A primer on clinical trials

*written by an outsider
During the end-of-year holiday break I started writing a short, illustrated primer. My goal was to explain the essence of clinical trials. To make this accessible to a broad audience, I used simple language and avoided mathematical expression.

The guiding question, which was suggested to us by Clayton Christensen, is: Is this drug right for me? In the primer I explain why we need testing and what kinds of tests we need to do before we are able to answer this question. I keep in mind the following principle from Maria Zuber: Keep only those tests that are absolutely necessary.

As I started to put together the primer, I realized that the focus should not be solely on the patient, but on the pairing between the study drug and patients. This subtle but important shift places us squarely in the center of clinical trials.

To simplify matters to the fullest extent possible, I ask the reader to postpone consideration of ethical issues. I also remove all stakeholder interactions; the primary interaction of interest is medical, between the study drug and the patients. There is very little mention of money, IP, marketing, or even the FDA. I’ll bring these important components into the picture soon, but not in the beginning.

I thought that, after all these simplifications, the primer would be easy to write. I was planning to present most of the primer as a week note. It wasn’t long until I realized the complexities associated with drug-patient pairings. The source of complexity lies in the variability of patients, both in the way in which the study drug can affect them medically, and in the ways in which the patients perceive the risks associated with the drug.

From the 50 slides I’ve written so far, I’m including this diagram of a patient. (I was never any good at drawing people, so I use a rectangular shape for a patient.) On one side is a check mark, the size of which indicates the degree of efficacy of the study drug on this particular patient. On the other side is an X, showing the degree of side effects. Underneath is a pivot which balances the benefits from drug efficacy on one side with risks on the other.

When the same study drug is paired with multiple patients, the balance may pivot in either direction depending on: the degree of drug efficacy, the extent of side effects, and the patients’ willingness to accept risk.

With a moment’s thought, it can be seen that this diagram points to the difficulties in answering the guiding question on whether the study drug is appropriate for a particular patient.

The exercise in putting together this primer has been a fascinating experience. An interesting finding for me is the inherent internal tension within clinical trials that arises purely from drug-patient pairings.

While the primer does not offer recommendations for changing the system of clinical trials, it does bring in some of the thinking of our team members and project advisors. For instance, at the FDA, we talked about balancing risk and benefit on a case-by-case basis, and also the need to broaden the research questions of clinical trials to provide more useful information to practicing clinicians. We also heard Mary Woolley’s reasoning for increasing medical research, Nancy Kass’s thoughts on the increasing role of learning healthcare systems, a widespread consensus, heard from organizations in Cleveland, Ohio, Columbus, South Carolina and all the way from Johannesburg, South Africa, on engaging practicing physicians in research, and the need to include quality of life, which was discussed during the 2015 Albright Challenge. In the primer, it is shown how all of these ideas and thoughts are tied together to address the initial guiding question and to bring greater clarity into the internal tension within clinical trials.

Ethical considerations, stakeholder interactions and other layers of clinical trials, including cost, data, legal and workflow, will be added to this primer, and this seems to be a good way to include further input from the rest of the team. My hope is that the primer will bring a fresh viewpoint of clinical trials which can help our team to innovate as we move forward with the project.

Tak Igusa