59; 95% CI, $10.92–$16.25). Patient-reported satisfaction with pain-related medication was inversely associated with patient-rated CLBP severity. As severity increased, significantly lower proportions of patients reported satisfaction

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G. Taylor-Stokes et al.

Figure 1. Association between patient-rated chronic low back pain (CLBP) severity and overall analgesic requirements. (A) Physician-reported level of analgesia required (as measured on a 1–10 visual analog scale [VAS], where 0 ⫽ no analgesia and 10 ⫽ strongest analgesia [eg, opioids]); P ⬍ 0.0001 for overall association. (B) Number of medications currently prescribed; P ⬍ 0.05 for all pairwise comparisons.

amount of pain relief (Figure 6). This relationship was demonstrated by lower satisfaction scores with each increasing CLBP severity level as well as greater proportions of patients who reported being dissatisfied.

A

B

100%

3% 14%

13%

180%

5% 5% 11%

150%

23%

120%

13% 21%

90%

9% 19%

60%

18%

30%

57%

29%

53%

20% 24%

39% 7% 20% 22%

55%

Muscle relaxant

Opioid + 3

Strong Opioid Weak Opioid

36% 11%

Anti-convulsants

43%

0%

Tramadol Nonopioid analgesic COX2s

Opioid + 2

19%

75% 32%

27%

50%

24%

Opioid + 1 Monotherapy

22%

36%

25%

31% 24%

NSAID 16%

Moderate (719)

Severe (245)

9%

6%

0%

te od er a M

M

ild

(1

(6

35

36

)

Mild (386)

)

33% 31%

Opioid + 4 or more

02

17%

Anti-depressants

)

% of Patients

210%

22%

(2

8% 8%

24%

Steroids

ve re

240%

9% 14%

% of Patients

270%

Se

with their medication, and the mean satisfaction score also decreased; P ⬍ 0.0001 for all pairwise comparisons (Figure 5). The decrease in overall satisfaction was paralleled by satisfaction with both the duration and

Figure 2. Relationship between chronic low back pain patients and drug prescribing patterns. (A) Percent of patients receiving different drug classes. Total percentages ⬎100% because of polypharmacy. (B) Number of combination therapies in patients prescribed opioids. COX2s ⫽ cyclooxygenase-2 inhibitors; NSAID ⫽ nonsteroidal antiinflammatory drug.

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Weak opioid

80%

Strong short-acting opioid

Strong long-acting opioid

70% 22%

% of Patients

60%

17% 8%

50%

13% 17%

11%

40% 30%

16% 20%

9%

5%

10%

17%

4%

18%

23%

26%

25% 28%

8% 18%

22%

18%

11% 0%

21%

26%

10%

2% 6%

21%

7% 25%

28% 13%

32%

24%

First Second Third Fourth line line line line (386) (203) (89) (45)

24% 12% Fifth line (25)

16%

22%

20% 13%

25%

30% 7%

10%

5%

7%

First Second Third Fourth Fifth line line line line line (719) (460) (262) (120) (63)

First Second Third Fourth Fifth line line line line line (245) (173) (117) (57) (27)

Moderate

Severe

Mild

Figure 3. Uptake of opioids among patients at different levels of chronic low back pain severity.

Similarly, a greater proportion of physicians expressed dissatisfaction with pharmacologic control of their patients’ CLBP as patient-rated CLBP severity increased (Figure 7A). The primary reason expressed by physicians for their dissatisfaction was inadequate analgesic response (Figure 7B); 77% of physicians stated lack of efficacy as their reason for dissatisfaction across all severity categories.

DISCUSSION Pain management in patients with CLBP remains challenging despite the development of numerous guidelines. Although treatment relies on a multidisciplinary approach that includes nonpharmacologic modalities, the use of pain medications is integral to management strategies. Current guidelines recommend acetamino-

Figure 4. Monthly (A) utilization and (B) costs of over-the-counter (OTC) medications among patients with different levels of self-reported chronic low back pain (CLBP) severity. *P ⬍ 0.05 versus mild and moderate severity.

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Figure 5. Association between patient-rated chronic low back pain severity and overall patient satisfaction with pain-related medications. P ⬍ 0.0001 for all pairwise comparisons.

phen and NSAIDs as first- and second-line therapy, respectively, with opioid and other drugs as third-line therapy or part of a regimen of polypharmacy, depending on need and severity.4 –7 Part of the challenge lies in determining severity and when to initiate the various therapies.

This study observed significant relationships between patient-reported CLBP severity and medication prescribing patterns. Although this investigation was not a validation study and did not attempt to provide detailed psychometric evaluation of self-reported CLBP severity, the results nevertheless suggest that

Figure 6. Patient satisfaction with amount and duration of pain relief according to patient-rated chronic low back pain severity.

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Figure 7. Physician satisfaction with treatment of patients’ chronic low back pain (CLBP). (A) Proportion of physicians satisfied with control of their patients’ CLBP. (B) Reasons expressed by physicians for their dissatisfaction.

asking patients to self-rate their CLBP severity may be of value for informing decisions regarding treatment options. It should also be noted that despite greater use of OTC and prescription medications, including opioids, at higher levels of CLBP severity there was substantial dissatisfaction among patients and physicians with regard to pharmacologic management of the condition, suggesting that pharmacologic options remain less than optimal in providing analgesic efficacy. With respect to treatment patterns, acetaminophen, which is generally considered first-line pharmacologic therapy,4 –7 was used by a comparable proportion of patients across severity categories (⬃20%). This relatively low use may be related to its unproven analgesic potential in CLBP.12 In contrast, NSAIDs, which are recommended when acetaminophen is inadequate, were the predominant first-line therapy regardless of CLBP severity and were prescribed as first-line therapy in more than half of patients. However, opioids were the most commonly prescribed class of drug overall regardless of severity, and were not only prescribed to more than three-quarters (78%) of patients with severe CLBP, but also to almost one-third (32%) of patients who rated their CLBP as mild. Although the use of weak opioids was predominant among patients with mild CLBP, strong opioids were used to a greater extent by patients with severe CLBP. The high use of opioids is consistent with a recent burden of illness study that also reported

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opioids as the most frequently prescribed medications with respect to both proportion of patients and number of prescriptions (Gore et al. Submitted for publication), although no correlation was made with CLBP severity. Although it should be noted that opioids are frequently used as rescue medication or on an as-needed basis, use of opioids even among patients with mild CLBP in our study may suggest that current treatment recommendations are not necessarily being followed in clinical practice. The high use of opioids is likely indicative of the challenges in managing this condition. These challenges were also highlighted by other observations such as the proportion of patients prescribed multiple medications; almost half of patients (48%) with mild CLBP and up to 70% with severe CLBP were prescribed at least 2 other medications in addition to opioids. Furthermore, despite the use of opioids and polypharmacy, lack of therapeutic efficacy contributed to both patient and physician dissatisfaction with treatment, which substantially increased at greater levels of CLBP severity. The significant associations observed between patient-rated CLBP severity and prescribing of medications further supports our premise that asking patients to self-rate the severity of a condition provides a clinically adequate method of establishing severity. This association with patient-reported outcomes included qualitative and quantitative measures, including pain

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G. Taylor-Stokes et al. severity, interference of pain on daily function, and health status. Combined, these results provide complementary evidence indicating the potential utility of patient-rated CLBP severity. The interpretation and generalizability of this study is subject to several limitations. Our inferences may not necessarily extend to other populations because our study population consisted of physicians and patients who agreed to participate. It is possible that these individuals may have had characteristics and perceptions different from those who refused to participate, thereby introducing selection bias. Physicians were asked to recruit the next 11 consecutive patients diagnosed with CLBP, limiting the generalizability of the results. Our study population was restricted further to a subset of patients and physicians from the United States. An analysis of a study population from other countries could provide greater consensus on the relationships reported here and the appropriateness of our approach to determining CLBP severity. With regard to the diagnosis of CLBP for inclusion, CLBP is a heterogeneous condition that may often be of nonspecific origin, and in the absence of clear pathologic involvement, diagnosis is dependent on the diagnostic skill of the treating physician. Because physicians with different specialties participated in the study, there could have been differences in diagnostic criteria and abilities. It is therefore possible that misdiagnosis may have occurred in a small proportion of the sample population. In addition, patients were not screened for pending compensation claims or litigation, which often influence outcomes.20,21 The cross-sectional nature of DSPs precludes determination of causality. Therefore, no cause and effect imputation was made for the ratings of CLBP severity or other assessments, and any links should be considered associative rather than causal. Although we report on those medications that the participating physicians reported as being prescribed to participating patients, actual adherence to the medication regimens was not captured; prescribing of a particular medication does not necessarily imply use. In addition, because OTC use and costs were self-reported by patients for the prior 6-month period, there was the potential for recall bias.

CONCLUSIONS The observed relationship between patient-reported CLBP severity and medication prescribing patterns suggests that this rapid assessment may be of value for in-

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forming decisions regarding treatment options. The data also suggest that despite greater use of medications at higher levels of CLBP severity, current options remain less than optimal in providing analgesic efficacy. New and more effective medications to treat CLBP are needed.

ACKNOWLEDGMENTS This study was funded by Pfizer Inc. Dr. Ross was not financially compensated for his collaboration on this project. Mr. Taylor-Stokes, Mr. Lobosco, and Mr. Pike are employees of Adelphi and were paid consultants to Pfizer Inc in connection with the conduct of this study and the development of the manuscript. Dr. Sadosky is an employee of and also owns stock in Pfizer Inc. The authors thank E. Jay Bienen for editorial assistance in the preparation of this manuscript, which was funded by Pfizer Inc. All authors were involved in study design, review of statistical analysis plan, results review, and draft manuscript review. Mr. Taylor-Stokes, Mr. Lobosco and Mr. Pike conducted the analyses of the study.

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17. Cleland J, Gillani R, Bienen EJ, Sadosky A. Assessing dimensionality and responsiveness of outcomes measures for patients with low back pain. Pain Pract. 2011;11:57– 69. 18. Taylor-Stokes G, Lobosco S, Pike J, Sadosky AB, Ross E. Relationship between self-reported low back pain severity and other patientreported outcomes: results from an observational study. J Spinal Disord Tech. In press. 19. Anderson P, Benford M, Harris N, Karavali M, Piercy J. Real-world physician and patient behaviour

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Address correspondence to: Alesia Sadosky, PhD, Pfizer Inc, 235 East 42nd Street, MS 235/9/2, New York, NY 10017. E-mail: alesia.sadosky@ pfizer.com

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