Phase II clinical trials aim to potentially screen out ineffective and identify effective therapies to move forward to randomized phase III trials. Single-arm studies remain the most utilized design in phase II oncology trials, especially in scenarios where a randomized design is simply not practical. Due to concerns regarding excessive toxicity or ineffective new treatment strategies, interim analyses are typically incorporated in the trial, and the choice of statistical methods mainly depends on the type of primary endpoints. For oncology trials, the most common primary objectives in phase II trials include tumor response rate (binary endpoint) and progression disease-free survival (time-to-event endpoint). Interim strategies are well-developed for both endpoints in single-arm phase II trials. The advent of molecular targeted therapies, often with lower toxicity profiles from traditional cytotoxic treatments, has shifted the drug development paradigm into establishing evidence of biological activity, target modulation and pharmacodynamics effects of these therapies in early phase trials. As such, these trials need to address simultaneous evaluation of safety as well as proof-of-concept of biological marker activity or changes in continuous tumor size instead of binary response rates. In this dissertation, we extend a predictive probability design for binary outcomes in the single-arm clinical trial setting and develop two interim designs for continuous endpoints, such as continuous tumor shrinkage or change in a biomarker over time. The two-stage design mainly focuses on the futility stopping strategies, while it also has the capacity of early stopping for efficacy. Both optimal and minimax designs are presented for this two-stage design. The multi-stage design has the flexibility of stopping the trial early either due to futility or efficacy. Due to the intense computation and searching strategy we adopt, only the minimax design is presented for this multi-stage design. The multi-stage design allows for up to 40 interim looks with continuous monitoring possible for large and moderate effect sizes, requiring an overall sample size less than 40. The stopping boundaries for both designs are based on predictive probability with normal likelihood and its conjugated prior distributions, while the design itself satisfies the pre-specified type I and type II error rate constraints. From simulation results, when compared with binary endpoints, both designs well preserve statistical properties across different effect sizes with reduced sample size. We also develop an R package, PPSC, and detail it in chapter four, so that both designs can be freely accessible for use in future phase II clinical trials with the collaborative efforts of biostatisticians. Clinical investigators and biostatisticians have the flexibility to specify the parameters from the hypothesis testing framework, searching ranges of the boundaries for predictive probabilities, the number of interim looks involved and if the continuous monitoring is preferred and so on.

Instream structures are used to reinforce channel margins, redirect flows, and create habitat, but there is little consensus about their design or whether they function as intended. In this study, 536 instream structures in the state of Maryland were assessed to determine the effect of structure-, project-, and watershed-scale factors on performance. Structures were assessed using a 19 point scoring system based on structural stability, sediment transport, and overall function. Structure-scale variables related to the construction, geometry, and placement, and differed for six structure families: bank protection (BP), full and partial span vanes (FSV), constructed riffles (RF), regenerative stream conveyances, and step pools. Project- and watershed-scale variables related to flow, erosion resistance, and design approach. Relationships between structure scores and explanatory variables were evaluated using regression analysis. Structure performance was strongly influenced by the individual project, suggesting that design quality, construction, and maintenance are as important as specific design features. Structure durability decreased if there was additional urban development following construction. Results also indicated that restoration activities have a "protective effect" on nearby structures. For rock BP, imbricated rock walls performed better than stone toe, due to increased structure height and boulder size. Rock FSVs that were keyed into the bank at angles between 35° and 90° were more durable, while RFs performed best when constructed using downstream grade control and increased substrate depth. The results of this study provide insight into design and project features that contribute to structure success. / Master of Science / Stream restoration aims to rehabilitate streams that have been impacted by humans, and log or rock structures in the channel are utilized to protect the bed and banks, redirect water away from the banks, and create habitat for aquatic organisms. However, there are few design standards for these structures. In this study, 536 instream structures in the state of Maryland were assessed to determine the effect of design and site characteristics on performance. Structures were scored for performance based on structural stability, sedimentation, erosion, and function. Design characteristics related to structure construction and placement, while site conditions related to the project and watershed characteristics. Statistical analyses were used to determine the relationship between structure performance and design and site characteristics. Structure performance was strongly influenced by the restoration project, indicating that design quality, construction, and maintenance are as important as specific design features. Structure durability decreased if there was additional urban development in the watershed following construction. Results also indicated that when structures were used in series, there was a "protective effect" on other nearby structures. Rock walls performed better as height increased, while rock weirs that were constructed into the streambank between 35° and 90° were more durable. These results provide insight into design and project features that contribute to structure success.