Identify your village (and listen to them)
Designing a clinical trial truly takes a village, and you need to identify the villagers early. As trainees, the value of mentorship is frequently underscored. But the importance of, and the nuance involved in managing, collaborating, and support cannot be overstated. Meet with a biostatistician to ensure your sample size calculations are correct. Work closely with the research pharmacist to ensure the medication formulation is available; decide on the manner of distribution so as not to inconvenience subjects; create a budget with an experienced manager. Seek out research coordinators often for assistance in creating case report forms, learning appropriate documentation, and crafting responses to Institutional Review Board concerns. Ask clinic personnel about arranging consent or follow-up visits around subjects’ clinic appointments. Present a draft of the protocol to your colleagues, as you will ultimately need them on board to recruit patients. And most importantly, listen to them ... all of them. Get your biases in check and write down all constructive criticism. Thoughtfully address each concern encountered to your satisfaction (and your mentor’s) and present to your village again. Rinse and repeat. Throw nothing under the rug, because if you do, it will eventually rear its head while you are in the throes of the study.
In retrospect, there were concerns raised by faculty and grant reviewers that I did not adequately address. First was the feasibility of screening, recruiting, and enrolling 80 patients during a busy clinical fellowship. While I took this criticism as a reflection of my personal commitment to the project, it was actually a call to consider the impact on clinical (and familial) responsibilities. But as I started enrolling patients, I realized there were logistic issues implied in this suggestion. I could not recruit subjects in Clinic A if I was assigned to see patients at the same time in Clinic B. Patients were not likely to come back another day for study-related discussions. Second, I designed eligibility criteria to make the data as clean as possible. Limiting the study to subjects with Crohn’s disease, in clinical and biochemical remission, without complications of their disease, who also have vitamin deficiency, may be an unrealistic recipe to recruit 80 people in a limited period of time. Finally, I designed laboratory follow-up schedules based on the pharmacokinetics of the drug alone, failing to consider the clinical milieu from which study subjects were recruited. Neglecting the fact that many patients obtain labs with their infusions, my study increased lab draw burden, heaped more patient reminders onto my plate – and more concerning – decreased overall study compliance. In short, trial design cannot be done in a vacuum or by just poring over published data. There are logistical and patient-related considerations that require early input from physicians and clinical staff in order for all the moving parts of a clinical trial to successfully work in harmony.
Create a timetable and follow it
Make a recruitment timetable very early on in the enrollment period. Set up biweekly meetings with mentors to discuss enrollment numbers and reflect on any unforeseen challenges. And be sure to celebrate the wins as well – not matter how small. In our study, falling behind on recruitment goals forced me to amend the stringent eligibility criteria and add additional manpower to help with reminders for laboratory follow-up and patient screening. These pivots caused study delays and cost resources. Ultimately, having a timetable forced me to take pause when it became clear I could not finish the study in the allotted time.
