Alex John London, PhD
Department of Philosophy, Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, Pennsylvania.
Jonathan Kimmelman, PhD Studies of Translation, Ethics, and Medicine, Biomedical Ethics Unit, McGill University, Montréal, Quebec, Canada.
Clinical Trials in Medical Center Advertising
Many well-established medical centers advertise the opportunity for clinical trial participation to suggest that they offer patients a therapeutic edge. A billboard for Georgia Cancer Center reads “Clinical Trials: Another Rea- son to See Us First” (https://jagwire.augusta.edu/archives /39855). A Johns Hopkins video encourages patients to participate in such trials, because “[they] open up new treatments that [patients] otherwise would not have available to them” (https://www.youtube.com/watch ?v=8ZKjQa4gFeQ&feature=c4-overview-vl&list =PL0A17443C77172961). Cancer Treatment Centers of America states that it “offers clinical trials as part of our commitment to bringing our patients new and innovative cancer treatment options…” (http://www.cancercenter .com/clinical-trials/).
Such portrayals of trial participation involve a 2-way transfer of associations: the prestige of research is mar- shaled to elevate the reputation of the medical centers and the therapeutic mission of medical centers is in- voked to bolster participation in clinical trials. Although this reciprocal branding of clinical trials and medical centers may increase trial participation in the short term, the therapeutic branding of studies perpetuates misconceptions that distort patient expectations and nourish movements that would weaken the research enterprise.
First, advertising that brands trials as a therapeutic op- tion often uses communicative strategies that are anti- thetical to evidence-based decision making. For ex- ample, Seattle Cancer Alliance’s statement that “every improvement in cancer treatment has been the result of rigorous clinical trials” (https://www.youtube.com/watch ?v=6wPHMSgjHh4) invokes the inverse fallacy. The probability that lottery winners purchased tickets from convenience stores might be high, but the probability of winning the lottery if you buy tickets from convenience stores is very low. Similarly, a recent American Society of Clinical Oncology policy statement on phase 1 trials1 uses large responses observed in phase 1 trials of pembrolizumab to bolster the consideration of phase 1 trials of cancer treatment as a therapeutic option for eligible patients. However, appeals to salient and unrepresentative cases, as opposed to systematically obtained, population-level evidence, contradict the very logic of evidence-based medicine.
Second, the therapeutic branding of trials fosters the impression that participation offers advanced access to the breakthrough treatments in tomorrow’s pharmaco- peia. For example, Rutgers Cancer Institute of New Jer- sey says that it is “committed to providing the latest and best treatment options for cancer patients through clini- cal trials—outsmarting cancer with science” (http://www .cinj.org/clinical-trials/clinical-trials-overview). This
statement obscures the fact that the odds of receiving tomorrow’s effective therapies in clinical trials are much slimmer than appreciated. It is tempting to think that the probability of accessing a safe and effective drug in trials mirrors the 10% probability that a new drug in early trial phases goes on to receive US Food and Drug Administration (FDA) approval.2 However, this belief ignores a basic point about prelicense trials: they sample many variables, such as drug doses, schedules, indications, and contraindications, in search of an “ensemble” of values for these variables that will unlock a drug’s clinical value.3 Because numerous ensembles are tested for each new drug, the probability of receiving a therapeutically active intervention ensemble in prelicense trials is considerably lower than 10%.
Third, advertising trials alongside innovative and proven treatments implies that interventions tested in clinical trials are at the cutting edge of medicine. For ex- ample, MD Anderson Cancer Center advertises “clinical trials,” alongside immunotherapy and proton beam therapy, as one of its many ways of “fighting cancer” (https://www.ispot.tv/ad/w5gn/md-anderson-cancer -center-confronting-cancer-how-to-fight?autoplay=1). However, a surprisingly large volume of research is aimed not at advancing breakthroughs, but instead at developing “me-too” drugs (chemical agents sufficiently similar to an approved drug that they are likely to achieve comparable clinical effects via the same mechanism of action), optimizing standard therapies, or repurposing already approved drugs toward new indications. Fewer than half of all drug approvals by the FDA from 2001 to 2010 involved first in class treatments.4 An analysis of 2 approved tyrosine kinase inhibitors, sorafenib and sunitinib, found that 92% of clinical trials were aimed at extending the approved use for these drugs to new indications, rather than seeking a first FDA approval; in only 3 of 57 indications tested were these efforts successful.5,6
Finally, strong messages equating access to clinical trials with therapy imply that unproven drugs are al- ready established as therapy. This message contradicts the raison d’être of trials, which is to determine whether a drug has value relative to the standard of care.
Undermining the Mission
of Academic Health Centers
A core mission of academic medical centers is the genera- tion of scientific knowledge that advances patient care. Using trials to attract patients undermines that mission in pernicious ways.
Such messages imply that persons accessing un- proven treatments are at a medical advantage over those who cannot access those treatments. This same claim ani- mates movements such as the “right to try,” advocates of less-stringent drug regulations, and clinics that market unproven cell-based interventions directly to patients. In using their commitment to science to attract patients, many medical centers ironically reinforce the message of those who would diminish the role of clinical trials in drug evaluation.
Meeting the demand for clinical trials that such advertising gen- erates also potentially encourages medical centers to offer trial options even where scientific rationales are weak. Although on its face, more research is better, not every clinical challenge has hypotheses of suf- ficient maturity to justify the expenditures of time and capital required for testing. We have described above the cautionary tales of sorafenib5 and sunitinib6 testing; others have noted the very low yield associated with the testing of combination therapies in cancer.7 Pursuing such long odds consumes health care resources, including space and expertise to administer and monitor the effects of investigational treatments. These resources are potentially less available for other services that have better evidentiary backing. Already, a large fraction of trials are unable to recruit their target sample8; a surfeit of studies that are un- likely to produce novel treatments or clinical approaches potentially diverts patients from trials that might have greater effect on treatment alternatives.
There are other reasons to question the use of access to clini- cal trials in medical center advertisements. It obscures the fact that many patients receive standard of care comparators in trials (and, according to the principle of clinical equipoise, such patients should
not be at a medical disadvantage compared with their peers in ex- perimental treatment arms). It conceals the fact that patients in trials often endure research procedures or extra clinic visits that lack any therapeutic orientation. It also potentially fosters unrealistic expec- tations that discourage some patients from initiating discussions about palliative options. Our focus, however, is on the way that such practices are self-defeating for health care centers that are genu- inely committed to the mission of medical research.
Although there is a nonzero possibility of medical benefit from participation in such studies, medical centers and professional so- cieties have a responsibility to communicate in ways that do not engender unwarranted expectations. There are undoubtedly pa- tients who value extra contact with health care teams and some who will accept even extremely small odds of personal benefit.
Nevertheless, medical centers and professional societies should present clinical trials primarily as an opportunity to advance the sci- ence needed to unlock better health care options for others with- out inflating the prospect of direct medical benefit. Although a more measured presentation of clinical trials may mean that medical cen- ters recruit fewer patients or host fewer trials, more judiciously selected clinical research can have a greater payoff for future pa- tients. Above all, medical centers and professional societies should refrain from broadcasting messages that subvert the rationale for rigorous clinical evaluation of new treatments.