Study design
Sample population
This cross-sectional, observational study included FM patients recruited from 18 community-based physician offices (15 general practitioners and 3 rheumatologists) in France. Since there are no definitive criteria for FM diagnosis, patients were required to have a prior diagnosis of FM by a rheumatologist or pain specialist, to have experienced widespread pain (above and below the waist and on both sides of the body) for at least 3 months, and to have experienced pain in the past 24 hours. Patients also were required to have been in treatment at the enrolling physician's practice for at least 3 months. All patients were older than 18 years of age and were excluded if they had participated in an investigational drug study within 30 days prior to the survey or had a concomitant illness unrelated to FM that was likely to confound the assessment of FM. The protocol was approved by central and local accredited ethics committees. No medical interventions or invasive procedures were required by the study protocol. All patients provided written informed consent.
Data collection procedures
Site study staff identified potential patients when they presented for routine visits. Once patients provided written informed consent, they were asked to complete a self-administered patient questionnaire. Site staff completed a case report form (CRF) based on review of the patient's medical records and conducted an assessment of FM using the Manual Tender Point Survey (MTPS) exam [19]. Recorded data included patient's clinical characteristics; patient specific pain associated with FM; current and previous medications for FM; concomitant medications prescribed for depression, anxiety, or insomnia; and FM-related office visits, diagnostic tests, and hospitalizations. Information collected via the patient questionnaire and CRF was not associated with a patient's personal identification information but was associated with a study-specific identifier assigned at enrollment to allow linking of individual patients' clinical and survey data in the analysis.
Patient questionnaire
The patient questionnaire included five validated instruments that assess the impact of FM on aspects of HRQoL and symptoms (such as pain, sleep, anxiety, and depression): the Fibromyalgia Impact Questionnaire (FIQ) [20], the EuroQol (EQ-5D) [21], the Medical Outcomes Study (MOS) Sleep Scale [22], the Brief Pain Inventory-Short Form (BPI-sf) [23], and the Hospital Anxiety and Depression Scale (HADS) [24]. Patients were asked to rate their current overall health on a scale from 0 to 100, where 0 represents 'worst possible health' and '100' represents 'perfect health'. Patients were also asked to estimate what their overall health status would be, on the same scale, if they had complete relief from FM (pain-free overall health). In addition, study-specific questions were developed to assess perceived treatment effectiveness, treatment satisfaction, and FM impact on productivity and health resource use (HRU).
Patient perception of treatment effectiveness and satisfaction
To assess perception of FM treatment effectiveness, patients were asked questions relating to prescription medications, non-prescription medications (e.g. over-the-counter medications), and other treatments, including physical treatments (physical therapy/massage, acupressure/acupuncture, chiropracty), and herbs, vitamins, or other supplements. Patients were specifically asked how effective their prescription medications were for relieving their FM symptoms over the past 4 weeks. Response options for any question on effectiveness were: extremely effective, very effective, somewhat effective, a little effective, and not at all effective. Similarly, perceived satisfaction with treatment was assessed through questions relating to prescription medications, non-prescription medications, and other treatments (listed above). Patients were specifically asked how satisfied or dissatisfied they were with the pain relief experienced with their prescription medications over the past 4 weeks. Patients could respond to any question on satisfaction with: extremely satisfied, somewhat satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, and extremely dissatisfied.
Health-related quality of life and core symptom domains
The EQ-5D utility score (derived from the health state valuation score) assesses HRQoL across 5 domains, each scored separately: mobility, self-care, performance of usual activities, pain or discomfort, and anxiety or depression [21]. A scoring formula developed by the EuroQol Group is used to assign utility values for each patient's health valuation. Health state valuation scores range from -0.594 to 1.00, where higher scores indicate better health state [21].
The FIQ is a brief 10-item assessment measuring FM patient status, progress, and outcomes in the area of physical impairment, feeling good, work missed, doing work, pain, fatigue/tired, rested, stiffness, anxiety, and depression [20]. Each of the 10 subscales included in the FIQ is scored from 0 to 10. The FIQ total score (range: 0-100) is the sum of the 10 FIQ subscale scores, with higher scores indicating a greater impact of FM on the patient. We utilized patients' FIQ total scores to define FM severity as follows: total scores of 0- < 39 considered mild; total scores of 39- < 59 considered moderate; and total scores of 59-100 considered severe [25].
The BPI-sf includes an evaluation of pain intensity and an evaluation of the interference of pain over the past 24 hours on general activity, mood, walking, work, relationships with others, sleep, and enjoyment of life [23]. The intensity of pain is assessed with four items (pain at its worst, at its least, on average over the past 24 hours, and currently) on an 11-point numeric rating scale ranging from 0 to 10, where higher scores indicate higher severity of pain. The BPI Pain Severity Index score (range: 0-10) is the mean of worst, least, average, and current pain, with previously established cut points for chronic neuropathic pain of 0-3, 4-6, and 7-10 considered mild, moderate, and severe, respectively [26].
The MOS Sleep Scale includes 12 items that measure seven key constructs of sleep: sleep disturbance, snoring, awakening short of breath or with a headache, sleep adequacy, somnolence, optimal sleep, and sleep quantity [22]. With the exception of optimal sleep (1 item; scored as 0 [not optimal] or 1 [optimal]), sleep quantity (1 item; scored as 0-24 per hours of sleep where higher numbers reflect more sleep), and sleep adequacy (2 items; combined score of 0-100, where higher scores indicate greater sleep adequacy), each of the other subscales and the additional 9-item Sleep Problems Index, were scored from 0 to 100 where higher scores represent worse sleep outcomes.
The HADS is designed to assess the presence and severity of mood disorders and has been used extensively in a variety of patient populations [24]. The HADS includes 14 items, of which 7 assess anxiety (HADS-A) and 7 assess depression (HADS-D); subscale scores range from 0 to 21, with higher scores representing more symptoms and poorer emotional well-being. Scores of 0-7 on either subscale are considered normal, 8-10 considered mild, 11-14 considered moderate, and 15-21 considered severe levels of anxiety and depression, respectively.
Healthcare costs
Annual direct and indirect costs associated with FM were calculated in 2008 Euros using a societal perspective. Costs included direct medical costs (diagnostic tests, physician office visits, prescription medications, hospitalizations, and patient out-of-pocket costs, e.g. from prescription medications, non-prescription medications, and other treatments for FM), direct non-medical-related costs (assistance with activities of daily living), and indirect costs (days missed from work or on disability due to FM).
Costing algorithms were developed to assign 2008 unit costs to each unique type of resource utilized. Unit costs assigned to office visits and office-based procedures were based on current physician fee schedules (i.e. Classification Commune des Actes Médicaux [CCAM]) [27]. Unit costs assigned to hospitalizations were based on current hospital case-rate payments (i.e. Programme de Médicalisation des Systèmes d'Information [PMSI]) [28]. Medication costs were based on private quotes for current drug price lists (i.e. Thériaque) [29]. Unit costs assigned to days missed from work and disability were based on Eurostat wage data. The average cost of FM, per patient, was summed for the 3-month time horizon based on the data collected, and the mean annual cost of FM, per patient, was calculated based on the 3-month data.
Statistical analyses
Summary statistics were calculated including mean, standard deviation (SD), median, and range for continuous variables and frequency distributions for categorical variables. Data are given as mean (± SD) unless otherwise indicated. To evaluate the impact of FM severity on patient- and physician-reported outcomes, mean outcomes and costs were compared across FM severity levels (mild, moderate, and severe based on FIQ total scores [25]) the Kruskal-Wallis test. Frequency outcomes were compared across FM severity levels using Fisher's exact test. Statistical significance was evaluated at the 0.05 level, with no adjustments for multiple comparisons. The data were held and analyzed by Covance Inc (Gaithersburg, MD, USA). All analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC, USA).