I will never forget her initials

ST[1]. I will never forget her initials; for clinical trials staff, initials are second nature because subject names are verboten and randomization numbers are impossible to remember. ST participated in a government-sponsored clinical trial while I was working as a Clinical Research Associate a few years ago. The study was supported by the National Cancer Institute Cooperative Group Program in partnership with a pharmaceutical company. ST was born and raised in west Baltimore City; a hard-working mother and grandmother who still liked to go out dancing in the clubs every weekend. She was young for a grandmother, still in her early 60’s. ST had breast cancer and was determined to beat it; frankly, she had too much to do to be slowed down by a little cancer. The medical oncologist mentioned the possibility of a clinical trial, and the research nurse discussed the trial with her a number of times before she consented to participate.

The clinical trial was a particularly elaborate one, designed to test the efficacy of a new drug on breast cancer at a number of different stages with a number of different potential chemotherapy regimens. As a result, the study protocol was around 120 pages long (a fairly standard length), and there were six treatment arms (three standard of care arms and three experimental arms). ST had never graduated college, but she had a good, skilled job and a quick mind. She was an active participant in the consent process and consulted her daughter, who was a nurse, whenever she needed an outside medical opinion. After she consented but before her first treatment, ST asked a question that I will never forget. She asked, “So how is this going to work? This study has six arms for the different drugs right…. but I only have two arms. So how am I going to be treated?” It took us a moment to recognize the source of confusion, and then we proceeded to review the concept of a clinical trial treatment “arm” and to remind her that she would not receive the treatments through an IV in her arm but rather through a portacath (small device inserted under the skin in the upper chest that is connected to a vein). Years later when the treatment was long over and we were still following ST on study, we would all laugh about her six arms and what an expert she became within weeks of starting treatment.

Now obviously, ST’s question evokes all sorts of questions about the informed consent process and patient education; but it also shines a spotlight another more controversial issue, protocol design and complexity. A clinical trial protocol is literally “…the written description of a clinical study. It includes the study’s objectives, design, and methods. It may also include relevant scientific background and statistical information.” That is the NIH’s definition on clinicaltrials.gov, but to clinical research staff all around the world; the study protocol is the bible. It is the document that you use to run the study. It is taken literally and guides every step we take. There may be other forms of clinical trial documentation such as laboratory manuals and special safety reporting directions, but if those documents contradict the protocol; the protocol always wins (unless the sponsor says otherwise and then amends the protocol). ST was only trying to wrap her mind around what that protocol design meant for her that day as she imagined what her treatment and life was going to be like for the next few months. We, as clinical research staff, would spend the next decade enrolling, treating, and following patients using that complex protocol as our guide. The protocol is that vital to the clinical trials system and yet, almost every diagram of the clinical trials process jumps right over and past its development (see Figure 1).

Figure 1. The clinical trials process as it is typically represented. It starts with an approved protocol. Where did the protocol come from? How and why did the researchers decide to structure the study the way they did? Who actually does what during the study?

Clinical trial protocol complexity is only one of many factors the project team is considering as it works to identify and develop progressive strategies that will enable a more rapid and cost effective clinical trials system. There is no easy way for someone like me, who is serving as an advisor to the project team, to describe exactly how clinical research staff run these enormously complex trials and to express all of the factors that make running a clinical trial so complicated (sometimes needlessly complicated). However, I can provide guidance as the project team starts planning an actual clinical trial. The team will be drafting a clinical trial protocol for a drug repurposing study- an old drug being used for a new indication. Apart from actually running a trial, drafting a protocol is one of the best educational processes for understanding the system, the stakeholders, the methods and design problems, the safety issues and reporting processes, the regulatory and ethical issues, the statistical and analytical considerations, as well as the documentation, monitoring, and administration. It is truly an overhead view of all of the moving parts; the project team is about to get their hands dirty!

I am already inspired by the way the project team breaks down and examines the clinical trials system in a way I never would have even considered. I cannot wait to see what they can do with a clinical trial protocol.


Photo. Here I try my very best to keep up and take it all in at the project team’s latest working retreat (April 23, 2015).

[1] I have changed the patient’s initials for the sake of confidentiality.
Jen Bernstein