1,721,135 research outputs found
OVERRUNNING DATA METHODS: COMPARISONS BASED ON REAL DATA TRIALS
No full textIntroduction. Sequential trial designs foresee one or more interim analyses (IA) before the full sample size has been reached. Such IA has the primary purpose to terminate the trial when futility or superiority of one of the interventions becomes clear, according to pre-specified stopping rules. Overrunning occurs when data continue to be collected also if a stopping criterion has been reached. Overrunning data collected according to the trial protocol are considered valid and should be included in the analyses but they could influence the results and change the conclusions. Over the years many proposals to deal with overrunning were proposed. Deletion method includes overrunning data, ignoring the interim analysis that has led to the stopping of the trial. The methods of combining p-values rely on the idea to make two different analyses, one on the sequential portion of the data and one on the overrunning part, and to combine them by weighting their p-values. The repeated confidence interval approach is a further alternative to adopt for the overrunning problem.
Objective. Comparing different methods for overrunning under a variety of data generating mechanisms.
Methods. Two real clinical trials are considered as motivating examples. The first trial was designed to test superiority assuming response rates (death) for Test and Reference treatment respectively of 9% and 15% and a power of 90%. The second trial was designed assuming response rates for Test and Reference drug respectively of 50% and 45%, a non-inferiority margin of 15% and a power of 80%. Both the trial designs considered also O’Brien and Fleming stopping criteria for three IAs and 2.5% one-sided significance levels. These motivating examples are used as base for simulation studies.
Results. Preliminary results show similar behaviors for deletion and combining p-values methods. Repeated confidence interval approach show null hyphothesis refusal rates of 1-2% smaller in some of the considered simulation scenarios.
Conclusion. Repeated confidence interval approach seems to be the most conservative method
Surrogate endpoints of clinical benefit
No full textMeasurement of solid tumor response to treatment relies mainly on imaging. WHO tumor response criteria and, more recently, RECIST (response evaluation criteria in solid tumors) have provided means to objectively measure tumor response in clinical trials with imaging. These guidelines have been rapidly adopted in clinical practice to monitor patient treatment and for therapy planning. However, relying only on anatomical information is not always sufficient when evaluating new drugs that will reduce a tumor's functionality while preserving its size. Finding more reliable and reproducible measures of tumor response is one of the most important and difficult challenges facing modern radiology as it requires an entirely new approach to imaging. The aim of this book is to address the assessment of response to treatment by adopting a multidisciplinary perspective, just as occurs in real life in a comprehensive cancer center. Oncologists and imaging experts consider two cancer models, locally advanced disease and metastatic disease, jointly exploring both conventional and advanced means of measuring response to standard treatment protocols and new targeted therapies
Muscle tenderness in different types of facial pain and its relation to anxiety and depression: A cross-sectional study on 649 patients
No full textTo evaluate in patients with different types of facial pain the association between muscle tenderness and a set of characteristics, 649 consecutive outpatients with facial myogenous pain (MP), TMJ disorder, neuropathic pain (NP) and facial pain disorder (FPD) (DSM-IV) were enrolled. For each patient a psychological assessment on the Axis 1 of the DSM-IV and standardized palpation of pericranial and cervical muscles were carried out. A pericranial muscle tenderness score (PTS), a cervical muscle tenderness score (CTS) and a cumulative tenderness score (CUM, range 0-6) were calculated. Univariate analyses (one-way analysis of variance or chi(2) test) indicated that both age- and sex-distribution, tenderness scores and prevalence of psychiatric disorders markedly differed between groups. The prevalence of depression was highest in FPD patients (44.9%). Both muscle tenderness scores (either PTS or CTS) and prevalence of anxiety were higher in patients with MP than in those with TMJ or NP. To assess associations between CUM score and patients' demographic and clinical characteristics an ordered logit model was fit and interactions between psychiatric disorders and diagnostic groups were tested. The analysis showed that, regardless of the diagnostic group, anxiety and depression independently increase the likelihood of having one point higher muscle tenderness score (OR=1.55, 95% CI: 1.13-2.12 and OR=1.56, 95% CI: 1.10-2.21, respectively). A careful screening for the presence of an underlying psychiatric disorder, either anxiety or depression, should be part of the clinical evaluation in patients suffering from facial pain
Alta concordanza e alta prevalenza: il paradosso del Kappa di Cohen
No full textLa statistica Kappa di Cohen è la misura di concordanza maggiormente utilizzata in letteratura. In alcuni casi però la statistica risulta essere affetta da un fastidioso paradosso. Questo paradosso fa sì che la statistica Kappa venga stimata in maniera distorta, assumendo valori che spesso portano a sottostimare e quindi a trarre conclusioni errate sulla reale concordanza presente nei dati. Una possibile soluzione a questo problema è rappresentata dalla statistica AC1 di Gwet, una misura di concordanza alternativa alla Kappa che si dimostra maggiormente robusta al paradosso. Un esempio su dati reali verrà utilizzato per illustrare gli effetti del paradosso e le caratteristiche della statistica AC
Computing hospitalization rates in presence of repeated events: impact and countermeasures to avoid misinterpretation
No full textRATIONALE, AIMS AND OBJECTIVES:
The admission rate, including both first and recurrent events, is a clear overall measure of hospital utilization, its variability accounting for individual propensity to disease recurrence.
METHOD:
In this paper, we compared two variance estimators derived from the Poisson and negative binomial distribution of directly and indirectly age/gender-standardized hospitalization rates allowing for multiple events. The latter approach accommodates departures from the assumption of randomness of repeated events required by the Poisson distribution. We apply these methods to a retrospective cohort based on hospital discharge data in 2001 of Piedmont (north-western Italy) residents.
RESULTS:
Estimated standard errors under the negative binomial for both directly and indirectly standardized rates result in almost twice those under the Poisson distribution.
CONCLUSION:
Our analysis confirms that ignoring the typical non-random nature of repeated events underestimates the true variance of rates and can lead to biased optimistic interpretation of study results
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