Abstract
Background:
Spinal muscular atrophy (SMA) is a genetic disorder characterized by muscle loss. In December 2016 the FDA approved the first and only treatment drug for SMA: Spinraza (nusinersen). Despite excitement and optimism, there are no published data on the perceptions of individuals with SMA and their families about the benefits, risks, and challenges associated with treatment.
Objective:
This qualitative interview study sought to characterize the perspectives of patients/families with SMA who did not want, or were unsure about, receiving this new innovative treatment for a previously untreatable and often fatal condition.
Methods:
Individuals and families were recruited via advertisements on Facebook groups related to SMA and through the Stanford Neuromuscular Contact Registry. Participants completed a demographic questionnaire and participated in a semi-structured interview via voice conferencing. Interview questions focused on: 1) experiences with SMA, 2) opinions about Spinraza treatment, and 3) factors considered in decisions regarding treatment.
Results:
Thirteen people were interviewed: ten adults with SMA (ages 27–48, nine with Type II) and three parents of minor children with SMA (one each of Types I, II and III). Qualitative content analysis identified a range of opinions about Spinraza treatment: five were uninterested (2 adults, 3 parents), four adults were still deciding whether to pursue treatment, three adults were interested or in the process of pursuing treatment, and one adult was currently receiving the drug after overcoming significant reluctance. Participants described several key factors influencing their treatment decisions, including: concerns about risk factors and side effects, high cost, insurance coverage, time involvement, and lack of data about efficacy. Participants reported learning about most of these factors through parent/patient testimonials on SMA-specific social media groups.
Conclusions:
Participants reported basing decisions about pursuing Spinraza on a variety of practical and value-based considerations. They described carefully weighing the perceived potential benefits and risks of treatment through the lens of their current quality of life and prognosis. These findings suggest that providers should be aware that some patients and parents, especially those with Types II-IV, may approach treatment decisions differently than parents of children with SMA I. Informed treatment decisions can be supported through: 1) the collection and dissemination of better data on Spinraza treatment in these populations; 2) clear communication about risks, side effects and eligibility; 3) improved access to payment and treatment facilities; and 4) facilitation of discussions between providers and patients/families about identity and disability in the context of goals of care and other life and support challenges.
Keywords
INTRODUCTION
The recent emergence of gene therapy technologies has led to the development of therapies to treat once incurable diseases. One important recent example is with the development of effective treatments for spinal muscular atrophy (SMA). SMA is a genetic disorder characterized by muscle atrophy due to the degeneration of motor neurons. There are four types of SMA categorized by the functional outcome of the muscle weakness. Individuals with Type I have onset within the first few months of life and experience the most severe symptoms, including lack of head support, never achieving the ability to sit unassisted, and difficulty breathing and swallowing. Type I patients usually die in the first 1-2 years of life. Type II patients achieve the ability to sit independently but are never able to walk. Individuals with Type III gain motor milestones to the point where they can walk without support but lose function over time and may need a wheelchair. Individuals with Type IV experience the mildest symptoms with later onset, often after age 30 years, and moderate but progressive muscle weakness. SMA is the most common genetic cause of infant mortality with an incidence of 1 in 11,000 births [1, 2].
In December 2016 the FDA approved the first and to date only drug to treat SMA: Nusinersen (Spinraza) [3]. Spinraza is a genetic treatment that works by utilizing and up-regulating a redundant gene to produce working protein in the body that is missing in people with SMA [4]. Spinraza treatment begins with four loading doses in the first eight weeks of starting the medication, and then maintenance dosing every four months thereafter. It is administered via an intrathecal injection. For people with spinal fusion or severe scoliosis, fluoroscopy guided lumbar puncture or other non-fluoroscopy approaches are used.
The approval of Spinraza has been met with controversy and concern about ethical issues related to cost, access and potential risks [5]. The average cost of Spinraza is $750,000 for the drug alone in the first year, followed by $375,000 annually for the rest of the patient’s life. Spinraza is covered by most major commercial payors. In the United States, if a patient is denied coverage by their insurance, the manufacturer, Biogen, will provide the drug free of charge [6, 7]. In spite of this, there have been numerous media reports of patients and families having challenges getting insurance coverage or getting access to administration sites [8, 9].
There is some literature about experiences and perspectives of individuals and families of children with SMA [10, 11], however most if not all of these studies predate the approval and availability of Spinraza. Some of these articles have focused on patient, parent and provider perspectives on newborn and prenatal screening, and the influence of perceptions of quality of life on these perspectives. In a mixed-methods study, Boardman et al found that the majority (75%) were in favor of population screening programs (pre-conception and prenatal), but that perceptions about screening varied according to severity (type) of SMA, with more severely affected individuals with Type II SMA being less likely to support population-level screening and view SMA positively than those with milder, later onset and/or fluctuating symptoms (Types III/IV) [12, 13]. It is not clear how these results, or how views of patients and families with SMA about disability identity and quality of life may influence perspectives on treatment, although there are some anecdotal reports of patients who are conflicted about Spinraza treatment [14, 15].
While the approval of Spinraza has been heralded by many as bringing optimism and hope to many individuals with SMA, there is no information regarding the perceptions and individual preferences of individuals with SMA about this treatment. Specifically, there is no data about how and why some patients and families may be hesitant to pursue, or decide to forego, Spinraza treatment, and what factors influence these decisions. Characterizing these perspectives can help support providers and families in making informed treatment decisions about Spinraza, and in optimizing care for individuals and families with SMA.
MATERIALS AND METHODS
Study design
The purpose of the study was to explore the perspectives and decision processes of individuals with SMA and parents of children with SMA who are uncertain, ambiguous, or have decided against pursuing treatment with Spinraza. Quantitative and qualitative data were gathered over four months between late 2017 and early 2018, approximately one year after Spinraza was approved. The Stanford Institutional Review Board approved all aspects of this study.
Procedures
Participants were recruited via three approaches: 1) posting an announcement to SMA and muscular dystrophy Facebook support group pages (with permission of a moderator if the group was closed) (Table 1); 2) emailing an announcement to the Stanford Neuromuscular Contact Registry; and 3) snowball sampling. The Facebook group pages were identified by using the search terms “SMA”, “spinal muscular atrophy”, and “muscular dystrophy”. Recruitment materials described the study as, “a new study that aims to explore why individuals/parents of children diagnosed with Spinal Muscular Atrophy do not want to pursue Spinraza (nusinersen) treatment or are unsure about the new treatment drug.” Participants were eligible for an interview if they were English speaking, had a diagnosis of SMA or an affected child with SMA, lived in the United States, were aware of Spinraza’s approval, and had either now or in the past expressed uncertainty or concerns about treatment. Interviewees completed a demographic questionnaire using RedCap database (version 8.4.1).
Names of Facebook groups that received invitations to the study
The interview guide was developed by a research team including three senior researchers (specializing in neurogenetics, bioethics, and qualitative research design) and one Stanford School of Medicine graduate student. The guide went through two rounds of piloting and refinement, including cognitive interviewing with four people. A final interview guide included questions framed to allow participants to discuss their experience with SMA, opinions on treatment, and what factors they considered in their decision process regarding treatment (see Supplementary Material 1). All interviews were conducted using Zoom, a secure voice conferencing application. After completing the interview, participants were given a $10 Amazon gift card, sent via email, as a thank you for participating in the study.
Data analysis
Interview recordings were transcribed and uploaded into Dedoose, a qualitative data management and analysis software program (version 8.0.31). Initial codes were formulated a priori based on the semi-structured interview guide. Additional codes were developed iteratively after initial review of the transcripts to produce both structural and thematic codes. Content analysis was conducted by two team members (MP and HKT) to describe participants’ views about Spinraza treatment [16]. These two investigators independently coded all transcripts and reached consensus through discussion about any discordance. Once all coding was finished, summaries of each code’s output were completed, and larger themes were identified. Recruitment was halted when data saturation was achieved (e.g. no emergence of new codes) [17].
RESULTS
Sixteen individuals responded to the study advertisements. Two prospective interviewees were excluded; one who did not live in the United States and one whose child passed away from SMA prior to Spinraza’s approval. One interview was excluded from analysis because the participant’s child was receiving Spinraza and they did not report any hesitation or deliberation about pursuing treatment. Interviews from thirteen participants were analyzed: ten adults with SMA (ages 27–48 yrs.) and three parents, each with at least one affected child (ranging from infancy to college-aged). Interviews ranged from thirty minutes to one-hour and thirty minutes. Of those interviewed, by self-report 15.4% either had or were the parent of an individual with SMA type I (one adult and one parent), 69.2% either had or were the parent of an individual with SMA type II (eight adults and one parent), and 15.4% either had or were the parent of an individual with SMA type III (one adult and one parent of a child with SMA). The majority of the participants were female (76.9%), Caucasian (84.6%) and had at least some college education (92.3%). There was a wide geographic distribution, with participants residing in: Alaska, Arkansas, California, Florida, Illinois, Minnesota, New Jersey, and Texas. See Table 2 for further demographic details.
Characteristics of individuals who participated in a qualitative study on the perspectives of individuals and parents of children diagnosed with SMA on Spinraza treatment
Factors that influence treatment decisions
Participants described nine key factors influencing their decisions about Spinraza treatment (Table 3). These factors were not presented as distinct entities, but rather discussed concurrently and often as related and connected phenomena. We asked participants which, if any, was most influential in their decision process. As seen in Table 3, there was not one factor that a majority cited as being the most influential. Factors clustered into three general categories: factors related to information, barriers to access, and overarching goals and values of those individuals diagnosed with SMA.
Factors influencing decisions about Spinraza treatment
Access to information about Spinraza
Participants described getting information about Spinraza from a variety of sources, both digital and traditional, including: Biogen (the drug company that produces Spinraza), FDA reports, CureSMA.org, clinicians, peers, and social media, specifically Facebook groups. All participants stated that they were members of one or more Facebook groups for individuals with SMA and a majority (n = 10) volunteered that this platform was their primary source of trusted information.
“Definitely ⋯ the Facebook group [has been the most helpful]⋯ I definitely trust when somebody in the group posts something that they did their due diligence to research it and find that article and share it with us. I receive a lot more information that way than even through⋯ provider emails, Navigating SMA and some other SMA group, Cure SMA maybe⋯ I get 1/10th of the information from these sources than I actually do from the Facebook group.” – P11 (Adult, SMA III)
Participants described depending on social media as a source of logistical information about Spinraza coming directly from SMA patients and families including: research updates, descriptions of how to navigate insurance and reimbursement, listings of clinics that will perform the injections, and the injection protocols at various clinical sites. Participants also highlighted the unique ability of social media to allow sharing of videos and photos of progress of first-person experiences of Spinraza injections and post injection progress. As one adult with SMA II said, “I joined all the Facebook groups and it sounds like everyone’s blogging their exact details about their experience, so I feel like I actually know step by step what happens⋯”– P12 (Adult, SMA II)
A few participants described concerns about the reliability of some information from social media. For example, one adult described confusion about social media information about eligibility for those with spinal fusions: “I don’t know if it was true but it was going around the [Facebook] group and some of my peers [said] that if you had scoliosis surgery, it would knock you out of being able to receive it [Spinraza].” – P11 (Adult, SMA III) Another adult described how a doctor criticized her use of social media to obtain information: “The doctors got really upset with me because they said it’s [information from social media] not data it’s anecdotal and I shouldn’t pay attention, but it’s all that I have.”– P12 (Adult, SMA II)
Lack of empiric data about Spinraza
Several participants with SMA Types II and III (n = 7) cited lack of data on efficacy and long-term effects of Spinraza in adults with SMA as a key concern and barrier to deciding whether to pursue treatment.
“I guess in the beginning I wouldn’t say I was jealous, but I was frustrated that there wasn’t more research done on adults and it was approved for adults through all ages, but I think in the beginning the oldest person that they had tried it on was 15. When I was 15, I had lot more strength than I do in my 40’s⋯ if they were going to do all that research and get it approved across the board then I felt like they should’ve thought about that and done some studies with adults.” – P11 (Adult, SMA III)
All parents (n = 3) also described concerns about the lack of data about outcomes if treatment needed to be stopped in the future, for example if insurance decided to stop covering it.
“What happens if she doesn’t get the drug? After we do the loading doses, what happens if she’s sick and she can’t get the drug? How far back are we going to regress? What happens if no insurance is ever guaranteed? What happens if we can’t pay for it? What happens if⋯ she’s 13 and tells me, “I don’t want to do this any more. I’m old enough to make my decisions. I don’t want to do it.” How far back are we going to regress if we take her off of it? That emotional rollercoaster of knowing she could get stronger and then not knowing what would happen off of it terrified us.” – P3 (Parent, SMA II)
Risk factors/Side effects
Most interviewees (n = 12) expressed concern about risk factors and side effects of Spinraza, and said this influenced their treatment decisions. Some expressed specific concerns about the lumbar puncture and anesthesia, including breathing or bleeding complications, extreme pain, spinal headaches, and bacterial meningitis. They were concerned that these potential adverse outcomes would interfere with their daily lives. Many also did not know what to expect about potential long-term risk factors, in part because of the lack of long-term data about the drug: “I’m not too excited about any side effects... If I’m going to get into spinal injections, I want to make sure that the long-term effects of it are not going to come back and bite me down the line” – P1 (Adult, SMA III)
Despite concerns, the three adult participants who were interested in pursuing Spinraza and the one ambivalent adult who had started receiving the drug at the time of the interview felt that the benefits of treatment outweighed the risks or side effects. As a participant said: “As far as painful, or being painful, or uncomfortable, I’m not worried about that. Again, it’s like headaches or something. It seems like my sacrifice is worth the outcome it would do for you.” – P9 (Adult, SMA I).
Cost/Insurance
Almost all participants (n = 11) mentioned the high cost of Spinraza as a barrier or potential barrier to accessing treatment. They stated that they would not be able to afford the drug if it were not covered by insurance or by the drug company, now or in the future. They also described a slow and arduous process to get insurance approval, and concerns that some may not get insurance coverage at all. Two participants stated that their insurance providers (Kaiser and Medi-Cal) had already denied coverage of their treatment. As one adult said: “I think that there’s a non-negligible percentage of the SMA community who are still fighting very, very hard to get access to Spinraza... and I know now it’s because of the insurance blockages.” – P14 (Adult, SMA II) Another adult described the arduous process of getting an insurance denial and then applying for coverage of the drug through the Biogen “Free Drug Program” [7]:
“If you’re lucky it’s going to take six months, if you’re not it’s going to take around nine to ten months to get the first dose⋯it’s just a battle between the insurance and the doctor, if they approve it or they deny it. If the insurance denied it three times it is possible to get a free version through Biogen, so either way it’s going to take around at least half a year.” – P10 (Adult, SMA II)
Others said that even if the drug itself was paid for by insurance or through the drug company, there were still many other associated costs with the procedure that make getting treatment challenging, including transportation fees and the cost of missing work. One adult said, “without the insurance there’s no way it would happen, because even with Biogen support they don’t cover the procedures that I need as an adult to go along with it, so the cost would have been impossible” – P12 (Adult, SMA II). Despite the challenges of working with insurance, several participants felt that it would be possible to get coverage for treatment: “it has been extremely difficult but it’s doable.” – P12 (Adult, SMA II).
Many participants (n = 9) expressed concern about the need for lifelong medical insurance coverage to pay for anticipated lifelong treatment. Several expressed concern about the implications of doing anything that might require changes to insurance coverage, such as changing jobs. One participant feared that with the advent of a treatment for SMA, insurance companies might stop paying for other services and equipment needed by SMA patients.
“The problem is I worry that down the line⋯if I say, “Hey, insurance company, will you pay for my new wheelchair,” and the insurance company says, “Well, why aren’t you getting Spinraza,” and I say, “Well, because I don’t want to get Spinraza,” and they’re like, “Well, we’re not going to pay for your new wheelchair because, theoretically, you wouldn’t be in a wheelchair if you took Spinraza,” – P1 (Adult, SMA III)
Time
Time was referenced as a barrier to accessing Spinraza in three ways: 1) the length of time required to get approval for and receive Spinraza; 2) the time burden required to get regular injections and manage side effects; and 3) the need for a lifelong commitment to treatment with the drug. Ten participants stated concerns about the amount of time involved in getting the drug. Three participants specifically stated concerns about the time for communication and approvals between insurance companies, Biogen, and clinicians. Some (n = 4) mentioned they felt that this wait time was unacceptable because of the progression of their disease.
A majority of participants also asserted that the cumulative time needed to get the injections could be lengthy, referencing that many peers have had to take off work before and after each intrathecal injection due to travel and/or side effects. One participant said, “I had one friend that got it, and he really didn’t notice a big change, and, I don’t know, he’s missed three weeks of work due to spinal headaches⋯ that was a real deterrent.” – P1 (Adult, SMA III) Other participants (n = 3) described concerns about the amount of time it would take to get to clinic sites, given the limited number of facilities that are providing the drug and the lack of proximity to where they live.
Several participants expressed concerns about the length of time needed for the potentially life-long commitment to Spinraza treatment. They were unsure that they want to be tied to a treatment that is expensive, possibly painful, and potentially disruptive to their daily life. As one adult with SMA II said, “If it was even like once a year that you had to get a new dose or something I think that would be better but it’s every four months and just the thought of having to do that for the rest of my life to receive any of the benefits, it’s daunting.” – P11 (Adult, SMA II).
Transportation/Travel
A few participants (n = 3) described specific challenges around lack of transportation to the clinic sites that would make getting Spinraza very difficult. Even with reliable transportation, commuting can be a challenge for patients in wheelchairs and frequently requires support from a personal care assistant, family member, or friend. Some participants expressed that these are challenges they already experience when getting their routine medical care, so adding more travel time and need for transportation assistance on top could pose a significant barrier. One adult with SMA II said: “How’s it going to affect our life; there’s inconveniences with the extra doctors appointments that we already have and don’t necessarily want more of.” – P8 (Adult, SMA II).
Others also noted that clinics that offer Spinraza are very far away, requiring more time, money for travel, and assistance on a regular basis.
“There’s a lot of hassle. First of all, my city where I live in doesn’t have any administration site. I would have to travel in order to pursue it. I work full time, so I have a job and I only have a limited amount of time off⋯ I don’t have money to pay someone to travel with me out-of-town and possibly get a hotel if I need it.” – P1 (Adult, SMA III)
Quality of life and functional status
Several patients and parents described the quality of life and functional status of the adult or child with SMA as influencing treatment decisions to pursue treatment. Some individuals (n = 3) who still had some level of independence, such as eating or operating a wheelchair believed they had the time to gather more data and/or wait for a better drug. As one adult said: “I feel like while I’m not physically healthy, I’m not sick either⋯ I’m still at a point in my life that I can wait it out for a bit longer⋯ It’s only been a year since it’s come out and with any type of technology or medicine, the longer it’s used, and the more people use it, the better it gets.” - P11 (Adult, SMA II).
One participant explained that her (recently deceased) child with SMA I was so significantly impacted that, in her opinion, Spinraza would have been unlikely to positively affect movement or improve his quality of life.
“Dr. [Name] was pretty much like even if we put some loading doses in, he is still going to have to go onto a ventilator and really the decision came down to are you willing to have a child that just lays in a bed all day on a ventilator and can’t do anything and is that right for your child? Like what’s the humane thing to do? What’s the compassionate thing to do?... So it was a quality of life issue for me⋯ you have to understand at this point my son, he could barely move a finger. He was like completely paralyzed so there was no like, his chest was already caving in, and he would have lived a horrible life, even with the drug. - P2 (Parent, SMA I)
Other patients, mostly adults with SMA II (n = 5), believed that Spinraza’s ability to stop or slow progression was enough motivation to pursue treatment. They did not want to lose function and depend on more assistance than they already required. They viewed Spinraza as potentially allowing them to have a higher quality of life with the maintenance of their independence.
“I want to feed myself, I want to use my phone independently. I want to drive my chair without having to think about it. It’s all these little things that I kind of didn’t even consider⋯ Before that progression I was able to have a certain level of independence and interdependence that I was really comfortable with and this new progression has required a different level of help from others that was new and scary and felt pretty invasive and uncomfortable.” – P14 (Adult, SMA II)
Alternative treatment options
Participants were asked if they viewed Spinraza as a cure and/or wanted alternative treatments if and when they became available. None of the participants viewed the drug as a cure, but they used this question as an opportunity to explain and articulate their perception of this treatment and why it did not constitute “a cure” (Table 4). Reasons included the amount of effort/medical care to get the drug administered, the length of time that the drug is needed, the perceived lack of significant functional improvements or reversals of functional decline, and the lack of significant changes in the kinds of activities that they would be able to engage in.
Several participants with SMA II or III had decided not to pursue Spinraza treatment (n = 2) or were undecided (n = 3), in part because they were aware of other drugs in the drug development or approval pipeline. Despite concerns about their own disease progression, they were willing to wait for a treatment that was less invasive, costly, or time-consuming. Many participants stated that they would be more likely to take a drug that was, for example, a one-time pill.
Illustrative participant responses to the question: “Do you view Spinraza as a cure?”
“The idea of travelling somewhere and having to get out of my chair, go through an injection in my spine. The idea of the cost being $125,000 each shot... If it was a pill, like if it was a prescribed pill, and my doctor was like, “Yeah, take this. I’ll prescribe it for you. Go pick it up at the pharmacy.” Yeah, I’d be all over that.” – P1 (Adult, SMA III)
Others felt that future treatments, specifically gene therapy, would be more effective than Spinraza, though they understood this technology is still in the clinical trial phase. As one parent said, “I think the real cure is going to be in the gene therapy where they can just correct the gene at birth, that’s going to be the real cure. But Spinraza is kind of like a band-aid until the gene therapy comes through in my opinion.” – P2 (Parent, SMA I).
Disability identity
Some individuals/parents with SMA Types II and III (n = 4) viewed Spinraza treatment in part through a disability identity lens. Two adults with SMA (Types II and III) expressed concerns about the cost of the drug putting a price tag on their worth, and more broadly, on disability in general. They were alarmed that the medical community, insurance companies, and society would rather spend an exorbitant amount for adults with SMA to gain, at most, a small amount of function back, rather than using these funds to provide them with what they need to survive comfortably and independently.
“I’m 40 years old, right. ⋯ Based on my progression, what I can see, I’ve given myself 20 good years. If I took that 20 years and I put that towards Spinraza, like if I took 20 years of Spinraza, then it would amount to about I think close to eight million dollars, right. If I had eight million dollars handed to me and somebody said, “[Interviewee], you can either take Spinraza and you might be able to open the hell out of this Ziploc container⋯ or you can take this eight million dollars and get all the intended care you need to never have to fight to get a new wheelchair. You can swim in a pool. You can have an accessible home. You can go anywhere you want to go. You never have to worry about your van breaking down.” Everything that I could ever need that would help me stay healthy and independent, I could buy with this eight million dollars, right, over being able to open a Ziploc container really well. I would be more cured if I put $8 million towards that than to this drug. To me, the priority is very medically-driven⋯ the cost, it really hurts me, it hurts people and it hurts our world because it’s putting a value on the idea of a cure that really isn’t really there... an overall idea of disability being so atrocious that being able to open a Ziploc container is more important than having a full life that you can engage with.” – P1 (Adult, SMA III)
These participants critiqued Spinraza as part of a medical model of disability: it made them feel as though they had a sickness and others were trying to cure or “fix” them. As one adult said, “It’s like you’re broken and people are constantly trying to fix you” – P1 (Adult, SMA III). They viewed SMA as part of their identity as disabled people, and though they had physical differences, did not feel as though it was an illness to eradicate. They expressed concern that this new drug, as well as others that are currently in the pipeline, might perpetuate negative views about their condition and about disability in general.
One participant described her challenge in reconciling her decision to get Spinraza with her disability identity and advocacy work. She described deciding to pursue treatment after being surprised by some new functional declines and prioritizing her desire to maintain as much independence and functional ability as possible for as long as possible. However, the treatment decision was difficult for her, and one that she described still struggling with two weeks after starting injections.
“How do I reconcile being a disability rights activist and being in the movement, and making out my life’s work while still pursuing Spinraza, they still seem inherently contradictory to me and I don’t have an answer for how to reconcile them. I was kind of just in denial about it for a while⋯ and then I got to neurology and as soon as they got the needle into the hole for the lumbar puncture I started sobbing because I felt like I was betraying my community, my values. I didn’t know who I was anymore.” – P14 (Adult, SMA II)
Two parents of children with SMA (Types II and III) specifically stated that they would rather put their efforts into living a life that is not focused on medical treatment or a medical model of disability, but rather on participation in meaningful activities and positive self worth. One parent said, “It just is not a good fit for our family and our lifestyle because our whole goal with [Child] is to not make her feel disabled, to not have her life focused around hospitals⋯ That would take her out of school and out of her social life. I think that would⋯ destroy her and send her into a depression.” – P3 (Parent, SMA II) One parent of a college-aged child with SMA Type III echoed worry about the potential disruption of treatment to daily life.
“It seems to me that when you do these treatments you have to be resting for three days after or something. Your life is revolved around these treatments and certainly that’s some other factor that needs to be looked at for somebody. For instance, my daughter’s in an ivy league college and if she wants to go get treatment. I mean⋯ “ – P4 (Parent, SMA Type III)
DISCUSSION
The goal of this study was to characterize the perspectives of patients/families with SMA who did not want, or were unsure about, receiving Spinraza treatment. The participants in this study framed their decisions about pursuing Spinraza as nuanced, challenging and context-specific. Somewhat surprisingly, cost was not the main factor described. Rather, participants described a blend of numerous factors influencing treatment decisions including, but extending beyond cost: availability of information, risk factors and side effects of treatment, insurance approval challenges, time constraints, transportation and travel to clinical sites, functional status, disability identity, and the hope for an alternative drug. These factors were not described independently of one another, but rather were enmeshed, with some participants describing more than five factors in a single train of thought. This revealed the complexity and difficulty involved in treatment decisions for some.
Our study suggests that at least some patients and families are not getting adequate or accurate information about treatment, and that Spinraza may have introduced as much confusion as it has hope. Some of this lack of information can be attributed to the accelerated approval of Spinraza, which was authorized by the FDA after reviewing data derived from clinical trials involving fewer than 200 patient-subjects over just a few years [3, 18]. Many participants also expressed concerns about the lack of trial data for adults with SMA types II-IV, and the lack of data about long-term benefits and side effects.
Because of this limited information, participants described using social media to find information and patient testimonials about the drug. Other studies have demonstrated that social media, specifically Facebook, provides an easy, interactive platform for people to communicate about medical information, including about unique conditions [19]. Our participants described their trust and confidence in the information about Spinraza that they gathered from Facebook. However, our study also demonstrated that some individuals receive misinformation from social media sources, including about treatment practices and eligibility. This is consistent with studies of social media showing misleading information about drugs soon after their approval [18]. Participants reported a desire for other, potentially more reliable sources of information in an easily accessible location, such as the Biogen website, where drug data, testimonials, eligibility information, and procedure protocols can be found. It also suggests that clinicians should be aware of, and perhaps observe, the disease- and treatment-specific social media groups in order to inform patients, and discuss the information they find there.
Spinraza, like many innovative therapies, has the ability to turn a life-threatening disability into a chronic condition, but likely fails to mitigate or eliminate all functional limitations and symptoms. King and Bishop have described this phenomenon as “palliative intervention” [18]. In such a context, both the treatment itself and the process of getting treatment affects short- and long-term quality of life in both positive and negative ways. According to the World Health Organization, quality of life is defined as individuals’ perceptions of their situation in life in the context of culture, values, goals, expectations, standards, and concerns [20]. In weighing the factors described above, our participants generally articulated one of two perspectives: 1) the long-term functional improvements of Spinraza treatment outweigh any potential other challenges to quality of life, and 2) the short-term challenges and impacts of treatment on quality of life do not outweigh any potential benefits. Participants who prioritized functional independence above all else were willing to sacrifice short-term impacts on time, money, and concerns about disability identity to achieve those goals. In contrast, others were not willing to do so.
Our findings on disability identity suggest that some people across SMA subtypes struggle with reconciling Spinraza treatment and cost with their perspectives on disability identity. Specifically, individuals with Types II and III expressed concern about the cost putting a price tag on their worth, and giving credence to a medical model of disability that viewed them as something to be “fixed” or ignored other expensive equipment and supports that are perhaps more essential to improving their functional ability and quality of life. Given the specific requirements for Spinraza treatment (e.g., repeated trips to a hospital that may be far away for injections, time off of work or school), several adults and parents expressed concern that pursuing treatment would lead to a shift away from a focus on quality of life, and in fact reduce quality of life by interfering with other activities.
These findings are not inconsistent with those from other studies. Several publications have described distinct preferences and views of quality of life and identity among adults with SMA Type II, as compared to parents of children with SMA Type I and adults with SMA Type III [9, 22]. In general, those who have had a disability most of their lives, and who find it relatively static (e.g. Type II adults) view the condition as an “integral and highly valued part of their sense of self”. Those who see declines in function, or in whom onset is later, generally have a less positive view of the condition and more positive perspectives on population genetic screening or potential treatment or cures [9, 23]. Our findings showed concern about the influence of treatment based on a disability identity perspective from each of Types I, II and III, but due to our small sample size we cannot reliably detect or assess between-subtype differences about these issues.
Our results suggest that clinicians should engage patients in explicit discussions about a variety of topics related to treatment decisions. First, they should elicit patients’ awareness and knowledge about the natural history of SMA. Among our participants not pursuing Spinraza treatment, there was no spontaneous mention of potential functional decline and disease progression, as there was among participants pursuing or undecided about treatment. There are several possible explanations for this observation. Participants may have chosen not to pursue Spinraza knowing full well the imminent functional decline they will face, or they may have decided against it, not recognizing the totality of its progression. This cannot be discerned from our study, but nonetheless highlights the need for clinicians to ensure patients have knowledge of the disease, treatment, risks and benefits, and potential alternate drugs in development, in order to make informed decisions.
Clinicians also should discuss and ask questions about patients’ values, goals, and knowledge base (Table 5) while improving dissemination of information about Spinraza. In order to make value-based treatment decisions, self-awareness by the patient is key [24]. However, patients do not always have this consciousness and so clinicians should be prepared to assist patients with self-reflection and an understanding of personal desires. By being attuned to these values and priorities, clinicians may garner trust and allow for shared decision-making to occur between practitioner and patient. Further, although only a minority of participants mentioned disability identity, it is clearly relevant and emotionally, socially and practically important to some. Clinicians should ask patients about this topic and their concerns, and provide appropriate supports, counseling and referrals to resources.
Recommendation of information to discuss with patients and families considering Spinraza
Limitations
There are several important limitations to this study. Our participants were relatively homogenous in race and ethnicity and we had a small sample size, although the sample is well-within empirically established sample sizes for achieving data saturation in qualitative research for this kind of thematic analysis [25]. The experiences, values, and priorities of different types of SMA, as well as age cohorts have been demonstrated to vary across SMA subtypes in other studies [12, 22]. All participants were self-selected, with a majority recruited from Facebook. Therefore, there may be response bias from those who utilize social media. However, several studies have documented that using social media to recruit participants for research from rare disease or hard-to-reach populations can be as, if not more, effective than traditional methods, and leverage documented ways in which patients and families currently interact and gather disease-based information [26–29]. We had few participants/parents with SMA Type I and did not have any participants with SMA Type IV. We also did not interview any adolescents about Spinraza, whose perspectives may not have aligned with adults or parents of children with SMA. Because we only interviewed participants in the US, we cannot comment on the views of participants in other countries, or the relevance of these findings to other countries or health care systems.
This study was focused on exploring the perspectives of those who were unsure about, or who did not want Spinraza. We did not recruit individuals or parents who had no hesitation about Spinraza. Because of this, our study may not reflect perceptions of the SMA community as a whole. Follow-up studies are needed to extend this exploration into the broader SMA community, including those who have no hesitation about treatment, and to follow the perspectives of patients/parents over time and as experience with Spinraza increases.
We did not ask participants to weigh each factor influencing treatment decisions. Therefore, we do not know how much each factor contributed to each participant’s decision. We also did not ask participants specific questions about functional decline or disability identity, so our analysis is limited to those participants who brought it up spontaneously in their responses.
CONCLUSION
This study sought to characterize the perspectives of adults with SMA and parents of children diagnosed with SMA who are ambivalent about, or do not want to pursue, Spinraza treatment. In our study population, the decisions about Spinraza treatment were based on many factors including: logistics of treatment (cost, time), perceived short and long term benefit and risk, disability identity, and quality of life (both current and potential future). Some prioritized the short-term challenges of obtaining treatment whereas others believed that the long-term functional improvements outweighed any barriers. Many (n = 9) were undecided about Spinraza and/or interested in a more easily accessible drug that they hope might be available in the future. These findings highlight the need for better information dissemination and improved discussion between patients/families and clinicians about the values and priorities, maximizing informed and shared decision-making.
Additional research is needed to validate and extend these results across the SMA community, especially as Spinraza becomes more widely used and available, as well as if other drugs for SMA are approved. Future studies may include larger sample sizes that include more diversity in demographics, SMA subtype, and functional status. Research looking specifically at individuals who are currently getting injections would provide additional information about motivations and expectations, as well as potential benefits and harms. Because lack of information was a commonly stated influence, research on clinician understandings of Spinraza, as well as the conversations between clinicians and their patients around treatment, may elucidate information gaps and strategies to address them.
CONFLICT OF INTEREST
The authors declare that they have no conflicts of interest to disclose.
HUMAN STUDIES AND INFORMED CONSENT
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
ANIMAL STUDIES
No animal studies were carried out by the authors for this article.
Footnotes
ACKNOWLEDGMENTS
This study was completed in partial fulfillment of the requirements of the first author’s Master of Science degree in Human Genetics and Genetic Counseling from Stanford University’s School of Medicine. We would like to thank the NSGC Neurology SIG and Stanford University for funding this project as well as our participants and the SMA community for making this study possible.
