Psychometric characteristics of the short form 36 health survey and functional assessment of chronic illness Therapy-Fatigue subscale for patients with ankylosing spondylitis.

BACKGROUND: We evaluated the psychometric characteristics of the Short Form 36 (SF-36) Health Survey and the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale in patients with ankylosing spondylitis (AS). METHODS: We analyzed clinical and patient-reported outcome (PRO) data collected during 12-week, double-blind, placebo-controlled periods of two randomized controlled trials comparing adalimumab and placebo for the treatment of active AS. The Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and other clinical measures were collected during the clinical trial. We evaluated internal consistency/reliability, construct validity, and responsiveness to change for the SF-36 and FACIT-Fatigue. RESULTS: The SF-36 (Cronbach alpha, 0.74-0.92) and FACIT-Fatigue (Cronbach alpha, 0.82-0.86) both had good internal consistency/reliability. At baseline, SF-36 and FACIT-Fatigue scores correlated significantly with Ankylosing Spondylitis Quality of Life scores (r = -0.36 to -0.66 and r = -0.70, respectively; all p < 0.0001). SF-36 scores varied by indicators of clinical severity, with greater impairment observed for more severe degrees of clinical activity (all p < 0.0001). FACIT-Fatigue scores correlated significantly with SF-36 scores (r = 0.42 to 0.74; all p < 0.0001) and varied by clinical severity (p < 0.05 to p < 0.0001). CONCLUSIONS: The SF-36 is a reliable, valid, and responsive measure of health-related quality of life and the FACIT-Fatigue is a brief and psychometrically sound measure of the effects of fatigue on patients with AS. These PROs may be useful in evaluating effectiveness of new treatments for AS.

Translation and validation of non-English versions of the Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire.

BACKGROUND: The Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire is a unidimensional, disease-specific measure developed in the UK and the Netherlands. This study describes its adaptation into other languages. METHODS: The UK English ASQOL was translated into US English; Canadian French and English; French; German; Italian; Spanish; and Swedish (dual-panel methods). Cognitive debriefing interviews were conducted with AS patients. Psychometric/scaling properties were assessed using data from two Phase III studies of adalimumab. Baseline and Week-2 data were used to assess test-retest reliability. Validity was determined by correlation of ASQOL with SF-36 and BASFI and by discriminative ability of ASQOL based on disease severity. Item response theory (Rasch model) was used to test ASQOL's scaling properties. RESULTS: Cognitive debriefing showed the new ASQOL versions to be clear, relevant and comprehensive. Sample sizes varied, but were sufficient for: psychometric/scaling assessment for US English and Canadian English; psychometric but not scaling analyses for German; and preliminary evidence of these properties for the remaining languages. Test-retest reliability and Cronbach's alpha coefficients were high: US English (0.85, 0.85), Canadian English (0.87, 0.86), and German (0.77, 0.79). Correlations of ASQOL with SF-36 and BASFI for US English, Canadian English, and German measures were moderate, but ASQOL discriminated between patients based on perceived disease severities (p < 0.01). Results were comparable for the other languages. US English and Canadian English exhibited fit to the Rasch model (non-significant p-values: 0.54, 0.68), confirming unidimensionality. CONCLUSION: The ASQOL was successfully translated into all eight languages. Psychometric properties were excellent for US English, Canadian English, and German, and extremely promising for the other languages.

Cost effectiveness of lopinavir/ritonavir compared with atazanavir in antiretroviral-naive patients: modelling the combined effects of HIV and heart disease.

BACKGROUND AND OBJECTIVE: The choice of initial highly active antiretroviral therapy (HAART) should take into account the need to balance efficacy, adverse event risk, resistance concerns for the treatment of HIV and treatment costs. Increased risk of coronary heart disease (CHD) may be of special concern in the selection of HAART therapy, because differences in potential CHD risk have been reported for different regimens. This study aimed to estimate the long-term combined effects of HIV disease and antiretroviral (ARV)-related risk for CHD on quality-adjusted survival and healthcare costs for ARV-naive patients. METHODS: A previously validated Markov model was updated and supplemented with the Framingham CHD risk equation. In the model, the average patient was male, aged 37 years and had a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir or unboosted atazanavir as the first protease inhibitor (PI). Clinical trial data were used to estimate the differences between these two therapies. The daily PI costs were $US18.52 for lopinavir/ritonavir and $US22.08 for atazanavir. Other costs were estimated from Medicaid billing databases and average wholesale drug price reports. All model costs were reported as the 2004 present value in US currency. The model's time horizon reflected a patient's lifetime, and the perspective of the analysis was that of the healthcare system and did not include indirect costs in the model cost estimates. Various CHD risk levels were tested in the sensitivity analysis. RESULTS: In the base case, the model predicted a median duration of initial PI regimen of 5.6 years for lopinavir/ritonavir and 3.8 years for atazanavir. Over 10 years, patients who started on atazanavir had 30 additional AIDS events per 100 patients. Only 0.7 additional CHD events per 100 patients occurred for those who started on lopinavir/ritonavir. The model estimated 10-year total healthcare cost savings of $US12,543 per patient in the lopinavir/ritonavir group. The lifetime incremental cost effectiveness of lopinavir/ritonavir versus atazanavir was $US6797 per quality-adjusted life-year gained. CONCLUSION: Lopinavir/ritonavir is a highly cost-effective regimen relative to atazanavir for the treatment of HIV. The effect of lopinavir/ritonavir on long-term CHD risk was minimal compared with the increased risk of AIDS/death projected for a less efficacious first PI regimen. The cost of lipid-lowering drugs and treatment of CHD for patients taking the lopinavir/ritonavir regimen was only 1.2% of the cost of AIDS care per person, which was too small to have a significant effect on the overall cost savings with lopinavir/ritonavir therapy. Thus, a decision to forgo potency and durability in an ARV regimen for an ARV-naive patient in favour of a less potent regimen with an improved lipid profile may prove to be costly over time, in terms of both budget impact and life expectancy.

Substitution with lopinavir/ritonavir improves patient-reported outcomes including quality of life in patients who were intolerant to their antiretroviral therapy.

PURPOSE: Adverse effects are important determinants of quality of life (QOL) during highly active antiretroviral therapy (HAART). The PLATO study investigated the association between changes in patient-reported outcomes including QOL and substitution with lopinavir/ritonavir in patients experiencing side effects (SEs). METHOD: HIV-1-infected participants (N = 849) with undetectable viral load experiencing Grade-2 SEs of the protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component of their HAART regimen were randomized to immediate (baseline) or deferred (week 4) substitution with lopinavir/ritonavir soft-gel capsules 400/100 mg bid. The primary endpoint was change in the total score from the AIDS Clinical Trials Group (ACTG) Symptoms Distress Module (ASDM), supplemented with two items for nephrolithiasis. Secondary endpoints included Medical Outcomes Study (MOS)-HIV scores and Center for Epidemiologic Studies-Depression (CES-D) scores. RESULTS: Immediate substitution resulted in improved ASDM total score at week 4 compared with deferred substitution (p <.001) and significant improvements in all MOS-HIV domains, while significant improvement was observed in CES-D scores at week 8. Primary SEs resolved at week 8 in 65% of participants in the immediate substitution group. Suppression of HIV-1 was maintained. Treatment was well-tolerated and associated with elevations in cholesterol and triglycerides. CONCLUSION: Substitution with LPV/r improved patient-reported outcomes including QOL in patients experiencing Grade-2 SEs, while maintaining viral suppression.

Cost-effectiveness of lopinavir/ritonavir versus nelfinavir as the first-line highly active antiretroviral therapy regimen for HIV infection.

PURPOSE: Selecting the optimal treatment regimen for antiviral-naive patients may be difficult, given the concern about the antiviral activity, the development of drug resistance, and the increase in drug costs. This study evaluates the costs and effectiveness of using lopinavir/ritonavir (LPV/r) vs. nelfinavir (NFV), both coadministered with stavudine and lamivudine, as the first HAART regimen in treating HIV patients, based on the results from the published clinical trial M98-863. METHOD: A Markov model was developed using a combination of viral load (VL) and CD4 count as surrogate markers to define health states. VL and CD4 count data from the 48-week analysis of the clinical trial were used as measures of effect. The impact of resistance difference between NFV and LPV/r was also examined. RESULTS: Over the first 5 years, the model estimated that LPV/r could save $3,461 USD per patient in total HIV care costs compared with NFV. If the resistance advantage of LPV/r was taken into account, the cost savings by LPV/r increased to $5,546 USD. For longer term projection, without considering the resistance difference, the incremental cost-effectiveness ratio (CER) for LPV/r vs. NFV was $6,653 USD per quality-adjusted life-year (QALY). This CER compares favorably to therapies for HIV disease and for common drug treatments for other conditions and is well within accepted thresholds for health policy makers. CONCLUSION: When treatment options are being considered, this study suggests that use of LPV/r in the first antiretroviral regimen, as compared to NFV, is cost-effective based on improved efficacy and resistance.

Patient and parent preferences for immunoglobulin treatments: a conjoint analysis.

OBJECTIVES: The purpose was to quantify patient and parent preferences for administration attributes of immunoglobulin (IG) treatments; and determine which administration attributes were most important to users of IG treatment and whether patients and parents have similar preferences for administration attributes. METHODS: US adult patients and parents of children with a self-reported physician diagnosis of a primary immunodeficiency disorder completed a best-practice web-enabled choice-format conjoint survey that presented a series of 12 choice questions, each including a pair of hypothetical IG-treatment profiles. After reviewing current therapies, each profile was defined by mode of administration, frequency, location, number of needle sticks, and treatment duration. Before answering the choice questions, respondents were told to assume all treatments worked equally well. Choice questions were based on a D-efficient experimental design. Preference weights for attribute levels were estimated using random-parameters logit for each sample (adult patients and parents). Tests were performed to determine potential interactions among the administration attributes. All respondents provided online informed consent. RESULTS: In total, 252 patients and 66 parents completed the choice questions appropriately. Overall, both groups preferred a home setting, monthly frequency, fewer needle sticks, and shorter treatment durations of IG treatment relative to alternative choices (p<0.05). Mode of administration was the least important attribute to both samples; however, parents strongly preferred self-administration to an appointment with a healthcare professional (p<0.05), whereas patients slightly preferred self-administration but were indifferent to the two modes. LIMITATIONS: Respondents evaluate hypothetical treatments and differences can arise between stated and actual choices. CONCLUSIONS: Considering the hypothetical treatments evaluated, IG treatments that provide the option of a home setting, monthly frequency, fewer needle sticks, and shorter treatment durations may address the needs of both patients and parents. Patients and parents have different preferences for administration attributes of IG treatments.

Adalimumab reduces pain, fatigue, and stiffness in patients with ankylosing spondylitis: results from the adalimumab trial evaluating long-term safety and efficacy for ankylosing spondylitis (ATLAS).

OBJECTIVE: To evaluate the effect of adalimumab on pain, fatigue, and stiffness in patients with active ankylosing spondylitis (AS). METHODS: The Adalimumab Trial Evaluating Long-Term Safety and Efficacy for Ankylosing Spondylitis (ATLAS) was an ongoing 5-year study that included an initial 24-week, randomized, placebo-controlled, double-blind period. Patients were randomized to adalimumab 40 mg or placebo by subcutaneous injection every other week. Pain was assessed by the bodily pain domain scores of the Medical Outcomes Study Short Form-36 Health Survey (SF-36) and also by total back pain and nocturnal pain using visual analog scales. Fatigue was measured by the SF-36 vitality domain and question 1 of the Bath AS Disease Activity Index (BASDAI). Morning stiffness was measured by the mean of BASDAI questions 5 and 6. RESULTS: Of 315 patients enrolled, 208 received adalimumab 40 mg and 107 received placebo. At Week 12, adalimumab-treated patients experienced significant improvement compared with placebo-treated patients in the SF-36 bodily pain score (p < 0.001), total back pain score (p < 0.001), nocturnal pain score (p < 0.001), fatigue (p < 0.01), and morning stiffness (p < 0.001). Pain, fatigue, and morning stiffness were significantly correlated (p < 0.001) with baseline values of patient-reported health-related quality of life (HRQOL), and physical function, and with improvements in these values at Week 12 by regression analysis. Treatment effects occurred rapidly (within 2 wks) and were maintained through 24 weeks of treatment. CONCLUSION: Adalimumab significantly improved symptoms of pain, fatigue, and stiffness in patients with AS. Improved symptoms were associated with improved physical function and HRQOL.

Evaluation of the patient acceptable symptom state as an outcome measure in patients with ankylosing spondylitis: data from a randomized controlled trial.

OBJECTIVE: To evaluate the feasibility/acceptability, reliability, external validity, and discriminant capacity of the Patient Acceptable Symptom State (PASS) concept in patients with active ankylosing spondylitis (AS). METHODS: PASS was assessed by asking patients to respond yes or no to a single question: "Considering all the different ways your disease is affecting you, if you would stay in this state for the next months, do you consider that your current state is satisfactory?" during the 24-week, randomized (2:1 ratio), double-blind, placebo-controlled portion of an adalimumab study of 315 patients. RESULTS: PASS reliability was high (kappa = 0.86) in patients with stable disease. Significantly more patients who answered yes to PASS than patients who answered no to PASS were responders based on the ASsessment in Ankylosing Spondylitis (ASAS) International Working Group criteria for 20% improvement (75% who answered yes versus 29% who answered no), the ASAS criteria for 40% improvement (61% versus 16%), the ASAS partial remission criteria (37% versus 3%), and > or =50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (65% versus 19%; P < 0.001 for all comparisons), demonstrating external validity of the PASS concept. More adalimumab-treated than placebo-treated patients achieved PASS at week 12 (42.3% versus 22.4%; P < 0.001), and more adalimumab-treated than placebo-treated patients achieved sustained PASS through week 20 (34.6% versus 12.3%; P < 0.001), indicating excellent discriminant capacity. CONCLUSION: PASS is a feasible, acceptable, reliable, and valid assessment of satisfactory health state in patients with AS.

Health-related quality of life outcomes in patients with active ankylosing spondylitis treated with adalimumab: results from a randomized controlled study.

OBJECTIVE: To evaluate the impact of adalimumab on health-related quality of life (HRQOL) in patients with active ankylosing spondylitis (AS). METHODS: Patients >or=18 years enrolled in the Adalimumab Trial Evaluating Long-Term Efficacy and Safety in Ankylosing Spondylitis, a randomized controlled study, were randomly assigned to receive either adalimumab 40 mg subcutaneously or placebo every other week for 24 weeks. ASsessment of Ankylosing Spondylitis (ASAS) International Working Group criteria were used to evaluate clinical efficacy. HRQOL outcomes were assessed using the Short Form 36 (SF-36) Health Survey and Ankylosing Spondylitis Quality of Life (ASQoL) Questionnaire. RESULTS: A total of 315 patients enrolled (208 in the adalimumab group and 107 in the placebo group). Patients in the adalimumab group showed significant improvements in SF-36 Physical Component Summary (PCS) and ASQoL scores versus placebo at weeks 12 and 24 (P < 0.001). The observed differences between adalimumab and placebo patients exceeded the a priori minimum important difference (MID) at the group level, and significantly more adalimumab-treated patients achieved improvements greater than the MID on the patient level. These data suggest the HRQOL improvements were clinically meaningful. No differences were observed in SF-36 Mental Component Summary (MCS) scores. Significant differences favoring adalimumab were observed for SF-36 domains physical function, bodily pain, role-physical, general health, vitality, social function, and role-emotional. There was significant association between HRQOL improvements (measured by SF-36 PCS and MCS, and ASQoL scores) and ASAS clinical responses (P < 0.001). CONCLUSION: Adalimumab significantly improved physical health status and overall HRQOL through 24 weeks in patients with active AS.