Enrollment and Stopping Rules for Managing Toxicity in Phase II Oncology Trials with Delayed Outcome

Stopping rules for toxicity are routinely used in phase II oncology trials. If the follow-up for toxicity is long, it is desirable to have a stopping rule that uses all toxicity information available, not only information from patients with full follow-up. Further, to prevent excessive toxicity in such trials, an enrollment rule is needed. The enrollment rule informs an investigator about the maximum number of patients that can be enrolled depending on the current enrollment and all available information about toxicity. We give recommendations on how to construct Bayesian and frequentist.Doctor of Public Healt

Enrollment and Stopping Rules for Managing Toxicity Requiring Long Follow-Up in Phase II Oncology Trials

Monitoring of toxicity is often conducted in Phase II trials in oncology to avoid an excessive number of toxicities if the wrong dose is chosen for Phase II. Existing stopping rules for toxicity use information from patients who have already completed follow-up. We describe a stopping rule that uses all available data to determine whether to stop for toxicity or not when follow-up for toxicity is long. We propose an enrollment rule that prescribes the maximum number of patients that may be enrolled at any given point in the trial. Key words: Delayed outcome, Phase II oncology trial, Pocock boundary, Stopping rule, Enrollment rule

Comparing oncology clinical programs by use of innovative designs and expected net present value optimization:which adaptive approach leads to the best result?

Designing an oncology clinical program is more challenging than designing a single study. The standard approaches have been proven to be not very successful during the last decade; the failure rate of Phase 2 and Phase 3 trials in oncology remains high. Improving a development strategy by applying innovative statistical methods is one of the major objectives of a drug development process. The oncology sub-team on Adaptive Program under the Drug Information Association Adaptive Design Scientific Working Group (DIA ADSWG) evaluated hypothetical oncology programs with two competing treatments and published the work in the Therapeutic Innovation and Regulatory Science journal in January, 2014. Five oncology development programs based on different Phase 2 designs, including adaptive designs, and a standard two parallel arm Phase 3 design were simulated and compared in terms of the probability of clinical program success and expected Net Present Value (eNPV). In this article we consider eight Phase2/Phase3 development programs based on selected combinations of five Phase 2 study designs and three Phase 3 study designs. We again used the probability of program success and eNPV to compare simulated programs. For the development strategies we considered, the eNPV showed robust improvement for each successive strategy, with the highest being for a three-arm response adaptive randomization design in Phase 2 and a group sequential design with 5 analyses in Phase 3

Mathematical Model Based on BP Neural Network Algorithm for the Deflection Identification of Storage Tank and Calibration of Tank Capacity Chart

The tank capacity chart calibration problem of two oil tanks with deflection was studied, one of which is an elliptical cylinder storage tank with two truncated ends and another is a cylinder storage tank with two spherical crowns. Firstly, the function relation between oil reserve and oil height based on the integral method was precisely deduced, when the storage tank has longitudinal inclination but has no deflection. Secondly, the nonlinear optimization model which has both longitudinal inclination parameter α and lateral deflection parameter β was constructed, using cut-complement method and approximate treatment method. Then the deflection tank capacity chart calibration with a 10 cm oil level height interval was worked out. Lastly, the tank capacity chart was corrected by BP neural network algorithm and got proportional error of theoretical and experimental measurements ranges from 0% to 0.00015%. Experimental results demonstrated that the proposed method has better performance in terms of tank capacity chart calibration accuracy compared with other existing approaches and has a strongly practical significance

Effect of Drought and Topographic Position on Depth of Soil Water Extraction of <i>Pinus sylvestris</i> L. var. <i>mongolica</i> Litv. Trees in a Semiarid Sandy Region, Northeast China

Drought and topographic position are the most important factors influencing tree growth and survival in semiarid sandy regions of Northeast China. However, little is known about how trees respond to drought in combination with topographic position by modifying the depth of soil water extraction. Therefore, we identified water sources for 33-year-old Mongolian pine (Pinus sylvestris L. var. mongolica Litv.) trees growing at the top and bottom of sand dunes by comparing stable isotopes &#948;2H and &#948;18O in twig xylem water, soil water at various depths and groundwater during dry and wet periods. Needle carbon isotope composition (&#948;13C) was simultaneously measured to assess water use efficiency. Results showed that when soil moisture was low during the dry period, trees at the top used 40&#8722;300 cm soil water while trees at the bottom utilized both 40&#8722;300 cm soil water and possibly groundwater. Nevertheless, when soil moisture at 0&#8722;100 cm depth was higher during the wet period, it was the dominant water sources for trees at both the top and bottom. Moreover, needle &#948;13C in the dry period were significantly higher than those in the wet period. These findings suggested that trees at both the top and bottom adjust water uptake towards deeper water sources and improve their water use efficiency under drought condition. Additionally, during the dry period, trees at the top used shallower water sources compared with trees at the bottom, in combination with significantly higher needle &#948;13C, indicating that trees at the bottom applied a relatively more prodigal use of water by taking up deeper water (possibly groundwater) during drought conditions. Therefore, Mongolian pine trees at the top were more susceptible to suffer dieback under extreme dry years because of shallower soil water uptake and increased water restrictions. Nevertheless, a sharp decline in the groundwater level under extreme dry years had a strong negative impact on the growth and survival of Mongolian pine trees at the bottom due to their utilization of deeper water sources (possibly groundwater)