Personalized Diversity
Individual + Context – Assumptions
In my younger days as a soccer (football) coach, I often did a mind exercise: What if my assumptions turned out to be wrong? What if the star player, instead of leading the team to victory, suffered an early, game-ending injury? Or getting two quick, unexpected goals scored against your team after it has been dominating? What would I do?
Good scientists ask questions like that all the time. They don’t let assumptions get in the way of evidence. That was a quality shared by the two trailblazers who shaped modern myeloma research and treatment.
When speaking to patients and medical students, Robert Kyle always reminded them, as confident as he was in his methods and decisions, there was a lot of room for doubt. He knew his assumptions could be wrong. Every patient lecture included the same warning: “There is no safe drug!” Someone, somewhere was going to have a side effect. It even happens with aspirin a few times a year.
For all his boldness, Bart Barlogie understood change. He knew he might well be proven wrong and searched for better ways of doing things, always trying to improve the best-known standard. He wouldn’t be nostalgic, for example, about VAD if a better therapy would be found. It was one more bridge needed to get him where he wanted to go, closer to curing myeloma.
Challenging assumptions is at the heart of scientific inquiry. As I mentioned in my last article, Diverse Disparities, the lecture by Dr. Marie von Lilienfeld from Ruhr University in Bochum, Germany tested some long-held thoughts about myeloma and cancer disparities. So much so that I had to find time to speak with her to further talk about her ideas. Will her views challenge any of your assumptions?
“When you say diversity medicine, everybody wakes up, either in a good or bad way,” Lilienfeld began. “Diversity” has unfortunately become politicized and polarizing on both sides of the Atlantic. “Personalized medicine is appropriate, but that’s already been taken in oncology, it’s a settled term for a type of targeted therapy,” which, Lilienfeld observes, “is interesting because it completely ignores the person and focuses only on the tumor.”
She tried “individualized,” but that didn’t do either. It carried a danger of patients being treated only according to data, as objects. Other factors not normally measured, Lilienfeld felt strongly, “had to be taken into account from a medical point of view.”
Things like where people live. Near an industrial or power generating zone? A rural farm? Or where they work? What kind of work? How do they socialize? Did they have a strong or weak familial and/or personal network, and so on. Does the confluence of these various influences in every individual have medical significance?
“It may be that not every disparity is medically relevant,” Lilienfeld speculated, “for me, the most important task is to determine what is and isn’t relevant.” Chemotherapy provides an example relatable to most cancer patients. “It is well known, for example, that women have more toxic side effects from chemotherapy.
“And that begs the question: ‘What’s the reason?’ The cause could be as relatively simple as dosing. Many women get a stronger dose than men just because they weigh less. In this case, the reason not 100% gender, but also one of body weight. And that interests me,” Lilienfeld said. “What differences are important, and how can I address them right away?”
To further emphasize her point, “Sometimes weight matters, sometimes it doesn’t. But when it comes to chemotherapy, it does. That’s what I mean by contextual.” It is, in a sense, comprehensive personalized medicine. While “contextual medicine” may be the most accurate description, the term would make eyes glaze over even more.
In this case, context differs substantially on both sides of the Atlantic as well. Anecdotally, Lilienfeld estimates the vast majority of Germans, when they hear “lack of diversity” or “disparity,” they mostly think of gender. We agreed, in the United States, the same proportion would likely answer race or ethnicity.
Seemingly every major cancer center in the United States has at least one staff member working on racial disparities. It is now well known that there are specific characteristics that can be overwhelmingly identified in the genetics and biology of Black populations. Rather than study race, many German centers have staff devoted to study gender disparities. One, according to Lilienfeld, recently established a chair for disparities faced by persons with developmental and physical disabilities. Each one does have data supporting the existence of gender disparities. Proof of specific genetic mutations do exist in certain subpopulations of women and outcomes are worse when compared to the same disease in men.
Still, are we, asks Lilienfeld, looking in the right places? Do we need to “open our eyes to what is really important,” such as looking at scientific, not subjective categories. For instance, “you can identify a specific gene in the lab, under the microscope, without looking at who it comes from, that means taking measurements and comparing them…One could say this is a ‘racial effect.’ Looking at it closely, though, we see it is a blood antigen. It may be that skin color has nothing to do with it.”
Proven racial disparities in the United States (and western Europe), on the other hand, are “so much more prevalent in Blacks as compared to whites and outcomes are different.” This intrigues Lilienfeld even more since “observed globally, in Africa (myeloma) is rarer as compared to western Europe and the United States. That means, to me, it can’t be race alone, it must be something else that makes a difference. But we’re not far enough along to know why.”
Moreover, “I’m not completely sure if there is a genetic connection. I’m more convinced that it’s possibly only environmental, or more precisely, of what the susceptibility of this community, of this group might be.” Nor does she close the door on genetic propensity, but “it would surprise me if it played the main role, I would tend to think it doesn’t and lean more toward environment and social factors.”
The role of genetics, however, shouldn’t be downplayed. “Is it the genetics of the tumor cell or the genetics of person?” Lilienfeld asks. “And I think this is very interesting, because the interaction between the tumor cells and the genetics of the person who has the tumor are not well understood in general. But we have a relatively good understanding what kind of roles the genes of the tumor cell play – high-risk, ultra high-risk, and standard-risk and so on.
“And these are the things we try to better understand, to systematize and be as precise as possible in making definitions.” Especially now. The United States Food & Drug Administration (FDA) now requires clinical trials to be diverse to include targets for specific subpopulations. This is forcing its counterpart, the European Medicines Agency (EMA) to either accept FDA definitions – like American conceptions of race, refine them, or create their own. But how would individual context be turned into tangible data and goals in clinical studies?
Lilienfeld confesses to having more questions than answers. One method to identify and quantify elements of intersectionality – taking into consideration multiple types of disparities to form a more accurate picture of than any one of those categories do alone – is a surprisingly low-tech tool that can be used in the clinic Lilienfeld calls a wheel of visibility (Rad der Sichtbarkeit).
Consisting of concentric circles, much like an archery target. The central ring, the optimal target, represents the center of societal benefits – the optimal levels of education, income housing, access to transportation, etc. As the rings radiate from the center, the levels become less favorable. For example, if the center represents the best insurance, each ring moving outward would a lesser amount or level of benefits, with the outside ring being those without any insurance at all. For housing, the center ring would be the most affluent homeowner with the outer rings moving toward rental to homelessness.
By layering each over the other, one would get an immediate picture of what benefits or challenges a person might have. It is, as Lilienfeld notes, a beginning only. Quantifying, ranking, and applying the information broadly to clinical care for individuals is still in early stages.
Lilienfeld closed our conversation by repeating a challenge she made at a clinical meeting about diversity and equity in clinical trials: “I believe we need to slow down.” She faced resistance. The paradigm of research activity is closer to “full speed ahead,” rarely, if ever, look back.
“I have the impression,” Lilienfeld continued, “that we, in our western European and American societies, put ‘innovation’ on the same level as a technology, that it is something tangible.” Instead, we need to take a step or two back in time to reflect on goals and tactics, think about what the purposes of patient care.
I completely understand and agree with the point she was making. It is the same reason I started this Substack on myeloma history, as I explained in my inaugural article. My thoughts about patient education have changed dramatically in past few years.
In my view, patient education is optimal when it looks at concepts, not trying to keep up with the latest studies, for people decades removed from their last science class. Plus, the vast majority of studies have little-to-no relevance in one’s day-to-day care or prognosis decisions. Taking a step back to appreciate ideas, to think about and formulate ideas for discussions with your physicians and nurses, those are the priorities I wish for patients and caregivers.
As a myeloma advocate, I hope to see more global cooperation and standardization when it comes to diversity medicine, disparities research, or whatever it is named. Until proven otherwise, I think this would unravel some tangled, currently unanswered questions about myeloma and cancer. Even negative findings would be vitally important if only to give direction to future research.
The problem today is that diversity and disparities have become alienating political issues having nothing to do with science or healthcare. Dr. Lilienfeld and I lamented that the term “diversity” is currently a nonstarter in the United States, having become an “ideology” to some, not a means toward fairness for some and opportunity for many.
Making an assumption is one thing, making an assumption about motives is another, but I’ll try to make one here. I have heard many variations of this theme: “I’m being told I’m the reason this problem exists. I had nothing to do with creating it. So don’t blame me or make me pay for it.” This can become an unnecessary obstacle to the entire patient community.
In Germany, the neo-Nazi party the AfD has stated in its party programme that, if elected, all scientific research that is “ideological” will be forbidden to be funded, taking cues from similar movements in the United States. Lilienfeld finds it all very troubling and explains:
“We also want participation, we want lay-persons to participate, we want dialogue with people. I absolutely want to remain scientific and sensible. And I want our arguments to be substantive, I don’t want them to be accepted because someone feels sorry or they say, ‘this has to be corrected’ or something like that, but because they are simply right. It’s not good science it we don’t bear that in mind, that it means something.”1
“We don’t want to solve all the problems of the world – we can’t, really – but we’d like to make a small contribution,” said Lilienfeld as she summed up her hopes for the Ruhr University’s Institute of Diversity Medicine.
I hope those small changes will do what science does best. Challenge our assumptions.
Wir möchten auch Partizipation, wir möchten auch Laien Partizipation, wir möchten Dialog mit den Menschen. Ich möchte unbedingt das wir Wissenschaftlich und nüchtern bleiben. Und ich möchte das unsere Argumente an sich tragen, also nicht das sie tragen, weil mir irgend Jemand leidtut oder weil irgendwas, sagen wir, “has to be corrected” oder irgendwie sowas, sondern weil sie einfach richtig sind. Es ist keine gute Wissenschaft, wenn wir das nicht berücksichtigen und ich möchte, dass das trägt. (English in original.)
I do not understand the nazi paragraph about not funding ideological programs.