Hard Questions

Whose needs come first – the patient’s or the trial’s?


Debra Banks (not her real name) had hope. There was a clinical trial open at an academic hospital 200 miles from where she lived. She would commute or find local housing. It would cost her, but this is what her savings were for, she reasoned. What expense could be more important than her life?

Next came the tests. Blood tests, an ultrasound of her heart, breathing tests. She gave vials of blood, lay in scanners, and eagerly jumped through every hoop placed before her. Then came the call from the trial coordinator. Her heart ultrasound showed a mild dysfunction in how it pumped. It excluded her from the trial.

“Not eligible.” The two words that took away everything reverberated in her mind. Her heart had never caused her any problems before. So after the shock wore off, she tried to bargain with the trial coordinator: Had the study drug been shown to cause or worsen heart damage? Could they repeat the ultrasound? Did this blip in her heart function really matter?

When the trial coordinator couldn’t answer all these questions, she encouraged Debra to come into the clinic and talk to the doctors directly. That’s where I met her.

Debra found herself in the middle of a painful crossroads she had no interest being in. What happens when the needs of an individual patient and the needs of medical research are at odds? From Debra’s perspective, she had one goal. She wanted the therapy that would give her the best chance of living.

But the aim of the trial was not to help Debra – not directly, at least. Clinical trials help patient populations. The goal is to add to a body of knowledge: To study new therapies, demonstrate safety and efficacy, and ultimately find better treatments. The bulk of benefit goes to future patients, not individual participants. If an individual participant does benefit, all the better. But this is a bonus, not a requirement.

In order to meet these goals, trials come with inclusion and exclusion criteria. These are often strict. Individuals with certain other medical conditions are frequently excluded, as the person needs to be able to tolerate the toxicities of the drug being tested.

Dr. Ilana Yurkiewicz is a fellow at Stanford (Calif.) University.

Dr. Ilana Yurkiewicz

This, of course, is very different from our usual approach to patient care. Outside of trials, the needs of the individual patient are our North Star. Instead of inclusion and exclusion criteria, we have guidelines: general goalposts that hint at the right answer, but are able to be bent based on individual circumstances. It’s something I love about medicine. Part science, part art. Part algorithmic, part creative.

I can give chemotherapy to a patient with a low platelet count, if I think it’s best. I can override an elevated bilirubin. I can simply not check a heart ultrasound in the first place, if I don’t believe it will change my management.

I understand why trial criteria exist. I fully support investing in novel therapies that will help future patients on a large scale. There will invariably be individuals for whom a clinical trial is unsafe or inappropriate for a multitude of reasons, and our job as oncologists is to make that call and convey that news.

Still, that can be hard to square with the human being sitting in front of you. Debra was only in her mid-50s. She was an artist, an educator, a parent. She was a person who was so, so not ready to die. That she would because of a glitch in her heart function – the significance of which nobody knew – was excruciating.

While we can’t enroll every patient in every trial, the least we can do is comb through trial criteria thoughtfully. With the role of clinical investigator comes great responsibility. Are we choosing a cutoff because it makes clinical sense – or because that’s how it was done before? Is there a medical justification behind each and every exclusion criterion? A careless cutoff is not just a line on a protocol. It can be the difference between someone’s last hope – and no more options.

Every time I saw Debra in clinic, she asked about the trial. Then one day she stopped asking. She was distracted by more pressing problems. Her breathing had worsened and her energy levels were so low she could hardly get out of bed. Debra became sicker and sicker until she could no longer request the last hope that might make her better.

A wonderful physician-scientist I worked with once said she split her time between patient care and medical research because they complement each other. Whenever she lost a patient, she turned that pain into motivation to delve deeper into her research. She coped with individual loss by helping to make small, incremental improvements for the needs of many.

I think about this, months later, as I look around the empty exam room where I first met Debra. I imagine a roomful of patients, alive and healthy, for whom the research she was excluded from has benefited.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

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