by Bridget Mueller MD PhD | Jul 7, 2023 | Clinical trials
By Bridget Mueller, MD PhD.
The PAIRED Project team is always excited to meet new research participants. Usually, our research coordinators have spent a lot of time talking to them in advance and planning out the details of the visit over multiple phone calls. But surprisingly often, after all this lead up, the participant doesn’t show up and then stops answering our calls. Some of our Gen Z team members started using the term “ghosting” to describe these events, referencing the broader cultural phenomenon of abruptly cutting off all contact without explanation.
As someone relatively new to clinical research, I found the phenomenon confusing. And after spending several days talking to our team members and my own clinical patients, I’ve concluded that there is neither a simple nor single answer. People are complex and the reason an individual decides, seemingly at the last minute, not to participate in a study is likely multi-faceted, involving social, cultural, and logistical barriers. But I have a hunch that personality may play an important and perhaps underappreciated role in ghosting (at least in the research context). In a classic experiment called “the open field test,” a mouse is placed in a 3-foot by 3-foot white plexiglass box for five minutes. Normally, mice spend the first minute walking cautiously along the edges, remaining in the shadows, before exploring the open, bright center. Out in nature, this evolutionarily adaptive behavior reduces the risk of being spotted by a flying predator. But mice who are more vulnerable to stress spend the majority of the five-minute test hugging the perimeter of the box. Even when baited with a few tasty peanut butter morsels, most don’t venture to the center of the box for long.
As an introvert, I felt a connection to these cautious and sensible mice. Is a peanut butter chip really worth being eaten by a hawk? Maybe our ghosters are like me and my perimeter-hugging mice. Despite a genuine desire to participate in a clinical trial, perhaps when the time comes to actually leave home to meet new people, answer personal questions, give blood, and engage in all the other research procedures, the fearful brain takes over and our prospective participant turns off the phone and remains on the couch.
So, how, as scientists, do we increase the likelihood that an introvert in pain will show up for the studies that are needed to find new treatments? Community engagement? Fewer in-person study visit requirements? I’m not sure, but the Paired Project is going to start asking. We’re acknowledging that participating in science can be hard, particularly when in pain, and we will ask every potential participant, “What can we do to make this visit easier for you?” We’ll let you know what we learn.
by PAIREDProject | Jun 9, 2023 | Clinical trials, Pain
By Jessica Robinson-Papp, MD MS
Every Thursday afternoon, I meet with my collaborator and friend, Dr. Monica Rivera Mindt. Dr. Monica Rivera Mindt. Dr. Rivera Mindt is a community engaged researcher who has spent decades living and working in the Harlem neighborhood of New York City focusing on brain health, specifically the mechanisms underlying racial and ethnic disparities in cognitive decline. Last week we got to talking about the different ways we have engaged with communities and how successful it has been in supporting many of our studies, particularly those focused on brain health. Today it’s the norm to include people with lived experience in the design, execution, and reporting of all kinds of clinical research. But like many things that we start to take for granted, if we don’t periodically stop to reflect on why we do something, we risk losing purpose and authenticity. Following our conversation, I wanted to remind myself of the fundamental reasons for community engagement in research. Why do we think it’s a good idea and what do we know about its effects on outcomes? I also wanted to think more specifically about community engagement in the context of pain research. So I indulged myself in little reading.
I found a comprehensive chapter on ResearchGate (published in 2008) describing the evolution of Community Based Participatory Research (CBPR) titled: “The theoretical, historical, and practice roots of CBPR,” by Bonnie Duran DrPH of the University of Washington in Seattle. Dr. Duran traces the history of CBPR back to the 1940s when the term “action research” was coined to describe a self-reflective and collaborative quality improvement method. She also draws a lineage to CBPR from the social justice movements of the 1960s and 1970s which sought to reduce inequities between researchers and study participants, including providing greater access to and control over study results and their dissemination. This historical context suggests that diverse stakeholders were originally included in research both for their unique insights and also for ethical reasons.
Many years later, patient-engaged research got a boost from the Affordable Care Act (aka Obamacare) which led to the establishment of the Patient-Centered Outcomes Research Institute (PCORI) in 2010. PCORI’s mission is to “fund research that helps people make better-informed healthcare decisions based on their needs and preferences.” As a funder of research, PCORI is unique in that it requires researchers to include patient input in their research process. This was still pretty novel at the time of PCORI’s founding; a Pubmed search of the term “patient engagement” shows a inflection point right around 2010 with increasing numbers of publications in years since. Requiring patient input for studies of healthcare delivery, such as those funded by PCORI, seem like common sense. If your goal is to help a group of patients make informed choices it seems obvious that you’d need to involve those very people in your study design. But it would still be nice to prove that patient engagement improves these studies. PCORI set out to do just that in an article published in 2019. Since all PCORI studies require patient engagement, a formal comparison of studies with and without patient engagement wasn’t possible. Instead, the authors reviewed 126 articles describing PCORI-funded research and performed a qualitative analysis of text pertaining to patient engagement. They concluded that “…findings suggest that engagement contributes to research that is better aligned with patients’ and clinicians’ needs.” This is encouraging, although a cynic might wonder about the likelihood of PCORI-funded researchers including negative statements about patient engagement in their publications.
So too in the field of pain research has patient engagement become a popular idea. The International Association for the Study of Pain (IASP) published a fact sheet on the topic last year. The Helping to End Addition Long Term (HEAL) initiative, the body within the National Institutes of Health (NIH) that funds pain research has also emphasized the importance of patient engagement. But does it really make sense to seek the patient perspective in all forms of pain research?
It feels slightly scandalous to suggest, but is it possible that patient engagement has gone too far, and that by extending it past its original purpose we are diluting its power? This question may be particularly relevant to tightly regulated areas of research, such as early drug development, in which study design may be mostly dictated by budgetary limitations and the requirements of regulatory bodies such as the Food and Drug Administration (FDA). The needs of patients must still guide such research, but what if the perspective of the clinician-scientist on these needs is enough? Clinicians interact extensively with patients absorbing their perspectives over hundreds and thousands of encounters. This is effectively qualitative research, albeit informal. The idea of the clinician as patient proxy is unpleasant, it sounds authoritative and paternalistic. But is the engagement of a handful of people with lived experience really likely to be less biased, or is it just something that’s become accepted as a “best practice” without strong rationale? If it’s the latter, we should be brave and acknowledge own our own expertise as clinician-scientists, while respecting the time and wisdom of community members by engaging with them only when their input really matters and when we can engage whole-heartedly.
It’s quite likely that there will never be strong quantitative evidence that patient engagement improves research. That doesn’t mean we shouldn’t do it, rather we should strive to engage patients in research areas where common sense and the historical origins of CBPR indicate it’s important, particularly research involving ethical and/or value-based decisions.
by PAIREDProject | May 25, 2023 | Clinical trials, Pain
By Mary Catherine George, PhD
The eternal question my family and friends ask me is, “Why are you involved in scientific research for pain treatments?” My first career was as a professional opera singer. My journey into scientific research was accidental. I loved singing, yet suddenly, I had no job with the opera company that hired me. My brother worked at St. Vincent’s Hospital in “the Village” in New York City; he suggested I talk to the doctor he was working with because they needed help in their research program. I needed a job, so the doctor showed me a file drawer full of paper. It didn’t seem scary, so I said yes. Little did I know my experience working in research during the HIV/AIDS epidemic would teach me a profound lesson – the power of research. I witnessed so many people diagnosed with HIV/AIDS, with limited choices or prospects for survival, they would show up for the few research studies available. All with the hope for a possible treatment.
Dr. George as the Countess in the Marriage of Figaro
Thankfully, HIV/AIDS is no longer a death sentence; because of successful research studies, treatments were developed and continue to be developed. Eventually, I transitioned my work to the Mount Sinai Health System. I became curious about how individuals who suffer with chronic pain can have the same medical problem but have a different pain experience. Every patient had a unique view of how they experienced their pain. Pain is a complex condition, and many factors, such as environment, culture, disease, personality, and life experiences, can influence how each of us experience pain. I decided to return to school and get a doctoral degree in Health Psychology because I wanted to help understand more about the elements that play a role in how we experience pain and well-being.
I am now in the process of working to develop a technological treatment for chronic pain. I am still at the beginning, yet engaging in research offers an opportunity to learn, discover, and advance what we know. It is how to help all those who suffer daily from chronic pain. Research can often be complex because we must show how something works and demonstrate safety, which means working closely with research participants doing a lot of tests during several study visits. Many patients would prefer not to participate in a research project, because the drug or device is not approved by the Food and Drug Administration (FDA). Yet, sometimes the opportunity to understand how we experience our health and pain can come from a different, unexpected direction. That is what research has taught me.
Living with chronic pain can often feel as if we are under a magnifying glass because the feelings of discomfort are so oversized. Exploring or seeing or thinking about chronic pain from a unique new perspective can change that experience. During recovery from my hip replacement, I used a brief mindfulness technique that I was taught in a research study. The idea of exploration outside of what I previously knew helped my health and well-being.
Curiosity can be a viewpoint that offers new insights into our human experience. Pain is something we all experience as humans. Is it any wonder it sparks my curiosity? Finding better treatments and offering ways to reduce pain can help so many people. No matter how difficult it is to make new treatments, scientific researchers are inspired to continue working hard to find medicines that will help. I am excited that I am part of this group of researchers. We cannot do this alone. We can only develop new therapies as a community. I know the important lesson I learned was persistence, because what I witnessed in the early part of my research career taught me to keep trying. The heart of research for me is being surrounded by a team whose members all want to improve the lives of those who suffer with chronic pain.
by PAIREDProject | May 19, 2023 | Clinical trials, Pain
The last several years have been an exciting time for pain research, as the tragedy of the U.S. opioid epidemic funneled attention and resources toward efforts to find new, non-addictive pain treatments. We’ve all seen the numbers, millions and millions of Americans with chronic pain, and few if any safe and effective treatments. There’s an old observation among researchers that common diseases are common until you try to study them, then suddenly there are no patients to be found.
At the PAIRED Project we’re part of a nationwide consortium for pain clinical trials called EPPIC-Net and recruiting patients to be in our first two clinical trials, one for knee osteoarthritis and one for diabetic peripheral neuropathy, has been a challenge. But like any challenge it’s also an opportunity to learn and we’ve been thinking a lot about why this has been so hard and how we can do better.
For our HIV-focused studies, like EVA and SALUD, recruitment has been much easier. Maybe understanding why would help us with our pain studies. Well first of all, it’s a different disease. HIV has a moving history that’s inspired books, movies, and musicals. It also has a legacy of vibrant and persistent advocacy. On World AIDS Day last year, when members of our team joined VOCAL-NY activists near the Stonewall National Monument, a chant broke out: “When people with AIDS are under attack, what do we do… Standup, fight back!” For many people living with HIV, the HIV is a part of their identity. There are a lot of conditions like that, they’re usually the ones that have associations, walks, challenges, ribbons, recognizable abbreviations (like MS, ALS), maybe a celebrity or two. These same conditions also tend to have medical homes, clinics devoted to the care of those patients’ specific needs. Since the beginning of our careers we have been a part of meeting these needs for people living with HIV. Dr George is our veteran, she was even there for the first HIV treatment trials. So when a new HIV study comes up, it’s easier to ask the community to participate when there’s a history of trust built over time.
But what if there’s less history, and less of a clearly identifiable community? Chronic pain isn’t a single, defined disease like HIV. It hasn’t been a rallying cry or a reason to march. It’s an experience common to many disorders, including the ones we’re trying to study, knee osteoarthritis and diabetic peripheral neuropathy, but also many others. From a drug development perspective, especially in the early stages, it makes a lot of sense to think of chronic pain disorders in aggregate because their treatments tend to overlap, a drug that works for diabetic peripheral neuropathy pain is likely to also work for fibromyalgia. But drug development requires people to participate in clinical trials, and from a recruitment perspective chronic pain as a disease focus is very tricky.
Why? Well, recruitment to any research study can be thought of as the process of finding interested and eligible patients. Eligibility is pretty straightforward and controllable. The researcher writes the inclusion and exclusion criteria for the study and could always change them if they are too strict. Many research studies are conducted in large health systems with electronic health records that (with appropriate privacy protections in place) could be programmed to produce lists of patients that meet a set of criteria.
Interest, however, is much more complicated. Why might a person want to participate in a clinical trial? Maybe they want access to a new experimental drug that they couldn’t get otherwise. For very serious or potentially fatal diseases (cancer, ALS) access makes sense as the main driver. But what about when your life is not in immediate danger from your disease, what if instead you are long suffering neither better nor worse from month to month, from year to year. Why participate in a study, especially now when the energetic barrier to get out and participate in anything seems so much higher than it did before?
As a pain research community we desperately need good answers to this question. Chronic pain needs a story that inspires books, movies, and musicals. It needs to go viral. Then we and our research participants could be characters in the narrative of how this terrible condition was ultimately conquered. The story of chronic pain can be compelling, but it requires creativity to tell well. Perhaps it is a story of how a universal experience that is one of our most basic defense mechanisms, something we all need to survive, can turn on us… a story of chronic pain as an allegory.
EPPIC-Net’s mission is critical, we must learn how to sustainably bridge the gap between early drug development and the large clinical trials that ultimately lead to the approval of new pain medications. At the conclusion of one investigators’ meeting, then NIH director Francis Collins sang a folk song, “If not now tell me when.” One line in this song is: “Although there will be struggle we’ll make the change we can.” We make change by performing the research, but also by telling its story.
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