paywalled: Requirements to Assess Feasibility of Phase 0 Trials during Major Abdominal Surgery: Variability of PARP Activity

Requirements to Assess Feasibility of Phase 0 Trials during Major Abdominal Surgery: Variability of PARP Activity

Abstract

Purpose: The aim of this study was to evaluate the feasibility of phase 0 trials in the setting of a routine surgical procedure. Logistic considerations, tissue sampling and tissue handling, and variability of a biomarker during surgery, in here PARP, were evaluated. 

Experimental Design: Patients with highly suspicious or proven diagnosis of advanced ovarian cancer, planned for debulking surgery were asked to allow sequential tumor biopsies during surgery. Biopsies were frozen immediately and PARP activity was measured subsequently.

Conclusions: Conducting phase 0 trials during surgery seems to be feasible in terms of logistic considerations. In preparation of a phase 0 trial during surgery, a feasibility study like this should be conducted to rule out major interactions of the surgical intervention with respect to the targeted biomarker.

open access: ecancer - Phase 0 clinical trials: towards a more complete ethics critique

Phase 0 clinical trials: towards a more complete ethics critique

Summary

In efforts to modernise the entire drug-development process, making it more efficient, less costly, and ultimately of real benefit to patients, The Federal Drug Administration (FDA) authorised the use of exploratory IND or early Phase I (Phase 0) studies. Quite different in structure from Phase I, II, and III studies, the Phase 0 construct understandably poses a set of ethical problems not seen in the other research phases and so far not adequately addressed by ethicists. In an effort to deal with this deficiency, this paper proposes an ethics critique, based not on the usual concept of benefit, but on the means–end relation, and placed within an ethic of science derived from the practice of science.

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To date, the ethics analysis of Phase 0 clinical trials has remained incomplete [1–3]. Focusing, for the most part, on the Phase 0 construct itself, the analysis has neglected the larger economic context in relation to which Phase 0 trials must be understood for any complete analysis.......

"The Ethics of the Phase 0 Construct
It is clear from the way the Phase 0 construct is described in both the Critical Path Initiative and the Guidance that the FDA is promoting it as a means to achieve an end, namely, solving the “pipeline problem”. If so, then an ethics assessment of the construct should start by asking whether the end justifies the means in moral terms.......