Statistical analysis of Goal Attainment Scaling endpoints in randomised trials.

Goal Attainment Scaling is an assessment instrument to evaluate interventions on the basis of individual, patient-specific goals. The attainment of these goals is mapped in a pre-specified way to attainment levels on an ordinal scale, which is common to all goals. This approach is patient-centred and allows one to integrate the outcomes of patients with very heterogeneous symptoms. The latter is of particular importance in clinical trials in rare diseases because it enables larger sample sizes by including a broader patient population. In this paper, we focus on the statistical analysis of Goal Attainment Scaling outcomes for the comparison of two treatments in randomised clinical trials. Building on a general statistical model, we investigate the properties of different hypothesis testing approaches. Additionally, we propose a latent variable approach to generate Goal Attainment Scaling data in a simulation study, to assess the impact of model parameters such as the number of goals per patient and their correlation, the choice of discretisation thresholds and the type of design (parallel group or cross-over). Based on our findings, we give recommendations for the design of clinical trials with a Goal Attainment Scaling endpoint. Furthermore, we discuss an application of Goal Attainment Scaling in a clinical trial in mastocytosis.

Dose-finding study of valspodar (PSC 833) with daunorubicin and cytarabine to reverse multidrug resistance in elderly patients with previously untreated acute myeloid leukemia.

INTRODUCTION: This trial was designed to determine the maximum tolerated dose of intravenous daunorubicin (DNR) in combination with valspodar and to test the feasibility of P-glycoprotein modulation using valspodar in elderly patients with previously untreated acute myelogenous leukemia receiving standard induction chemotherapy. METHODS: Patients > or =60 years of age with previously untreated AML received valspodar (10 mg/kg/24 h by continuous intravenous infusion [CIV] on days 1-4 with a 2-mg/kg loading dose on day 1) in conjunction with two cycles of induction chemotherapy consisting of cytarabine (200 mg/m(2) CIV on days 1-7), and DNR (35 mg/m(2) [cohort 1] or 45 mg/m(2) [cohort 2] on days 1-3, intravenous bolus). Patients were assessed for dose-limiting toxicities (DLT), response rate, event-free and overall survival, and pharmacokinetics of valspodar and DNR. RESULTS: Valspodar was well tolerated at the lower DNR dose level (ie, 35 mg/m(2)) resulting in a 21% rate of DLT and only three toxic deaths. Treatment-related mortality was unacceptably high at the 45 mg/m(2) DNR dose level. The complete response rate was 49% overall and similar in both cohorts. The median overall survival of patients was 333 days in cohort 1 compared to 98 days in cohort 2. At baseline, 70% of assessable patients were P-glycoprotein positive. CONCLUSION: Substantial inhibition of P-glycoprotein activity can be achieved in this patient population at clinically tolerable doses of valspodar and DNR. The maximum tolerated dose of DNR was established as 35 mg/m(2). This regimen is being further evaluated in phase III trials.

[Computed tomographic measurements of breast density]. / Computertomographische Dichtemessungen in der Mamma.

From histogram analysis the value of computed tomography for early detection of breast carcinoma or differentiation of benign and malign processes of the breast was evaluated. The results show, that CT is not applicable and gives no improvement of diagnostics.

[The reduction of radiation burden in mammography using film-screen combination systems]. / Reduktion der Strahlenbelastung bei der Mammographie durch Einsatz von Film-Folien-Kombinationen.

The comparison of mammographic image recording systems TF-13-nonscreen film and ORTHO-MA with MIN-R screens leads to the necessary conclusion, that mammography should be carried out only with screen film combinations and an anti-scatter grid. This means improved contrast and a reduction of radiation dose to 1/3 of the dose of TF 13. Since in the GDR the film XR 10 still is used as mammographic film the fourfold of the internationally possible dose is required. The urgent change of the situation can only be achieved with respective imports.

[The use of CT in meniscopathy]. / Der Einsatz der CT bei der Meniskopathie.

The results of CT examination of meniscopathies in 54 patients, most of them competitive athletes, are presented. CT has an overall accuracy of about 90 per cent and can hence be used for diagnosing a lesion of the meniscus with a reasonable amount of safety, while being rapid and avoiding unnecessary exposure to stress. This method, therefore, should be a focal point of the imaging methods and thus be placed between the specialist doctor's findings and possible surgery. The pros and cons of CT compared with other imaging methods are discussed.

[Radiation dosage of the lens and gonads in selected CT studies]. / Die Strahlenbelastung von Linse und Gonaden bei ausgewählten CT-Untersuchungen.

The article is a compilation of data on the radiation exposure during the most important CT examinations. The influencing parameters are assessed and their effects are discussed. Conclusions are drawn to modify the practical approach. These results are compared with those reported in international literature.

[Radiation exposure of the lens during CT of the orbital area]. / Die Strahlenbelastung der Linse bei CT im Orbitabereich.

The exposure of the lens to irradiation in CT examination of the orbita was determined in a total of 80 patients via thermoluminescence dosimetry. Depending on a wide variety of parameters, exposures between 6.5 and 75 mGy were found with a mean of 28 mGy. By analysing the influence values thickness of layer and mAs product, suggestions for optimising orbita CT examinations are evolved.

On the persistence of tumor initiation in two-stage carcinogenesis on mouse skin.

The persistence of the initiated state during two-step carcinogenesis in mouse epidermis is a generally accepted phenomenon, however, conflicting results exist with regard to the degree of irreversibility relative to the age of the animals. Several factors such as age-dependent alterations in the response of the epidermis to the promoter and skin damage following the initiation step have been proposed to account for the observed discrepancies. In the present investigation we have tried to circumvent skin-damaging effects of topically applied 7,12-dimethylbenz[a]anthracene by intragastric administration of the drug. Tumor production by topical promotion with 12-O-tetradecanoylphorbol-13-acetate was subsequently determined in 600 female NMRI mice using intervals of 4, 8, 16, 24, 32 and 40 weeks between initiation and promotion. Independent of the delay between the initiating and promoting step, we observed a similar time course and extent of tumor production in the different experimental groups. This indirectly proves that the promoting capacity of 12-O-tetradecanoylphorbol-13-acetate is age-independent and that during aging no substantial loss of initiated cells occurs in mouse epidermis.