By Adam Cohen
The author decided to learn about clinical research by volunteering as a study participant there was only one, small problem.
I’ve never been a big fan of needles. The very mention of the word takes me back to the allergy shots I received as a kid. Every spring and summer, ragweed and pollen reduced me to a sneezing, itchy, red-eyed mess. Still, if my mom had given me a choice, I would have opted to live with a perpetual case of hay fever, because the cure seemed so much worse.
Even now, just thinking about my weekly visits to Ms. DeSilets, a kindly nurse who lived around the corner, makes my heart quicken. And not in a good way.
The antiseptic tang that filled the air when she twisted the cap from the bottle of rubbing alcohol. The faint whoosh, whoosh, whoosh the cotton ball made while she wiped my skin clean. Then—don’t look, don’t look, why did I look?!—the grab of the needle as she plunged its slim shaft into my shoulder.
Still, like so many fears, I suspect this one originated from a deeper place. Something evolutionarily hardwired, like a primordial dread of snakes and high places.
My aversion to needles stops me from giving blood. It transforms my annual physical into the nadir of my year, a vein-pricking nightmare that marches inexorably toward me for 364 days. On numerous occasions, the mere sight of a needle buried in the skin, extracting or inserting vital fluids through an attached tube, has left me dizzy and drenched in sweat.
When a nurse ran an epidural into my then-wife’s lower back in preparation for the birth of our first son, it was I who nearly passed out. “Hello!” I remembered Julie saying with—understandable—irritation as the nurse and her mother attended to me. “I’m the one with a needle in my spine about to have a baby.”
So, it’s hardly surprising that, in 17 years of working at OMRF, I’ve never volunteered as a clinical research subject. Until now.
In clinical research, scientists study health and illness in people. Simply put, this work involves human participants, and it offers researchers a way to probe the hypotheses they’ve developed in laboratories.
At OMRF, much of that clinical research centers on autoimmune disease. In these conditions, which include lupus, multiple sclerosis, type I diabetes and rheumatoid arthritis, the immune system becomes unbalanced and, as a result, turns its weapons on the body’s own cells. To date, researchers have identified more than 80 different autoimmune illnesses. The National Institutes of Health estimates that, together, these disorders affect approximately 25 million Americans.
Dr. Judith James leads OMRF’s research efforts in autoimmune disease. She heads the foundation’s Arthritis & Clinical Immunology Research Program, where more than a dozen different laboratories seek out more effective ways to treat and prevent autoimmune diseases. James also serves as OMRF’s Vice President of Clinical Affairs, a position that marries laboratory investigation with clinical initiatives, a category that includes both patient care and human research studies.
An M.D. rheumatologist and Ph.D. immunologist, James has spent more than a quarter-century studying how autoimmune diseases begin. From the get-go, clinical research studies have served as a keystone for her work.
“We are focused on trying to understand the difference between human health and pathogenic conditions—disease,” says James, who holds the Lou C. Kerr Endowed Chair in Biomedical Research. “To do that, we need participants from a broad variety of different health statuses.”
Like clinical studies done by most medical researchers, James’ revolve around the collection of biological samples from human subjects. Volunteers fill out questionnaires about their medical histories, then donate blood (and, on occasion, saliva, hair and other biological materials). The volunteers typically fall into two, distinct groups: those with the condition that researchers wish to study, and healthy “controls.”
“Healthy controls give us a way to compare the group we’re looking at with a ‘normal’ population,” says James. To the extent that researchers can control or match as many variables—things like age and gender—in the healthy participants with those of the study population, it allows them to tune out potentially confounding factors and zero in on what might be causing different health outcomes in the two groups.
In autoimmune disease, though, there exist many shades of gray. Sometimes, individuals who think they are healthy may, in fact, be carrying certain proteins in their blood known to predict the onset of conditions like lupus and rheumatoid arthritis. These people may have some clue, like an affected relative or a stray symptom, that they could be teetering on the edge of autoimmune illnesses. Or they may have no idea at all. Either way, it’s this group that plays a central role in James’ research.
“Over the past decade, we’ve been trying to understand where autoimmune disease starts. We’ve learned that some is genetic risk, and some is the development of abnormal blood proteins,” she says. “We also know that family members of patients sometimes have the same blood markers but never go on to get sick.”
Separately, observational studies had found that when physicians treated autoimmune disease patients with a common anti-malarial medication, the patients showed improved mortality rates and lower incidence of heart disease, diabetes and other disease-related complications. Better still, the drug, Plaquenil (hydroxychloroquine), has been available to patients for many years and, says James, “has a very low side-effect profile.”
Fitting these pieces together, James and her colleagues hypothesized that if they were able to identify individuals at risk for developing autoimmune illness—before they actually developed full-blown disease—giving them Plaquenil might slow disease onset. It might also lessen the symptoms when illness eventually took hold.
“Even when patients come to the doctor and get all the best medicines we currently have, the disease still leads to deformities, shortened lifespans and things we just can’t fix,” James says. “Now, we might be able to dial this back and prevent people from moving into full-blown lupus.”
To test the theory, James and her fellow researchers organized a pair of clinical research studies. One (known as SMILE) examines people predisposed to lupus, while the other (StopRA) looks at those likely to develop rheumatoid arthritis. Both follow the same blueprint: identify at-risk individuals, split them into two groups—one treated with Plaquenil, the other with placebo—and see what happens next.
Recruiting volunteers who don’t know they might develop lupus or RA seems like a metaphysical impossibility. Yet, it turns out, that’s precisely where I come in.
OMRF’s Rheumatology Center of Excellence is tucked into the first floor of the foundation. I walk by it every day multiple times—on my way to the cafeteria, a conference room or one of many other destinations. Other than when I guide an occasional lost patient to its doors, the space rarely registers a blip on my consciousness. But on this day, it lights up all the synapses in my frontal lobe.
I sit in the Center’s infusion suite, in a chair designed to allow someone to draw blood from either of the occupant’s arms. But at this moment, I am otherwise occupied.
Terese Aberle, a physician assistant with more than a decade of experience working with lupus and RA patients at OMRF, is going over my screening questionnaire with me. I’ve filled out five pages detailing my general health history, plus another form devoted specifically to issues I might have with my connective tissue, a telltale signal of autoimmune disorders.
Most of my answers to the “Have you ever had…?” queries are no. This bodes well for my health, but not for my eligibility for the SMILE and StopRA trials. Still, one particular response has piqued Aberle’s interest.
“Tell me,” she says, “about your fingers changing color in the cold.”
Sometimes, I explain, my fingertips become white or purple after I’ve finished a long run on a winter day.
She palpates my fingers. “Any sores?” I shake my head no. “Any pain or numbness when they warm up?” Again, no.
“The color change could be a sign of Raynaud’s syndrome,” which can be linked to certain autoimmune diseases, she says. But because I have none of the secondary symptoms, she explains, “It’s probably nothing to worry about.”
Aberle proceeds to examine the joints in my fingers and toes, squeezing gently at each juncture. She shows particular interest in the joints that connect my fingers to my hands and my toes to my feet. “If you had rheumatoid arthritis, those would be swollen and sore,” she says. Happily, mine are neither.
By the end of our session, Aberle tells me she’s found no overt signs of autoimmune disease. Oddly, I feel somewhat deflated. “Does that mean I can’t be part of the study?”
“We’ll still go ahead and draw your blood,” Aberle tells me. “If you test positive for certain biomarkers, we could still enroll you.”
If not? “We’ll use your samples as healthy controls for the Oklahoma Immune Cohort,” a collection of other clinical research studies of autoimmune diseases.
Although I’m neither a Ph.D. nor an M.D., I’d wanted to contribute to the research that goes on at OMRF. And now, she’d assured me, I could. All that remains is to draw eight vials of blood from my arm.
Like all research involving human participants, studies at OMRF are overseen by an institutional review board, or IRB. Created when Congress signed the National Research Act into law in 1974, IRBs provide an independent review of studies that seek to use human subjects to answer a research question. Their charge is three-fold: ensuring that research is conducted in an ethical manner; verifying adherence to federal regulations and state laws; and protecting the rights and welfare of human subjects.
Lawmakers saw the need to create IRBs in the wake of World War II, where Nazi physicians and scientists conducted savage experiments on concentration camp prisoners. But ethically questionable research happened in the U.S., too. The notorious Tuskegee syphilis study denied treatment to hundreds of black men living with the disease for decades, even after penicillin became a known cure. And at Philadelphia’s Holmesburg Prison, researchers in the 1950s and 1960s exposed inmates to a variety of dangerous compounds, including the active ingredient in Agent Orange, the cancer-causing defoliant used by American forces in the Vietnam War.
IRBs introduced a novel concept. Rather than scientists operating autonomously, an independent committee would oversee their work. “The IRB’s focus is the person volunteering to participate in the research,” says Dr. Eliza Chakravarty, who chairs OMRF’s IRB. “Our goal is to ensure that the design of the study is as safe as it can be for the participant. And to guarantee that people are fully informed of the potential risks and benefits before they enroll in a study.”
IRBs consist of individuals from a wide range of backgrounds: people with scientific and medical training, legal experts, ethicists and members of the community at large. Like a jury, each member brings unique perspective and expertise. Together, the group possesses knowledge and insights greater than any of its individual members. This diversity of viewpoints and talents, along with the board’s independence, makes the IRB an ideal body for ensuring that every research project involving human participants is conducted in an ethical, safe and legal manner.
An attorney, I joined OMRF’s IRB in 2004, as its legal expert. While I’d already spent a decade practicing law, this represented my first foray into the realm of human-subjects research. In the 15 years since, what I’ve learned about this highly regulated area of the law could fill a textbook. Nevertheless, in a field as highly regulated, complicated and rapidly evolving as this, what I don’t know would also fill a tome, and probably a thicker one at that.
While one of our charges is to review and approve each of the more than 100 protocols that are typically active at OMRF, the task that occupies the lion’s share of our time is monitoring the 30 or so clinical trials underway in the foundation’s clinics at any given time. Unlike a simple blood draw, where participants would expect neither considerable risk nor benefit from participation, clinical trials test experimental treatments on patients suffering from disease.
“In the development of new medications or other approaches to treat a disease, we need to go through a scientifically rigorous process that ultimately will tell us in an objective way if our approach is effective,” says Dr. Gabriel Pardo, Director of OMRF’s Multiple Sclerosis Center of Excellence. “We also look at whether the therapy is safe. Are we putting people at risk for other problems?”
Every drug available in the modern era has gone through this process, says Pardo, who currently oversees clinical trials for roughly two dozen multiple sclerosis medications at OMRF. And for patients with conditions like MS, trials offer direct benefits.
“First, they receive access to medication that is not otherwise available that might prove to be very effective or even revolutionary for their disease management, and this access usually comes years before the therapy would be approved by the FDA,” Pardo says. Also, the study sponsors—usually, the pharmaceutical companies who’ve developed the new treatments—provide the treatment free of charge. “That means patients often don’t have any out-of-pocket expenses.”
For those affected by MS, a progressive condition that can rob its victims of mobility, balance and sight, a typical course of treatment involves regular infusions with biologic drugs. The annual cost of treatment with even one such medication can run $40,000 or more. Patients without insurance, or those whose insurance won’t pay for certain drugs or carries significant deductibles or copays,
“My medication was $3,400 a month, and my insurance didn’t want to pay,” says Tonja Martin of Oklahoma City, who was diagnosed with MS in 2010. “So, I had to start using my money I’d saved for retirement to pay for it.”
Pardo, who was treating Martin, offered her the chance to participate in a clinical trial of an MS medication that had yet to reach the market. Like many such studies, this one was a “double-blind” trial, meaning that neither she nor Pardo would know if she was receiving the experimental drug or a placebo. Still, Martin jumped at the opportunity.
“I decided to try it, and the program had me go in for an infusion every six months,” she remembers. Like most new biologic treatments for MS and other autoimmune diseases, this one was time-consuming; the infusion process took seven hours. Still, Martin quickly found that it paid dividends. “I knew after the second treatment something was different.”
Even though she couldn’t know for sure, she was convinced her I.V. treatments contained the medication, not placebo. “I went from dizzy and feeling like I was falling to having a more normal life—more energy and more confidence doing things. I felt like I used to feel.”
Martin continued on the trial until its conclusion. At that point the sponsor, a drug company, “unblinded” the trial and revealed that she had, in fact, been on the drug. The company then permitted her to continue receiving the medication as part of continued evaluation of the drug’s benefit and side effects at no cost through 2021.
Not every clinical trial works out this way. Some drugs prove ineffective. Others carry side effects that end up outweighing their benefits. And, regardless, many patients receive doses of placebo rather than experimental therapies.
Still, for Martin, the process has been “miraculous. I had relapsing-remitting MS, and now I’m living symptom-free.” She’s received almost seven years of free medication, saving her hundreds of thousands of dollars in potential drug costs. “I don’t know what I would have done. Literally.”
Martin opted to take part in the trial because “whether it worked for me or not, at least I would have tried to help and would have been a part of helping others.” That desire, born of altruism, has now paid dividends she scarcely dared hope for. “OMRF,” she says, “has saved my life.”
As it turns out, my blood draw is no big deal. Jackie Keyser, a registered nurse with decades of experience, looks approvingly at my right arm as she ties a rubber band around my bicep. “You have good veins,” she says. “This should be easy.”
She gently slides a needle into the hollow of my elbow, makes a bit of small talk with me, and before I know it, she’s pulling the rubber band from my arm.
“All done?” I ask, finally mustering the courage to look.
“Yes,” she says, removing the needle and applying pressure to my vein for a moment before wrapping it with a bandage. “You did great.”
A week later, I’m sitting at my desk, when Keyser’s name pops up on my phone. When I answer, she tells me, “We have your test results.”
My complete blood count came back normal. The same was true for my anti-CCP antibody test, which indicates that I neither have nor am at risk for rheumatoid arthritis.
A test of my anti-nuclear antibodies (ANA), a possible signal for lupus, came back at slightly elevated levels. But, Keyser explains, “As we grow older, these tend to run a little bit higher.” So, as a 51-year-old, I had nothing to worry about.
I won’t, I realize, be needed for the StopRA or SMILE trials. My role in this process will end with this phone call. Still, I confess, I’m a bit disappointed I can’t be of more help. I’ve only just gotten started, and already I’m done.
That’s not exactly true, she reminds me. Researchers will store my blood as part of the Oklahoma Immune Cohort. There, they’ll use it for years to come, comparing my immune system to those of patients with conditions like lupus, MS and RA.
Besides, Keyser reiterates, “This is very good news. You’re a perfect healthy control.” I hang up the phone, letting her words sink in.
After a moment, I make a promise to myself to volunteer for another research study. In the grand scheme of things, maybe needles aren’t so bad after all.
