RESUMEN
In this paper, we propose two new methods for computing confidence intervals for the difference of two independent binomial proportions in small sample cases. Several test-based exact confidence intervals have been developed to guarantee the nominal coverage probability in small sample cases. However, these methods are sometimes unnecessarily too conservative because they use the exact p-value for constructing confidence intervals by maximizing the tail probability to account for the worst configuration. In order to reduce conservatism, our new methods adopt the p-value weighted by two types of functions instead of the maximum p-value. Our proposed methods can be regarded as quasi-exact methods. The performance evaluation results showed that our methods are much less conservative than the exact method. Compared with other existing quasi-exact methods, generally, our methods possess coverage probabilities closer to the nominal confidence level and shorter expected confidence widths. In particular, the beta weighing method provides the most reasonable balance between accurate coverage probability and short interval width in small sample cases.
Asunto(s)
Distribución Binomial , Intervalos de Confianza , Tamaño de la Muestra , Ensayos Clínicos como Asunto/estadística & datos numéricos , Humanos , Modelos Estadísticos , Proyectos de InvestigaciónRESUMEN
We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) (p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) (p = 0.049), severe appetite loss (p = 0.011), and high serum levels of carbohydrate antigen 19-9 (p = 0.019) and C-reactive protein (p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK (p = 0.007) and pAkt (p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.
RESUMEN
Global clinical studies conducted in various countries and regions are increasing. Race and extrinsic ethnic factors are key covariates that may affect the pharmacokinetics (PK), efficacy, and safety of the drug. Genetic similarity among East Asian populations has been confirmed; thus, PK, efficacy, and safety in these populations are expected to be similar, but this has not been confirmed. This study presents a comparison of PK and safety among East Asians from clinical studies sponsored by Pfizer. Four compounds with different characteristics, including mechanism of actions and PK profiles, were selected, and retrospective PK and safety comparisons in East Asians were conducted. No distinct differences were observed in PK and safety across the 4 compounds. These results are consistent with previous reports on PK comparisons and meet the expectations based on genetic similarity among East Asians. Extrapolation of these findings to other compounds should be done with caution, but these results should support the consideration of mutual use of clinical data among East Asian countries.