Analyzing Health-Related Quality of Life Data to Estimate Parameters for Cost-Effectiveness Models: An Example Using Longitudinal EQ-5D Data from the SHIFT Randomized Controlled Trial

Introduction

The aim of this article is to discuss methods used to analyze health-related quality of life (HRQoL) data from randomized controlled trials (RCTs) for decision analytic models. The analysis presented in this paper was used to provide HRQoL data for the ivabradine health technology assessment (HTA) submission in chronic heart failure.

Methods

We have used a large, longitudinal EuroQol five-dimension questionnaire (EQ-5D) dataset from the Systolic Heart Failure Treatment with the I _f Inhibitor Ivabradine Trial (SHIFT) (clinicaltrials.gov: NCT02441218) to illustrate issues and methods. HRQoL weights (utility values) were estimated from a mixed regression model developed using SHIFT EQ-5D data (n = 5313 patients). The regression model was used to predict HRQoL outcomes according to treatment, patient characteristics, and key clinical outcomes for patients with a heart rate ≥75 bpm.

Results

Ivabradine was associated with an HRQoL weight gain of 0.01. HRQoL weights differed according to New York Heart Association (NYHA) class (NYHA I–IV, no hospitalization: standard care 0.82–0.46; ivabradine 0.84–0.47). A reduction in HRQoL weight was associated with hospitalizations within 30 days of an HRQoL assessment visit, with this reduction varying by NYHA class [?0.07 (NYHA I) to ?0.21 (NYHA IV)].

Conclusion

The mixed model explained variation in EQ-5D data according to key clinical outcomes and patient characteristics, providing essential information for long-term predictions of patient HRQoL in the cost-effectiveness model. This model was also used to estimate the loss in HRQoL associated with hospitalizations. In SHIFT many hospitalizations did not occur close to EQ-5D visits; hence, any temporary changes in HRQoL associated with such events would not be captured fully in observed RCT evidence, but could be predicted in our cost-effectiveness analysis using the mixed model. Given the large reduction in hospitalizations associated with ivabradine this was an important feature of the analysis. Funding: The Servier Research Group.

     

Etanercept in the treatment of active refractory Crohn's disease: a single-center pilot trial

OBJECTIVES: Etanercept, an injectable tumor necrosis factor (TNF) receptor fusion protein, binds and inactivates human TNF and is used in active rheumatoid arthritis. Blocking TNF with monoclonal antibodies has also been beneficial in Crohn's disease. We attempted to determine the efficacy and safety of etanercept for induction of clinical, endoscopic, and histological improvement in patients with moderate to severe Crohn's disease despite standard treatment. METHODS: Ten patients with active Crohn's disease were treated with etanercept (25 mg s.c.) twice per week for 12 wk. Background therapy was kept stable during the trial. Crohn's disease activity index (CDAI), Inflammatory Bowel Disease Questionnaire, and C-reactive protein levels were measured at weeks 0, 2, 4, 8, and 12. Colonoscopies were performed before and after therapy in responders; endoscopic biopsies were scored for inflammation. RESULTS: At week 2 after the start, a clinical response (deltaCDAI > or = 70) was observed in 6/10 patients (median = 305 [294-418] to 166 [107-392]), with reduction in serum C-reactive protein levels (median = 17.2 [6.8-67.2] to 9.1 [0.9-17.2] mg/dl). Colonoscopies showed a reduction in inflammatory lesions in the four patients who attained remission (CDAI < 150), whereas the inflammatory score of the biopsies did not decrease significantly. No moderate or severe adverse events were observed. CONCLUSIONS: Etanercept may be effective in Crohn's disease refractory to standard therapy.     

Differentially private genome data dissemination through top-down specialization

Advanced sequencing techniques make large genome data available at an unprecedented speed and reduced cost. Genome data sharing has the potential to facilitate significant medical breakthroughs. However, privacy concerns have impeded efficient genome data sharing. In this paper, we present a novel approach for disseminating genomic data while satisfying differential privacy. The proposed algorithm splits raw genome sequences into blocks, subdivides the blocks in a top-down fashion, and finally adds noise to counts to preserve privacy. The experimental results suggest that the proposed algorithm can retain certain data utility in terms of a high sensitivity.     

The impact of major depressive disorder on the short- and long-term outcome of Crohn's disease treatment with infliximab

BACKGROUND: Major depressive disorder is the most common psychiatric diagnosis in Crohn's disease. In other chronic diseases, evidence suggests that depression influences the course of the disease. Strong evidence of such a mediating role of major depressive disorder in Crohn's disease has never been found. AIM: To assess the relationship between major depressive disorder and outcome of treatment of luminal Crohn's disease with infliximab. METHODS: In this prospective study, 100 consecutive unselected patients underwent assessment of psychosocial, demographical disease-related biological and clinical parameters at baseline and at 4 weeks after infliximab. Major depressive disorder was diagnosed using the Patient Health Questionnaire. Subsequently, the patients were followed up clinically until the next flare or during 9 months. RESULTS: The Crohn's disease responded in 75% of the patients, and remission was achieved in 60%. The presence of major depressive disorder at baseline predicted a lower remission rate (OR = 0.166, 95% CI = 0.049-0.567, P = 0.004). At follow-up, 88% of the patients needed retreatment. At univariate regression analysis, major depressive disorder significantly decreased time to retreatment (P = 0.001). Multivariate Cox regression confirmed major depressive disorder as an independent determinant of active disease both at baseline and at re-evaluation (hazard ratio = 2.271, 95% CI: 1.36-3.79, P = 0.002). CONCLUSION: Major depressive disorder is a risk factor for failure to achieve remission with infliximab and for earlier retreatment in patients with active luminal Crohn's disease. Assessment and management of major depressive disorder should be part of the clinical approach to patients with Crohn's disease.     

Phytochemical constituents and anticancer activities of Tarchonanthus camphoratus essential oils grown in Saudi Arabia

Tarchonanthus Camphoratus L. is traditionally known for its various medicinal purposes. In this study, the T. camphoratus essential oil (TCEO) was isolated via steam distillation, and its chemical constituents were determined using GC–MS. The in vitro antiproliferative effects of TCEO on A549, HepG2, MCF-7 cancer cells, and HUVEC non-tumor cells was investigated using an MTT assay. Flow cytometry analysis was conducted to evaluate cell cycle distribution using propidium iodide staining, and cell death mode using Annexin V-FITC/PI assays. The expression of some apoptosis related genes was investigated using qRT-PCR. Major constituents of TCEO included fenchol, borneol, 3-cyclohexene-1-methanol and 3-ethyl-3-methyl. Cell viability test showed that TCEO is highly effective against MCF-7 cells with IC₅₀ 12.5 µg/mL. Cell cycle arrest at the G1/S phase, and apoptosis mediation were evident in the presence of TCEO. Gene expression analysis of several pro-apoptotic and anti-apoptotic genes revealed the initiation of apoptosis in TCEO-MCF-7 cells. In conclusion, our study confirms the antiproliferative activity of the T. camphoratus essential oil.     

Is haloperidol or a benzodiazepine the safest treatment for acute psychosis in the critically ill patient?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether haloperidol or a benzodiazepine is the safest treatment for acute psychosis in the critically ill patient. Altogether 294 papers were found using the reported search, of which nine presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that haloperidol should be considered the first line drug for agitated patients post cardiac surgery, however lorazepam either alone or in conjunction with haloperidol is an acceptable alternative.