The “Clinical Trials in Trouble” column underscores how the inertia that is inherent in the system blunts the wide-eyed curiosity that drove us into medicine in the first place. Dr. Simone correctly points out that conflating Phase I and Phase II trials into a “Learn” phase is one way to expedite the process. The “scientific question” process adopted by cardiologists is another partial solution.
Identifying the most important research questions first then leads to the next set of questions: How do we most effectively decide if an intervention is worthwhile in the clinic?
Recently I had the opportunity to act as “matchmaker” in bringing together a physicist, Dr. Lou Massa of Hunter College, who applies quantum chemistry to help solve questions regarding the quantum energies of large molecules such as insulin, with an expert in targeted therapy, Dr. Will Pao of Memorial Sloan-Kettering Cancer Center. They are exploring a collaboration to determine if Dr. Massa's work can help to screen thousands of potential targeted therapies before they are developed to see if they “match” quantum energies with the putative “target.”
I believe such cross collaboration of many disciplines is the future of medical research. It attracts other thought leaders from different arenas and stimulates a dialogue that energizes the clinical trial process with new ideas. This is already being done with nanotechnology in cancer therapeutics. I also have discussed with some of my older classmates from the Cornell School of Electrical Engineering about collaborating with the newly created biomedical engineering program there. This would allow us to implement some mathematical modeling techniques that could give us a new perspective in approaching issues such as: (1) cancer screening based upon the sum of the known individual biologic models that already exist; and (2) developing models for metastases, angiogenesis, and other processes. This only scratches the surface.
And let us not forget the impact of cancer research on public health issues. I believe that whatever scarce resources exist for clinical trials, that we need to be responsible in trying to assess the potential aggregate benefit to society (i.e., do we need to spend another billion dollars to develop another targeted therapy with marginal benefit as defined by measurement of surrogate end points?).
Hilbert's problems were a list of 23 problems in mathematics put forth by German mathematician David Hilbert at the Paris conference of the International Congress of Mathematicians in 1901.1 I believe we should create a set of the most pressing unanswered questions in oncology as did Hilbert that are prioritized by not only our colleagues but also by our non-medical collaborators.
We have the intellectual capital to do great things but the regulatory inertia of the current clinical trials process in oncology is about to suffocate the potential for new and profound breakthroughs that will benefit our patients. In James Gleick's biography of Richard Feynman, Genius,2 he talks about how the Nobel laureate from my alma mater, Cornell, figured out how the space shuttle blew up because he did his thinking in the “orthogonal plane.” We need to do the same.
Anthony F. Provenzano, MD
Chief, Medical Oncology
Lawrence Hospital Center
Reply from Dr. Simone:
Many thanks for your thoughtful response to my column. I would add another advocate of taking a radically new approach to such issues. Clayton Christensen is an advocate of “disruptive innovation,” exemplified in his most recent book, The Innovator's Prescription, which specifically addresses health care. Unless clinical trials bureaucracy can extricate itself from continuing to use a 50-year-old model in today's environment, change will not come from them. I suspect that outside forces (like the one you describe) that experiment with radically new approaches will be necessary.
2. Gleick J: Genius: The Life and Science of Richard Feynman, 1993