At the conclusion of the clinical trial, the regimen will be declared active or inactive. Optimal twostage designs for phase ii clinical trials. Mostly these trials are conducted in a twostage design with a futility threshold speci. Clinical trial design elizabeth ness, rn, ms nurse consultant education center for cancer research, nci agenda types of clinical trials clinical trial design general principles and terminology phase i iii clinical trial designs types of clinical trials clinical trials prevention screening early detection diagnostic imaging qol. A multiarm multistage clinical trial design for binary. An evaluation of a simon 2stage phase ii clinical trial design incorporating toxicity monitoring article in contemporary clinical trials 323. For the minimax twostage design to attain 90% power at the significance level of 0. It contains functions for designing studies such as simon. In a twostage design, the patients are divided into two groups or stages.
Twostageintroduction stage design in phase ii clinical trial. Optimal two stage designs for phase ii clinical trials. Nov 22, 2016 optimal two stage designs for phase ii clinical trials richard simon, controlled clinical trials 10. Clinical trial design elizabeth ness, rn, ms nurse consultant education center for cancer research, nci agenda types of clinical trials clinical trial design general principles and terminology phase i. Balanced twostage designs for phase ii clinical trials. Deepdyve is the easiest way to get instant access to the academic journals you need. Advanced designs of cancer phase i and phase ii clinical trials. Usual methodology of cancer phase ii trials consists in testing the null hypothesis. The standard rate is assumed to be p 0 under the null hypothesis i. In choosing an appropriate 2 stage design to use, study investigators have two sets of decisions to make. Clinical trial design and data analysis functions rdrr.
Phase ii clinical trials determine whether a drug or regimen has sufficient activity against disease to. An adaptive simon twostage design for phase 2 studies of. This program generates simons admissible twostage designs simon, 1989. Operating characteristics of a simon twostage phase ii. Gehans and simons designs have two stages, flemings designs can have two or more stages, and ensigns threestage design combines the first stage of gehan. Deepdyve is the easiest way to get instant access to the.
Seamless phase iiiii trial design phases ii and iii are interwoven into a single trial. For phase ii oncology trials, simons twostage design is the most. Deepdyve is the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Package clinfun april, 2018 title clinical trial design and data analysis functions version 1. In cases where there are few, or no effective therapies, p 1 is generally chosen to be 20%, the conventional lower bound for a promising response rate.
The most common type of trial design is the simon 2 stage design ye and shyr, 2007 with the primary assumption of a homogeneous population. Screened selection design for randomised phase ii oncology. In phase ii clinical trial, randomized design is proposed to establish the sample size for the study to obtain the treatment with greatest response rate for further phase iii study. Twostage designs optimal under the alternative hypothesis. If the number of responders is above a critical value in the. Ray and rai expanded the concept to allow for continuous toxicity monitoring during a phase ii clinical trial based on the simon 2 stage design.
A small group of patients are enrolled in the first stage. Optimal twostage designs in phaseii clinical trials. Usual methodology of cancer phase ii trials consists in testing the null hypothesis 0 versus 1. Simons twostage design with unknown stage 1 stopping. Innovative trial designs to evaluate new treatment. A study proceeds to the second stage unless the null hypothesis, that the true. Bayesian twostage designs for phase ii clinical trials. Two stage simon, gehan designs allow trial to be terminated at end.
A reanalysis of one real phase ii clinical trials on metastatic cancer. Flemings twostage design this program generates flemings fleming, 1982 twostage designs for phase ii single arm clinical trials that are admissible similar to jung et al. Sample size tables for clinical studies, 3rd edition. Such trials are often conducted in a multiinstitution setting where designs of more than two stages are difficult to manage. Simon 8 proposed two designs for this type of trial. The simon twostage optimal design is often used for phase ii cancer clinical trials. All patients are followed up for longterm endpoints.
The primary objective of a phase ii clinical trial of a new drug or regimen is to determine whether it has sufficient biological activity against the disease under study to warrant more extensive development. A rescue strategy for handling unevaluable patients in simons. The primary objective of a phase ii clinical trial of a new drug or regimen is to determine whether it. Robustness of oddsratio in a stratified group sequential trial with binary outcome measure. Optimum and minimax designs for a range of design parameters are tabulated. Further discussion of the design and some concluding remarks are given in section 5. In a two stage design, the patients are divided into two groups or stages. The 2stage design incorporates an early termination point, which allows the investigator to discontinue patient accrual if a desired endpoint has not been. Seshan description utilities to make your clinical collaborations easier if not fun. Calculates optimal and minimax 2stage phase ii designs given by richard simon ph2simon. Optimal twostage designs for phase ii clinical trials sciencedirect.
Clinical trial design, phase i, phase ii, maximum tolerated dose mtd. The design approach considered here is to specify the parameters p0,pl,c. A singlestage design is estimated using flemings singlestage procedure with the exact binomial distribution fleming, 1982. The rapid enrollment design red for phase i trials. A hybrid geometric phase iiiii clinical trial design based on treatment failure time and toxicity peter f.
The primary objective of a phase ii clinical trial of a new drug or regimen is to. A study proceeds to the second stage unless the null hypothesis, that the true tumour response rate is below some specified value, is already accepted at the end of stage one. Single trial protocol with prespecified decision rules for regimen selection. Who who handbook for reporting results of cancer treatment book. For example, the first line in table 1 corresponds to a design with p0 0. A targeted design proposed by jones and holmgren jh jones cl, holmgren e.
Simons minimax and optimal and jungs admissible two. Pdf minimax and admissible adaptive twostage designs in phase. Example simons design dichotomous outcome usually in phase ii trial suppose that we want to test h0. Extending simons work, our algorithm allows the investigation. This lecture covers a very special form of phase ii clinical trials. This program generates simon s optimal twostage designs simon, 1989 and admissible designs from jung et al.
The literature on adaptive clinical trial design has focused on samplesize reestimation, changing the plan for interim analyses, or modifying randomization weights chow and chang 2007, muller and schafer 2001, rosenberger and lachin 1993, karrison, huo, and chappell 2003, and kim et al. A study proceeds to the second stage unless the null hypothesis, that the true tumour response rate is below some. Twostage designs optimal under the alternative hypothesis for. The design two stages the design could have more than two stages, but less practical and not used enroll n.
Exact p values for simons twostage designs in clinical trials. An adaptive simon twostage design for phase 2 studies of targeted therapies, contemporary clinical trials 28. Pdf multistage designs for phase ii clinical trials. An evaluation of a simon 2stage phase ii clinical trial. Phase ii twostage singlearm clinical trials for testing. Boundary problem in simons twostage clinical trial designs. In choosing an appropriate 2stage design to use, study investigators have two sets of decisions to make.
Clinical study design is the formulation of trials and experiments, as well as observational studies in medical, clinical and other types of research e. The 2 stage design incorporates an early termination point, which allows the investigator to discontinue patient accrual if a desired endpoint has not been achieved in the first stage of the trial. Flemings two stage design this program generates flemings fleming, 1982 two stage designs for phase ii single arm clinical trials that are admissible similar to jung et al. Twostage phase ii oncology designs using shortterm. For the minimax two stage design to attain 90% power at the significance level of 0. Simon s twostage design and the admissible twostage design have been commonly used in practice for singlearm phase ii clinical trials when the primary endpoint is binary. The simon two stage optimal design is often used for phase ii cancer clinical trials. These designs can also be used for pilot studies of new regimens where toxicity is. As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in phase ii efficiently select regimens for subsequent evaluation in largerscale phase iii trials. Phase ii clinical trials with timetoevent endpoints. The goal of a clinical study is to assess the safety, efficacy, and or the mechanism of action of an investigational medicinal product imp or.
Pdf background simons twostage design is the most widely implemented among multistage designs in phase ii clinical trials to assess the activity of. As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in phase ii efficiently select regimens for subsequent evaluation in larger. Regimens are selected for phase iii stage on the basis of an intermediate endpoint. Simon s like design with relaxed futility stopping. Exact p values for simons twostage designs in clinical. First, they have to define an appropriate p 1 and p 0. Optimal twostage designs for phase ii clinical trials richard simon, phd biometric research branch, national cancer institute, bethesda, maryland abstract. Randomized phase ii trial as an internal pilot to test response rates in standard clinical trial designs, the sample size is determined by the power at a given. The literature on adaptive clinical trial design has focused on samplesize reestimation, changing the plan for interim analyses, or modifying randomization weights chow and chang 2007, muller and. We propose the screened selection design ssd, which is a practical multi stage, randomised phase ii design for two experimental arms. The primary objective of a phase ii clinical trial of a new drug or regimen is to determine whether it has sufficient biological activity against the disease under study to warrant. A hybrid geometric phase iiiii clinical trial design based. Sample size tables for clinical studies pdf free download. They developed theoretical expressions for the power, nominal size, average sample size, and probability of early termination of the combined procedure.