Heart-type fatty acid-binding protein for risk assessment of chronic thromboembolic pulmonary hypertension.

Heart-type fatty acid-binding protein (H-FABP) is a reliable marker of myocardial injury and was recently identified as a predictor of outcome in acute pulmonary embolism. The aim of the present study was to investigate the prognostic value of H-FABP in chronic thromboembolic pulmonary hypertension (CTEPH). In total, 93 consecutive patients with CTEPH were studied. During long-term follow-up (median duration 1,260 days, interquartile range (IQR) 708-2,460 days), 46 (49%) patients had an adverse outcome, defined as CTEPH-related death, lung transplantation or persistent pulmonary hypertension after pulmonary endarterectomy (PEA). Baseline H-FABP levels in plasma ranged from 0.69-24.3 ng x mL(-1) (median (IQR) 3.41 (2.28-4.86) ng x mL(-1)). Cox regression analysis revealed a hazard ratio of 1.10 (95% confidence interval 1.04-1.18) for each increase of H-FABP by 1 ng x mL(-1), and continuous elevations of H-FABP emerged as an independent predictor of adverse outcome by multivariable analysis. PEA was performed in 52 patients and favourably affected the long-term outcome. Kaplan-Meier analysis revealed that patients with baseline H-FABP concentrations >2.7 ng x mL(-1), the median value of the biomarker in the surgically treated population, had a lower probability of event-free survival after PEA. Heart-type fatty acid-binding protein is a promising novel biomarker for risk stratification of patients with chronic thromboembolic pulmonary hypertension.

Quality of life assessment in a cross-cultural context: use of the Rotterdam Symptom Checklist in a multinational randomised trial comparing CMF and Zoladex (Goserlin) treatment in early breast cancer.

AIM: The aim of the study is to investigate quality of life (QoL) in the context of a multinational trial. The questions addressed are: is the Rotterdam Symptom Checklist (RSCL) 1) feasible and 2) reliable in cross cultural research, 3) is earlier validation confirmed in a multinational trial and 4) are there systematic differences in QoL across cultures? PATIENTS AND METHODS: Patients with histologically confirmed stage II, node positive breast cancer, were randomised in a multinational trial (the 'ZEBRA-study') comparing standard chemotherapy (CMF) or temporary ovarian ablation by treatment with a LHRH analogue (Zoladex, Goserlin). Patients originating from 13 countries completed a QoL questionnaire at baseline and three months after the start of treatment. RESULTS: 1) The questionnaire was completed by 689 patients at the first and 544 at the second measurement (response 78% and 68% respectively). The proportion of missing data was < 2.5% for 87.8% and 92.7% of the items at the respective time points. 2) Reliabilities of the physical and psychological distress scale were ranging from 0.68 to 0.90 across cultures. Reliability of the activity scale ranged from 0.42 to 0.89. 3) The structure at baseline was in agreement with the two factor structure proposed earlier. 4) Cross-cultural comparison indicated a systematic difference in QoL across cultures (P = 0.0028-< 0.0001) as well as a difference in change across cultures. CONCLUSIONS: QoL assessment using the RSCL proved feasible in the context of multinational clinical trials. Psychometric qualities were satisfactory. Systematic differences in QoL were found between cultures. This finding implies that in multinational clinical trials, treatment comparisons with respect to QoL should carefully account for a differential impact of cultures on the results.

Compliance with QOL assessment in multi-centre German breast cancer trials.

The compliance with QOL assessment in German breast cancer trials is reported. The results indicate that the response to fill in QOL forms in cancer clinical trials seems to depend more on the clinical centre and the attitude of the treating physician than the individual patient. A strategy of globally eliminating centres that produce high rates of missing QOL data from the analysis of QOL is discussed. The adoption of such a strategy will reduce the number of patients available for analysis, but on the other hand increase the relative amount of non-missing data.

Assessment of quality of life in clinical trials.

This paper is intended as an overview of developments in the assessment of quality of life (QOL) in clinical trials over the last decade from the viewpoint of clinical biostatistics. In the first part we deal with aspects of obtaining adequate measurements of quality of life. A literature survey shows that a large number of quite heterogeneous measurement approaches for use in clinical trials exist, a substantial percentage of which cannot be regarded as sufficient for their actual measuring purpose. In the second part we review statistical methods applied to and adapted for the analysis of QOL data. Underlying the analysis should be the assumption of QOL as a stochastic process. Applied analysis procedures are again investigated in a literature survey. Finally, critical conclusions are outlined and suggestions for further research are given.

Statistical analysis of quality of life data in cancer clinical trials.

In clinical trials endpoints other than total and/or disease-free survival are gaining more and more interest. In particular, quality of life (QOL) or the well-being of patients has emerged as a synonym for variables describing the subjective reactions of patients towards their disease and its treatment. The statistical analysis of such QOL data is complicated firstly by the large number of variables measured and their obvious lack of objectivity. The construction of suitable aggregate measures allowing a reduction of the measurements into a (preferably) unidimensional index are discussed in the context of an analysis at a fixed time point during the course of treatment. A second problem arises from the consideration that a patient's well-being is subject to changes over time. We discuss the modelling of QOL by suitable stochastic processes which are extensions of a multistate disease process. This allows QOL events to be incorporated into methods of survival analysis by either estimating the relevant transition probabilities between states or calculating quality-adjusted survival times. Finally, some brief guidelines for the planning of clinical trials including QOL measurements will be proposed.