Sample Size Calculation in Oncology Trials: Quality of Reporting and Implications for Clinical Cancer Research.

OBJECTIVES: Sample size calculation (SSC) is a pivotal step in clinical trial conception and design. Herein, we describe the frequency with which oncology phase III trials report the parameters required for SSC. MATERIALS AND METHODS: We systematically searched for phase III trials published in 6 leading journals, which were accompanied by editorials from January 2008 to October 2011. Two blinded investigators extracted required and optional parameters for SSC according to the primary endpoint. RESULTS: We retrieved 140 eligible phase III trials. The median target sample size was 596 subjects (50 to 40,000); in 66.4% of cases, the number of enrolled subjects was at least 90% of the target. The primary endpoint was a continuous variable in 5.7%, categorical in 30.0%, and a time-to-event variable in 64.3% of phase III trials. Although nearly 80% reported a target sample size, only 27.9% of the trials provided all the required parameters for proper SSC. The most commonly reported parameters for sample size computation were α (93.6%) and ß (90.7%) errors. The parameters least reported were the expected outcomes in the control or experimental groups, each provided in only 57.9% of trials. CONCLUSIONS: The quality of SSC reporting in phase III cancer trials is poor. Such incomplete reporting may compromise future study designs, pooling of data, and interpretation of results. Lack of transparency in SSC reporting may also have ethical implications.

Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2.

PURPOSE: To compare single-agent pemetrexed (P) versus the combination of carboplatin and pemetrexed (CP) in first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2. PATIENTS AND METHODS: In a multicenter phase III randomized trial, patients with advanced NSCLC, ECOG PS of 2, any histology at first and later amended to nonsquamous only, no prior chemotherapy, and adequate organ function were randomly assigned to P alone (500 mg/m(2)) or CP (area under the curve of 5 and 500 mg/m(2), respectively) administered every 3 weeks for a total of four cycles. The primary end point was overall survival (OS). RESULTS: A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011. The response rates were 10.3% for P and 23.8% for CP (P = .032). In the intent-to-treat population, the median PFS was 2.8 months for P and 5.8 months for CP (hazard ratio [HR], 0.46; 95% CI, 0.35 to 0.63; P < .001), and the median OS was 5.3 months for P and 9.3 months for CP (HR, 0.62; 95% CI, 0.46 to 0.83; P = .001). One-year survival rates were 21.9% and 40.1%, respectively. Similar results were seen when patients with squamous disease were excluded from the analysis. Anemia (grade 3, 3.9%; grade 4, 11.7%) and neutropenia (grade 3, 1%; grade 4, 6.8%) were more frequent with CP. There were four treatment-related deaths in the CP arm. CONCLUSION: Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.

Soroconversäo da vacina tríplice viral em crianças de 9 e 15 meses de idade / Soroconversion of the MMR vaccine in childrens at 9 and 15 month

A resposta sorológica à vacina tríplice viral foi avaliada em 109 crianças de nove meses de idade, sem história prévia de vacinaçäo contra sarampo, e em 98 crianças de 15 meses de idade, que comprovadamente receberam a vacina monovalente contra o sarampo aos nove meses. A vacina trivalente utilizada continha as seguintes cepas de vírus do sarampo, cepa Urabe Am9 de vírus da caxumba e cepa Wistar RA 27/3 de vírus da rubéola. Um número significantemente maior de crianças do grupo de 15 meses de idade apresentava anticorpos pré-vacinais contra sarampo e caxumba. As taxas de soroconversäo para o sarampo, caxumba e rubéola foram elevadas em ambos os grupos, nä havendo diferenças estatisticamente significantes entre os mesmos. Os títulos de anticorpos pós-vacinais contra a rubéola foram significantemente mais elevados no grupo de crianças de 15 meses de idade. Nenhum evento adverso sério imputável à vacinaçäo foi ibservado.