The Subject Is a Patient

Abstract

Although it is common in academic and government research settings to speak of study participants as “subjects,” this perspective piece argues against doing so. In particular, the relationship of the study physician with study participants is unique and still retains many elements of the usual patient-physician relationship that exists in general clinical practice.

“Our clinical trial participants are study subjects, not patients,” I overheard one of my nonclinical colleagues say to another. “This is not a clinician-patient relationship.”

I’m a research physician conducting early phase clinical trials at the National Institute on Drug Abuse (NIDA) Intramural Research Program, and hearing that my study patients weren’t actually “patients” was news to me. That view is understandable on one level, because my physician-patient relationship with our study participants is unique among my teammates. I certainly also have dual loyalties given that I am charged with doing both what is best for the patient and for the study. While these interests mostly align, there is always the possibility that they might conflict, requiring me to prioritize one over the other. This might be seen as a contrast with having solely the usual responsibility to do what is in the patient’s best interest, as I clearly did when I worked in full-time clinical medicine. But in actual practice as a study physician, these competing dual loyalties never conflict, because the same Hippocratic Oath I took as a medical student still applies now just as it always has. That means the patient’s best interest always supersedes the needs of the study. Even if that were not the case, does having 2 potentially conflicting priorities really relegate my patients, all of whom are people with substance use disorders (SUDs), to being merely “subjects,” as if they had more in common with the rodents housed in our basement animal facility than with “real” addiction patients being seen in clinical settings?

The challenges of navigating my 2 roles as patient fiduciary and study steward were apparent to me almost immediately upon starting this job. I withdrew one of my first study patients over his objections because I was concerned that the risks to his well-being outweighed any benefits from continuing him. He wasn’t initially very happy with me for doing that, but after we sat and talked it out, he did come to agree that I was probably right about him struggling more with being in the study than he had been admitting to us or even to himself. I never did convince him that his (apparent to me) cannabis withdrawal was probably playing a major role in the sleep disturbances, irritability, and other symptoms he was experiencing, given that he had suddenly ceased his prior heavy cannabis use to be in the study. He just didn’t view his cannabis use as a problem or think of cannabis as being a drug that one could withdraw from. After that, I made sure to ask other study candidates who used cannabis regularly what their previous experiences with quitting were like, and I warned them up front that yes, you can withdraw from cannabis, just like you could withdraw from any psychoactive substance that you quit using suddenly.

Then there was the study candidate who was newly diagnosed with hypothyroidism by our physician assistant during her screening workup. I advised her that until we got her thyroid function stable, I would not medically clear her to be enrolled in an Investigational New Drug (IND) study. Since she already had her own primary care physician (PCP), we gave her a copy of her labs and instructed her to follow up with her doctor to be evaluated and likely started on levothyroxine. The upshot is that she did go to her PCP; she did get started on levothyroxine; she did get her hypothyroidism under control (as monitored both by us and by her own doc); and she did successfully enroll in and complete that IND study several months later. She has subsequently come back to do other studies and training sessions with our staff, and while I’d be hard-pressed to argue that she’s currently my patient, I definitely do think of her as a former patient. There is also always the possibility of her becoming my patient again in the future if she qualifies for one of the new studies that we are constantly developing and launching.

We’ve screened other study candidates who never even make it to that point because I determined that, in my professional judgment, they would be better served by receiving bona fide, Food and Drug Administration-approved, addiction treatment rather than being in a clinical trial. These tend to be folks who have a lot of medical comorbidities that might make it hazardous for them to be in an IND study, or even a drug-repurposing study. I explain to these higher-risk candidates that the best medical course of action for them is to engage in evidence-based addiction treatment, not study trial participation that has no direct therapeutic benefit to them. As with any medical advice that doesn’t fit with the person’s preconceived notions or goals, some candidates are more open to hearing that message from me than others are. But for any candidate who is open to entering treatment for their SUD, our team does what we can to help facilitate that process for them.

Participating in our clinical studies may be the most positive interactions with the medical care system that some of my patients have ever had, and I try to take advantage of this unique opportunity to engage with them in hopes of bettering their health and overall life situations. I introduce myself to prospective study candidates as “the study doc,” explaining my role by saying, “it’s my job to make sure that you’re safe while you’re participating in our study.” Particularly for our most intense IND studies, which literally entail admitting people to a locked ward for 2 or 3 weeks, I am both heavily invested and also vested in monitoring the condition of these potentially vulnerable people who volunteer for our studies and entrust us with their health and well-being. One of our medical team members sees our patients daily while they’re enrolled and evaluates them for any medical issues they may be having. Sometimes there are no medical issues to discuss, and then we can just shoot the breeze. At NIDA, I have plenty of time to sit down with my patients, talk to them, and get to know them in a way that I rarely could when I was running from room to room while in traditional clinical practice.

In certain ways, this scenario evokes that idealized golden era in medicine that inspired many of us to go into this career in the first place. The only other chance I have had to spend so much time with my patients was as a medical student, when I was just responsible for a couple of patients at once, and my goal was to learn as much as I possibly could from my interactions with each one. Now, like then, I hear all kinds of stories from my patients about topics that may not be strictly medical, but that still significantly influence their lives and health. For example, since some of our studies require a standardized diet, the biggest complaint I get is about people not liking the food. It turns out that hospital food isn’t all that much tastier now than it was when I was in training. Even so, it’s not like the food or the living situation at the Clinical Research Unit is the worst that it could be, either. Several patients have told me that being here actually is kind of like a vacation to them, in the sense that it gets them off the street and gives them a break from dealing with the stresses of living the “drug-using lifestyle” for a while. I’ve also had several patients swear that the hospital food is way better than what they got while in prison, a comparison that I can only take their word for but have no reason to doubt.

It remains puzzling to me how anyone could conclude that working in clinical research somehow does not involve patients or patient care, given that our entire enterprise revolves around our study patients and their care. I struggle to understand why some people view these subacute periods of me providing clinical care to patients in studies lasting a few weeks to several months, as somehow being less of a clinical care scenario than the care I provided as an emergency physician or a medical toxicologist, both scenarios where the period of care might only have lasted several hours. Many of my medical toxicologist colleagues in private practice or at academic institutions continue to work emergency department shifts as a significant component of their practice; as a government-employed physician scientist, I am essentially alone among them in performing full-time clinical research. Since coming to NIDA, I’ve been asked at various times by several of these colleagues whether I have “given up all clinical practice.” My response to this question is always to say that no, I have most definitely not given up all clinical practice. It’s just that now, all of my patients are people who happen to be enrolled in clinical trials.