Comorbidity indices for clinical trials: adaptation of two existing indices for use with the FREEDOM trial in women with postmenopausal osteoporosis.

UNLABELLED: Two comorbidity indices were adapted for use in the FREEDOM trial and significantly correlated with the number of medications and impaired health status at baseline. The indices have applications for the analysis of clinical trial data and would allow for the appropriate adjustment of comorbidities when evaluating clinical trial outcomes. INTRODUCTION: The purpose of this study is to adapt two published comorbidity indices for use with the FREEDOM clinical trial evaluating postmenopausal women with osteoporosis. METHODS: FREEDOM enrolled women aged 60-90 years with a bone mineral density T-score <-2.5 at the lumbar spine or total hip and ≥-4.0 at both sites. Comorbidity indices were calculated using methods described by Sangha (Arthritis Rheum 49:156-163, 2003) and Wolfe (J Rheumatol 37:305-315, 2010) following modification. The adapted Sangha index included 12 conditions with a summary score of 0-12; the adapted Wolfe index included 7 conditions with a weighted summary score of 0-8. Higher scores indicated greater comorbidity. A panel of clinicians independently reviewed subjects' medical histories using a systematic process based on Medical Dictionary for Regulatory Activities (MedDRA) preferred terms to map specified comorbid conditions. Spearman correlations between the adapted indices and baseline subject characteristics expected to be associated with comorbidities were examined. RESULTS: Of the 7808 subjects in this study, 74 % had ≥1 comorbidities based on the adapted Sangha or Wolfe comorbidity indices. The mean (SD) adapted Sangha and Wolfe comorbidity indices were 1.4 (1.2) and 1.4 (1.3), respectively. Both indices correlated positively with age, body mass index, and the number of medications (r = 0.54 to 0.55) at baseline and inversely correlated with health-related quality of life (r = -0.22 to -0.30) (all P < 0.0001). Further, when either the adapted Sangha or Wolfe index was included as a covariate for assessing mortality over 36 months in the FREEDOM population, the hazard ratio of the comorbidity index indicated that the mortality risk increased by 27 or 28 %, respectively, for each unit increase in the adapted index (both P < 0.0001). CONCLUSIONS: Our work suggests these comorbidity indices may be adapted for use with clinical trial data, thereby allowing for the appropriate adjustment and reporting of covariates in the evaluation of clinical trial outcomes in an osteoporotic population.

Impact of brodalumab treatment on psoriasis symptoms and health-related quality of life: use of a novel patient-reported outcome measure, the Psoriasis Symptom Inventory.

BACKGROUND: Psoriasis symptoms have a significant negative impact on health-related quality of life, impairing physical functioning and well-being. OBJECTIVE: To evaluate the impact of brodalumab, a human anti-interleukin-17R monoclonal antibody, on psoriasis symptom severity as measured by a novel patient-reported outcome measure, the Psoriasis Symptom Inventory, and dermatology-specific health-related quality of life as measured by the Dermatology Life Quality Index (DLQI). METHODS: This was a secondary analysis of a phase II, randomized, double-blind, placebo-controlled clinical study of patients with moderate-to-severe psoriasis (n = 198) treated with brodalumab or placebo. This analysis assessed Psoriasis Symptom Inventory scores and DLQI scores over time. Analyses were conducted on all patients who were randomized and received one or more injections of the study drug according to intention to treat using last observation carried forward to impute missing data. RESULTS: At week 12, subjects in the brodalumab groups had significant improvements in mean Psoriasis Symptom Inventory total scores [8.5 (70 mg), 15.8 (140 mg), 16.2 (210 mg) and 12.7 (280 mg)] compared with placebo (4.8). Mean improvements in DLQI were clinically meaningful (≥ 5.7) in the brodalumab groups (6.2, 9.1, 9.6 and 7.1, respectively) and significantly greater than placebo (3.1). Improvements in Psoriasis Symptom Inventory were observed as early as week 2 and in DLQI by week 4. All eight Psoriasis Symptom Inventory item scores improved significantly among the brodalumab groups by week 12. CONCLUSIONS: Results were from a single randomized clinical trial and may not generalize to broader patient populations. However, treatment with brodalumab provided significant improvement in psoriasis symptoms in patients with moderate-to-severe psoriasis.

Association between osteoporosis treatment change and adherence, incident fracture, and total healthcare costs in a Medicare Advantage Prescription Drug plan.

UNLABELLED: We examined the association between osteoporosis treatment change and adherence, incident fractures, and healthcare costs among Medicare Advantage Prescription Drug (MAPD) plan members. Treatment change was associated with a small but significant increase in adherence, but was not associated with incident fracture or total healthcare costs. Overall adherence remained low. INTRODUCTION: We examined the association between osteoporosis treatment change and adherence, incident fractures, and healthcare costs among MAPD plan members in a large US health plan. METHODS: We conducted a retrospective cohort study of MAPD plan members aged≥50 years newly initiated on an osteoporosis medication between 1 January 2006 and 31 December 2008. Members were identified as having or not having an osteoporosis treatment change within 12 months after initiating osteoporosis medication. Logistic regression analyses and difference-in-difference (DID) generalized linear models were used to investigate the association between osteoporosis treatment change and (1) adherence to treatment, (2) incident fracture, and (3) healthcare costs at 12 and 24 months follow-up. RESULTS: Of the 33,823 members newly initiated on osteoporosis treatment, 3,573 (10.6%) changed osteoporosis treatment within 12 months. After controlling for covariates, osteoporosis treatment change was associated with significantly higher odds of being adherent (medication possession ratio [MPR]≥0.8) at 12 months (odds ratio [OR]=1.18) and 24 months (OR=1.13) follow-up. However, overall adherence remained low (MPR=0.59 and 0.51 for the change cohort and MPR=0.51 and 0.44 for the no-change cohort at 12 and 24 months, respectively). Osteoporosis treatment change was not significantly associated with incident fracture (OR=1.00 at 12 months and OR=0.98 at 24 months) or total direct healthcare costs (p>0.4) in the DID analysis, but was associated with higher pharmacy costs (p<0.004). CONCLUSIONS: Osteoporosis treatment change was associated with a small but significant increase in adherence, but was not associated with incident fracture or total healthcare costs in the MAPD plan population. Overall adherence to therapy remained low.

Impact of clinical fractures on health-related quality of life is dependent on time of assessment since fracture: results from the FREEDOM trial.

UNLABELLED: In the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study, women with incident clinical fractures reported significant declines in health-related quality of life (HRQoL). The largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain. INTRODUCTION: In the FREEDOM trial, denosumab significantly reduced the risk of new vertebral, hip, and nonvertebral fractures. We evaluated the effect of denosumab on HRQoL and the association between incident clinical fractures and HRQoL. METHODS: The FREEDOM trial enrolled 7,868 women aged 60-90 years with a total hip and/or lumbar spine BMD T-score <-2.5 and not <-4.0 at either site. Women were randomized to receive denosumab 60 mg or placebo every 6 months, in addition to daily calcium and vitamin D. HRQoL was assessed with the Osteoporosis Assessment Questionnaire-Short Version (OPAQ-SV) at baseline and every 6 months for 36 months. The OPAQ-SV assesses physical function, emotional status, and back pain. Higher scores indicate better health status. RESULTS: No statistically significant differences in mean change in HRQoL from baseline to end of study were found when comparing treatment groups. Compared with women without any incident fractures during the study, women with incident clinical fractures reported significant declines in physical function (-4.0 vs. -0.5) and emotional status (-5.0 vs. -0.8) at month 36 (P < 0.001 for both). Importantly, time-dependent covariate analyses demonstrated that the largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain. CONCLUSIONS: These findings not only demonstrate that incident clinical fractures impact HRQoL but also contribute new information regarding the impact of these fracture events on HRQoL over time.

Accrediting organizations and quality improvement.

This paper reviews the various organizations in the United States that perform accreditation and establish standards for healthcare delivery. These agencies include the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), the National Committee for Quality Assurance (NCQA), the American Medical Accreditation Program (AMAP), the American Accreditation HealthCare Commission/Utilization Review Accreditation Commission (AAHC/URAC), and the Accreditation Association for Ambulatory HealthCare (AAAHC). In addition, the Foundation for Accountability (FACCT) and the Agency for Healthcare Research and Quality (AHRQ) play important roles in ensuring the quality of healthcare. Each of the accrediting bodies is unique in terms of their mission, activities, compositions of their boards, and organizational histories, and each develops their own accreditation process and programs and sets their own accreditation standards. For this reason, certain accrediting organizations are better suited than others to perform accreditation for a specific area in the healthcare delivery system. The trend toward outcomes research is noted as a clear shift from the structural and process measures historically used by accrediting agencies. Accreditation has been generally viewed as a desirable process to establish standards and work toward achieving higher quality care, but it is not without limitations. Whether accrediting organizations are truly ensuring high quality healthcare across the United States is a question that remains to be answered.