We’re now well over half a year into the Covid-19 pandemic, and the lack of a vaccine is excruciating. With dozens of candidate vaccines generating countless headlines about positive results in early stage trials, it’s tempting to see any further delay as unnecessary. If we know that these vaccines work, can’t we follow China’s lead by picking one and starting mass distribution?
If only things were so simple. The sad truth is that large-scale trials are more than a needless formality. Promising drugs fail more often than not, and when solutions arrive, they’re not always as perfect as we might imagine.
I've lived this. Ten years ago, I was diagnosed with life-threatening melanoma at the age of 20. At the time, effective pharmaceutical treatments were close to nonexistent. So when a drug called ipilimumab made headlines after a successful trial in terminal melanoma patients, my family set out to acquire the drug for me by any means necessary.
We quickly realized that I could only get the drug by enrolling in a clinical trial. As far as I was concerned, the only risk of the trial was the prospect of receiving a placebo. I was convinced that oncologists already knew that the drug worked and that any further trials were an exercise in bureaucratic box-checking. Never mind that the drug hadn’t yet been tried in patients like me, that the side effects weren’t fully understood, and that I’d be taking roughly 15 times as much of the drug as the patients in the original trial. My oncologist explained these risks to me; I nodded my head and refused to absorb what he was saying.
The ensuing decade confirmed that I got the most important point right: ipilimumab really does save lives. The results of my trial suggest it increased survival by about 10% for patients like me. That’s not a large effect, but it’s better than nothing, and in 2011, ipilimumab became the first ever FDA-approved drug shown to extend the lives of melanoma patients. More significantly, it launched the immunotherapy revolution – a wave of drugs that have transformed oncology and saved hundreds of thousands of lives.
But my trial also demonstrated precisely what else high dose ipilimumab does to patients. In my case, highlights included weeks of vomiting, months of excruciating corneal lesions, and, oddly, a decade (and counting) of acne. In one particularly scary moment, a CT scan revealed new spots on my right lung that appeared to be tumors. I underwent surgery to remove and biopsy them. Only then did we learn that the spots were simply inflammation caused by the drug. Today, oncologists know not to perform surgery in that situation precisely because patients like me endured unnecessary operations.
Let me be clear: I’d enroll in that trial again in a heartbeat. Survival statistics suggested I had a one-in-four chance of making it to my 30th birthday, so an experimental drug was a risk I was happy to take. But the experience permanently disabused me of the notion that “a promising drug” and “a well-understood drug” are one and the same.
Perhaps my desperate logic applies to the individuals at the highest risk from Covid-19. For them, the urgent need for immunity may outweigh all of the uncertainty about efficacy and side effects. But that would be the exception rather than the rule. I was dealing with a confirmed case of a deadly disease; “first, do no harm” was hardly the guiding principle.
The calculus looks quite different when you’re considering prevention of a respiratory infection rather than treatment of cancer. For young adults in particular, the absolute risk of death from Covid-19 is quite low, with fewer than one death involving Covid-19 per 100,000 people aged 15-24 through the first 7 months of the pandemic. Against that baseline, a vaccine needs to be both very safe and very effective to exceed the cost-benefit threshold.
When I hear people excitedly discuss the latest positive news about one Covid-19 vaccine or another, I see a reflection of how I felt ten years ago. After six months of a devastating pandemic, there’s an unbearable temptation to seize on a promising pharmaceutical and declare it to be the solution. Sadly, though, we still have a lot more to learn more about these vaccines. The good news? With 11 different vaccines in phase III trials, we’re well on our way to finding the best solution.