Abstract

The drug development paradigm in oncology has changed in recent times as developments in science and technology have led to more targeted therapies. Drug products are receiving marketing approvals based on single randomized studies enrolling 100-200 patients, including early phase (phase II) clinical trials. In this paper, we examine the likelihood of observing a significant treatment effect when in fact the true treatment effect is modest to null by exploring a range of sample sizes via simulation studies. Results showed that the Cox model performed appropriately in studies as small as n = 50 and extreme treatment effect estimates were very rarely observed when the true treatment effect was modest to null, at least for the examples considered under our assumed conditions. It appears that a hazard ratio of large magnitude observed in a small study is likely to be indicative of a true treatment effect, although of uncertain magnitude. However, the simulation assumes a well-conducted study with minimal to no amendments or adaptations and a non-ambiguous endpoint, which unfortunately is not often the case in the early phases of drug development. As the paradigm in oncology changes, randomized phase II studies can no longer be seen as simply supporting go/no-go decisions. When promising drugs are evaluated in trials with overall survival as an endpoint, companies may want to consider providing a pre-specified contingency statistical analysis plan in anticipation of unexpectedly promising survival results. Methods A total of 345 skin surface swab samples were collected from clinically diagnosed common wart (n = 166), plantar wart (n = 142), flat wart (n = 5), both common and plantar warts (n = 15) and common and flat warts (n = 1). DNA extraction and amplification were carried out using an established PCR, FAP primer pair-based method to detect HPV DNA. We measured HPV DNA negative samples by PCR with β-globin primer pair to confirm the availability of DNA.

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