Author
James P. Young
Bio: James P. Young is an academic researcher from Pfizer. The author has contributed to research in topics: Pregabalin & Placebo. The author has an hindex of 11, co-authored 21 publications receiving 5991 citations.
Papers
More filters
••
TL;DR: Using a standard outcome across chronic pain studies would greatly enhance the comparability, validity, and clinical applicability of these studies, and the application of these results to future studies may provide a standard definition of clinically important improvement in clinical trials of chronic pain therapies.
Abstract: 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.
4,568 citations
••
TL;DR: Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo and was well tolerated and improved global measures and health-related quality of life.
Abstract: 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.
627 citations
•
TL;DR: Pregabalin monotherapy provides clinically meaningful benefit to patients with FM and all pregabalin treatment groups showed statistically significant improvement in assessments of sleep and in patients' impressions of their global improvement.
Abstract: OBJECTIVE: To evaluate the efficacy and safety of pregabalin for symptomatic relief of pain associated with fibromyalgia (FM) and for management of FM. METHODS: This multicenter, double-blind, placebo-controlled trial randomly assigned 748 patients with FM to receive placebo or pregabalin 300, 450, or 600 mg/day (dosed twice daily) for 13 weeks. The primary outcome variable for study objective 1, symptomatic relief of pain associated with FM, was comparison of endpoint mean pain scores between each pregabalin group and placebo. The outcome variable for study objective 2, management of FM, included endpoint mean pain scores, Patient Global Impression of Change (PGIC), and Fibromyalgia Impact Questionnaire (FIQ)-Total Score. Secondary outcomes included assessments of sleep, fatigue, and mood disturbance. RESULTS: Patients in all pregabalin groups showed statistically significant improvement in endpoint mean pain score and in PGIC response compared with placebo. Improvements in FIQ-Total Score for the pregabalin groups were numerically but not significantly greater than those for the placebo group. Compared with placebo, all pregabalin treatment groups showed statistically significant improvement in assessments of sleep and in patients9 impressions of their global improvement. Dizziness and somnolence were the most frequently reported adverse events. CONCLUSION: Pregabalin at 300, 450, and 600 mg/day was efficacious and safe for treatment of pain associated with FM. Pregabalin monotherapy provides clinically meaningful benefit to patients with FM.
276 citations
••
TL;DR: This randomized, placebo-controlled trial of 300, 450, and 600 mg/d of pregabalin monotherapy demonstrated that all 3 doses were efficacious for up to 14 weeks for the treatment of fibromyalgia and were well tolerated by most patients.
269 citations
••
TL;DR: Pregabalin, dosed BID, reduced neuropathic pain associated with PHN and was well tolerated; it also reduced the extent to which pain interfered with sleep.
Abstract: Objective: This trial evaluated the efficacy and safety of pregabalin dosed twice daily (BID) for relief of neuro-pathic pain associated with postherpetic neuralgia (PHN).Research design and methods: The 13‐week, double-blind, placebo-controlled study randomized 370 patients with PHN to pregabalin (150, 300, or 600 mg/day BID) or placebo.Main outcome measures: Primary efficacy measure was endpoint mean pain score from daily pain diaries. Secondary efficacy measures included endpoint mean sleep-interference score from daily sleep diaries and Patient Global Impression of Change (PGIC). Safety evaluations included adverse events (AEs), physical and neurologic examinations, 12-lead ECG, vital signs, and laboratory testing.Results: Pregabalin provided significant, dose-proportional pain relief at endpoint: difference from placebo in mean pain score, 150 mg/day, –0.88, p = 0.0077; 300 mg/day, –1.07, p = 0.0016; 600 mg/day, –1.79, p = 0.0003. Weekly mean pain scores significantly improved as early as wee...
255 citations
Cited by
More filters
••
University of Washington1, University of Rochester2, AstraZeneca3, University of Queensland4, Pfizer5, Tufts University6, University of Pennsylvania7, Endo International plc8, University Health Network9, Harvard University10, Purdue Pharma11, Novartis12, National Institutes of Health13, Dalhousie University14, GlaxoSmithKline15, Food and Drug Administration16, Élan17, Abbott Laboratories18, University of California, San Diego19, United States Department of Veterans Affairs20
TL;DR: In this article, the authors 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, and develop a core set of outcome domains would facilitate comparison and pooling of d
Abstract: 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
3,476 citations
••
2,819 citations
••
University of Rochester1, University of Washington2, Saint Louis University3, University of Toronto4, University of Texas MD Anderson Cancer Center5, University of Pennsylvania6, Johns Hopkins University7, Yale University8, National Institutes of Health9, Pfizer10, Food and Drug Administration11, NorthShore University HealthSystem12, Merck & Co.13, Allergan14, University of Copenhagen15, Purdue Pharma16, Celgene17, University of Oxford18, Élan19, GlaxoSmithKline20, Johnson & Johnson21, Duke University22, Oregon Health & Science University23, Endo International plc24, AstraZeneca25
TL;DR: A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments as discussed by the authors.
2,581 citations
••
University of Rochester1, University of Washington2, University of Pennsylvania3, Johns Hopkins University4, Harvard University5, Yale University6, Ludwig Maximilian University of Munich7, AstraZeneca8, University of Queensland9, Tufts University10, Merck & Co.11, National Institutes of Health12, Endo International plc13, Food and Drug Administration14, University of Toronto15, Purdue Pharma16
2,441 citations
••
TL;DR: 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.
Abstract: 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.
2,337 citations