After years spent as an investigator on countless hematology and cancer clinical trials, all initiated with the noble intent of improving my patients’ lives through what we all hoped would be better therapies, I have finally arrived at one conclusion that I believe to be virtually unassailable: Contract research organizations (CROs) are an invasive weed – an administrative kudzu – that infests the clinical trial process.
Perhaps I am being a bit dramatic in my declaration.
CROs, which came into existence in the 1980s to outsource research regulatory requirements, have the potential to improve the quality of data collection and trial standardization. These are, after all, specialists in the day-to-day minutiae of clinical trial conduct – the kings of compliance! The sultans of Serious Adverse Events! The lotharios of labs out of range! The foremen of Form U.S. Food and Drug Administration 1572! Why, then, do those of us who have dedicated our careers to exploring novel therapeutics view the Quintiles, Parexels, PRAs, and Covances of the world more as the troglodytes of trial torture?
Recently, members of our study team (nurses, pharmacists, research coordinators, and other physicians) and I met with the CRO representative who would be monitoring our cancer center to start the site initiation visit (SIV) for a clinical trial we were opening at our cancer center. This takes the majority of a day as we review the trial’s “instruction manual” – the protocol – and our responsibilities as investigators, and as the CRO monitor tours the cancer center to see our base of operations. (The SIV is distinguished from the “pre-SIV,” a visit that occurred a couple of months earlier and accomplished the same tasks – only it didn’t count.)
I went to take a seat, but before my tush could meet the welcome embrace of the chair’s cushion, the CRO monitor shoved a piece of paper and a pen toward me.
“You need to sign this,” she said.
“What is it?” I asked.
“It shows that you attended the SIV,” she answered.
“But you can see that I’m here. What does my signature add to that fact?” I asked.
“We need it for our records,” she said, confidently. This was a frequent refrain throughout the day, as the CRO’s records are apparently tantamount to Holy Scripture. I signed the paper.
“Here,” she said, shoving three more pieces of paper in front of me. I looked down at my team members’ signatures. “You need to initial and date next to everyone’s signature.”
“Why do I need to do that?” I asked.
“It’s the site delegation log,” she answered.
“But why can’t I just initial and date once for everyone?” I asked. “I can even initial and date once at the top of the page and make arrows going down to indicate it applies to everyone,” I offered, helpfully.
“Because it’s the site delegation log,” she answered, confidently. “We need it for our records.”
I quickly calculated whether it would take less time to argue with her or to sign and date the paper 17 times, and opted for the latter.
“Here,” she said again, shoving another paper toward me. “I need you to sign this, write your initials, and write the numbers 0 through 9 in the box where it says to do that.”
“Do I dare ask why?” I dared to ask.
“We need this so that when we are going through the medical records, we will know which handwriting is yours,” she answered.
“But we have electronic medical records. I don’t sign or date anything manually anymore. My signature and initials and numbers look like those of everyone else who uses the Calibri font on the computer. How does this help you?” I asked.
She maintained her composure. “We need it for our records.” I reviewed my previous mental calculation, then filled out the form.
“Let’s get started,” she said. We all turned to the screen on which her slides were displayed. “This is a phase II study in patients with acute mya … mya … mya …”
“Myelogenous,” I offered.
“Myelogenous loo … loo …”
“Leukemia,” I said.
She continued reading her slides, one after the next, verbatim, pronouncing some of the words correctly, some phonetically. I looked around at my team members’ faces and saw the dreamy looks of people who had drifted off to their happy places. It was clear that nobody was paying attention, because we had all read the protocol cover-to-cover already.
This may seem painful, but I had experienced worse.
One monitor started our SIV by playing a recording of her own voice reading the slides off her iPhone, as she sat quietly, pushing the “slide advance” button on her remote. I stopped that meeting after a few minutes, incensed that she would waste my team’s time with this laziness.
Another monitor insisted on a repeat SIV when our cancer center moved from one building to another, claiming that he couldn’t be sure of the sanctity of the study’s conduct because we were in a completely new building. He even threatened putting the trial on hold, which would have prevented one of our patients from receiving his treatment, until we complied.
“Any questions?” our current monitor asked.
“No,” I answered quickly, as my team recovered from their respective reveries.
“Now I’m going to review with you your responsibilities as an investigator,” she said to me, pointedly.
“I’m aware of them already, thanks,” I said. “I’ve been an investigator on a bunch of trials over the past decade and a half, and we undergo training every three years, in which we review our responsibilities as an investigator.” I smiled at her.
She smiled back at me, nonplussed, and advanced to the “investigator responsibilities” slide. “As the primary investigator …” she started, but I didn’t hear much after that. I was in my happy place, somewhere on a beach on Sanibel Island, sipping a fruity drink.
Over the coming years, I would often hear from our CRO monitor – or her replacement, or his replacement – with reminders about upcoming monitor visits, letters about prior monitor visits, and entreaties to log into the CRO’s website to create a unique username and password and sign off on a number of forms electronically so I could save the CRO time and money.
Oh, and there were the many queries about adverse events, their causes, and their attributions, with the ever-so-subtle implication that we were assigning more blame for toxicities than we should to the study drug. One colleague of mine got so incensed about the banality of these queries that when a monitor continued to question him about the cause of his patient’s coronary artery disease, he photocopied the entire chapter on the subject from Braunwald’s Heart Disease textbook and faxed it to her.
Careful monitoring of therapeutic clinical trials, particularly for hematologic and cancer indications, is necessary to ensure patient safety and assess drug efficacy. But the self-righteous zeal with which CROs have introduced bureaucratic nonsense to the administrative requirements of these trials – delivered at the hands of poorly trained emissaries – is insulting to highly skilled research teams, adds substantial costs to the conduct of these studies, and impedes progress in the war on cancer.
Can somebody please stop the madness? For the records.
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Ein Bericht von Mikkael Sekeres, MD, MS,