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Phase 0 clinical trials: towards a more complete ethics critique

Author Interview

T Patrick Hill

Senior policy fellow at the Edward J Bloustein School of Planning and Public Policy at Rutgers, and a clinical research ethics consultant at the Cancer Institute of New Jersey, both in New Brunswick.

1)  Briefly tell us about your career so far For the past twelve years, I have taught ethics and consulted in clinical research ethics. At Rutgers University I teach undergraduate courses in public health law and ethics, as well as graduate courses in ethics for urban planning and public policy. As a consultant, I formed my own company, Applied Ethics Enterprises LLC, and have secured contracts with such clients as the Cancer Institute of New Jersey (an NIH accredited comprehensive cancer center), The Neonatology Division of the Robert Wood Johnson University Medical Center, The Religious Coalition for Reproductive Choice and the New Jersey Department of Health and Senior Services. In addition, I have served as ethics consultant to the NIH’s project on translational research and currently work with NextLevelPharma.  At the same time, I like to write. Among my more recent papers are: Rare Tumors: An Appeal for Justice (Bentham online); Theologians, Science and Reductionism (Sightings, University of Chicago); Ethical Issues in the Use of Fluids and Nutrition: When Can They Be Withdrawn? (In Health Care Issues: Critical Issues for the 21st. Century; Jones and Bartlett Publishers)

 

2)  What inspired you to become a researcher/doctor? As a formally trained ethicist, I have seen the need for an intellectually rigorous conversation between ethics and clinical science, a conversation for which both ethicists and clinical scientists are ill-prepared to the extent that neither really understands the language of the other. For me at least, the challenge has been applying the logic of the language of ethics to the practice of clinical research and in turn learning the language of clinical science and its logic in order to understand what might be the ethical import of clinical research itself, together with its consequences. As a practice of science, clinical research is the pursuit of clinical truth as something found and as a condition of its practice, it requires what Jacob Bronowski called the habit of truth on the part of investigators. In that sense, science possesses its own moral compass. Understanding and interpreting that compass has, I am convinced, opened up a new world of relevance and service for ethics.

 

3)  How did you get into the field of policy and medical ethics? My career began working with a grassroots organization, The New Jersey Citizens Committee on Biomedical Ethics. Funded by the Robert Wood Johnson Foundation, the Citizens Committee worked with the citizens of New Jersey to educate them about end-of-life issues and with the New Jersey Legislature to enact legislation for the use of durable powers of attorney and advance directives. Subsequently, I served as a research scholar at the Park Ridge Center for The Study of Health, Faith and Ethics in Chicago where I completed a 4-year research project on aging and religious traditions. From there, having completed my doctorate at the University of Chicago, I returned to New Jersey to teach and to consult.

 

4)  Can you give us some background for what led to the development of ‘phase 0’ trials? The traditional clinical research model of Phase I, II, and III, has come to be recognized as inefficient, taking too long and too much money to complete. The need is to discover much sooner, with fewer patients/subjects, and at lower doses what novel agents are likely to be effective. Coming directly between lab studies and Phase I, the Phase 0 construct requires less preliminary data, etc. than a Phase I and is designed to identify quickly and efficiently likely successful agents that can more quickly bring the benefits of subsequent research to patients in need.

 

5)  Please tell us about your paper It is an attempt to provide a more complete ethics assessment of the Phase 0 construct for clinical research. Given its goals and methodology, it cannot be assessed in quite the same way as the Phase I,II, or III constructs. It requires very few participants, dosage is at sub therapeutic levels and the study duration is no more than 14 days. As result there is virtually no possibility of benefit or harm. And since benefit is a major requirement for the ethical warrant of our traditional model for clinical trials, an alternative assessment is required. The one I have proposed is based on the means-end relationship since Phase 0 is designed as a means to solve the so-called pipe line problem resulting from the inefficiencies of our existing clinical research model. My assessment consists in asking whether the end – a more efficient research model - justifies using the Phase 0 construct as the means to secure that end or goal. That depends on the moral standing of such a goal – what can be said of it that justifies it ethically. If it is ethically warranted – and I argue that it is then it will justify the use of the Phase 0 construct in clinical research as means so long as Phase 0 itself does not compromise the ethical integrity of the goal. Again, I argue that it does not.

 

6)  How do you see the future for clinical trials in oncology? I am optimistic about the future for clinical trials in oncology. But I do think we have to go back to the drawing board with our clinical research model which simply has not kept pace with advances in relevant technology that increasingly supply us with more and more sophisticated tools for the use of biomarkers, imaging and assays, in particular to measure PD and PK characteristics. The Phase 0 construct has the capacity to lead the charge here and may contribute in one additional area that I believe is critical to this reform. That is moving away from a deterministic understanding of research in favour of a methodology based on probability. Here the challenge is to identify research methodologies that enable us to proceed rationally in the face of the uncertainty inherent in research.

 

7)  If you manage to get any spare time, what do you fill it with? My wife and I have a vacation home situated on a modest mountain side in Vermont. When there, I spend as much time as I can, snow shoeing in the winter, kayaking on Lake Whitingham in the summer and fall, walking with our golden retriever, Tana, and gazing at a night sky that displays its stars in all their brilliance like no other that I know.

Read Patrick Hill's article in full

 



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Published by

Cancer Intelligence