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

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.

11 comments

  1. Charlie says:

    Well, I did warn the folks here……and I had some posts deleted when I told the truth about Radicava based on some in-depth research I had done.

  2. Gary Moser says:

    Despite all the potential negative aspects uncovered in the article, my wife has shown a remarkably positive outcome with improved swallowing function just after the first round of treatment.

    • Charlie says:

      We are naturally curious…what is the expected timescale duration of infusions ? Six months? A year ? For life?
      What outcomes are physicians expecting if ,say, infusions are stopped after,say, one year?
      What data is available from Japan and South Korea on pALS there who have had Radicava infusions for a year, and then possibly ceased?
      It’s great that someone is feeling better and improving, but the challenge is surely to have a form of treatment that shows improvements in ALL pALS and Radicava was never going to be prescribed for the majority of pALS because the data did not support the proposition.

      Best wishes to you and your wife for continued improvement.

      • Thomas Farrell says:

        Thanks Charlie as I am scheduled to begin this treatment next week. I was diagnosed 2 1/2 years ago with Bulbar Onset, but to date I have lost ability to walk. However I can stand and transfer on my own. I can not justify going thru with this procedure. Please take my share of funds and use it for some positive, known research for our benefit. To date I have heard no positive research that will help any of us long term. Sure you get 2 out of 1,000 that may feel better for a brief time, but when and if they stop, how fast will they then decline? I have chose to embrace this disease and help anyone that I possibly can to get thru the hard times. God Bless

        • Terri Metz says:

          Thank you Thomas. I am kind of feeling the same way. I was diagnosed with ALS a few weeks ago. My legs have been getting weaker for 2 years and no one seemed to be able to figure out what was going on. I can still walk with my walker. I am on Riluzole. The more I think about the side effects of the infusions the less I want to receive them. My quality of life will be horrible. It is not like this drug will make you feel better – it won’t. I think it will just make your suffering longer.

    • Callie says:

      My husband has shown a huge improvement in his energy levels and improved grip strength. We initially went to Japan for treatment and spoke to the doctor who did the research on Radicava. He stresed that this is a drug only for early onset ALS patients, so I’m not sure why the drug companies in the U.S. are giving it to everyone. It is not a one size fits all medicine.

      • Charlie says:

        “He stressed that this is a drug only for early onset ALS patients, so I’m not sure why the drug companies in the U.S. are giving it to everyone.”

        Follow the money for the answer to this question, Callie.

  3. Thomas Harrison says:

    It has been said that each patient is different. That each developes and progresses with the disease differently? Well can it be said that each patient may respond differently to each medication given to them? Also isn’t each patient in need of whatever may be of use in order to be saved from this terrible disease? Just the opportunity of a chance needs to be allowed everyone for without that opportunity of a chance there is no chance and that is as cruel as the disease itself

    • Charlie says:

      The data shows that pALS who are more than 15 months (IIRC) post diagnosis, will not likely benefit. They are saying it has already been tried but not found effective in that pALS subgroup.

      • Joe Anile says:

        Joe From Australia
        Having watched 5 family members pass away with this b—–
        of a condition, we grasp at any new potential break through.
        Because the pressure of time, are we jumping through hoops that is not worth the outcome. Still we need to encourage all research as long as it is motivated buy ethics and not money.

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