Ethical Factors Should Be at Core of Radicava Treatment Discussions, Researchers Argue

When discussing potential Radicava (edaravone) treatment with amyotrophic lateral sclerosis (ALS) patients, physicians need to take great care in presenting facts in an ethical and scientifically sound manner, warn two researchers who believe that mainstream reports of the treatment may be misleading.

The duo — Crystal Yeo, MD, PhD, from Houston Methodist Hospital and Zachary Simmons, MD, from the Pennsylvania State University College of Medicine — authored an article that presented the various aspects they argue should be part of every Radicava treatment discussion.

The piece, “Discussing edaravone with the ALS patient: an ethical framework from a U.S. perspective,” was published in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.

Yeo and Simmons are concerned that popular accounts of Radicava — including statements by the ALS Association (‘‘a great deal of excitement’’) and the U.S. Food and Drug Administration (‘‘after learning about the use of edaravone to treat ALS in Japan, we rapidly engaged with the drug developer about filing a marketing application in the United States’’) — had failed to transmit the key fact that far from all patients are likely to benefit from the treatment.

“Given the general level of enthusiasm in the lay press and among advocacy groups for approval of this new drug, patients may not be aware that the benefits of edaravone are modest, even in the selected subgroup of the pivotal study,” they wrote.

The initial clinical trial in Japan had found an impact of Radicava treatment on slowing disease progression only in a subgroup of patients who were in earlier disease stages. The subsequent Phase 3 clinical trial (NCT01492686) enrolled only patients with these, milder characteristics — proving the treatment to slow disease progression to a small degree.

Still, the treatment is approved for all patients. Moreover, patients were treated for only six months in the Phase 3 study, so no one knows if a potential treatment effect exists beyond that time point.

Authors of the trial publication underscored this fact, by stating that “There is no indication that edaravone might be effective in a wider population of patients with ALS who do not meet the criteria.”

But since patients most often do not possess the expertise to evaluate scientific publications, they may “mistakenly believe that a drug approved for all patients with ALS must be effective for all patients,” the duo argued.

It is in this context the role of the physician becomes particularly important, they maintained.

Why explanation is needed

“A physician who takes time to understand the clinical trials that lead to drug approval, and who can compassionately frame the medical facts in the context of the patient’s needs and goals, is an invaluable resource to patients,” they wrote.

When discussing potential Radicava treatment with a patient, however, physicians need to take into account aspects other than potential benefits, which are limited in the case of Radicava.

Although side effects of the treatments are considered mild, there is a risk of infection and blood clots caused by the indwelling intravenous catheter.

But negative aspects come in many shapes and forms, Yeo and Simmons argued. The intense treatment schedule — with 10 to 14 treatment days in a 28-day cycle — is an aspect that needs to be considered. So should the cost of the treatment, estimated at about $140,000 per year.

Meanwhile, the benefits or impact of Radicava treatment on patients’ quality of life is not clear. Although health-related quality-of-life questionnaires spoke in favor of the treatment, such tools do not take into account psychological, existential, and support factors that may have a larger impact on overall quality of life, the duo wrote.

Studies also show that overall quality of life in ALS patients is not linked to physical function and strength. Rather, factors such as family, friends, finances, job, and religion or spirituality, appear more important.

In the end, such considerations need to take into account every patient’s treatment goals. Such goals can range from extending life to providing comfort, including all possible scenarios in between.

So, for one patient, the intense treatment schedule may take away valuable family time or time with other pleasurable activities, contributing negatively to quality of life. In another, the schedule may be acceptable if it allows the patient to live long enough to experience a certain life event.

Discussing non-curing treatment options in patients with a terminal illness such as ALS also has its specifics. Patients in such situations may be desperate to try a treatment. Many patients with ALS also suffer cognitive decline or dementia, making the patient group particularly vulnerable to biased information, researchers said.

In addition, since a cure for ALS is not likely in the near future, the same ethical considerations also will need to be included in discussions of future treatments with a modest impact on disease progression.

“It is our responsibility as physicians to ensure that our discussions with our ALS patients concerning their treatment decisions about edaravone and future therapies are made in accordance with the ethical principles outlined here, always aimed at facilitating the best QOL [quality of life] as viewed by the patient,” Yeo and Simmons concluded.

In the U.S., Radicava is developed by Mitsubishi Tanabe Pharma America.