Minimal clinically important difference (MCID) for work productivity and activity impairment (WPAI) questionnaire in psoriasis patients.

BACKGROUND: The clinical meaningfulness of improvements in the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI-PsO) reported by patients with psoriasis in response to treatment is unknown due to the lack of any publications that report minimal clinically importance differences (MCID) for WPAI-PsO outcomes. OBJECTIVE: To determine the MCIDs for the work productivity loss and activity impairment domains of the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI-PsO) using results from three Phase 3 trials of ixekizumab. METHODS: MCIDs for WPAI-PsO domains were derived using treatment agnostic data from patients participating in UNCOVER-1/-2/-3. The analysis included patients randomized to placebo and two ixekizumab treatment groups (ixekizumab either every 2 weeks or 4 weeks) from the trials. WPAI-PsO was administered at baseline and Week 12 for UNCOVER-1/-2/-3 and at Weeks 24, 36, 52 and 60 in UNCOVER-1/-2. MCIDs for the WPAI-PsO domains through Week 12 were derived using an anchor-based method supplemented with the distribution-based method. Anchors included 75%/90%/100% improvement in Psoriasis Area and Severity Index, Static Physicians Global Assessment (sPGA[0] and sPGA[0,1]) and Dermatology Life Quality Index MCID). MCIDs were triangulated using receiver operating characteristics (ROC) and distribution-based methods. RESULTS: The analyses included 3126 patients (Placebo: 792, Ixekizumab: 2334). All anchors were shown to be valid. Significant differences in the domains of WPAI-PsO were observed between patients achieving clinically meaningful improvement in the validated anchors (all P-values < 0.001). ROC analyses suggested a 20% improvement in the work productivity loss or activity impairment components best represented the benefit of meeting a clinical meaningful improvement in the validated anchors. The distribution-based method supported the results of the anchor-based method. CONCLUSION: The MCIDs for both the work productivity loss and the activity impairment domains of WPAI-PsO were estimated to be 20% in patients with PsO.

Self-reported health outcomes in patients with psoriasis and psoriatic arthritis randomized to two etanercept regimens.

BACKGROUND: Moderate/severe psoriasis combined with psoriatic arthritis (PsA) impairs health-related quality of life (QoL). Etanercept, a fully human tumour necrosis factor-α receptor fusion protein, is approved for treatment of both diseases. OBJECTIVE: To compare patient-reported health outcomes (PROs) of two etanercept regimens in patients with moderate/severe psoriasis and PsA. METHODS: In this randomized, double-blind, multicenter study, participants received etanercept 50 mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n = 373) for 12 weeks and open-label etanercept 50 mg QW for 12 additional weeks. PROs included: the EuroQOL-5D (EQ-5D), which measures general health status and consists of the utility index measuring five dimensions of health, and a visual analogue scale (VAS) allowing patients to assess health status; the Dermatology Life Quality Index (DLQI), which measures the impact of skin disease on QoL; the Health Assessment Questionnaire-Disability Index (HAQ-DI), an assessment of physical function; the Hospital Anxiety and Depression Scale (HADS), which screens for anxiety and depression symptoms; and individual questions on general health, disease activity, fatigue, itching, joint pain and morning stiffness. RESULTS: At baseline, patients reported QoL worse than that seen in many chronic medical conditions. Significant within-group improvements in each PRO occurred from baseline to Week 12 (P < 0.001) in both groups and were maintained at Week 24; DLQI, EQ-5D, HAQ-DI and self assessments improved significantly (P < 0.001) from baseline as early as Week 3. At Week 12, but not Week 24, improvement in DLQI, itching and psoriasis activity was greater in the BIW arm (P ≤ 0.004). Improvements in other PROs were always similar between groups. CONCLUSIONS: Greater improvements in PROs specific to skin disorders were seen with etanercept BIW than QW at Week 12, but not at Week 24. Both etanercept regimens led to sustained PRO improvements, starting as early as Week 3.

The Resource Utilization in Dementia (RUD) instrument is valid for assessing informal care time in community-living patients with dementia.

OBJECTIVE: Informal care is a significant component of the societal resource use and costs in dementia care. Thus it is fundamental that assessments of informal care are valid. Thus the aim was to analyse the validity of time estimates with the Resource Utilization in Dementia (RUD) instrument. DESIGN: Prospective observational study. SETTING: Community sample. PARTICIPANTS: Fourteen married and cohabiting patient-caregiver pairs. MEASUREMENTS: Comparisons of estimates of caregiver time by recall with the RUD instrument, by diaries and by direct observation, with calculation of agreement statistics for recall vs. diary and recall vs. direct observation to assess accuracy of the time estimates derived from recall. RESULTS: The patients and their caregivers participated in 47 diaries and 30 observation sessions. The agreement between diaries and recall estimates was high for personal ADL (intra-class correlation (ICC) 0.93), supervision (ICC 0.87) and total time (ICC 0.91) and lower but acceptable for instrumental ADL (ICC 0.75). Regarding observation vs recall estimates, the corresponding figures were for personal ADL (ICC 0.81), for instrumental ADL (ICC 0.74), for supervision (ICC 0.78) and for total time (ICC 0.80). CONCLUSION: The RUD instrument appears to accurately estimate the amount of informal care provided by caregivers to dementia patients.

Predicting 10-year care requirements for older people with suspected Alzheimer's disease.

OBJECTIVE: To describe the types and costs of care received for 10 years after the identification of an older person with suspected Alzheimer's disease (AD) by using data from 3254 patients with suspected AD who participated in the National Long Term Care Survey (NLTCS). METHODS: By using a Markov model derived using grade of membership techniques, the following were determined: survival probabilities at 10 years; years of survival during the 10 years; years in institutions; years with two or more impairments in basic activities of daily living; hours of paid and informal care while the older person lived in the community; and costs of paid community, institutional, and medical care. RESULTS: Greater degrees of cognitive impairment present when AD was identified were associated with reduced predicted probability of surviving 10 years, increased predicted number of years spent in institutions, increased hours of care required while affected individuals remained in the community, and increased costs of paid community, institutional, and medical care. Substantial differences between men and women were seen: severity-adjusted 10-year costs were almost two times higher for women with AD than for men ($75,000 compared with $44,000); according to sensitivity analysis, average 10-year costs might be as high as $109,000 for women and $67,000 for men. CONCLUSIONS: AD imposes a substantial burden on older persons. Interventions that slow the progression of the disease may therefore affect community survival as well as healthcare costs.

Model of complications of NIDDM. I. Model construction and assumptions.

OBJECTIVE: To develop a model of NIDDM for analyzing prevention strategies for NIDDM. RESEARCH DESIGN AND METHODS: A Markov type model with Monte Carlo techniques was used. Age, sex, and ethnicity of cohort was based on U.S. data. Incidence rates of complications were also based on community and population studies. RESULTS: Nonproliferative retinopathy, proliferative retinopathy, and macular edema are predicted in 79, 19, and 52%, respectively, of people with NIDDM; 19% are predicted to develop legal blindness. Microalbuminuria, gross proteinuria, and end-stage renal disease related to diabetes are predicted in 53, 40, and 17%, respectively. Symptomatic sensorimotor neuropathy and lower-extremity amputation are predicted in 31 and 17%, respectively. Cardiovascular disease is predicted in 39%. Higher rates of complications (1.1-3.0x) are predicted in minority populations. Predicted average life expectancy is 17 years after diagnosis. CONCLUSIONS: A probabilistic model of NIDDM predicts the vascular complications of NIDDM in a cohort representative of the incident cases of diabetes in the U.S. before age 75 years. Predictions of complications and mortality are consistent with the known epidemiology of NIDDM. The model is suitable for evaluating the effect of preventive interventions on the natural history of NIDDM.

Model of complications of NIDDM. II. Analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia.

OBJECTIVE: To analyze the health benefits and economics of treating NIDDM with the goal of normoglycemia. RESEARCH DESIGN AND METHODS: Incidence-based simulation model of NIDDM was used. Hazard rates for complications were adjusted for glycemia using risk gradients from the Diabetes Control and Complications Trial. Treatment costs were estimated from national survey data and clinical trials. Incremental costs and benefits were expressed in present value dollars (3% discount rate). Life-years were adjusted for quality of life, yielding quality-adjusted life-years (QALYs). RESULTS: Comprehensive treatment of NIDDM that maintains an HbA1c value of 7.2% is predicted to reduce the cumulative incidence of blindness, end-stage renal disease, and lower-extremity amputation by 72, 87, and 67%, respectively. Cardiovascular disease risk increased by 3% (no effect of treating glycemia is assumed). Life expectancy increased 1.39 years. The cost of treating hyperglycemia increased by almost twofold, which is partially offset by reductions in the cost of complications. The estimated incremental cost/QALY gained is $16,002. Treatment is more cost-effective for those with longer glycemic exposure (earlier onset of diabetes), minorities, and those with higher HbA1c under standard care. CONCLUSIONS: The incremental effectiveness of treating NIDDM with the goal of normoglycemia is estimated to be approximately $16,000/QALY gained, which is in the range of interventions that are generally considered cost-effective.

Mannitol injections: with or without filter needles? A cost-effectiveness analysis.

A clinical economic evaluation was conducted to assess the cost-effectiveness of filtration of i.v. mannitol injections. Clinical decision analysis was used to model the costs and benefits of using filter needles for undiluted, i.v. push injections of mannitol 25%. Sensitivity analysis conducted by varying all uncertain variables to test best and worst case scenarios revealed that the use of filter needles is a cost-effective measure in all relevant scenarios.

Pharmacoeconomic analysis of ondansetron versus metoclopramide for cisplatin-induced nausea and vomiting.

A pharmacoeconomic analysis of ondansetron versus metoclopramide use in patients receiving high-dose cisplatin therapy is reported. A meta-analysis of the literature was performed to synthesize the results of clinical trials of ondansetron and metoclopramide for the prevention of nausea and vomiting in patients receiving high-dose cisplatin therapy. A cost-benefit analysis was performed by constructing a decision tree of the possible outcomes of treatment with ondansetron or metoclopramide. Clinical outcomes were measured by counting the emesis episodes occurring within 24 hours after the antiemetic was given and the extrapyramidal reactions occurring after metoclopramide was given. The improvement in quality of life was transformed to an increase in quality-adjusted life years (QALYs) in order to conduct a cost-utility analysis. Only direct costs of drug, materials, and labor were included in the cost calculations. The meta-analysis, combined with empirical observations, yielded expected emesis rates of 2.03 and 2.69 per patient for ondansetron and metoclopramide, respectively. The rate of extrapyramidal symptoms for metoclopramide recipients was 6.8%. The cost-benefit analysis yielded estimated total costs of $139 ($211) and $116 ($154) per 40-kg (70-kg) patient receiving ondansetron and metoclopramide, respectively. The cost-utility analysis yielded an incremental cost of ondansetron of $168,391 ($407,667) per QALY in 40-kg (70-kg) patients. Sensitivity analysis showed robustness of the expected outcomes except in a best-case scenario. A cost-utility analysis suggested that, compared with metoclopramide, ondansetron provides a small antiemetic benefit at a large additional cost.

Mesalamine capsules enhance the quality of life for patients with ulcerative colitis.

Patients with ulcerative colitis tend to be young, potentially at peak lifetime productivity levels, and the disease can be devastating in its effects on the quality of life in these individuals. No treatment for ulcerative colitis can be comprehensively evaluated without careful attention to its impact on such psychosocial issues. The quality of life was evaluated in 374 ulcerative colitis patients using mesalamine capsules at 1 g, 2 g, and 4 g daily versus placebo in an 8-week, randomized, dose-response, placebo-controlled, double-blind, multicentre trial. Function-related quality of life parameters were assessed in this study, including five pertinent clinical symptoms and seven general life capabilities. These parameters have been previously shown to be valid, reliable, and responsive to the disease activity of ulcerative colitis. All of the parameters were recorded using a 10-cm visual analogue scale, except trips to the toilet which were recorded in patients' diaries. The mean change was calculated from baseline and endpoint data. Mesalamine at 2 g and 4 g daily was significantly superior to placebo in improving each of the 12 quality of life parameters (P < 0.05). These results indicate that controlled-release mesalamine significantly enhances the quality of life for patients with either left-sided ulcerative colitis or pancolitis.