New Year’s Eve Reflection: On Safety, Efficacy, and Hope

She was a 39 year old woman with cancer, originally diagnosed six years ago*. As I looked over her chart notes, I was particularly struck by one entry, and I read it over several times:

“Patient had a significant disruption in treatment due to an unplanned pregnancy, healthy baby girl now 10 months old.”

This statement had serious implications. I pictured her finding out that she was pregnant as she was being administered big-gun medication for her already advanced disease. How did her doctors counsel her? Did they recommend that she terminate the pregnancy? Did she wrestle with the decision? Did she regret her decision? No doubt her cancer had spread further during that substantial hiatus. I imagined that it must have been an incredibly difficult situation, and my heart went out to her.

But I will never know any of those details, nor even her name, ever. As a medical monitor for our company’s cancer immunotherapy clinical trials, one of my jobs is to determine if patients who want to join a trial are eligible. We do this by reviewing their enrollment packet, which is essentially an application that the patient and their oncologist put together when they want to try one of our drugs in development. It’s made up of redacted bits of the patient’s record, including medical chart notes, labs, CT scan and MRI reports, and sometimes screenshots of tumor images with measurements. It must contain all the information that we require in order to make a decision.

All the trials I work on are Phase 1, so, this is a drug being tested in humans for the first time. This means several things: One, there’s enough research supporting the hypothesis that it might work. Two, there’s meaningful data from cell and animal studies suggesting that it’s probably safe, and may be effective, in humans. And three, the FDA has reviewed and signed off on the rationale.

That all sounds solid, but really, no one knows for sure about safety and efficacy at this stage. That’s why it’s possible to be ‘too healthy’ for a Phase 1 trial, meaning, the situation may not be desperate enough to warrant taking part in early testing. The patient must have advanced or metastatic cancer that has failed all approved and appropriate therapies. Many have also failed other experimental therapies. On the other hand, a patient can’t be so sick that there’s little point in their making the effort and taking the risks.

As I flipped through the PDFs in the mother’s enrollment packet, I learned that she was married, with one older child, and that she now had widely metastatic cancer. Even though there are thousands of FDA-approved cancer treatments available, and even more experimental therapies further along in development than ours, she had no more options among any of these. Maybe she had tried things that weren’t effective, or maybe she had had unacceptable side effects, or maybe she had a contraindication. In any case, she and her doctors were looking at Phase 1 trials.

Generally, once a company has published data signaling that one of their drugs in development is safe and may actually be effective, people take notice. In the case of this young woman, either she or her oncologist had learned about this particular drug we’re developing, and knew that it had indeed helped other patients with her type of cancer. So here she was, jumping at the chance to get in. My job was to comb through her packet of information and match it against all of our inclusion and exclusion criteria, which is a long list of objective checkboxes developed to ensure that a patient is sick enough– but not too sick– to participate. Even one seemingly small piece of data could make her ineligible: a few points off on a particular lab value, a few millimeters out of range on tumor size, a teensy new met on a brain MRI… This is the reality. 

I imagined that as I was reading her chart, she was waiting to hear if she was accepted. Maybe she had discussed the trial with her husband. Maybe she had her phone nearby. Maybe they already had hope that this drug would work as well for her as it has for some others. 

As I reflect back on 2022, everything about this one young woman’s case sums up how I feel. I quit clinical medicine in late 2021 to work in biotech. Learning about her situation provides perspective; being in a position to give her some hope is validating. And it’s true, we do have several promising agents in various stages of development. Just being honest, we’ve recently presented some positive Phase 1 data, but it’ll be years before approval. We need to run more advanced trials designed to look at clinically meaningful outcomes like overall survival and comparing with standard of care. And then there’s more regulatory hoops to jump through.

But with her story, and really with every desperate patient’s story that projects through their chart notes, we as a team feel a greater urgency to move these big, clunky, complex trials forward as fast as we can. Our informal slogan is: “The patients are waiting,” because as we witness every day in our work, they are.

*Though the information I review is always redacted–meaning, any personally identifying information has been deleted– and we have multiple clinical trials all over the world at hundreds of different hospitals, I have still altered or omitted any potentially identifying details about patients, their doctors, their hospitals, and the specific trial they may have been involved in.