Question

An investigator wants to design a two-armed phase Il study to determine the difference in time-to-progression between a chemotherapy agent and the same chemotherapy agent combined with a new kinase inhibitor for patients with stage IV pancreatic cancer. He is well aware that phase Il studies are not meant to replace phase Ill studies, but he wants to try to carry out a preliminary study that will lead to support for a phase Ill study. His statistician told him that, at a = 0.05 and ß = 0.1, to detect a A of 0.2 he will need 82 patients per arm. He realized that the time needed to accrue this many patients at his institution would be more than 4 years and he wanted to modify these parameters to complete the study faster. He considered the following changes. Which of the changes would result in an increased likelihood of discarding an active drug?

Answer 1

Increasing the level of significance or decreasing the power of a clinical trial increases the likelihood of discarding an active drug, which should be avoided in the interests of effective drug development. Clinical trials progress through multiple phases, with pharmacokinetics being central to identifying drug candidates with the desired properties.

Step-by-step explanation:

When considering the design of a two-armed phase II study in clinical trials, the investigator is faced with trade-offs that can affect the likelihood of discarding a potentially active drug (also known as a Type II error or ß). In this context, the ßa parameter represents the level of significance, and the ß parameter represents the power of the study. To reduce the time to accrue patients for the study, the investigator could consider increasing ßa (accepting a higher chance of a false positive result), decreasing the power of the study (ß), or decreasing the effect size (Δ) that the study is designed to detect. However, increasing ßa or decreasing the power would increase the likelihood of discarding an active drug, which is not desirable.

The clinical development of a drug proceeds through phase I to phase IV trials, with each phase having specific goals regarding safety, efficacy, pharmacokinetic properties, and dosage. Pharmacokinetics plays a crucial role in these phases, as it helps to identify the most suitable drug candidates with optimal absorption, distribution, metabolism, and elimination properties. Advanced pharmacokinetic studies, often involving bioanalysis with techniques such as liquid chromatography coupled with mass spectrometry, are integral from early discovery throughout clinical development and post-approval monitoring.