In the JournalsPerspective

Right to Try Act may undermine palliative care in pediatric oncology

Ashley F. Lanzel, MD 
Ashley F. Lanzel
James V. Lavery, PhD 
James V. Lavery

The Right to Try Act has raised concerns about late referrals to palliative care, particularly for children with cancer, according to a commentary published in JAMA Oncology.

Ashley F. Lanzel, MD, pediatric hematology/oncology fellow at Emory University/Children’s Hospital of Atlanta, told HemOnc Today that the idea for this commentary originated from her experience treating children with diffuse intrinsic pontine glioma (DIPG) and other high-grade gliomas.

“I was faced with families who had tried many different things, and they knew that with DIPG there is no cure,” she said in an interview. “Typically, children die between a few months to maybe 2 years. I saw that sometimes these patients and their families weren’t having palliative care consults or hospice involvement until literally the last few days of life.”

In commentary, Lanzel and James V. Lavery, PhD, Conrad N. Hilton chair in global health ethics and professor in the Hubert department of global health in the Rollins School of Public Health at Emory University, discussed ethical implications of the Right to Try Act, which was signed into law in May 2018. The act is intended to increase access to investigational drugs for individuals with life-threatening illnesses. The authors noted that the act is partly driven by the incorrect perception that the development and availability of life-saving medications is being hampered by regulatory obstacles and overly cautious research protocols.

“Essentially, the argument is that we need less red tape to go through to get access to the drugs in general, and then patients do not have to wait for the FDA to say ‘yes’ or ‘no’ to have access to those drugs,” Lanzel said. “Really, it was a push from policy holders to bypass the FDA. But more than 90% of requests under the FDA’s Expanded Access regulations are already granted quickly, so I see a lot of value in the FDA continuing to do their job. I also understand this from the parents’ perspective, which is the desire for their children to have more treatment options. So, it’s really a hard place to be.”

Increase in cure-seeking behavior

According to Lanzel and Lavery, the discussion around Right to Try has focused more on how the act is different from FDA’s Expanded Access regulations and less about its potential unintended negative consequences.

The Right to Try Act could impact palliative care for adults more directly, because children in many states can access investigational drugs while receiving palliative care or standard care, depending on insurance coverage, the authors wrote. However, it may negatively affect the timing of palliative care among terminally ill children.

“Although the necessary supporting evidence has not been generated, to our knowledge, it seems reasonable to be concerned that a general increase in cure-seeking behavior would likely exacerbate rather than improve the timeliness of palliative care referrals in pediatric oncology,” Lanzel and Lavery wrote. “For instance, if the [Right to Try] Act results in a clinical environment in which more patients and families seek or are offered opportunities to pursue a cure, this could bolster attitudes within patient, family and cancer care support communities (including those on social media) to pursue cures that could make discussion about palliative care seem discouraging or defeatist. Additionally, the [Right to Try] Act can systematically influence the continuity of pediatric oncologic and delay palliative care.”

The researchers discussed some of the issues surrounding incorporation of palliative care into cancer treatment. These services are generally supported by public and/or private third parties, donations and out-of-pocket payments. The NIH has significantly increased funding for palliative care research, however, this resulted in just 391 NIH grants for palliative care research, only 25 (6.4%) of which pertained to pediatric palliative care.

Meanwhile, the Palliative Care and Hospice Education and Training Act, which would require the Department of Health and Human Services to offer support for palliative care and hospice education, failed to pass in the House and Senate.

‘We need to zoom out’

Lanzel said many parents of children with terminal cancer diagnoses struggle to find a balance between pursuing treatment options and ensuring quality of life. She said parents may initially say they are “looking for a miracle,” but later may shift their focus to other milestones, such as a birthday celebration or a Make-A-Wish experience.

“These families have many other hopes,” she said, “and often, there just isn’t enough time to explore those things when you’re pursuing treatment, because there are so many aspects of treatment to focus on: radiation or chemotherapy, the next phase 1 trial,  or where you’ll have to travel for treatments. There’s a lot of planning involved.”

Lanzel recounted a conversation she once had with a patient’s mother, who was grappling with a choice between treatment and a highly-anticipated family trip.

“They had won a trip to Disney World — the children had never been to Disney World,” Lanzel said. “But, she said, ‘I’m trying to decide, because there’s one more spot open for this clinical trial, and I don’t know if he’s going to be eligible.’ The tests for the trial were going to conflict with the trip. Can you imagine having to make that decision?”

Parents of children with cancer are faced with similarly difficult choices every day, Lanzel added. The decision whether to initiate palliative care doesn’t need to be so difficult, she said.

“Families love palliative care once they’re involved, but many families don’t know about palliative care or, if they do, they may associate it with end of life,” she said. “Oncologists are sometimes waiting for the families to ask for it. So, there’s this kind of dance in terms of who starts the conversation. When parents become really determined to find cures, it’s very challenging to oncologists to have that difficult discussion.”

She said both clinicians and families can perhaps have more clarity on this issue if they take a step back from a single-minded focus on cure.

“Typically, there needs to be a broader conversation,” she said. “I’ve heard people say we’re not just looking at the tree, we’re looking at the bark, focusing on all these tiny medications instead of looking at the big picture, the forest. We need to zoom out and have these larger conversations.”

Lanzel and Lavery called for more research into the Right to Try Act’s influence on patients, particularly among children with cancer. They noted that the goals of offering supportive care and investigational drugs are not necessarily at odds. 

 “Although the right to receive comfort measures seems to conflict with investigational drug use, such conflict is not inevitable,” they wrote. “Providing concurrent access to cancer-directed agents and palliative care is considered a standard of care by the American Academy of Pediatrics.” – by Jennifer Byrne

For more information: Ashley F. Lanzel, MD, can be reached at 1531 Dickey Drive. Atlanta, Georgia 30322; email: ashleylanzelmd@gmail.com. 

Disclosures: Lanzel reports no relevant disclosures. Lavery reports serving on the bioethics advisory panel of Pfizer.

Ashley F. Lanzel, MD 
Ashley F. Lanzel
James V. Lavery, PhD 
James V. Lavery

The Right to Try Act has raised concerns about late referrals to palliative care, particularly for children with cancer, according to a commentary published in JAMA Oncology.

Ashley F. Lanzel, MD, pediatric hematology/oncology fellow at Emory University/Children’s Hospital of Atlanta, told HemOnc Today that the idea for this commentary originated from her experience treating children with diffuse intrinsic pontine glioma (DIPG) and other high-grade gliomas.

“I was faced with families who had tried many different things, and they knew that with DIPG there is no cure,” she said in an interview. “Typically, children die between a few months to maybe 2 years. I saw that sometimes these patients and their families weren’t having palliative care consults or hospice involvement until literally the last few days of life.”

In commentary, Lanzel and James V. Lavery, PhD, Conrad N. Hilton chair in global health ethics and professor in the Hubert department of global health in the Rollins School of Public Health at Emory University, discussed ethical implications of the Right to Try Act, which was signed into law in May 2018. The act is intended to increase access to investigational drugs for individuals with life-threatening illnesses. The authors noted that the act is partly driven by the incorrect perception that the development and availability of life-saving medications is being hampered by regulatory obstacles and overly cautious research protocols.

“Essentially, the argument is that we need less red tape to go through to get access to the drugs in general, and then patients do not have to wait for the FDA to say ‘yes’ or ‘no’ to have access to those drugs,” Lanzel said. “Really, it was a push from policy holders to bypass the FDA. But more than 90% of requests under the FDA’s Expanded Access regulations are already granted quickly, so I see a lot of value in the FDA continuing to do their job. I also understand this from the parents’ perspective, which is the desire for their children to have more treatment options. So, it’s really a hard place to be.”

Increase in cure-seeking behavior

According to Lanzel and Lavery, the discussion around Right to Try has focused more on how the act is different from FDA’s Expanded Access regulations and less about its potential unintended negative consequences.

The Right to Try Act could impact palliative care for adults more directly, because children in many states can access investigational drugs while receiving palliative care or standard care, depending on insurance coverage, the authors wrote. However, it may negatively affect the timing of palliative care among terminally ill children.

“Although the necessary supporting evidence has not been generated, to our knowledge, it seems reasonable to be concerned that a general increase in cure-seeking behavior would likely exacerbate rather than improve the timeliness of palliative care referrals in pediatric oncology,” Lanzel and Lavery wrote. “For instance, if the [Right to Try] Act results in a clinical environment in which more patients and families seek or are offered opportunities to pursue a cure, this could bolster attitudes within patient, family and cancer care support communities (including those on social media) to pursue cures that could make discussion about palliative care seem discouraging or defeatist. Additionally, the [Right to Try] Act can systematically influence the continuity of pediatric oncologic and delay palliative care.”

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The researchers discussed some of the issues surrounding incorporation of palliative care into cancer treatment. These services are generally supported by public and/or private third parties, donations and out-of-pocket payments. The NIH has significantly increased funding for palliative care research, however, this resulted in just 391 NIH grants for palliative care research, only 25 (6.4%) of which pertained to pediatric palliative care.

Meanwhile, the Palliative Care and Hospice Education and Training Act, which would require the Department of Health and Human Services to offer support for palliative care and hospice education, failed to pass in the House and Senate.

‘We need to zoom out’

Lanzel said many parents of children with terminal cancer diagnoses struggle to find a balance between pursuing treatment options and ensuring quality of life. She said parents may initially say they are “looking for a miracle,” but later may shift their focus to other milestones, such as a birthday celebration or a Make-A-Wish experience.

“These families have many other hopes,” she said, “and often, there just isn’t enough time to explore those things when you’re pursuing treatment, because there are so many aspects of treatment to focus on: radiation or chemotherapy, the next phase 1 trial,  or where you’ll have to travel for treatments. There’s a lot of planning involved.”

Lanzel recounted a conversation she once had with a patient’s mother, who was grappling with a choice between treatment and a highly-anticipated family trip.

“They had won a trip to Disney World — the children had never been to Disney World,” Lanzel said. “But, she said, ‘I’m trying to decide, because there’s one more spot open for this clinical trial, and I don’t know if he’s going to be eligible.’ The tests for the trial were going to conflict with the trip. Can you imagine having to make that decision?”

Parents of children with cancer are faced with similarly difficult choices every day, Lanzel added. The decision whether to initiate palliative care doesn’t need to be so difficult, she said.

“Families love palliative care once they’re involved, but many families don’t know about palliative care or, if they do, they may associate it with end of life,” she said. “Oncologists are sometimes waiting for the families to ask for it. So, there’s this kind of dance in terms of who starts the conversation. When parents become really determined to find cures, it’s very challenging to oncologists to have that difficult discussion.”

She said both clinicians and families can perhaps have more clarity on this issue if they take a step back from a single-minded focus on cure.

“Typically, there needs to be a broader conversation,” she said. “I’ve heard people say we’re not just looking at the tree, we’re looking at the bark, focusing on all these tiny medications instead of looking at the big picture, the forest. We need to zoom out and have these larger conversations.”

Lanzel and Lavery called for more research into the Right to Try Act’s influence on patients, particularly among children with cancer. They noted that the goals of offering supportive care and investigational drugs are not necessarily at odds. 

 “Although the right to receive comfort measures seems to conflict with investigational drug use, such conflict is not inevitable,” they wrote. “Providing concurrent access to cancer-directed agents and palliative care is considered a standard of care by the American Academy of Pediatrics.” – by Jennifer Byrne

For more information: Ashley F. Lanzel, MD, can be reached at 1531 Dickey Drive. Atlanta, Georgia 30322; email: ashleylanzelmd@gmail.com. 

Disclosures: Lanzel reports no relevant disclosures. Lavery reports serving on the bioethics advisory panel of Pfizer.

    Perspective
    Yoram Unguru

    Yoram Unguru

    Lanzel and Lavery have appropriately highlighted several misgivings of the controversial Right to Try Act, including the potential effect Right to Try may have on initiating pediatric palliative care consultations.

    At its heart, Right to Try affords critically ill patients the ability to access experimental therapies that have yet to be proven safe or effective. On the face of it, Right to Try appears a compassionate and straightforward process aimed to help patients in need. Yet, as appreciated by Lanzel and Lavery, Right to Try misses the mark. Moreover, as the FDA has streamlined its Expanded Access program, making it easier for patients in need to access medications, the act’s exact role or purported advantage over Expanded Access are unclear.

    The authors note one possible unintended consequence of Right to Try. By fostering hope among children with cancer and their families, the already difficult process of integrating palliative care into the pediatric oncology experience may become even more cumbersome.

    Although many forms of hope exist, some families view access to experimental and novel medications as hope for cure. Hope is a powerful force. Patients and families who hope for a good outcome harbor therapeutic optimism. Therapeutic optimism has been found to empower some patients with life-limiting diseases such as cancer as well as represent (realistic) hope, relieve anxiety and even contribute to the healing process. Misappropriated or false hope, however, can lead vulnerable patients astray at the most inopportune time.

    Given hope’s sustaining force, some patients and parents are especially prone to suggestions and language that reinforces their beliefs about an experimental agent. Recent work by Miller and colleagues in the field of pediatric oncology confirms this observation. Specifically, pediatric oncologists frequently reinforced parental hopes concerning the therapeutic effects of investigational agents in phase 1 trials. In fact, two out of three physicians failed to mention no treatment and/or palliative care as options. With this in mind, one can easily appreciate how experimental medications accessed via Right to Try may further jeopardize palliative care participation.

    To assure that both patients’ and parents’ notion of hope represents therapeutic optimism and not unrealistic hope, before agreeing to a medication obtained via Right to Try, informed assent and permission (consent) is essential. This requires that the probable risks associated with the agent not exceed the probable risk from the patient’s disease. However, in the absence of adequate testing, it is unclear how such a determination can be reached or how patients and their surrogates can provide fully informed consent. Thus, while hope itself is not ethically problematic, it becomes an issue when misappropriated hope compromises patient/parent decision-making capacity. In the absence of data, transparency and disclosure are impossible. Investigational agents undergo rigorous testing in clinical trials, and only when proven both safe and effective are they made available for general usage.

    Access to investigational agents via Right to Try has many negatives. Allowing patients access to medications yet to be proven safe and effective directly violates patients’ trust, jeopardizes the clinical trials system and may even limit appropriate palliative care referrals. Fortunately, viable alternatives to Right to Try, such as the FDA Expanded Access program, afford ill patients and their families a mechanism to explore every option without compromising the patient’s well-being or the scientific imperative.

    References:

    Miller VA, et al. J Clin Oncol. 2014;doi:10.1200/JCO.2014.55.2585.

    Unguru Y. Pediatrics. 2017;doi:10.1542/peds.2017-0791.

    • Yoram Unguru, MD, MA, MS
    • The Herman and Walter Samuelson Childrens Hospital at Sinai
      Berman Institute of BioethicsJohns Hopkins University

    Disclosures: Unguru reports no relevant financial disclosures.