Managing Difficult Patient Encounters.

Family physicians commonly find themselves in difficult patient encounters that can result in dissatisfaction for the patient and physician. Successful navigation of these encounters includes recognizing common physician factors, such as systemic pressures, interpersonal communication, and situational issues. The practice of labeling patient types can lead to disparities in care and patient harm and should be avoided. When physicians recognize that they are in a difficult patient encounter, simple mindfulness approaches, such as the Name It to Tame It and CALMER approaches, can improve outcomes. CALMER approaches help physicians acknowledge which situations they can control, alter their thoughts about the situation, and tolerate uncertainty. Physicians working with patients to create a therapeutic bond can focus the encounter to understand the situation that the patient is experiencing and work to recognize and acknowledge strong emotions that are nonproductive. Negotiating an agenda can help manage expectations of what can reasonably be done during each visit. Supporting patients by validating their symptoms and helping them embrace uncertainty can enable them to take control of their diagnosis and focus on managing chronic conditions rather than curing them. Motivational interviewing is a useful tool to help patients take ownership of their illnesses and therapeutic goals. Self-care through reflection groups or personal coaching or counseling can help physicians feel supported and avoid burnout.

A Patient-Centered Perspective of Molluscum Contagiosum as Reported by B-SIMPLE4 Clinical Trial Patients and Caregivers: Global Impression of Change and Exit Interview Substudy Results.

BACKGROUND: Molluscum contagiosum is often characterized by persistent lesions and bothersome symptomology. What patients with molluscum contagiosum and/or caregivers consider to be meaningful measures of therapeutic success is unknown. OBJECTIVE: We aimed to collect patient experience data and assess Global Impression of Change from patients and/or caregivers participating in a large phase III molluscum contagiosum interventional trial. METHODS: The Berdazimer Sodium In Molluscum Patients with LEsions (B-SIMPLE4) phase III study enrolled 891 patients with molluscum contagiosum. Patients were randomly assigned to berdazimer gel, 10.3% or vehicle gel applied once daily for 12 weeks. Assessments of participant and investigator perceptions of complete lesion clearance were collected at weeks 12 and 24 along with Global Impression of Change scores from 1 (very much improved) to 7 (very much worse). A subset of 30 B-SIMPLE4 patients participated in the patient/caregiver experience exit interview to evaluate bothersome signs and symptoms. RESULTS: At week 12, among participants with a ≥ 75% molluscum contagiosum lesion count reduction from baseline (as assessed by investigators), 99% (373/376) reported improvement. Perceptions of complete clearance at week 12 were nearly 40% for both participant-reported and investigator-reported Global Impression of Change in berdazimer group vs 20% in the vehicle group: 82% (322/392) of participants in the berdazimer group and 60% (237/394) in the vehicle group reported their molluscum contagiosum lesions were either very much improved or much improved at week 12. Similarly, investigators scored 80% (314/393) of berdazimer and 54% (215/396) of vehicle participants as very much improved or much improved. From the exit interview, the mean duration of participant-reported molluscum contagiosum was nearly 2 years. The most frequently reported molluscum contagiosum-related signs and symptoms were itch (n = 20), scarring (n = 18), and pain (n = 13). Visibility and contagiousness of molluscum contagiosum were the most bothersome aspects to participants. The most frequently reported psychosocial impacts were self-consciousness (n = 15) and embarrassment (n = 14). Lesion clearance was an expectation of 28/30 study participants. Overall, 26/30 reported being very satisfied (n = 18) or satisfied (n = 8) with the changes in their disease over the duration of the trial; 23/30 stated that the change in lesion count was meaningful. A mean reduction of 18 lesions (76% decrease) from the baseline lesion count was reported by participants (n = 28). Although 22 of 28 had less than complete lesion clearance, 17 of 22 reported that the reduction in the number of lesions was meaningful. CONCLUSIONS: Molluscum contagiosum lesion reductions, with or without complete clearance, may be considered a therapeutic "success" by the patient/caregiver. CLINICAL TRIAL REGISTRATION: NCT04535531 (registered 2 September, 2020).

Qualitative interviews in patients with lipodystrophy to assess the patient experience: evaluation of hunger and other symptoms.

BACKGROUND: New treatments are being evaluated for lipodystrophy; however, limited information is available on the patient experience. Results of a prior patient panel showed that hunger and temperature-related symptoms were an issue for participants. Therefore, evaluation of any changes in these symptoms is recommended for inclusion in new treatment options. The objective of this study was to further understand the patient experience and to evaluate newly developed items of hunger and temperature regulation. METHODS: Individual, in-depth telephone interviews were conducted via semi-structured discussion guide. Telephone interviews were conducted with 21 US patients with generalized lipodystrophy (GLD) or partial lipodystrophy (PLD). Eligibility requirements included self-reported PLD or GLD. Interviews included open-ended concept elicitation followed by a review of newly developed items assessing hunger, temperature sensations, and patient globals. Interviews were conducted in two rounds, with the newly developed items assessing hunger revised after each round of interviews based on participant feedback. RESULTS: Results indicated that hunger-related symptoms were considered a current issue for greater than half (N = 11) of participants, and all but one reported this as an issue at some point in their lives. Specifically, participants most often reported symptoms of increased appetite and not feeling full. The cognitive debriefing process indicated that the hunger-related symptoms, temperature, and global impression of change and severity items were correctly interpreted and easily completed by the participants. While not a focus of the interviews, the concept elicitation results demonstrated that pain was a frequently reported and bothersome symptom in this patient population. CONCLUSIONS: This qualitative research provided evidence to support the use of clinical outcomes assessments such as hunger and temperature-related items in clinical trials.

Pulmonary hypertension due to interstitial lung disease or chronic obstructive pulmonary disease: a patient experience study of symptoms and their impact on quality of life.

Pulmonary hypertension resulting from chronic lung disease such as chronic obstructive pulmonary disease and interstitial lung disease is categorized by the World Health Organization as Group 3 pulmonary hypertension. To identify the symptoms and impacts of World Health Organization Group 3 pulmonary hypertension and to capture data related to the patient experience of this disease, qualitative research interviews were undertaken with 3 clinical experts and 14 individuals with pulmonary hypertension secondary to chronic obstructive pulmonary disease or interstitial lung disease. Shortness of breath, fatigue, cough, and swelling were the most frequently reported symptoms of pulmonary hypertension due to chronic obstructive pulmonary disease or interstitial lung disease, and shortness of breath was further identified as the single most bothersome symptom for most patients (71.4%). Interview participants also described experiencing a number of impacts related to pulmonary hypertension and pulmonary hypertension symptoms, including limitations in the ability to perform activities of daily living and impacts on physical functioning, family life, and social life as well as emotional impacts, which included frustration, depression, anxiety, isolation, and sadness. Results of these qualitative interviews offer an understanding of the patient experience of pulmonary hypertension due to chronic obstructive pulmonary disease or interstitial lung disease, including insight into the symptoms and impacts that are most important to patients in this population. As such, these results may help guide priorities in clinical treatment and assist researchers in their selection of patient-reported outcome measures for clinical trials in patients with pulmonary hypertension due to chronic obstructive pulmonary disease or interstitial lung disease.

The Humanistic and Economic Burden of Chronic Idiopathic Constipation in the USA: A Systematic Literature Review.

BACKGROUND: Chronic idiopathic constipation (CIC) is a functional gastrointestinal disorder with an estimated prevalence of 16% in the USA; however, the humanistic and economic burden of CIC is poorly characterized. AIM: This systematic literature review aimed to assess the humanistic and economic burden of CIC in adults in the USA. METHODS: Two systematic literature searches of English-language publications on the humanistic and economic burden of CIC in adults in the USA were conducted using electronic databases and other resources. Both searches included the terms "chronic idiopathic constipation" and "functional constipation". Specific terms used in the search on humanistic burden included "quality of life", "SF-36", "SF-12", and "PAC-QOL"; search terms for economic burden included "cost", "resource use", "absenteeism", and "productivity". RESULTS: Overall, 16 relevant articles were identified. Health-related quality of life (HRQoL) appeared to be reduced in patients with CIC compared with controls and the general US population. Abdominal (r=0.33-0.49), stool (r=0.23-0.33), and rectal symptoms (r=0.53) appeared to be associated with reduced HRQoL. Younger age and female sex were associated with reduced overall HRQoL and greater symptom severity. Direct outpatient costs were higher in patients with CIC than those without CIC (US$6284 vs US$5254). Patients with CIC and abdominal symptoms reported more days of disrupted productivity per month than those without abdominal symptoms (3.2 days vs 1.2 days). The overall prevalence of complementary and alternative medicine use by patients with CIC was similar to that in the general US population. CONCLUSION: The reduced HRQoL and increased costs associated with CIC indicate unmet therapeutic need in this disorder. Further research is required to better understand the humanistic and economic burden of CIC in the USA.

The atopic dermatitis itch scale: development of a new measure to assess pruritus in patients with atopic dermatitis.

Introduction: Pruritus is the primary symptom of atopic dermatitis (AD). The objective of this study was to develop a patient-reported outcome (PRO) instrument for daily administration in clinical trials to measure AD-related itch in adolescents and adults that would meet the standards described in the US Food and Drug Administration's (FDA's) PRO Guidance.Materials and methods: Six focus groups were conducted with 49 patients with AD (32 adults; 17 adolescents). Three iterative rounds of cognitive debriefing interviews were conducted in 26 patients with AD (17 adults; 9 adolescents) to pretest and refine the instrument.Results: AD-related itching was considered the most bothersome AD symptom by nearly two-thirds of the focus group participants. The items in the initial version of the instrument, named the Atopic Dermatitis Itch Scale (ADIS), were developed to reflect concepts most relevant to the assessment of itching as described during the focus groups. Based on results of the cognitive debriefing interviews, an 8-item final version of the ADIS was created.Conclusion: The ADIS is a content valid PRO instrument addressing the concepts critical to the measurement of AD-related itching. To our knowledge, it is the first instrument developed to assess AD-related itch in patients as young as 12 years following the recommendations of the PRO Guidance.

Evaluation of the fibromyalgia diagnostic screen in clinical practice.

RATIONALE, AIMS AND OBJECTIVES: Fibromyalgia (FM) is challenging to diagnose, especially in primary care settings. The Fibromyalgia Diagnostic Screen was developed to facilitate the diagnosis of FM in clinical practice. The objectives of this study were to assess the performance of the Fibromyalgia Diagnostic Screen in primary care and specialty clinics, using the 1990 American College of Rheumatology (ACR) diagnostic criteria as the gold standard, and comparing the Fibromyalgia Diagnostic Screen with the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ) and the modified 2010 ACR Fibromyalgia Diagnostic Criteria (ACR-FDC). METHODS: This multicenter, cross-sectional study included 150 adult chronic pain patients who underwent a physician-administered structured history and physical exam and completed the Fibromyalgia Diagnostic Screen, the LFESSQ and the modified ACR-FDC. The analyses determined the predictive ability of the Fibromyalgia Diagnostic Screen for FM. RESULTS: Item-level analyses provided support for the response categories and predictive ability of most of the Fibromyalgia Diagnostic Screen items. Additionally, the evaluation of the Fibromyalgia Diagnostic Screen scoring models demonstrated the greatest accuracy in predicting an FM diagnosis with a combination of patient items and clinician items that included an abbreviated tender point exam (sensitivity 0.68, specificity, 0.82). Sensitivity of the modified ACR-FDC and the LFESSQ was 0.87 and 0.86, respectively, with specificity 0.62 and 0.49, respectively. CONCLUSIONS: The Fibromyalgia Diagnostic Screen is a useful new clinical tool to aid in the evaluation of FM in clinical practice.

Sphygmomanometry-evoked allodynia in chronic pain patients with and without fibromyalgia.

BACKGROUND: Fibromyalgia is a chronic pain syndrome that affects about 2% of the U.S. general population, with greater prevalence among women (3.5%) than men (0.5%). Previous research results suggest that the experience of pain (allodynia) upon sphygmomanometry may indicate the presence of fibromyalgia. OBJECTIVE: The aim of this study was to confirm these findings in patients with fibromyalgia and other chronic pain conditions and evaluate the use of sphygmomanometry as a potential screening tool for the identification of patients with fibromyalgia. METHODS: A total of 150 people participated in this multicenter, cross-sectional observational study. The study included a physician-conducted evaluation to determine if the participant met the American College of Rheumatology (ACR) 1990 diagnostic criteria for fibromyalgia. The presence of sphygmomanometry-evoked allodynia was assessed during a seated cuff pressure inflation that was repeated three times on each arm. Each site was provided a sphygmomanometer to ensure standardization, and the pressure of the cuff at the moment of pain initiation was recorded. If the patient did not indicate pain prior to 180 mmHg, then the inflation was stopped, a notation of no pain was made, and a cuff pressure of 180 mmHg was recorded. The mean of the six cuff pressure measurements was used for the analyses. Logistic regression was performed to analyze the relationship between sphygmomanometry-evoked allodynia and fibromyalgia. RESULTS: The evaluable sample was 148 (one participant had too large an arm circumference for the sphygmomanometer and another did not receive the clinician evaluation of ACR-determined fibromyalgia diagnosis). Over half of the participants were determined to have an ACR diagnosis of fibromyalgia. Of these, 71 (91%) were women and had an average age of 54 years. Of the 70 participants with no fibromyalgia diagnosis, 42 (60%) were women and also had an average age of 54 years. Sixty-one (78%) of the fibromyalgia participants, compared with 25 (36%) of those with no fibromyalgia diagnosis, reported sphygmomanometry-evoked allodynia. The participants with fibromyalgia reported pain ata lower cuff pressure compared with those without fibromyalgia (132 mmHg vs. 166 mmHg, p < .01). The logistic regression showed that sphygmomanometry-evoked allodynia predicted an ACR-determined FM diagnosis (χ(2) = 19.4, p < .01). DISCUSSION: These findings support previous research suggesting that patients who report pain upon sphygmomanometry may warrant further evaluation for the presence of fibromyalgia.

Development of responder definitions for fibromyalgia clinical trials.

OBJECTIVE: To develop responder definitions for fibromyalgia (FM) clinical trials using key symptom and function domains. METHODS: Twenty-four candidate responder definitions were developed by expert consensus and were evaluated in 12 randomized, placebo-controlled trials of 4 medications for the treatment of FM. For each definition, the treatment effects of the medication compared with placebo were analyzed using Cochran-Mantel-Haenszel tests or chi-square tests. A meta-analysis of the pooled results for the 4 medications established risk ratios to determine the definitions that best favored medication over placebo. RESULTS: Two definitions performed best in the analyses. Both definitions included ≥30% reduction in pain and ≥10% improvement in physical function. The definitions differed in that one (≥30% improvement in FM [FM30] short version) included ≥30% improvement in sleep or fatigue, and the other (FM30 long version) required ≥30% improvement in 2 of the following symptoms: sleep, fatigue, depression, anxiety, or cognition. In the analysis of both versions, the response rate was ≥15% for each medication and was significantly greater compared with placebo. The risk ratio favoring drug over placebo in the pooled analysis for FM30 version 3 (short version) was 1.50 (95% confidence interval [95% CI] 1.24-1.82; P ≤ 0.0001); the risk ratio for FM30 version 6 (long version) was 1.60 (95% CI 1.31-1.96; P ≤ 0.00001). CONCLUSION: Among the 24 responder definitions tested, 2 were identified as most sensitive in identifying response to treatment. The identification of responder definitions for FM clinical trials that include assessments of key symptom and function domains may improve the sensitivity of clinical trials to identify meaningful improvements, leading to improved management of FM.

Toward development of a fibromyalgia responder index and disease activity score: OMERACT module update.

Following development of the core domain set for fibromyalgia (FM) in Outcome Measures in Rheumatology Clinical Trials (OMERACT) meetings 7 to 9, the FM working group has progressed toward the development of an FM responder index and a disease activity score based on these domains, utilizing outcome indices of these domains from archived randomized clinical trials in FM. Possible clinical domains that could be included in a responder index and disease activity score include pain, fatigue, sleep disturbance, cognitive dysfunction, mood disturbance, tenderness, stiffness, and functional impairment. Outcome measures for these domains demonstrate good to adequate psychometric properties, although measures of cognitive dysfunction need to be further developed. The approach used in the development of responder indices and disease activity scores for rheumatoid arthritis and ankylosing spondylitis represents heuristic models for our work, but FM is challenging in that there is no clear algorithm of treatment that defines disease activity based on treatment decisions, nor are there objective markers that define thresholds of severity or response to treatment. The process of developing candidate dichotomous responder definitions and continuous quantitative disease activity measures is described, along with participant discussions from OMERACT 10. Final results of this work will be published in a separate report pending completion of analyses.

Interpreting patient-reported outcome results: US FDA guidance and emerging methods.

In recent years, the US FDA has become more critical of instruments used to measure patient-reported outcomes (PROs) in clinical trials. To facilitate decisions related to the approval of drugs, labels and promotional claims based on PROs, the FDA created the Study Endpoints and Label Development (SEALD) group. SEALD has developed a PRO guidance related to the use of PRO measures used to support drug approvals and label claims, including recommendations for establishing thresholds for meaningful change at the individual level (i.e., defining a responder). This article examines in detail the FDA-recommended methodology for defining a responder and analyzing responder-based PRO measure results. We also present other responder analysis approaches for consideration in furthering the precision and interpretation of this methodology.

Content and criterion validity of the preliminary core dataset for clinical trials in fibromyalgia syndrome.

OBJECTIVE: Increasing research interest and emerging new therapies for treatment of fibromyalgia (FM) have led to a need to develop a consensus on a core set of outcome measures that should be assessed and reported in all clinical trials, to facilitate interpretation of the data and understanding of the disease. This aligns with the key objective of the Outcome Measures in Rheumatology (OMERACT) initiative to improve outcome measurement through a data driven, interactive consensus process. METHODS: Through patient focus groups and Delphi processes, working groups at previous OMERACT meetings identified potential domains to be included in the core data set. A systematic review has shown that instruments measuring these domains are available and are at least moderately sensitive to change. Most instruments have been validated in multiple languages. This pooled analysis study aims to develop the core data set by analyzing data from 10 randomized controlled trials (RCT) in FM. RESULTS: Results from this study provide support for the inclusion of the following in the core data set: pain, tenderness, fatigue, sleep, patient global assessment, and multidimensional function/health related quality of life. Construct validity was demonstrated with outcome instruments showing convergent and divergent validity. Content and criterion validity were confirmed by multivariate analysis showing R square values between 0.4 and 0.6. Low R square value is associated with studies in which one or more domains were not assessed. CONCLUSION: The core data set was supported by high consensus among attendees at OMERACT 9. Establishing an international standard for RCT in FM should facilitate future metaanalyses and indirect comparisons.

Fibromyalgia syndrome module at OMERACT 9: domain construct.

The objective of the module was to (1) establish a core domain set for fibromyalgia (FM) assessment in clinical trials and practice, (2) review outcome measure performance characteristics, (3) discuss development of a responder index for assessment of FM in clinical trials, (4) review objective markers, (5) review the domain of cognitive dysfunction, and (6) establish a research agenda for outcomes research. Presentations at the module included: (1) Results of univariate and multivariate analysis of 10 FM clinical trials of 4 drugs, mapping key domains identified in previous patient focus group: Delphi exercises and a clinician/researcher Delphi exercise, and breakout discussions to vote on possible essential domains and reliable measures; (2) Updates regarding outcome measure status; (3) Update on objective markers to measure FM disease state; and (4) Review of the issue of cognitive dysfunction (dyscognition) in FM. Consensus was reached as follows: (1) Greater than 70% of OMERACT participants agreed that pain, tenderness, fatigue, patient global, multidimensional function and sleep disturbance domains should be measured in all FM clinical trials; dyscognition and depression should be measured in some trials; and stiffness, anxiety, functional imaging, and cerebrospinal fluid biomarkers were identified as domains of research interest. (2) FM domain outcome measures have generally proven to be reliable, discriminative, and feasible. More sophisticated and comprehensive measures are in development, as is a responder index for FM. (3) Increasing numbers of objective markers are being developed for FM assessment. (4) Cognitive dysfunction assessment by self-assessed and applied outcome measures is being developed. In conclusion, a multidimensional symptom core set is proposed for evaluation of FM in clinical trials. Research on improved measures of single domains and composite measures is ongoing.

Patient perspectives on the impact of fibromyalgia.

OBJECTIVE: The objective of this study was to elicit and assess important symptom domains and the impact of fibromyalgia on patients' quality of life and functioning from a patient's perspective. The intention was to collect this information as part of an overall effort to overcome shortcomings of existing outcome measures in fibromyalgia. METHODS: This was a qualitative study in which six focus group sessions with 48 women diagnosed with fibromyalgia were conducted to elicit concepts and ideas to assess the impact of fibromyalgia on their lives. RESULTS: The focus groups conducted with fibromyalgia patients identified symptom domains that had the greatest impact on their quality of life including pain, sleep disturbance, fatigue, depression, anxiety, and cognitive impairment. Fibromyalgia had a substantial negative impact on social and occupational function. Patients reported disrupted relationships with family and friends, social isolation, reduced activities of daily living and leisure activities, avoidance of physical activity, and loss of career or inability to advance in careers or education. CONCLUSION: The findings from the focus groups revealed that fibromyalgia has a substantial negative impact on patients' lives. PRACTICE IMPLICATIONS: A comprehensive assessment of the multiple symptoms domains associated with fibromyalgia and the impact of fibromyalgia on multidimensional aspects of function should be a routine part of the care of fibromyalgia patients.

A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia.

UNLABELLED: The purpose of the study was to assess the efficacy and safety of pregabalin monotherapy in patients with fibromyalgia in a randomized, double-blinded, placebo-controlled trial. After 1 week of single-blinded administration of placebo, 750 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to pregabalin (300 mg/d, 450 mg/d, 600 mg/d) or placebo, administered twice daily for 14 weeks. The primary outcome variable was comparison of end point mean pain scores, derived from daily diary ratings of pain intensity (0 to 10 scale), between each of the pregabalin groups and the placebo group. If positive, additional primary efficacy parameters included the Patient Global Impression of Change (PGIC) and the Fibromyalgia Impact Questionnaire (FIQ) total score. Compared with placebo-treated patients, mean changes in pain scores at the end point in pregabalin-treated patients were significantly greater (P < .001: 300 mg/d, -0.71; 450 mg/d, -0.98; 600 mg/d, -1.00). Compared with placebo, significantly more pregabalin-treated patients reported improvement on PGIC (P < .01 for all 3 pregabalin doses) and significant improvements in total FIQ score for the 450 mg/d (P = .004) and the 600 mg/d (P = .003) doses. Compared with placebo, all 3 doses of pregabalin were associated with significant improvement in sleep. The most commonly reported pregabalin-related adverse events were dizziness and somnolence, which tended to be dose-related. PERSPECTIVE: 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. These results provide evidence that pregabalin is an important treatment option for patients with fibromyalgia.

Identifying the clinical domains of fibromyalgia: contributions from clinician and patient Delphi exercises.

OBJECTIVE: In evaluating the effectiveness of fibromyalgia (FM) therapies, it is important to assess the impact of those therapies on the full array of domains considered important by both clinicians and patients. The objective of this research was to identify and prioritize the key clinically relevant and important domains impacted by FM that should be evaluated by outcome assessment instruments used in FM clinical trials, and to approach consensus among clinicians and patients on the priority of those domains to be assessed in clinical care and research. METHODS: Group consensus was achieved using the Delphi method, a structured process of consensus building via questionnaires together with systematic and controlled opinion feedback. The Delphi exercises involved 23 clinicians with expertise in FM and 100 patients with FM as defined by American College of Rheumatology criteria. RESULTS: The Delphi exercise revealed that the domains ranked most highly by patients were similar to the domain rankings by clinicians. Pain was consistently ranked highest by both panels. Fatigue, impact on sleep, health-related quality of life, comorbid depression, and cognitive difficulty were also ranked highly. Stiffness was ranked highly by patients but not clinicians. In contrast, side effects was important to clinicians but was not identified as important in the patient Delphi exercise. CONCLUSION: The clinician and patient Delphi exercises identified and ranked key domains that need to be assessed in FM research. Based on these results, a conceptual framework for measuring patient-reported outcomes is proposed.

Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin.

This was a multicenter, double-blind (DB), placebo-controlled, randomized discontinuation trial to evaluate the efficacy of pregabalin monotherapy for durability of effect on fibromyalgia (FM) pain. The trial included a 6-week open-label (OL) pregabalin-treatment period followed by 26-week DB treatment with placebo or pregabalin. Adults with FM and 40-mm score on 100-mm pain visual analog scale (VAS) were eligible. During OL weeks 1-3, patients received escalating dosages of pregabalin to determine their optimal dosages. During OL weeks 4-6, patients received their optimal fixed dosages (300, 450, 600mg/d). To be randomized, patients must have had 50% decrease in pain VAS and a self-rating of "much" or "very much" improved on Patient Global Impression of Change (PGIC) at the end of OL. Double-blind treatment was with placebo or the patient's optimal fixed dosage of pregabalin. Primary outcome was time to loss of therapeutic response (LTR), defined as <30% reduction in pain (from OL baseline) or worsening of FM. A total of 1051 patients entered OL; 287 were randomized to placebo, 279 to pregabalin. Time to LTR was longer for pregabalin versus placebo (P<.0001). Kaplan-Meier estimates of time-to-event showed half the placebo group had LTR by Day 19; half the pregabalin group still had not lost response by trial end. At the end of DB, 174 (61%) placebo patients met LTR criteria versus 90 (32%) pregabalin patients. Pregabalin was well tolerated, though 178 (17%) discontinued during OL for treatment-related adverse events (AE), and more pregabalin than placebo patients discontinued for AEs during DB. In those who respond, pregabalin demonstrated durability of effect for relieving FM pain.

A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia.

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 patients' 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.

The effect of anxiety and depression on improvements in pain in a randomized, controlled trial of pregabalin for treatment of fibromyalgia.

OBJECTIVE: To assess symptoms of anxiety and depression in a large cohort of fibromyalgia patients and to determine the impact of these symptoms on response of pain to pregabalin treatment. DESIGN: Patients completed the Hospital Anxiety and Depression Scale at the baseline visit in a randomized, controlled trial of pregabalin for treatment of fibromyalgia. Mean anxiety and depression subscale scores were calculated, and proportions of patients by symptom severity were determined. The difference between the proportion of patients reporting anxiety and depression at baseline was tested using McNemar's test. Baseline anxiety and depression were evaluated as covariates by including them-as interaction terms with treatment-in an ancova model. A path analysis evaluated the association between improvements in anxiety and depression and pain relief. RESULTS: In total, 529 patients were enrolled. Significantly more patients reported anxiety symptoms (71%) than depressive symptoms (56%) (P < 0.0001). Improvement in pain symptoms with pregabalin compared with placebo did not depend linearly on baseline anxiety or depression scores. By path analysis, 75% of the pain reduction was not explained by improvements in anxiety and depressive symptoms. CONCLUSIONS: Anxiety symptoms were more common than depressive symptoms in this cohort. Our results suggest patients with fibromyalgia should be routinely assessed for the presence of both anxiety and depression. The pain treatment effect of pregabalin did not depend on baseline anxiety or depressive symptoms, suggesting pregabalin improves pain in patients with or without these symptoms. Much of the pain reduction appears to be independent of improvements in anxiety or mood symptoms.

The meaning of pain relief in a clinical trial.

UNLABELLED: Data from 207 subjects in the early postoperative period in a controlled clinical trial were used to examine the factors that contribute to global ratings of satisfaction with pain relief. Prerecovery to postrecovery period change scores in pain intensity were not significantly associated with level of satisfaction with pain relief. However, endpoint pain intensity, average pain intensity, recall rating of maximum pain, and actual maximum pain during the immediate postoperative period all predicted relief satisfaction. Of these predictors, average pain and change in pain were associated with relief satisfaction when controlling for all the predictors. The average pain levels reported by patients who rated themselves as being "very satisfied" and "somewhat satisfied" with the level of pain relief were 32.86 (on a 0 to 100 visual analogue scale [VAS]) and 40.00, respectively. Patients who were "slightly satisfied," "neither satisfied nor dissatisfied," and "slightly," "somewhat," and "very dissatisfied" reported similar levels of average pain during the recovery period (range = 51.37-56.32). The findings indicate that the primary variable related to relief satisfaction following surgery during the immediate postoperative period is an average of the pain intensity experienced during this time period. PERSPECTIVE: In order to be "very satisfied" with pain relief during the postoperative period, patients are not required to experience no pain. Rather, the study findings suggest that mild pain averaging less than 40 on a 0 to 100 VAS is adequate. However, moderate pain during the early recovery period averaging about 50 or more on a 0 to 100 VAS appears to be associated with dissatisfaction with pain relief.