How This Clinical Trial Went Terribly Wrong
September 12, 2014
As a lifelong asthma sufferer, I've always had alerts set up at ClinicalTrials.gov, a central clearinghouse for clinical trials. If a clinical trial for a new experimental drug came up in my area, I wanted to be notified so I could apply to participate. Even with insurance, asthma medication is expensive, and by participating in a trial I could not only get free treatment, I'd also get to contribute to the furthering of science. A true win-win for everyone.
Finally my chance came earlier this year. Amgen is a major pharmaceutical company with headquarters in my county, and my condition was such that I met the qualifications to come in and be evaluated. Typically, pharmaceutical companies don't conduct the trials themselves; they contract the work to clinics that specialize in running them. I was put in touch with such a clinic in Newport Beach, CA, about 45 minutes from my home, to see if I qualified for a trial of an injectable asthma medication with the potential to reduce or eliminate my dependence on inhalers. Ever since starting the Skeptoid podcast, inhalers had always been problematic for me because they caused me to lose my voice. If you've ever heard a show in which I sounded sick, the reason was probably asthma inhaler usage that week.
Arriving at the clinic, I found the people polite and friendly, but desperately disorganized. Over the course of my many visits, their being prepared for me (despite the 24-hour confirmation phone call) was the exception rather than the rule. Twice they had no choice but to apologize and send me home with nothing more than a $5 Starbucks card to show for two hours out of my work day. It was rare that I had to wait less than half an hour. Sometimes the person who was supposed to see me wasn't even scheduled to come in until an hour after my appointment time.
However, none of this is serious (or especially unusual). It certainly didn't deter me from wanting to participate. But some of the things that followed did, and compelled me to make some hard decisions, and ultimately caused me to voluntarily drop out. What follows are some of the details that gave me grave concern for this particular clinical trial.
Like any company testing a new drug, Amgen needed a very strictly controlled test group. We had to meet certain age and other physical requirements and be free of any potential drug interactions. We needed our asthma-induced limitations to fall within certain parameters. We needed to have already tried certain drugs that failed to adequately control our symptoms, and we needed to be currently taking a certain inhaled drug regularly.
It so happened that I had been recently seeing a specialist and had gone through nearly the full range of available treatments looking for a combination of drugs that would control my asthma, allow me to exercise without closing down, and yet not kill my voice. The drug that Amgen required subjects to be taking regularly was one that I'd had to reject because I couldn't record the show when I was on it, so I was effectively disqualified from the trial. Disappointed, I prepared to leave, when I was surprised to hear "That's OK, we'll just say you take it," and then, handing me a sample, "Here, now you have some."
Moment of Truth #1. It appeared to me they were fudging. However I knew nothing about their program, and couldn't know how significant this might be. I made a strong mental note of the red flag, and went along with it. And I saw them falsely note in my records that I was a daily, regular taker of this particular inhaled medication, having been quite clear with them that I had not, and would not, be a regular user of this medication.
Moment of Truth #2 came during one of the many whispering sessions they gave me. The lead technician had a disturbing habit of frequently pulling me into a corner or another room and whispering things like "We're just going to say that you take this medication." I had to fill out numerous questionaires, and she would often stand over me and whisper which answer I should mark. At last, one day after a battery of breathing tests, questionnaires, and vital-sign checks, it was required that the doctor (listed as the principal investigator on this study) verify all this, personally examine me, and sign off on it. Amgen was very clear on that point. "But he's not here today," she whispered, "so we're just going to mark this off and send it through. We've already done everything he was going to do anyway." By now I knew this contractor was willfully and knowingly giving Amgen invalid data, and I resolved to stick with it only long enough to see what more I could learn. I'd already decided I would not complete the trial and contribute bad data to a medical clinical trial.
All of the above paled in comparison to Moment of Truth #3, to which I alluded before: the breathing tests. The most important qualifier was that I react sufficiently well to the inhaled drug they falsely claimed I was taking regularly. This was done by giving me a tube connected to a machine connected to a computer, through which I had to sharply inhale, then exhale as hard and as long as possible, to the very limits of my endurance. This was quite taxing, and once I actually passed out. I had to repeat this until I achieved three consistent results. I would then take a nebulizer dose of the inhaled drug and repeat the whole test, and there had to be a certain percentage improvement over baseline to qualify for the study. This computer was owned by and directly connected to Amgen to leave no opportunity for clinics to fudge results. However, this particular clinic had a secret weapon.
In a separate room, they had their own duplicate machine, but not connected to anything. This was their "practice" machine. Before using Amgen's machine, they'd first take me into the other room and have me try various levels of sharp inhalations that were somewhat less than my maximum. My whispered instructions were to try a little harder, then try a little less, until I was able to consistently give just the poor enough "before" measurement Amgen wanted, followed by an "after" measurement that showed just the right amount of improvement. I'd then go back to the "real" computer and blow just exactly the desired counterfeit data into Amgen's system.
Once I was accepted into the trial and qualified to receive my first injections of Amgen-coded syringes that might contain the real test drug or a placebo, I resigned from the trial and now report it here. I debated whether or not to name names (as you can see I chose not to), as the value of the report is not to impugn individuals, but to illustrate how and why we should maintain a healthy skepticism even of randomized, controlled trials that are reported as having been well-designed, as I've no doubt this one will be.
The punchline? Upon my resignation, I was required to have early-exit interview by the doctor. But it was whispered to me that "He's not here today, so we'll just skip that."
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