Pharmacokinetic-Pharmacodynamic Modeling in Drug Development: Comments and Applications
Hartmut Derendorf, Günther Hochhaus in Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Phase IV trials are generally considered to be those conducted after FDA approval. From a regulatory standpoint, activities listed in Figure 1, including adverse reaction reporting during actual use, surveys and sampling, and inspections, are activities that occur after FDA approval. From a drug industry standpoint, phase IV studies include those studies after approval to (1) explore new indications for an approved compound, (2) explore the feasibility of new routes of delivery or new delivery systems, (3) establish the utility of the compound compared to other treatment modalities, or (4) support the safe and optimal use of the compound. In other words, phase IV studies are designed to answer those questions raised by earlier developmental efforts which remain unanswered, answer those questions which can only be answered through wider use of the compound, or answer new questions about the use of the compound which arise after approval.
100 MCQs from Dr. Guy Molyneaux and Colleagues
David Browne, Selena Morgan Pillay, Guy Molyneaux, Brenda Wright, Bangaru Raju, Ijaz Hussein, Mohamed Ali Ahmed, Michael Reilly in MCQs for the New MRCPsych Paper A, 2017
Drug development takes place in defined phases, which include the pre-clinical research and development phase (where experiments are carried out on cell cultures and animals) and the clinical phases I-IV (where experiments are carried out in humans). Phase I clinical trials are carried out on drug company premises or within a contract research organisation and include a small number of healthy volunteers to determine safety and correct dose. Phase II studies examine the drug’s efficacy, and are usually carried out as placebo-controlled, double-blind trials in the patient population. In Phase III, typically one or two doses of the drug are examined in thousands of patients over prolonged periods of time to further establish efficacy and to screen for uncommon side effects. Pharma companies can then apply for licence with the relevant government authority. Phase IV trials are carried out after the drug is marketed, to extend knowledge about side effects and to possibly extend the target indications. (26, pp 78–83)
Designing and Running a Clinical Trial
Trevor F. Cox in Medical Statistics for Cancer Studies, 2022
We now concentrate on clinical trials giving a brief overview of trial set up and the running of a trial. Clinical trials are generally categorised into four phases. These are, Phase I Trials are “first in man” trials. Drugs will have been developed in a laboratory and then tested on animals, before trying them out on humans. They involve a small number of subjects, often healthy volunteers.Phase II Trials are relatively small trials, generally ranging from 30 to 120 patients, that glean more information about the safety and efficacy of the drug or treatment being tested, and help set the dose level for a Phase III trial.Phase III Trials are confirmatory trials, in that they are designed to give a definitive answer to the hypothesis being tested, for example “Does this new cancer drug increase the median survival time of patients compared to the existing treatments?” A sample size of 500 to 1000 patients is not uncommon, with many centres involved in collecting the patient data.Phase IV Trials are run after a drug has been licenced to collect data on the long-term effects of the drug.
Patient-specific dose finding in phase I clinical trials
Published in Journal of Applied Statistics, 2018
Md. Moniruzzaman Moni, M. Iftakhar Alam
Clinical trials are controlled experiments conducted on human to evaluate toxicity and efficacy of new drugs. They usually proceed through four phases, namely phase I, II, III and IV, each with different objectives. Following pre-clinical and animal studies, phase I trial is the first experiment conducted on human, and it focuses on the safety of the drug. The primary interest of phase I trials is to identify the maximum tolerated dose (MTD). This is the dose with a toxicity probability closest to the pre-specified target value. Phase II trials are conducted at the MTD estimated from phase I trials to evaluate whether the new drug has sufficient activity and to refine knowledge of its toxicity profile. Phase III trials assess the effectiveness of the drug in comparison with the current standard treatments. Phase IV trials aim to detect any rare or long-term adverse effects over a large heterogeneous population.
Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2014
Published in Current Medical Research and Opinion, 2018
Bryan R. Deane, Sheuli Porkess
The disclosure rate for the smaller, earlier phase I/II trials was slightly lower than that for the larger phase III trials, which reached 95% (194/205) within 12 months and 96% (196/205) at 31 July 2016 (Table 1). As the approval date for the new medicines in this study was relatively recent, very few phase IV trials had been completed. Of the 24 trials for which results remained undisclosed at the end of the study, 15 related to the smaller, earlier phase I and II trials; five of these were phase I and 10 were phase II. Of the nine phase III (or II/III) trials that remained undisclosed at the end of the study, two were sponsored by a company which failed to provide any additional information during our consultation process, and seven were carried out in Asia by the Japanese parent company of the European MAH; results of three of these seven trials will be posted on ClinicalTrials.gov, while the others were not required to register and reporting of results was not mandatory under Japanese regulations (company communication).
Profile of tirzepatide in the management of type 2 diabetes mellitus: design, development, and place in therapy
Published in Expert Opinion on Pharmacotherapy, 2023
Lina Naseralallah, Bodoor Aboujabal
Herein, we summarize the evidence of tirzepatide efficacy for multiple endpoints relevant to T2DM. Our review is primarily based on evidence from two phase II [27,28] and eight phase III (clinical development program for tirzepatide, SURPASS and SURMOUNT) [29–36] double-blinded randomized controlled trials (RCT), which are summarized in Table 1 and Supplementary Table 1. We also present two post-hoc analyses [37,38] of Frias et al (2018) and one substudy [39] of SURPASS-3 as they provided a more comprehensive presentation than the original studies in relation to the outcomes of interest. Up until now, there have been no published phase IV trials. In addition, we considered results from published quantitative systematic reviews reporting on various efficacy endpoints [40–42].
Related Knowledge Centers
- Cell Culture
- Drug Development
- In Vitro
- In Vivo
- Pharmacovigilance
- Subject Research
- Vaccine
- Medical Device
- Preclinical Development
- Test Tube