Are Clinical Trials Being Oversold to Cancer Patients?

Roxanne Nelson, BSN, RN

April 16, 2018

UPDATED April 18, 2018 // Cancer patients are often encouraged to enter a clinical trial, especially when their disease has become metastatic and they have few options left. But are they getting the full picture?

A number of well-established medical centers frequently advertise the opportunity for patients to participate in clinical trials, implying that there may be a real benefit to doing so. Although many patients may in fact benefit from a clinical trial, a new article suggests that the advertisements may be fueling misconceptions.

The article was published online April 5 in JAMA Oncology.

The authors, Alex John London, PhD, Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, Pennsylvania, and Jonathan Kimmelman, PhD, Biomedical Ethics Unit, McGill University, Montreal, Quebec, Canada, point to several examples.

One is a billboard for the Georgia Cancer Center, in Augusta, that reads, "Clinical Trials: Another Reason to See Us First." Another is a video from Johns Hopkins University that encourages participation in clinical trials, because they can "open up new treatments that [patients] otherwise would not have available to them." A third example is an advertisement from the Cancer Treatment Centers of America that says trial participation is "part of our commitment to bringing our patients new and innovative cancer treatment options."

The two ethicists argue that "strong messages equating access to clinical trials with therapy imply that unproven drugs are already established as therapy" and that these messages contradict the very purpose of a clinical trial, which is to determine the efficacy and safety of a therapy.

They note that this type of portrayal of trial participation involves "a 2-way transfer of associations."

One is that the "prestige of research is marshaled to elevate the reputation of the medical centers and the therapeutic mission of medical centers is invoked to bolster participation in clinical trials." Although in the short term, this type of reciprocal branding of clinical trials and medical centers may increase enrollment, the therapeutic branding of studies "perpetuates misconceptions" that can distort a patient's expectations as well as "nourish movements that would weaken the research enterprise."

In an interview, Kimmleman told Medscape Medical News that he thinks that professional societies such as the American Society of Clinical Oncology (ASCO) and hospital associations should issue some ground rules for advertising that are premised on ethical principles and telling the truth. "An independent entity, such as a committee like an independent review body, ought to be reviewing and approving advertisements that invoke clinical research," he said. "Barring these voluntary measures, perhaps there is a need for regulating medical center advertisement much in the same way that we regulate commercial speech about pharmaceuticals."

However, Kimmelman emphasized that they are not calling these advertisements deceptive. "That implies there is an intent to mislead patients, and I have no basis for believing that is the case," he said.

Rather, he explained that this is a "collective action problem, with cancer centers competing with each other for patients, and one of the ways they do this is by using clinical trials to telegraph to patients that they are at the cutting edge of medicine.

"If any one cancer center stops doing this, they potentially lose patients to another center," he said. "It is better to solve this problem collectively by establishing industry-wide standards or regulations than to ask the more conscientious cancer centers to take a hit on their bottom line."

Kimmelman added that he suspects that if five to 10 of the "heavy hitter" cancer centers show leadership by reflecting greater balance in their advertising and messaging, others would follow that lead.

Misconceptions and Misbranding

One issue is that in advertising the trials as a therapeutic choice, centers frequently use strategies that are antithetical to evidence-based decision making, the authors note. As an example, they point to a statement from Seattle Cancer Alliance that states that "every improvement in cancer treatment has been the result of rigorous clinical trials." But this statement also "invokes the inverse fallacy," they argue. "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."

They also point out that it is a misconception that every clinical trial is testing a new cutting-edge therapy. In reality, a large portion of research is devoted to developing "me too" drugs, optimizing standard therapies, or repurposing drugs that have already been approved for another indication. From 2001 to 2010, fewer than half of all drugs that were approved by the US Food and Drug Administration involved first-in-class treatments.

Patients enrolled in clinical trials are not likely to receive "advanced access to the breakthrough treatments in tomorrow's pharmacopeia," despite therapeutic branding that may give that impression. Rutgers Cancer Institute of New Jersey, as an example, states that it is "committed to providing the latest and best treatment options for cancer patients through clinical trials — outsmarting cancer with science."

But in reality, note the authors, the odds of receiving "tomorrow's effective therapies in clinical trials" are far less than believed, because only about 10% of new drugs in early trials eventually enter the marketplace. That statistic may also be overly optimistic, because manufacturers typically evaluate many variables during the trial, such as dosing, schedules, and other factors, in search of an effective "ensemble" of values, the authors comment.

The authors also disagree with views held by ASCO about phase 1 trials. ASCO used "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," they write, but "appeals to salient and unrepresentative cases, as opposed to systematically obtained, population-level evidence, contradict the very logic of evidence-based medicine."

Responses to Criticism

In response to the concerns voiced in this article, Richard Schilsky, MD, ASCO's chief medical officer, explained that all patients should have the opportunity to participate in research. "Clinical trials are necessary to demonstrate safety and efficacy of a new therapy and the comparative benefit and efficacy of existing therapies," he said. "Communication about risks, benefits, and alternatives to treatment on a trial are key elements of the informed consent process."

Schilsky commented that ASCO believes that information regarding clinical trials needs to be presented objectively by the healthcare and research teams who are familiar with the patient. "A lack of overall awareness and understanding of clinical trials is an important barrier to participation, but this needs to be done within the context of understanding the purpose of research and uncertainty of treatment benefit — particularly with novel therapies."

Maurie Markman, MD, president of medicine and science, Cancer Treatment Centers of America, also weighed in. "As an organization, Cancer Treatment Centers of America will always do what is in the best interest of our patients," he told Medscape Medical News.

"We are proud of our focus on research and our work to identify new treatment options supported by scientific and investigational research," said Markman. "We strongly believe that offering clinical trials, and any communication around these offerings, is essential to improving patient care and advancing cancer treatment for patients now and in the future."

The Georgia Cancer Center also weighed in.

"Clinical trials are a cornerstone of this improvement, and the only way of making a difference in improving outcomes," said Sharad Ghamande, MD, associate director for clinical trials and research, Georgia Cancer Center, Augusta University. "If used judiciously, clinical trials in cancer offer opportunities for patients to extend life by sequencing new therapies with standard options that can be kept in reserve to extend life."

Gharmande explained that promoting awareness of the availability of access to clinical trials is also an integral part of trying to make a difference in the community. "Less than 5% of all cancer patients have the opportunity to enroll in clinical trials, and of those, less than 5% are minorities," he said.

And yet, he emphasized, the general population at large wonders "why we do not 'cure cancer.' This is one of the reasons promoting clinical trials is important. A greater awareness could mean more people enrolling in the trial."

He also pointed out that in a small city like Augusta, many of the residents are unaware that there is an active clinical trials program ongoing in their community. "Those patients often spend time, effort, and energy traveling across the country to avail themselves of clinical trial opportunities," said Ghamande. "It is important to be transparent and honest as we all deal with issues that have significant emotional undertones, but to pronounce these efforts as advertisement is unfair to all involved in cancer care."

Right to Try

In recent years, "right to try" advocates have been pushing for increased access to experimental compounds. The topic is highly controversial, and a bill recently was passed by Congress despite objections from major medical organizations, including ASCO, as reported by Medscape Medical News.

"This is a key argument in our paper," said Kimmelman. "If medical centers claim that accessing experimental and unproven drugs is therapeutic, they are making the exact same argument that right to try advocates are making."

He added that if academic medical centers are "truly committed to clinical research and advancing medical science, they are undermining that commitment by tacitly aligning themselves with advocates who claim we don't need clinical trials before drugs are made available to patients."

The article was funded by the Canadian Institutes of Health Research. Dr Kimmelman has received payment for serving on a data safety monitoring board for Dimension Therapeutics. Dr London has disclosed no relevant financial relationships.

JAMA Oncol. Published online April 5, 2018. Abstract


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