Design considerations in clinical trials with cure rate survival data: A case study in oncology.

For clinical trials with time-to-event as the primary endpoint, the clinical cutoff is often event-driven and the log-rank test is the most commonly used statistical method for evaluating treatment effect. However, this method relies on the proportional hazards assumption in that it has the maximal power in this circumstance. In certain disease areas or populations, some patients can be curable and never experience the events despite a long follow-up. The event accumulation may dry out after a certain period of follow-up and the treatment effect could be reflected as the combination of improvement of cure rate and the delay of events for those uncurable patients. Study power depends on both cure rate improvement and hazard reduction. In this paper, we illustrate these practical issues using simulation studies and explore sample size recommendations, alternative ways for clinical cutoffs, and efficient testing methods with the highest study power possible.

Design of adaptive two-stage double-arm clinical trials for dichotomous variables.

It is well known that flexibility is one of the major advantages of an adaptive two-stage design, and the intended adaptation should be as preplanned as possible to maintain the integrity of the clinical trial. The design of adaptive two-stage double-arm clinical trials for dichotomous variables was proposed by simulation and forecasting procedure at the planning stage. To further ensure the integrity of the clinical trial, the sample size scheme for each scenario, which was supposed to be based on the first stage, was provided in the protocol by Monte Carlo simulation. In addition, the study parameters were determined by comparing the assessment indexes such as total sample size, expected sample size and the test power at the first stage. Furthermore, Fisher's combination test and pooled data analysis were considered and compared through the simulation. The latter, which has the larger overall power and the better overall type I error control, with the same sample size was adopted for further simulation and statistical analysis in the clinical trial.

Comparative proteome analysis of serum from acute pulmonary embolism rat model for biomarker discovery.

Pulmonary embolism (PE) is a common, potentially fatal disease and its diagnosis is challenging because clinical signs and symptoms are nonspecific. In this study, to investigate protein alterations of a rat PE model, total serum proteins collected at different time points were separated by two-dimensional electrophoresis (2-DE) and identified using matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Bioinformatics analysis of 24 differentially expressed proteins showed that 20 had corresponding protein candidates in the database. According to their properties and obvious alterations after PE, changes of serum concentrations of Hp, Fn, DBP, RBP, and TTR were selected to be reidentified by western blot analysis. Semiquantitative RT-PCR showed DBP, RBP, and TTR to be down-regulated at mRNA levels in livers but not in lung tissues. The low serum concentrations of DBP, RBP, and TTR resulted in the up-regulation of 25(OH)D3, vitamin A, and FT4 (ligands of DBP, RBP, and TTR) after acute PE in rat models. The serum levels of Hp and Fn were detected in patients with DVT/PE and controls to explore their diagnostic prospects in acute PE because the mRNA levels of Hp and Fn were found to be up-regulated both in lung tissues and in livers after acute PE. Our data suggested that the concentration of serum Fn in controls was 79.42 +/- 31.57 microg/L, whereas that of PE/DVT patients was 554.43 +/- 136.18 microg/L (P < 0.001), and that the concentration of serum Hp in controls was 824.37 +/- 235.24 mg/L, whereas that of PE/DVT patients was 2063.48 +/- 425.38 mg/L (P < 0.001). The experimental PE rat model selected in this study was more similar to the clinical process than the other existing PE animal models, and the findings indicated instant changes of serum proteins within 48 h after acute PE. The exploration of these differentially expressed proteins or their combination with existent markers such as D-dimer may greatly improve the accuracy of the diagnosis of acute PE, but diagnostic tests are still needed to evaluate the sensitivity and specificity of these markers and also the number of false positives and false negatives.

Body mass index of male youths aged 18-20 years of the Han nationality living in different regions of China.

The study was conducted to assess the nutritional status and levels of body mass index (BMI, kg/m2) and to evaluate the geographical distribution of male youths of the Han nationality in China. In total, 60,773 male youths, aged 18-20 years, of the Han nationality, were categorized into underweight, normal-weight, overweight, and obesity according to the international adult BMI cut-offs. Different levels of nutritional status and BMI of male youths of the Han nationality were compared among different areas. The mean BMI for the whole country was 20.6 in urban areas and 20.0 in rural areas. BMI increased from 20.1 among 18-year old youths to 20.5 among 20-year old youths. The prevalence of underweight among the male youths was 21.6%, while the prevalence of overweight and obesity were 4.6% and 0.6% respectively. For urban youths, the prevalence of underweight, overweight, and obesity were 21.0%, 6.8%, and 1.1% respectively, while these were, respectively, 21.9%, 3.3%, and 0.3% for rural youths. The nutritional status of the male youths in North-China was at the highest level (21.1) among the six areas, and the prevalence of underweight, overweight, and obesity were 14.3%, 9.1%, and 1.4% respectively. The highest prevalence of underweight was 29.8% in the North-West region, and the lowest prevalence of overweight was 2.2% in the South-Middle region, while the lowest prevalence of obesity was 0.2% in the South-West region. The nutritional status of the male youths was significantly different among different areas. Underweight was still prevalent in all male youth groups. Nonetheless, overweight was more prevalent among urban youths than among rural youths and was more prevalent in the North region than in the South region.

Chinese literature associated with diagnosis of Helicobacter pylori.

AIM: To synthetically analyze and probe into the diagnosis of H pylori infection, we followed the principles of evidence-based medicine. METHODS: A total of 22 papers of prevalence survey and case-control studies were selected for studying about diadynamic methods. Using meta-analysis, we analyzed the different diadynamic methods of H pylori in China. RESULTS: Through meta-analysis, among the five diadynamic methods, the accuracy of polymerase chain reaction (PCR) was the highest (98.47%) and PCR was the most sensitive method (Sp: 99.03%). CONCLUSION: Among the five diadynamic methods, the accuracy of PCR is the highest and PCR is the most sensitive method to diagnose the infection of H pylori.

[Meta-analysis on Helicobacter pylori infection between sex and in family assembles].

OBJECTIVE: To understand and analyze the infection situation of Helicobacter pylori (H. pylori). METHODS: Extensively reviewing Chinese literature collecting the related with electronic documents in combination with manual retrieve and using Meta-analysis to do a quantitative analysis. RESULTS: Slight difference in the infection rate of H. pylori between men and women (95% CI: 0.0579-0.0963) was noticed. The infection rate of H. pylori in children whose parent was positive with infection of this bacteria was higher than that of children whose parent was negative (95% CI: 0.3378-0.5042). CONCLUSION: The infection rate of H. pylori showed gender difference with nature of family aggregation. Epidemiological studies of H. pylori was comprehensive and involved many aspects. Further investigation needs to be focused on infection rate and other risk factors.