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Clinical Trials
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
If a relevant level of efficacy is found in phase II, and no special toxicity concerns have been identified, the drug is ready for phase III – that is, a randomized trial comparing the new drug to placebo or standard treatment for the indication pursued. The gold standard for phase III trials is a randomized, double-blind, placebo-controlled and multicentre trial. Randomization means that the subjects are randomly assigned either to the experimental arm or to the standard/placebo arm. Double-blind means that neither the investigator/doctor nor the subject knows whether he or she is receiving the investigational drug or placebo/standard treatment. Placebo is an inactive substance that has been prepared in the same format as the investigational drug, and in such a way that it is impossible to know whether it contains the active substance or not. To include several centres in a trial is a way to minimize bias in patient selection, patient management, and so forth, that may otherwise differ between different sites/hospitals/countries in a way that may affect outcomes. The number of subjects required to prove a difference between the control arm and the experimental arm depends on how large the difference is between the two – the larger the difference the smaller the sample size required to prove it. Phase III trials generally include hundreds or even thousands of subjects.
Clinical Trials: the Statistician's Role
Published in Trevor F. Cox, Medical Statistics for Cancer Studies, 2022
Phase III trials are confirmatory trials that try to establish if one treatment is more efficacious than another. They can be two arm or multi-arm. They provide more information on adverse events and reactions, as well as subjects' quality of life. These are superiority trials, but sometimes Phase III trials are run to test whether a treatment is unacceptably less efficacious than another treatment (non-inferiority trial), or run to see whether a treatment has no better, nor worse efficacy than another treatment (equivalence trial).
The Great Influenza
Published in Rae-Ellen W. Kavey, Allison B. Kavey, Viral Pandemics, 2020
Rae-Ellen W. Kavey, Allison B. Kavey
Two universal vaccines are in clinical trials: on February 12, 2019, a team from the University of Wisconsin announced preliminary results from a successful Phase II trial of its nasal flu vaccine M2SR (Redee Flu). The vaccine is based on a novel approach to prevent replication of the influenza virus in humans, by introducing a live virus that cannot replicate but triggers a robust immune response ensuring broad protection.84 The results of Phase III trials are pending.
An evaluation of roxadustat for the treatment of anemia associated with chronic kidney disease
Published in Expert Opinion on Pharmacotherapy, 2022
Yu Kurata, Tetsuhiro Tanaka, Masaomi Nangaku
In conclusion, roxadustat is non-inferior to ESAs for the treatment of anemia in patients with CKD and has already been approved and introduced to the market in some countries. However, the results of phase III trials have raised some concerns about its safety, and appropriate use is essential. Since HIF-PHIs have been approved and used in clinical practice in Asian countries ahead of the rest of the world, recommendations for the appropriate use of HIF-PHI have been issued by the Asian Pacific Society of Nephrology (APSN) [91]. Especially for a drug with multifaceted effects such as roxadustat, the results of pre-approval clinical trials alone are insufficient to assess its safety. Continuous data collection is imperative, and post-marketing surveillance is already ongoing in Japan (NCT04408820).
Re-Analyzing Phase III Bremelanotide Trials for “Hypoactive Sexual Desire Disorder” in Women
Published in The Journal of Sex Research, 2021
The present analysis is limited in several ways. First, only two Phase III trials of bremelanotide were analyzed. Perhaps additional trials of bremelanotide would yield differing results. There is at least one other placebo-controlled trial of bremelanotide from an earlier phase in its development (Clayton et al., 2016). However, as a) FDA considers phase III trials to be “pivotal” in determining whether to approve a drug, b) usable data from the FDA NDA from the phase III (but not earlier phase) trials are available, and c) the phase II trial included women with DSM-IV diagnoses of female sexual arousal disorder, whereas Kingsberg et al. (2019) excluded participants with any female sexual dysfunction other than HSDD, only the two phase III trials were included in the current re-analysis. Nonetheless, the Phase II trial is briefly described for the sake of completeness (Clayton et al., 2016). The study used three different dosages, with one group receiving the 1.75 mg dose later used in the Phase III trials. Seven protocol-specified outcomes were listed in the study’s clinicaltrials.gov entry (Palatin Technologies, 2014), three of which were not reported in the Clayton et al. (2016) article. A subset of outcomes were reported among participants with either an exclusive or primary HSDD diagnosis. Briefly, for the 1.75 mg dose, Clayton et al. found statistically significant efficacy for bremelanotide on three of five reported outcomes among patients with either an exclusive or primary HSDD diagnosis.
Treatment of recurrent glioblastoma: state-of-the-art and future perspectives
Published in Expert Review of Anticancer Therapy, 2020
Vincenzo Di Nunno, Enrico Franceschi, Alicia Tosoni, Monica Di Battista, Lidia Gatto, Cinzia Lamperini, Santino Minichillo, Antonella Mura, Stefania Bartolini, Alba A. Brandes
Of note, statistical design of this study was planned through a screening design aimed to assess whether regorafenib showed more probability to improve overall survival compared to lomustine. This means that this phase II study was not powered enough to estimate an effective advantage in OS but was aimed at a preliminary assessment of regorafenib efficacy. Authors adequately specify this issue and concluded that regorafenib showed promising efficacy in patients with recurrent glioblastoma but a phase III trial is needed to confirm this benefit. In addition, some concerns about regorafenib efficacy are related to previous reports in which regorafenib failed to show a significant clinical improvement as well as to the short OS observed with lomustine, which is significantly different from what observed in other clinical trials [88]. Novel systemic agents are under investigation. Randomized phase III trials are currently assessing the role of different approaches. (Table 2).