CLINICAL TRIALS – the Good, the Bad, and the Semi-Ugly

We all do it. And, we’ll keep doing it. What is “it?” Judging from the title above, you’d think I’m talking about clinical trials for medical research, but that’s not exactly what I’m getting ready to examine. “It” is the bragging about clinical trials. Not the bragging about the number and scope of available trials where I’m as guilty as anyone. Rather, I’m talking about the new trend of boasting about a high percentage of one’s patients entering clinical trials, be it an individual physician or an institution.

Somewhere along the line, the public came to equate clinical trials with “better care,” “more advanced care,” or “cutting edge care.” And from there, it was just a hop, skip and jump to design a marketing strategy based on that misconception. So, my first point is this – a physician can provide top quality, cutting edge patient care without participating in a single clinical trial! That said, all improvements in medical care are 100% dependent on clinical trials, so it is critical that we have these studies in place. And, it is critical to enroll patients. It is so critical, in fact, that the Commission on Cancer, the organization that accredits hospital-based cancer programs, sets a mandatory minimum for enrollment in clinical trials (lest we get lazy about it).

In spite of public perception, though, clinical trials are not to be confused with “better care.” In fact, the volunteers randomized to the study group are at risk that something unforeseen could go wrong, prompting a too-late wish to have been assigned to the safer placebo group. In the earliest days of Herceptin™ research, access to the clinical trials was difficult. It helped to be living in Southern California where the drug was developed. Nevertheless, I had one newly diagnosed breast cancer patient in her 30s who wanted to be part of the clinical trials that, in the end, proved Herceptin™ to be a miracle drug for many. But it wasn’t so miraculous for my patient who traveled to California to enroll in the trial where she was given Herceptin™. She proved to be in that small group of patients where researchers discovered the potential of cardiac damage, especially when Herceptin™ was combined with Adriamycin™. She did not make it back to Oklahoma alive, instead, dying of the cardiac damage from the treatment regimen in her clinical trial. Her pioneering spirit is a great benefit to those women today where meticulous care is taken to avoid cardiac injury, and it can be argued that lives are saved accordingly. Yet, I still recall her unbridled enthusiasm to be part of a clinical trial where the experimental treatment ended her life, not the cancer.

The point is this — clinical trials are research trials, and some people are harmed in the study group, a fact often lost in the PR. “We turn more patients into guinea pigs than any other facility in the state” doesn’t quite have the same ring to it as what we hear on TV, does it?

Granted, in oncology research, terminal patients are given access to new treatments that are not otherwise available to others in the same boat. And in Phase 1 (is it safe?) and Phase 2 trials (is it effective?), a volunteer can usually receive the proposed new treatment rather than placebo. But in Phase 3 trials, where the new agent is further along in development, a volunteer is less likely to receive the experimental drug, given the mandate in late stage trials for a control group that receives the “standard of care.”

Yet, 50% of late stage trials fail, and 75% of early stage trials fail. Failure doesn’t necessarily mean “harm” was done, rather, it’s usually a simple lack of benefit. From the patient’s standpoint, that’s not a very attractive selling point. But from the researcher’s standpoint, it’s all good. Even a failed trial offers information. But what the public may not appreciate is that there are perks for the researchers, whether or not the trial is successful.

First and foremost, there’s dollars to be made. Researchers earn salary support and institutional income with each patient enrolled. Most academic centers are highly dependent on this income. The more patients who enroll, the better. Pharmaceutical-sponsored research can be very lucrative, whether the trial is successful or not. Many years ago, I experienced an encounter I call “The Graduate” moment for me, when a colleague was critical of my chosen line of research (it was non-income-producing), and told me to remember just one word – “Pharmaceuticals.” For Dustin Hoffman, it was “plastics,” but close enough. In a word, I was being told to consider switching my research focus to something else wherein a drug company could be pulled into play for the benefit of the university’s pocketbook.

Even if a researcher’s heart is not stirred by profit or job security, most scientists are happy with recognition. Thus, being the “top recruiter” to a clinical trial can bring such honors as “first author” on a paper, or a presentation at a meeting, or any of the other recognitions that define success in the academic setting.

On rare occasion, the desire for fame (with or without fortune) can be so strong that patient records are falsified in order to pump up the numbers recruited to clinical trials. One of the more famous examples occurred when, in the early 1990s, Dr. Roger Poisson at Saint-Luc Hospital in Montreal falsified data so that more women were admitted to NSABP clinical trials, most notably the B-06 trial that was the landmark study proving the equivalency of lumpectomy and mastectomy. Although falsified records were only documented in relatively few cases, his entire contribution of patients to the B-06 had to be tossed out, and all outcomes re-calculated. Because Dr. Poisson had been a top recruiter (personally adding 354 patients to the 2,163 in the trial), it threw the entire conclusion of the B-06 into doubt, prompting a nationwide panic about the safety of lumpectomy. And when NSABP head Dr. Bernard Fisher did not jump through the hoops fast enough to suit the federal government who had helped sponsor the research, he was stripped of his position by the feds. Later exonerated, the scandal may have contributed to the fact that Dr. Fisher never won the Nobel Prize (not yet anyway, he’s still alive in his 90s, while Dr. Poisson passed in 2013). Dr. Fisher has won every other award medicine has to offer, but the Nobel committee can be pretty stuffy when it comes to scandals.

But such extremes aside, there’s something semi-creepy about creating hierarchies based on enrollment in clinical trials wherein the researchers are guaranteed benefit, but the patients are not.

When an institution boasts 90% enrollment of its patients in clinical trials, hopefully it implies that the facility is participating in a large number of available trials so that there’s “something for everyone,” and that’s fine and dandy. But there’s another way to get 90% enrolled in clinical trials, even if only a few trials are open. Informed consent can be cast with an optimistic spin, such that the patient, at a highly vulnerable point in his or her life, may acquiesce to the pressure in order to please the doctor, a phenomenon well-documented. Here, the susceptible patient coupled to a convincing sales pitch does the trick.

The “clinical trial” has become so sacred that to proffer even a weak word of caution might be considered heresy. But remember, I stated at the beginning, “We all do it.” My facility brags about clinical trials just like everyone else. I suppose it’s better than bragging about nebulous qualities, like “the best doctors with the highest cure rates.” But make no mistake — boasting about clinical trials has an undeniable self-serving feature. The majority of researchers and basic scientists have their hearts in the right place, motivated independently of the perks from clinical trials. Still, there’s a used car salesman component here – you, the consumer, may or may not get a good deal, or you may even get a lemon, but you can rest assured the dealer and the dealership will not lose.

Advertisements