Much has been written in ASH Clinical News about the Orwellian nature of modern clinical trials, and for good reason: Almost all our readers have some experience with clinical research – it’s what we do. Consequently, I hope my story will resonate. To protect the innocent, the names and dates of the events herein have been changed and bear no resemblance to any real or living person, organization, time, or place (sort of). This is a reenactment of creeping awareness, acceptance, and ultimately… well for that, you have to read on.
I have, by now, participated in 53 clinical trials resulting in 89 publications over 24 years. And they used to be fun. Then one sunny Friday morning, a not-so-long time ago, they stopped being fun.
I had an epiphany of sorts that day: Everything I was experiencing … equated to what we now recognize as the dreaded “burnout.”
I arrived at my office to find an ominous-looking stack of EKGs, each stamped with an automated report of normality to which I dutifully signed NCS – not clinically significant, adding my initials and the date 23 times. Rather proud of myself for having expeditiously dealt with this “nuisance” before clinic started, I launched into the first emails of the day.
Two overnight messages requiring attention greeted me. The first reprimanded me for my overdue review of Investigator’s Brochure version 5.0, to determine if, somewhere in its 129 pages, there were any new safety data that might require a revision to the trial’s informed-consent form. The email had, quite rightly, a vaguely threatening tone. I punted that delicious task for the weekend. The second request related to e-signing case-report forms in a system I didn’t recognize, never fully understood, and for which my password had long ago expired. I gave up and moved that one to Monday.
Then, by unfortunate coincidence, at a quarterly finance meeting with our research office later that day, I learned that one of my clinical trials was losing money, in quite large amounts. The loss was not because of bad budgeting, but because opening and activating the study took more effort and time than anyone reasonably expected. That was compounded by the realization that this early-stage trial had 11 active sites competing every six weeks for three slots and enough eligibility criteria to enter the Guinness Book of World Records for the most reasons patients are unqualified for a trial. In summary, accrual was low and slow, yet the paperwork was relentless and the expenses outpaced potential revenue. I left the meeting feeling discouraged.
Clinic ended a little early that day and, before quitting time, I replied “yes to all” with respect to my contributions to a trial abstract submission to a major medical conference. A quick read of said abstract awakened my dislike for using the words “acceptable” and “manageable” to describe an agent’s evident toxicities. So, in a Friday afternoon act of defiance, I sharpened my figurative pencil and composed an objection to both that wording and the claim that the agent would be a “new standard of care” for patients with an “unmet need.” I am sure I upset the medical writer a little and the marketing team a lot, but I felt better – though I recognized that my solitary act of rebellion would change little.
Monday morning brought news that one of the trials in which I was engaged was being closed for “business reasons.” No appeals would be allowed, but the medical team at the sponsoring company offered apologies. What would I tell my patient who had just enrolled in the study? “So sorry, but your contribution to the future of blood cancer treatment was just cancelled without notice. Why don’t you keep volunteering to take the drug with unknown side effects or potential for benefit anyway?”
I guess that was the last straw, the thousandth cut, the culmination, the end of the road.
I had an epiphany of sorts that day: Everything I was experiencing – an increase in cynicism, apathy about the tasks at hand, irritability with people tasked with their required jobs, lack of satisfaction, and general disillusionment with the trial system – equated to what we now recognize as the dreaded “burnout.”
Conducting trials of drugs with manageable toxicity and encouraging activity is what we do – burnout be damned.
I decided then and there to quit engaging in clinical trials. I had plenty of other more rewarding things to focus on, and, working with a motivated team, I was refreshed daily by a sense of community and visible progress towards a shared vision. In other words, the very opposite of the recent clinical trial experience.
I felt immediate and palpable relief. My colleagues were less than thrilled, but graciously agreed to take over the thankless, ceaseless, mundane clinical trial–related tasks. The conscientious clinical research staff reluctantly accepted my decision, though I suspect they also were secretly pleased that I would not be the one asking for eligibility review of three patients at once. The sponsoring companies were mute, but I can imagine they weren’t pleased either.
Meanwhile, I was jubilant. No more mandatory meetings with monitors lecturing on our failings as collators and custodians of the precious data; no more investigator responsibility slideshows, mandatory Institutional Review Board videos, financial disclosures, case report form signoffs, investigator calls, slow-accrual guilt, toxicity attributions, tense discussions about pre-presentation press releases, or lawyerly monitoring of slides for compliance. No more lab signoffs, site initiation visits, site closing visits, budget reviews, market creep monitoring, or requests for conflict-of-interest disclosures.
Finally, released from the clinical trials club, I could be the one to ask the pointed questions at the end of a trial presentation. I could wax lyrical at journal club about poor design and biased reporting. An expanded universe of conflict-free consulting awaited me.
It took months, and repeated requests, to slowly reassign ownership or close each trial. (For any readers considering the same path, be aware that like a romance documented on social media, a speeding ticket, or an inferior vena cava filter, participating in an industry-supported clinical trial is difficult to extricate yourself from.)
Then, just as I cleared the last hurdle and was poised to skip merrily towards my new trial-free and resilient existence, the siren’s call arrived. The phone rang and a voice said, “Dr. Stewart, would you like to participate in our CAR T-cell trial for myeloma?”
Five seconds passed before I answered: “Yes.”
Go ahead, judge me! You may wonder why, with the goal line in sight, my resolve collapsed. I am still not entirely sure myself, but concluded that, at the end of the day, when there is still real unmet need, conducting trials of drugs with manageable toxicity and encouraging activity are what we do – burnout be damned.