May. National Cancer Research Month and having somehow morphed into a research geek, deeply passionate about the need to educate, to share what I've learned, and hopefully to dispel some of the things I hear, let's dig in.
First, a disclosure: This piece, presuming it is coherent and cohesive when complete, will be submitted to Clara Health's Patients Have Power Writing Contest. Yes, there will be prizes awarded and no, I don't expect to be the recipient of one of them.
However, I am *All In* with any initiative by any organization designed to shine a light on the need to help all of us understand that breakthroughs in medicine only happen through research, and research means conducting clinical trials. Above all else, clinical trials don't happen unless patients are stepping up to participate in trials for which they may be eligible.
Did you know, depending upon where you look for the information, a mere 3-5% of cancer patients participate in clinical trials? Let's look at the flip side. More than 90% of us may be walking around with answers locked inside our bodies which begs the question: "WHY?"
The truth is, there's no one simple answer. It's complicated. There is room for much improvement in every aspect of the process. A quick search on clinicaltrials.gov shows there are currently almost sixteen thousand trials across all diseases being studied that are currently recruiting, or are nearly ready to begin to recruit patients.
There's the first problem. How can any one doctor or office be expected to be fully versed on what trials might be appropriate for a particular patient? Then, if the trial is being conducted in a place that is outside of the doctor's office or institution, and presuming they are aware the trial is ongoing, would they suggest it as an option at the risk of having their patient seek treatment elsewhere? I have no answers but this is one place where an engaged patient, or a loved one acting on their behalf, might have impact.
Trolling through trials, however, is something most of us are not equipped to handle without assistance. It was years after my active treatment was over before I even learned that clinicaltrials.gov existed. The site was recently overhauled and it is now easier to fine tune the results but it's still an overwhelming process. With a host of other clinical trial matching services in play, there are other ways to search, but the space is still evolving making that a post for another day. The quickest answer I have for this, Just ASK. Don't wait for a red carpet rollout or a hand-engraved invitation, ask your medical provider if s/he knows of any ongoing trials, or if they don't personally know of any, ask how you might investigate on your own.
Having just made a suggestion, let's first acknowledge one thing: Disease Shock - as this leads directly to the next problem. When the word "cancer" is spoken, and you happen to be the person in whose body cancer has taken up residence, most of us become mentally crippled for a period of time as we attempt to navigate an emotional minefield that nothing can prepare us for. Speaking personally, when I showed up for my post-biopsy appointment in July of 2006, I knew. The night before the appointment, I just knew I was getting bad news the next morning. Knowing, and then hearing those words - anticipated fears now a reality, all I can say is that is akin to entering some sort of alternate universe.
I was armed with a list of questions. I asked none. I recall the doctor gently and kindly asking me with a bit of surprise if there was anything I wanted to ask her. Thankfully, my mom was beside me and she asked the most important questions about the immediate next steps. Not once did anyone in that room mention clinical trial participation as a treatment option. Even weeks later, at my first appointment with my oncologist when I learned I would need chemotherapy, I was still reeling and again, it was my mom and my very dear friend seated with me - taking notes and asking questions. Aside from asking if he was planning to test my tumor to help inform chemotherapy decisions using what was then newly available (Onco-Dx for the curious among you **), I was still in the cancer-mute phase. And again, participation in any sort of trial was never mentioned.
Fast forward, five years post-treatment: Early research findings were being presented at the annual San Antonio Breast Cancer Symposium. Watching from afar thanks to a lively twitter feed, I learned there was a trial for which I would have been eligible and one in which I know I would have participated. When I was finished with chemotherapy and the last big surgical procedure to have my temporary implants exchanged for the long lasting version was quickly approaching, I had a lengthy discussion with my oncologist regarding the need for medication for the next five to ten years. We discussed the risks and the benefits of each of the different drugs. My choice was a drug that is known to cause bone loss thus increasing the possibility of bone fracture. I clearly recall stating that I'd deal with a broken bone to reduce the risk of a cancer recurrence. The latter was terrifying. The former, in my mind, was just a plaster cast.
He never told me there was an open trial, currently recruiting patients just like me. The site of this particular trial was at a neighboring institution, just miles away from the hospital where I was being treated. The trial was designed to see if the addition of a second drug, already widely in use, would help mitigate problems associated with bone loss frequently seen in patients on certain post-chemotherapy medications including the drug we had decided was the best option for my circumstances. In the course of the study which I only learned of years later and did not participate in, there was an unexpected and far more important benefit observed by the research team. While the primary aim of the study was to assess whether this helped prevent bone loss and then, seeing how this may (or may not) have helped minimize fractures, they saw a reduction in the spread of cancer to the bones in the patients who began receiving this "add-on" treatment. It was an unanticipated finding and one that was a pretty big deal. Because of that observation, new studies have since been developed and are ongoing to validate those observations.
And what happened to me? Well, I had to fight to have this medication administered. Medically and technically, it is to address my ongoing bone deterioration. It is approved for use in osteopenia which, for the record, I was diagnosed with before I learned of my cancer. Had I been asked if I wanted to learn more about a possible study, I know I would have said yes. If I were more savvy, I would have been searching for possible trials, even though my cancer was found early.
I never asked, and no one on my treatment team ever uttered the words "clinical trial." Back then, I don't even know what I grasped of the research landscape. I'm sure, like so many still believe, enrolling in a clinical trial is the proverbial Hail Mary pass: Participating in research is only for those who've run out of all approved treatment options. Not.True. (Mostly Not.True.) Ditto that all too familiar phrase uttered by many, "I don't want to be a guinea pig!" or "What if I get stuck on the 'sugar pill'?" both of which are typical and understandable statements. Until we understand.
The single most important piece of the clinical trial process? Informed consent or, in a far more patient-focused world, I prefer to call this educated consent. That language makes it crystal clear that true understanding is at the very heart of any, every and all decisions along the entire process that may lead us to choose to participate in a clinical trial. What are the risks of participating? What exactly are you planning to do to my body? Who's paying for it? How much time will this require above my normal visit schedule? Center Watch takes an in-depth look and provides a plain language explanation of clinical trials and the different phases, informed consent and contains a wealth of additional information. It's worth the trip.
Technically, we are adding to a body of knowledge so in a sense, personally, I have no problem referring to myself as a lab rat. We may derive a benefit, we may not. Here's the thing and it's something that is a critical piece of this entire landscape. When there is a treatment that is known to be the best (or, in plenty of cases when there are a number of approved options) for any given disease, it cannot and will not be withheld. There are so many rules and regulations in place to protect the safety of everyone who chooses a clinical trial as a treatment option.
So, are you really a guinea pig? Not so much. The research and clinical community is generally studying things like adding a new drug to combine with the drug that you are likely already taking. Or, they may be studying things like increasing the dose. In both of these cases, they are trying to determine if a different dose or the addition of a new drug works better than what you are currently on. Said another way, they are *not* taking away what works - that would be unethical and it's simply not done. Even in those for whom there is no available treatment option, still, they aren't taking away anything. Sadly, there are too many subsets of patients who've run out of all treatments or who never had any available treatments to begin with. They are seeing if they can make the drug work better (or at all), or attempting to reduce side effects, to extend life, to preserve or improve quality of life. Admittedly, that's a gross oversimplification but that's the broad overview.
If some people are going to be on the real drug and others are going to be on a placebo (aka, the dreaded "sugar pill"), should you really care? Well, if that's what's stopping you here's a thought. If you participate you have a 50/50 shot of real drug vs. placebo. If you don't participate you have a zero shot of getting anything new or novel or in the best possible case, a breakthrough. And while I can't state with certainty how frequently this happens, if the research team sees a group of patients on the trial with what appears to be exceptional responses, the trial will be "unblinded" and everyone will be offered the real deal. What else happens? The rest of us, those not on the trial at all, now have to wait, likely years, for the findings to be presented, for the FDA to approve the drug while those of us who didn't want to be the guinea pig or risk being assigned to the placebo get to sit on the sidelines, spectators to what could be the next big thing.
As researchers and clinicians are now well beyond simply utilizing different treatment options and are looking at the characteristics of so many diseases and the interaction with other things happening in our bodies to understand things well beyond my pay grade, I'm hopeful we are at a true inflection point.
Precision medicine is not merely a buzzword. It holds the promise of allowing our clinicians to administer the best available medication in the most effective and tolerated dose, to the right patient, at the right time with the hope of delivering care that will afford the best outcome for each patient. Fulfilling the promise of precision medicine starts with the most basic science. It starts with tissue or fluid donation and continues along the entire trajectory to using new compounds or combinations of drugs, or reducing/increasing dosages, or even changing the dosing intervals. All of this requires rigorous testing before changes are made.
Researchers have ideas. They fight for funding. They develop trials along the entire trajectory - from "first in human" small studies to large post-approval observational studies to determine what is experienced outside of the controlled conditions in the lab to make real-world observations. None of their work can succeed without our clinical partners speaking with us about all of the available options. We must be willing to listen and carefully weigh every option. A substantial percentage of clinical trials are closed each year. They must meet accrual goals within a specified time frame. Closing a trial after successfully obtaining funding, getting the necessary pre-trial approvals in place and then expending funds to set up the lab is a lost opportunity to learn something. The loss of the money used to put everything in place troubles me - the money is gone forever and unless someone finds a way to begin growing a magic money tree, those were precious research dollars. Wasted. And tragic. While I can't provide an amount, I do know it's substantial. Add up the losses and then subtract from the already strapped funding circumstances and we have one of those dreaded "situations," that I do think can be resolved.
I submit that a rigorous examination of trials that were forced to close because of accrual/retention failure as a means to understanding what happened, in its entirety, with the hope of identifying the barriers and finding possible ways to address the problems. Was the eligibility to participate too narrow and if so, could it have been broadened? Perhaps the question being addressed wasn't one that was important to the target group of potential study participants? Maybe the requests being made of the participants were simply too burdensome? Or was it as I mentioned before: the failure to accrue (and/or keep people on the study) was the result of a communication gap; somehow the trial was lost in transition between the lab to the clinic, the clinical to potential, eligible patients. Scientist are the idea experts, determining which questions they believe must be answered to achieve better outcomes for patients. Regulators make sure every "i" is dotted, "t" is crossed. Aligning the goals and expectations of all by including patients in every part of the process may be one way to help mitigate this problem. While I'm on this soapbox, addressing concerns unique to all underrepresented ethnic and minority groups in culturally appropriate ways, might afford more diverse participation, with findings that prove to be much more robust and more accurately reflect nuances across all patient populations.
Clinical trials aren't for everyone but I have to believe, at least in the cancer space, the percentage is far higher than what we are seeing. I do think many more than 5% are willing to step up. While trials are designed with little wiggle room for switching things up, it is important for everyone to remember, simply because you decided to step up for a trial, you can change your mind. You control you and at any point, you are free to voluntarily withdraw from any trial and continue treatment using already approved drugs.
The bonus add on? You will be monitored closely. In fact, the likelihood is that you will be monitored far more closely than you would be if you are not part of a trial. The trial team may determine you must come off the trial if they observe things that are detrimental to you. In a perfect world, the criteria for eligibility should be expanded whenever possible-and that is an area in which I am currently lending my voice for the benefit of the widest possible group of patients. Without getting all science-y, adaptive clinical trials are being used to do just as its name suggests - adapt the trial to the what is being observed in patients by the research team. The I-SPY trials are a great example of this.
We're all in the same ballpark but each of us is standing on a different base. The clinicians are on their base, the researchers on another base, and we, the patients, are on yet another. It's time for everyone to bridge those bases, to begin communicating in ways each may hear and understand so we can hit this out of the park: For ourselves, for the possible benefit of at-risk family members, and for the greater good of all.
(Post script: to the cynics, the skeptics, those who continually insist "the cure is in the closet," you could be right and this may be true. The problem? Until we open the closet door and study what's inside, it will remain in that dark closet with the door firmly shut.)
**As if by magic, recent findings from a landmark trial using Onco-Dx to inform chemotherapy decisions were just presented at the annual ASCO meeting in Chicago. The findings from the TAILORx trial have been splashed all over the media and this is a big deal. The findings will spare many from overtreatment but the key take away for the purpose of this post: a big thank you to the 10K+ women who stepped up to help answer a big question for the rest of us!
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