Stakeholder Perspectives

”Patients have been the one missing player in system-level healthcare decision making for most of the modern healthcare system,” said Suzanne Schrandt, JD, Founder, CEO, and Chief Patient Advocate of ExPPect, Arlington, VA, USA and Chairperson for the ISPOR Patient Council.¹ Fortunately, that is changing. Patients’ voices are being heard and their input actively sought when assessing value to a population. But the value of an intervention to a specific patient must be viewed in the context of that person’s life circumstances, goals, and preferences—a unique lived experience.

Population-based studies can identify issues common to most patients. Questions such as, “What limitations to your daily activities does your condition cause?” usually elicit similar answers from people with the same disease. Patient advocates raise these issues in policy and research prioritization discussions. This article relates the individual experiences of 2 patients with common diseases and case vignettes from a rare disease population with a gene therapy treatment option. These stories illustrate both common themes and the importance of listening to individual patients.

 

Migraine
Migraine affects approximately 15% of the population. Headaches are most severe among working adults aged 18-64,² often occurring suddenly while the individual is at work. This affects productivity, relationships, and quality of life. People with chronic headaches must learn to cope with them and function in a society that expects dependability. Few people die as a direct result of headaches, but the life impact is often underappreciated. Frequent headaches disrupt daily life and create a burden for family members, coworkers, and others that must take care of the incapacitated person’s responsibilities.

 

"Patients’ voices are being heard and their input actively sought when assessing value to a population. But the value of an intervention to a specific patient must be viewed in the context of that person’s life circumstances, goals, and preferences—a unique lived experience."

 

Ellen* has lived with migraine for much of her adult life. “My first really severe headache came at age 25,” she remembers. “It was my first year in graduate school and I had a class each week with the department chairman. We had to read many papers and we never knew which of the 5 grad students he would call on to explain the paper. These ‘let-down’ headaches would occur Thursday afternoons and last until the next day. I slept in a bed with the lights out in severe pain with bad nausea and vomiting. Ibuprofen gave minimal relief, but it wasn’t until the early 90’s that I found dependable relief with an Imitrex (sumatriptan) injection. Both the injectable and the tablets caused side effects, but the side effects were nothing compared to the relief and the ability to do what needed to be done that day.

“I remember looking at my leg for about 5 minutes because the injection hurt. Can I do this? I need to do this! After the first few minutes of injection pain and trippy side effects, the pain would dissolve and float away pretty fast.” Over the next few years, other similar drugs appeared. “I tried all of them at one time or another,” Ellen says, “and settled on Maxalt (rizatriptan benzoate) for efficacy and fewer side effects.”

Ellen adds, “Before triptans, it was bedrest for bad headaches, so there was work and school lost time and many missed dinners or other events.” For a number of years, she didn’t have a primary care doctor. “After I lived through a headache, it wasn’t forefront on my mind. Pain is forgettable, even severe pain, when it doesn’t kill. No one talked about severe headaches back then. I had to get back to work.

“Two of my worst broke through the triptan tablets, probably because I took them too late,” she continued. “Both had me on the bathroom floor for hours; one at a friend’s dinner party and the other on Christmas Eve at my sister’s party. I don’t think I ever got sympathy that was meaningful. People can feel sorry for you, but it doesn’t help quality of life and who cares about sympathy when you are vomiting your guts out? It doesn’t help right at the time.”

Ellen reflected on the life impact of chronic headaches. “Probably my life would not have been hugely different because I am driven and am an overachiever. I work through pain unless I’m vomiting, then I get it over with and go back to work. That’s common for severe headache people. Life may have been easier without the worry of having a major headache and missing out on social events. I didn’t go to places that could trigger headaches. If it was a longer-haul flight for work, I had to account for that if I planned a presentation and had to come in a lot earlier if it involved travel. I avoided social events with heat, noise, alcohol, lots of people. I would never go to a New Year’s Eve party, for example.”

People with headaches need understanding from coworkers, family, and friends. If their migraines are frequent and not well controlled, they can’t function. That includes being interested in their kids’ days, cooking, driving a carpool, and being nice to their spouse. With frequent near daily headaches, frustration, anger, guilt, and anxiety can add to the suffering. It can break up a marriage. When people give up or use headaches as an excuse to not be there, contribute, or be in a good mood, when they give in to self-pity, they start believing it’s their life forever. It destroys relationships and leaves sufferers in their own misery. For some people, triptans and other newer drugs have been a game changer, but others continue to have their lives disrupted.

“Teenagers have issues with parents—mine just had a more medical focus. ‘Did you test your blood sugar?’ as opposed to ‘Did you have a good day at school?’”

 

Diabetes
Type 1 diabetes affects 1.6 million adult Americans.³ Without insulin, they would die within 3 years of diagnosis⁴ but with today’s technology they can have near-normal life expectancy.⁵ Small wearable devices monitor blood sugar levels and adjust insulin in real time. Chances are you know one of these patients without being aware they are diabetic. Onset in children is common, and training and motivation are essential. Diabetes affects overall health, self-image, and relationships, and the high cost of insulin causes financial burden.

Maggie* is a vibrant, energetic young adult diagnosed at age 8. She doesn’t remember a time when “you didn’t have to think about it. You could do whatever you want.” She was diagnosed early when her mother, a pharmacist, recognized the symptoms. “My parents were very good about it,” she remembers. “They said, ‘This is your disease. We will do whatever you need us to, but you have to handle this.’” They requested that clinic staff talk to Maggie directly. “’She is the one that needs to do it.’ They empowered me to handle it independently. They knew I could do the calculations.”

Classmates were intrigued when Maggie returned to school. “Everyone thought I was very cool, so I was thinking this isn’t so bad. Many people are embarrassed about becoming diabetic. I don’t think I ever experienced that. I got to miss a week of school and do all these things. My parents bought me a cell phone, which I thought was the coolest thing ever!” In adolescence, she “hated being diabetic and wasn’t doing everything I should have been. During your teenage angsty phase, some people sneak out of the house; I just stopped testing my blood sugar regularly.” There are challenges for a busy student, like the occasional acute hypoglycemic episode. “I remember being acute twice when I was taking a test,” she confided. “I was so low I couldn’t think, and I had to tell the teachers I couldn’t take the test. They said what are you talking about? You’re low? What do you mean? It was such a big deal for me to be OK that I would rather be high so I can take the test and not get that low.”

“There were 2 life-changing technological advancements in my college years. With the Tandem⁶ control, you set your basal rate and connect it to your desktop, so it always knows your blood sugar. You need to tell it you’re going to eat 50 grams of carbs, but the natural dips and peaks—it completely evens those out. It can’t increase your basal enough to mitigate having to bolus, but it does a good job. No random ups and downs. It pretty much levels this out.

"Only individual patients can say what matters most to them and surveys of patients with similar conditions will provide an aggregate overview."

 

“The other advancement was the Dexcom G4 continuous glucose monitor. It didn’t hurt and was consistent enough that you could trust it. The US Food and Drug Administration didn’t think so, but if you asked diabetics, we definitely did. Not having to test your blood sugar 8 times a day and having it on your phone? I’ll take that!”

Maggie continued, “Where you really see the value from a day-to-day perspective is the things that make your life so much easier, like Novolog (insulin aspart) insulin will keep me from dying in 2 weeks, but the Dexcom is great because it’ll keep me from dying in 40 years or tonight when my blood sugar goes low and I’m sleeping. It will like yell at me until I wake up. It’s all those small day-to-day, make-your-life-a-little-easier things that have been the most valuable to me. I remember having prior authorizations denied for my Dexcom or for other medications. Someone who’s not diabetic has absolutely no idea what this is like. How can they tell me I can’t have them?”

Like many chronic diseases, diabetes affects relationships. “Teenagers have issues with parents—mine just had a more medical focus. ‘Did you test your blood sugar?’ as opposed to ‘Did you have a good day at school?’ It’s always clear who my good friends are. If they know I’m diabetic and they’ve seen me be super low, they’ll keep snacks just in case. It’s not their responsibility, but it’s so sweet when they do that. It gives me extra insight into someone’s character.”

 

Rare Diseases: Spinal Muscular Atrophy
With major advances in treatment of common chronic diseases, researchers are now focusing on less common conditions. Estimates of the number of rare diseases range as high as 8000.⁷ Gene therapies for a few of them are now or soon will be available. Per patient cost will be very high, but those that are truly life changing are likely to be high value.⁸

Spinal muscular atrophy (SMA) is the first rare disease with a US Food and Drug Administration (FDA)-approved potential cure. Zolgensma (onasemnogene abeparvovec) is a viral vector gene therapy approved in 2019. The first children to receive it in trials are still thriving after 5 years. Untreated, their life expectancy is 2 years at best. Early treatment is essential, as interviews with parents eager to share their children’s stories demonstrate. Lucy received treatment 38 days after birth. She is a lively 1-year-old who crawls, climbs furniture, and can stand briefly unassisted. Her mother hopes that, “One day…we’ll see adults, teenagers, and children just all-out living daily life.”

Patti has given birth to 2 children with SMA. One died before gene therapy became available. Her sister, Addie, received it at age 2-1/2 months. “Stopping the progression of SMA means not watching my child decline,” says Patti. “It means watching her actually have the ability to feed herself [and] propel herself in her wheelchair, which is something I never thought I’d see.” Four-year-old Malachi was treated at 4 months. Like Addie, he uses a manual wheelchair.

Matteo, treated at age 27 days, is an energetic 4-year-old who has achieved all expected milestones, walks, runs, climbs stairs, and attends preschool. “We don’t need to do anything to manage Matteo’s SMA at this point,” says his mother, Nicole. “It really did change his prognosis. I think it’s important to share our story because it gives people hope. It shows people that the treatment is working.” His father sounds like a typical parent of a 4 year-old: “From the moment he wakes up until the moment he goes to sleep, he can outlast all of us!” Matteo already has far-reaching ambitions: “I want to be a chef astronaut, and cook on the moon.”

Elena and Milan watched their first daughter take her last breath in 2010. Their second daughter, Evelyn, received Zolgensma at 2 months and is now 4-and-a-half years old. “The timing of this with SMA is so crucial,” Elena emphasizes, “Because as long as you wait, the more strength the kid would lose.” After Evelyn received Zolgensma, her parents waited anxiously to see the results. “When she started to lift her head when she was on her tummy—this is nothing less than a miracle for an SMA child, because I knew personally that kids with Type 1 SMA, they do not… and Evelyn did! If you look at Evelyn and you don’t know anything about her, you would never think that she had any problems. She’s so independent now. I can’t believe she grows so fast.” Milan adds, “Every week was exciting. Every day she does something that makes me laugh. Every day she’s doing something great.” Their experience with Zolgensma gave Elena and Milan the courage to have another child, a sister who is SMA-free. “We were relieved to know that even if she did have SMA, there is hope,” Milan explained.

These and other videos of SMA families can be seen at https://www.zolgensma.com/family-videos. Their experiences encourage hope that future gene therapies may enable children with other genetic disorders to live fairly normal lives.

 

Other Rare Diseases
Several gene therapies for hemophilia are pending FDA approval. These deliver the gene for a missing blood-clotting factor without which patients are prone to severe bleeding and require regular infusions of the missing factor. Some are poorly controlled and have frequent emergency department visits and hospitalizations. They can die from acute bleeding, and bleeding into joints causes permanent damage and disability. Annual treatment cost often exceeds $1 million per patient, and patients’ financial burden is substantial. Because hemophilia is X-chromosome–linked, mothers deal with guilt feelings, knowing they are the source. Patients often have normal siblings, and parents struggle to balance time and attention among siblings. Family life can be interrupted by sudden trips to the hospital. β-thalassemia, a related blood disorder, also has a gene therapy pending FDA approval.

Patients with Duchenne muscular dystrophy gradually lose function and die as young adults. The dystrophin gene they need is too large to fit in the viral vector capsules, so a truncated form is being studied. Mindy Leffler has an adult son with Duchenne. Concerned that the standard trial endpoints (like the 6-minute walk test) do not reflect what matters to patients and parents, Mindy is developing better tools based on home videos taken by parents. Her company, Casimir LLC, has a HIPAA-compliant cellphone app to transmit these videos, facilitating data collection for clinical studies. “As my son will say,” she told the Institute for Clinical and Economic Review’s public review committee, “’Nobody cares about speed walking. Never wanted to speed walk. Don’t have any desire to do so, and it has nothing to do with my quality of life.”⁹

 

Resources to Improve Understanding
Whether the condition is common or rare, patients with chronic diseases face challenges that are often misunderstood by others. Survival, functioning in daily life, and quality of life are common concerns. The National Health Council website includes links to many responsible patient advocacy groups that provide education on their diseases.¹⁰ But to understand value to patients, there is no substitute for asking them. Only individual patients can say what matters most to them and surveys of patients with similar conditions will provide an aggregate overview. Patients with chronic disease want to be understood and health economists and policy makers need good information to assess the value of the expensive—but potentially curative—treatments being developed for rare diseases.

References

1. Watkins J. “Understanding Value: The Provider’s Perspective.” Value & Outcomes Spotlight. 2021;7(6):25-27.

2. Peters GL. Migraine overview and summary of current and emerging treatment options. Am J Manag Care. 2019;25(2 Suppl):S23-S34.

3. Centers for Disease Control and Prevention. Prevalence of Diagnosed Diabetes. Published December 29, 2021. Accessed February 14, 2022.

4. Distiller LA. Why do some patients with type 1 diabetes live so long? World J Diabetes. 2014;5(3):282-287.

5. Tran-Duy A, Knight J, Clarke PM, et al. Development of a life expectancy table for individuals with type 1 diabetes. Diabetologia. 2021;64(10):2228-2236. doi: 10.1007/s00125-021-05503-6

6. Tandem Diabetes Care. Creating new possibilities for people living with diabetes. Accessed February 12, 2022.

7. Haendel M, Vasilevsky N, Unni D, et al. How many rare diseases are there? Nat Rev Drug Discov. 2020;19(2):77-78.

8. Institute for Clinical and Economic Review. Adapted Value Assessment Methods for High-Impact “Single and Short-Term Therapies.” Published November 12, 2019. Accessed February 25, 2022. 

9. Leffler M. Remarks at the New England CEPAC public review of treatments for Duchenne muscular dystrophy, Cambridge, MA. (Video available at https://www.youtube.com/watch?v=SFI54OjjLZU. Ms Leffler’s remarks begin at 17:54.) Published July 25, 2019. Accessed March 4, 2022.

10. National Health Council. National Health Council Website member list. Accessed March 6, 2022.