Methodological issues regarding power of classical test theory (CTT) and item response theory (IRT)-based approaches for the comparison of patient-reported outcomes in two groups of patients - a simulation study

<p>Abstract</p> <p>Background</p> <p>Patients-Reported Outcomes (PRO) are increasingly used in clinical and epidemiological research. Two main types of analytical strategies can be found for these data: classical test theory (CTT) based on the observed scores and models coming from Item Response Theory (IRT). However, whether IRT or CTT would be the most appropriate method to analyse PRO data remains unknown. The statistical properties of CTT and IRT, regarding power and corresponding effect sizes, were compared.</p> <p>Methods</p> <p>Two-group cross-sectional studies were simulated for the comparison of PRO data using IRT or CTT-based analysis. For IRT, different scenarios were investigated according to whether items or person parameters were assumed to be known, to a certain extent for item parameters, from good to poor precision, or unknown and therefore had to be estimated. The powers obtained with IRT or CTT were compared and parameters having the strongest impact on them were identified.</p> <p>Results</p> <p>When person parameters were assumed to be unknown and items parameters to be either known or not, the power achieved using IRT or CTT were similar and always lower than the expected power using the well-known sample size formula for normally distributed endpoints. The number of items had a substantial impact on power for both methods.</p> <p>Conclusion</p> <p>Without any missing data, IRT and CTT seem to provide comparable power. The classical sample size formula for CTT seems to be adequate under some conditions but is not appropriate for IRT. In IRT, it seems important to take account of the number of items to obtain an accurate formula.</p

Patient-reported utilities in advanced or metastatic melanoma, including analysis of utilities by time to death

Background: Health-related quality of life is often collected in clinical studies, and forms a cornerstone of economic evaluation. This study had two objectives, firstly to report and compare pre- and post-progression health state utilities in advanced melanoma when valued by different methods and secondly to explore the validity of progression-based health state utility modelling compared to modelling based upon time to death. Methods: Utilities were generated from the ipilimumab MDX010-20 trial (Clinicaltrials.gov Identifier: NCT00094653) using the condition-specific EORTC QLQ-C30 (via the EORTC-8D) and generic SF-36v2 (via the SF-6D) preference-based measures. Analyses by progression status and time to death were conducted on the patient-level data from the MDX010-20 trial using generalised estimating equations fitted in Stata®, and the predictive abilities of the two approaches compared. Results: Mean utility showed a decrease on disease progression in both the EORTC-8D (0.813 to 0.776) and the SF-6D (0.648 to 0.626). Whilst higher utilities were obtained using the EORTC-8D, the relative decrease in utility on progression was similar between measures. When analysed by time to death, both EORTC-8D and SF-6D showed a large decrease in utility in the 180 days prior to death (from 0.831 to 0.653 and from 0.667 to 0.544, respectively). Compared to progression status alone, the use of time to death gave similar or better estimates of the original data when used to predict patient utility in the MDX010-20 study. Including both progression status and time to death further improved model fit. Utilities seen in MDX010-20 were also broadly comparable with those seen in the literature. Conclusions: Patient-level utility data should be analysed prior to constructing economic models, as analysis solely by progression status may not capture all predictive factors of patient utility and time to death may, as death approaches, be as or more important. Additionally this study adds to the body of evidence showing that different scales lead to different health state values. Further research is needed on how different utility instruments (the SF-6D, EORTC-8D and EQ-5D) relate to each other in different disease areas

Measuring the impact of cancer: a comparison of non-Hodgkin lymphoma and breast cancer survivors

Introduction Self-report instruments such as the Impact of Cancer (IOC) are designed to measure quality of life (QOL) impacts that cancer survivors attribute to their cancer experience. Generalizability of QOL findings across dis-tinct diagnostic categories of survivors is untested. W

Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy

To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy

Psychological process from hospitalization to death among uninformed terminal liver cancer patients in Japan

BACKGROUND: Although the attitude among doctors toward disclosing a cancer diagnosis is becoming more positive, informing patients of their disease has not yet become a common practice in Japan. We examined the psychological process, from hospitalization until death, among uninformed terminal cancer patients in Japan, and developed a psychological model. METHODS: Terminal cancer patients hospitalized during the recruiting period voluntarily participated in in-depth interviews. The data were analyzed by grounded theory. RESULTS: Of the 87 uninformed participants at the time of hospitalization, 67% (N = 59) died without being informed of their diagnosis. All were male, 51–66 years of age, and all experienced five psychological stages: anxiety and puzzlement, suspicion and denial, certainty, preparation, and acceptance. At the end of each stage, obvious and severe feelings were observed, which were called "gates." During the final acceptance stage, patients spent a peaceful time with family, even talking about their dreams with family members. CONCLUSION: Unlike in other studies, the uninformed patients in this study accepted death peacefully, with no exceptional cases. Despite several limitations, this study showed that almost 70% of the uninformed terminal cancer patients at hospitalization died without being informed, suggesting an urgent need for culturally specific and effective terminal care services for cancer patients in Japan

Health profiles of 996 melanoma survivors: the M. D. Anderson experience

BACKGROUND: The incidence and survival of melanoma are increasing, but little is known about its long-term health effects in adult survivors. METHODS: A health survey was available from 996 melanoma survivors (577 treated with surgery alone, and 391 with combined treatments). Their medical/physiologic and psychosocial responses were analyzed and compared with those of the survivors from other cancers. RESULTS: The melanoma survivors were 44.8 ± 12.8 years of age at diagnosis (significantly younger than the survivors of other cancers) and 63.7 ± 12.8 years at survey. Melanoma survivors were less likely to report that cancer had affected their health than survivors of other cancers (15.8% vs. 34.9%). The 577 individuals treated with surgery alone reported arthritis/osteoporosis, cataracts, and heart problems most frequently (less often than survivors of other cancers). The 391 individuals who had undergone combined treatments reported circulation problems and kidney problems generally as often as survivors of other cancers. Health problems were not associated with number of decades since diagnosis but with age at diagnosis, treatment modality, and family relationships. CONCLUSION: We present information from a large cohort of long-term survivors of melanoma. As a group, they were less likely to report that cancer had affected their overall health than survivors of other cancers; a number of disease related and psychosocial factors appear to influence their health profiles

The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors - results of a prospective study

<p>Abstract</p> <p>Background</p> <p>Few data exist on survival or health-related quality of life (QOL) related to herbal remedy use among long-term breast cancer survivors. The objective of this report is to examine whether herbal remedy use is associated with survival or the health-related QOL of these long-term breast cancer survivors.</p> <p>Methods</p> <p>In 1999-2000, we collected the information of herbal remedy use and QOL during a telephone interview with 371 Los Angeles Non-Hispanic/Hispanic white women who had survived more than 10 years after breast cancer diagnosis. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) questionnaire. Patients were followed for mortality from the baseline interview through 2007. 299 surviving patients completed a second telephone interview on QOL in 2002-2004. We used multivariable Cox proportional hazards methods to estimate relative risks (RR) and 95% confidence intervals (CI) for mortality and applied multivariable linear regression models to compare average SF-36 change scores (follow-up - baseline) between herbal remedy users and non-users.</p> <p>Results</p> <p>Fifty-nine percent of participants were herbal remedy users at baseline. The most commonly used herbal remedies were echinacea, herbal teas, and ginko biloba. Herbal remedy use was associated with non-statistically significant increases in the risks for all-cause (44 deaths, RR = 1.28, 95% CI = 0.62-2.64) and breast cancer (33 deaths, RR = 1.78, 95% CI = 0.72-4.40) mortality. Both herbal remedy users' and non-users' mental component summary scores on the SF-36 increased similarly from the first survey to the second survey (<it>P </it>= 0.16), but herbal remedy users' physical component summary scores decreased more than those of non-users (-5.7 vs. -3.2, <it>P </it>= 0.02).</p> <p>Conclusions</p> <p>Our data provide some evidence that herbal remedy use is associated with poorer survival and a poorer physical component score for health-related QOL among women who have survived breast cancer for at least 10 years. These conclusions are based on exploratory analyses of data from a prospective study using two-sided statistical tests with no correction for multiple testing and are limited by few deaths for mortality analysis and lack of information on when herbal remedy use was initiated or duration of or reasons for use.</p

An evaluation of the factors that affect the health-related quality of life of children following myelosuppressive chemotherapy

PurposeThe purposes of this study, in children who were assessed 1 week after the administration of myelosuppressive chemotherapy were: to compare the total and subscale scores on a generic measure of health-related quality of life (HRQOL) to normative data from healthy children and describe the relationships between demographic, clinical, and symptom characteristics of children with cancer and generic and disease-specific dimensions of HRQOL.MethodsPatients (n = 61) were predominantly male (52.5%), minority (63.9%), and 14.7 years of age. Children completed the Memorial Symptom Assessment Scale for 10- to 18-year olds, the PedsQL™ Generic and Cancer Modules, and the Karnofsky Performance Status (KPS) scale 1 week after the start of a chemotherapy cycle.ResultsThe mean number of symptoms per patient was 10.6. Compared with the normative sample, children with cancer reported significantly lower scores for the total scale and all of the subscales except emotional and social functioning. No significant differences were found between any demographic characteristics and total or subscale scores on the generic or disease-specific measures of HRQOL. Lower KPS scores were associated with poorer generic and disease-specific HRQOL scores. In addition, a higher number of symptoms was associated with poorer generic and disease-specific HRQOL scores. Finally, higher symptom distress scores were associated with poorer generic and disease-specific HRQOL scores.ConclusionAmong the demographic, clinical, and symptom characteristics studied, poorer functional status and higher symptom burden were associated with significant decreases in HRQOL in children who received myelosuppressive chemotherapy

Postoperative Deterioration in Health Related Quality of Life as Predictor for Survival in Patients with Glioblastoma: A Prospective Study

BACKGROUND: Studies indicate that acquired deficits negatively affect patients' self-reported health related quality of life (HRQOL) and survival, but the impact of HRQOL deterioration after surgery on survival has not been explored. OBJECTIVE: Assess if change in HRQOL after surgery is a predictor for survival in patients with glioblastoma. METHODS: Sixty-one patients with glioblastoma were included. The majority of patients (n = 56, 91.8%) were operated using a neuronavigation system which utilizes 3D preoperative MRI and updated intraoperative 3D ultrasound volumes to guide resection. HRQOL was assessed using EuroQol 5D (EQ-5D), a generic instrument. HRQOL data were collected 1-3 days preoperatively and after 6 weeks. The mean change in EQ-5D index was -0.05 (95% CI -0.15-0.05) 6 weeks after surgery (p = 0.285). There were 30 patients (49.2%) reporting deterioration 6 weeks after surgery. In a Cox multivariate survival analysis we evaluated deterioration in HRQOL after surgery together with established risk factors (age, preoperative condition, radiotherapy, temozolomide and extent of resection). RESULTS: There were significant independent associations between survival and use of temozolomide (HR 0.30, p = 0.019), radiotherapy (HR 0.26, p = 0.030), and deterioration in HRQOL after surgery (HR 2.02, p = 0.045). Inclusion of surgically acquired deficits in the model did not alter the conclusion. CONCLUSION: Early deterioration in HRQOL after surgery is independently and markedly associated with impaired survival in patients with glioblastoma. Deterioration in patient reported HRQOL after surgery is a meaningful outcome in surgical neuro-oncology, as the measure reflects both the burden of symptoms and treatment hazards and is linked to overall survival