Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of d

http://www.immpact.org/static/publications/Turk%20et%20al.,%202003.pdf

Core outcome domains for chronic pain clinical trials: IMMPACT recommendations.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/acr.20543

Measures of Adult Pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP)

Interpreting the Clinical Importance of Treatment Outcomes in Chronic Pain Clinical Trials: IMMPACT Recommendations

http://www.immpact.org/static/publications/Dworkin%20et%20al.,%202005.pdf

Topical Review and RecommendationsCore outcome measures for chronic pain clinical trials: IMMPACT recommendations

Aims and objectives.  This review aims to explore the research available relating to three commonly used pain rating scales, the Visual Analogue Scale, the Verbal Rating Scale and the Numerical Rating Scale. The review provides information needed to understand the main properties of the scales.

Background.  Data generated from pain-rating scales can be easily misunderstood. This review can help clinicians to understand the main features of these tools and thus use them effectively.

Method.  A MedLine review via PubMed was carried out with no restriction of age of papers retrieved. Papers were examined for methodological soundness before being included. The search terms initially included pain rating scales, pain measurement, Visual Analogue Scale, VAS, Verbal Rating Scale, VRS, Numerical/numeric Rating Scale, NRS. The reference lists of retrieved articles were used to generate more papers and search terms. Only English Language papers were examined.

Conclusions.  All three pain-rating scales are valid, reliable and appropriate for use in clinical practice, although the Visual Analogue Scale has more practical difficulties than the Verbal Rating Scale or the Numerical Rating Scale. For general purposes the Numerical Rating Scale has good sensitivity and generates data that can be statistically analysed for audit purposes. Patients who seek a sensitive pain-rating scale would probably choose this one. For simplicity patients prefer the Verbal Rating Scale, but it lacks sensitivity and the data it produces can be misunderstood.

Relevance to clinical practice.  In order to use pain-rating scales well clinicians need to appreciate the potential for error within the tools, and the potential they have to provide the required information. Interpretation of the data from a pain-rating scale is not as straightforward as it might first appear.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2702.2005.01121.x

Pain: a review of three commonly used pain rating scales.

Pain intensity is frequently measured on an 11-point pain intensity numerical rating scale (PI-NRS), where 0=no pain and 10=worst possible pain. However, it is difficult to interpret the clinical importance of changes from baseline on this scale (such as a 1- or 2-point change). To date, there are no data driven estimates for clinically important differences in pain intensity scales used for chronic pain studies. We have estimated a clinically important difference on this scale by relating it to global assessments of change in multiple studies of chronic pain. Data on 2724 subjects from 10 recently completed placebo-controlled clinical trials of pregabalin in diabetic neuropathy, postherpetic neuralgia, chronic low back pain, fibromyalgia, and osteoarthritis were used. The studies had similar designs and measurement instruments, including the PI-NRS, collected in a daily diary, and the standard seven-point patient global impression of change (PGIC), collected at the endpoint. The changes in the PI-NRS from baseline to the endpoint were compared to the PGIC for each subject. Categories of "much improved" and "very much improved" were used as determinants of a clinically important difference and the relationship to the PI-NRS was explored using graphs, box plots, and sensitivity/specificity analyses. A consistent relationship between the change in PI-NRS and the PGIC was demonstrated regardless of study, disease type, age, sex, study result, or treatment group. On average, a reduction of approximately two points or a reduction of approximately 30% in the PI-NRS represented a clinically important difference. The relationship between percent change and the PGIC was also consistent regardless of baseline pain, while higher baseline scores required larger raw changes to represent a clinically important difference. The application of these results to future studies may provide a standard definition of clinically important improvement in clinical trials of chronic pain therapies. Use of a standard outcome across chronic pain studies would greatly enhance the comparability, validity, and clinical applicability of these studies.

Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale

Context.—Pain is the most disturbing symptom of
diabetic peripheral neuropathy. As many as 45% of patients with
diabetes mellitus develop peripheral neuropathies.Objective.—To evaluate the effect of gabapentin monotherapy
on pain associated with diabetic peripheral neuropathy.Design.—Randomized, double-blind, placebo-controlled,
8-week trial conducted between July 1996 and March 1997.Setting.—Outpatient clinics at 20 sites.Patients.—The 165 patients enrolled had a 1- to 5-year
history of pain attributed to diabetic neuropathy and a minimum 40-mm
pain score on the Short-Form McGill Pain Questionnaire visual analogue
scale.Intervention.—Gabapentin (titrated from 900 to 3600
mg/d or maximum tolerated dosage) or placebo.Main Outcome Measures.—The primary efficacy measure was
daily pain severity as measured on an 11-point Likert scale (0, no
pain; 10, worst possible pain). Secondary measures included sleep
interference scores, the Short-Form McGill Pain Questionnaire scores,
Patient Global Impression of Change and Clinical Global Impression of
Change, the Short Form–36 Quality of Life Questionnaire scores, and
the Profile of Mood States results.Results.—Eighty-four patients received gabapentin and 70
(83%) completed the study; 81 received placebo and 65 (80%) completed
the study. By intent-to-treat analysis, gabapentin-treated patients'
mean daily pain score at the study end point (baseline, 6.4; end point,
3.9; n = 82) was significantly lower (P<.001) compared with
the placebo-treated patients' end-point score (baseline, 6.5; end
point, 5.1; n = 80). All secondary outcome measures of pain were
significantly better in the gabapentin group than in the placebo group.
Additional statistically significant differences favoring gabapentin
treatment were observed in measures of quality of life (Short Form–36
Quality of Life Questionnaire and Profile of Mood States). Adverse
events experienced significantly more frequently in the gabapentin
group were dizziness (20 [24%] in the gabapentin group vs 4
[4.9%] in the control group; P<.001) and somnolence (19
[23%] in the gabapentin group vs 5 [6%] in the control group;
P = .003). Confusion was also more frequent in the gabapentin
group (7 [8%] vs 1 [1.2%]; P = .06).Conclusion.—Gabapentin monotherapy appears to be
efficacious for the treatment of pain and sleep interference associated
with diabetic peripheral neuropathy and exhibits positive effects on
mood and quality of life.

/pdf/gabapentin-for-the-symptomatic-treatment-of-painful-3hioh8gzer.pdf

Gabapentin for the Symptomatic Treatment of Painful Neuropathy in Patients With Diabetes Mellitus: A Randomized Controlled Trial

Objective: To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN). Methods: The authors conducted a multicenter, parallel-group, double-blind, placebo-controlled, 8-week, randomized clinical trial in PHN, defined as pain for 3 or more months following herpes zoster rash healing. Patients (n = 173) were randomized to treatment with pregabalin or placebo. Patients randomized to pregabalin received either 600 mg/day (creatinine clearance > 60 mL/min) or 300 mg/day (creatinine clearance 30 to 60 mL/min). The primary efficacy measure was the mean of the last seven daily pain ratings. Secondary endpoints included additional pain ratings, sleep interference, quality of life, mood, and patient and clinician ratings of global improvement. Results: Pregabalin-treated patients had greater decreases in pain than patients treated with placebo (endpoint mean scores 3.60 vs 5.29, p = 0.0001). Pain was significantly reduced in the pregabalin-treated patients after the first full day of treatment and throughout the study, and significant improvement on the McGill Pain Questionnaire total, sensory, and affective pain scores was also found. The proportions of patients with ≥30% and ≥50% decreases in mean pain scores were greater in the pregabalin than in the placebo group (63% vs 25% and 50% vs 20%, p = 0.001). Sleep also improved in patients treated with pregabalin compared to placebo ( p = 0.0001). Both patients and clinicians were more likely to report global improvement with pregabalin than placebo ( p = 0.001). Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity. Conclusions: Treatment of PHN with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.

Pregabalin for the treatment of postherpetic neuralgia A randomized, placebo-controlled trial

A randomized, double-blind, placebo-controlled, parallel-group, multicenter, 8-week trial (with subsequent open-label phase) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy (DPN) For enrollment, patients must have had at baseline: 1- to 5-year history of DPN pain; pain score > or =40 mm (Short-Form McGill Pain Questionnaire [SF-MPQ] visual analogue scale); average daily pain score of > or =4 (11-point numerical pain rating scale [0 = no pain, 10 = worst possible pain]) One hundred forty-six (146) patients were randomized to receive placebo (n = 70) or pregabalin 300 mg/day (n = 76) Primary efficacy measure was endpoint mean pain score from daily patient diaries (11-point numerical pain rating scale) Secondary measures included SF-MPQ scores; sleep interference scores; Patient and Clinical Global Impression of Change (PGIC and CGIC); Short Form-36 (SF-36) Health Survey scores; and Profile of Mood States (POMS) scores Safety assessment included incidence and intensity of adverse events, physical and neurological examinations, and laboratory evaluations Pregabalin produced significant improvements versus placebo for mean pain scores (P < 00001); mean sleep interference scores SF-36 Bodily Pain subscale (P < 00001); total SF-MPQ score (P < 001); SF-36 Bodily Pain subscale (P < 003); PGIC (P = 0001); and Total Mood Disturbance and Tension-Anxiety components of POMS (P < 003) Pain relief and improved sleep began during week 1 and remained significant throughout the study (P < 001) Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo Most adverse events were mild to moderate and did not result in withdrawal Pregabalin was safe and effective in decreasing pain associated with DPN, and also improved mood, sleep disturbance, and quality of life

Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial.

Objective

Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel α2-δ ligand, for treatment of symptoms associated with FMS.



Methods

This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group.



Results

Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (−0.93 on a 0–10 scale) (P ≤ 0.001), and significantly more patients in this group had ≥50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups.



Conclusion

Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life.

/pdf/pregabalin-for-the-treatment-of-fibromyalgia-syndrome-3bigpswtkz.pdf

L. LaMoreaux

Papers

Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale

Gabapentin for the Symptomatic Treatment of Painful Neuropathy in Patients With Diabetes Mellitus: A Randomized Controlled Trial

Pregabalin for the treatment of postherpetic neuralgia A randomized, placebo-controlled trial

Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial.

Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial.