Understanding the needs of people with ALS: a national survey of patients and caregivers

Abstract

Objective: Amyotrophic lateral sclerosis (ALS) has profound effects on people with ALS (PALS) and caregivers. There is a paucity of research detailing and comparing PALS and caregiver day-to-day perspectives of ALS. Methods: A survey developed collaboratively by The ALS Association and a panel of experts in ALS care was designed to broadly sample the experience of PALS and caregivers with respect to physical and emotional symptoms, the efficacy of treatment approaches, and goals for future treatments. Specific physical symptoms assessed consisted of fatigue, pain, weakness, shortness of breath, difficulty sleeping, speech problems, depression and other mood changes, and cognitive changes. PALS, caregivers of living patients with ALS (C-LPALS), and caregivers of deceased patients with ALS (C-DPALS) were contacted by email to participate in a 30-minute online survey. Results: 887 PALS, 444 C-LPALS, and 193 C-DPALS responded to the survey. In comparison to PALS, C-LPALS perceived that PALS had significantly higher rates of all surveyed symptoms except for pain and weakness. Caregivers self-reported higher stress levels than PALS (p < 0.001). 35% (135/383) of caregivers reported experiencing a devastating or near devastating financial impact of ALS and 64% (247/383) of caregivers felt their own health had worsened. Caregivers were significantly less likely to perceive a positive response to treatment in comparison to PALS (p < 0.001). Conclusions: PALS and caregivers report a number of symptoms beyond weakness that affect daily life which may be targets of future interventions. There are opportunities to improve services and care for caregivers to reduce the burden of illness.

Keywords:

• Therapy
• epidemiology
• dementia
• ALS
• caregivers
• quality of life
• patient-reported outcome measures

Introduction

Amyotrophic lateral sclerosis (ALS) has wide-reaching effects on patients and caregivers. Symptom and function-based ALS outcome measures, such as the Revised ALS Functional Rating Scale (ALSFRS-R) (1), the CNS-Lability Scale (CNS-LS) (2,3), the Patient Health Questionnaire-9 (4), and pulmonary function tests help quantify the severity of a select set of ALS symptoms and overall patient function; however, these scales and metrics lack the ability to report the ALS patient’s overall experience in many symptomatic areas. Direct input from the patient is important in understanding the disease phenotype, developing the patient reported outcome measures, and measuring changes in disease states (5–9). Input from patients is also worthwhile to identify a broader spectrum of ALS symptoms, explore the aspects of the disease that are most and least effectively managed, and delineate patient priorities for research and trials.

Additional knowledge is also needed on the impact of ALS on caregivers and the impact of caregiver stress on disease outcomes for people with ALS (PALS). Qualitative interviews have provided some insight into caregiver needs (10–12), though few studies have evaluated the impact of caregiver burden on disease specific outcomes (13). Additionally, because some PALS develop frontotemporal dementia (FTD) (14,15), capturing the caregiver perspective may be a useful supplement when trying to measure the symptomatic burden of a patient with significant cognitive issues. Such patient and caregiver perspectives, preferences and priorities are often referred to as the “patient voice,” and are playing an increasingly important role in clinicians’ approaches to clinical care, scientists’ understanding of disease-based research, and in regulators’ shaping of the drug approval process.

We developed and conducted a survey for PALS and caregivers with the aim of eliciting PALS and caregiver perspectives on the biggest challenges of living with ALS, feedback on care, and priorities for clinical research. These data may help focus ALS clinicians, researchers, funders, and regulators, including the FDA, in targeting resources and therapies toward the most impactful issues for patients and caregivers.

Methods

Survey development

We developed an online open survey aimed at eliciting PALS and caregiver perspectives on ALS symptoms, treatment options, and research. The survey was developed collaboratively by The ALS Association and a diverse advisory committee comprised of regulatory and methodology experts, ALS researchers and clinicians, PALS, a caregiver, and representatives from industry. FDA regulators provided input, as well. In an adapted delphi process, an initial meeting was held, then draft questions were developed and subsequent rounds of review and agreement were performed to develop the final survey. After agreement by members of the advisory committee, final approval came from The ALS Association. The survey materials and dataset are available online on a repository for future researchers (16).

Survey format

The survey had two key parts. The first part was directed at PALS and included questions capturing their perspectives. This part was to be completed by PALS with or without physical assistance from a caregiver. The second part was directed at caregivers and was aimed at capturing both the caregivers’ perspectives on the PALS experiences with ALS and the caregivers’ own experiences supporting PALS. Caregivers were asked to identify as a current caregiver for a living PALS (C-LPALS) or a caregiver to a PALS who had died (C-DPALS). Respondents were not required to answer every question in the survey.

Participant recruitment

Participants self-reported as PALS or primary caregivers, were over 18 years of age, able to complete the survey in English, and had access to internet to complete a 30-min questionnaire. Estimates for survey completion time were generated from the experience of the survey development team.

We recruited participants through emails containing a brief description of the study and a link to the online survey and through online and social media advertising. Emails with links to surveys were sent to potential participants (PALS) from email contact lists held by local chapters of The ALS Association, the North East ALS Consortium (NEALS) Research Ambassador program for PALS and caregivers, the Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) network, and the National ALS registry. Web advertisements were posted on patient advocacy websites, including The ALS Association and NEALS. Social media posts from The ALS Association and NEALS describing the survey and providing a link to the online survey were created to support enrollment. The survey was made available from 11 October 2017 to 2 November 2017. We aimed to recruit at least 200 PALS and 200 caregivers. No incentives for survey completion were provided.

The study and all recruitment materials were approved by Western IRB with waiver of consent. No identifiable health information was collected.

Survey content

To capture a relevant snapshot of recent symptoms from PALS and C-LPALS, respondents were asked to consider the previous 2 weeks. To capture information about end-of-life care, C-DPALS were asked to consider the last 2 weeks of the PALS’ life. Symptoms in the survey were fatigue, pain, weakness, shortness of breath, difficulty sleeping, speech problems, depression or other mood changes including despair or hopelessness, and disturbances in thinking or concentration. Caregivers and PALS were asked to assess how well treatments and lifestyle changes manage the condition using one of five categories: significantly, a lot, somewhat, not at all, unsure. Stress was reported using five categories of response: none, low, medium, high, maximum. Current caregiver health compared to caregiver health prior to ALS diagnosis was reported using five categories: much worse, somewhat worse, the same, somewhat better, much better. Financial effects of ALS were rated on a five-point scale from 1 (no effect) to 5 (devastating).

Data analysis

We summarized demographic and survey questions across all groups (PALS, C-LPALS, and C-DPALS). Demographic data included age, sex, race, ethnicity, employment, insurance, and living situation. For each group, we summarized frequency of reported symptoms as a percent, including stress levels, fears, lifestyle changes, attitudes toward treatment and treatment barriers, and hopes for the future. Pairwise comparisons of proportions of problems reported, fears reported, lifestyle changes, attitudes toward treatment and treatment barriers and hopes for the future between PALS, C-LPALS, and C-DPALS were tested using a two-sample test for equality of proportions. Ordinal logistic regression was used to compare stress levels between PALS and C-LPALS and between C-LPALS and C-DPALS.

Each analysis was carried out for subjects with complete data only. Analyses were exploratory so were not adjusted for multiple testing. All tests were two-sided and assessed on an alpha of 0.05. Analysis were carried out using the R version 3.6 (17).

Results

Participant demographics

We received surveys from 887 PALS and 647 caregivers. Five of the surveys from caregivers did not indicate if the patient was living or deceased, and five surveys were misclassified as current vs. prior caregiver and were removed from the study for a total of 637 caregiver surveys. Among caregivers, 444 identified as C-LPALS, while 193 identified as C-DPALS. Across both PALS and all caregivers, the time from symptom onset to the time of survey completion was less than three years in 759/1524 (50%) total respondents (399 PALS and 360 caregivers) and more than 3 years in 761/1524 (50%) respondents (488 PALS and 273 caregivers).

Demographic data was available for 1003/1524 (66%) participants and is shown in Table 1. Most of the participants were white and aged 55–74 years. Most PALS were male while most caregivers were female. Most PALS were either retired or on disability with only 14% still working full time or part-time. Nearly half of caregivers were working full time or part time, while one-third were retired and fewer than 1 in 10 were unemployed. Most participants were on Medicare and nearly half had some form of private insurance (Table 1).

Table 1 People with ALS (PALS) and caregiver demographics.

	PALS		Caregivers
	Total responding (n)	n (%)	Total responding (n)	n (%)
Age (years)	620		383
<45		38 (6)		82 (21)
45–54		105 (17)		80 (21)
55–64		247 (40)		111 (29)
65–74		174 (28)		86 (22)
75 and older		56 (9)		24 (6)
Sex	620		383
Female		260 (42)		301 (79)
Male		360 (58)		82 (21)
Race	606		364
Black or African American		15 (2)		8 (2)
White		563 (93)		341 (94)
Other		28 (5)		15 (4)
Ethnicity	620		383
Hispanic or Latino		22 (4)		20 (5)
Not Hispanic or Latino		598(96)		363 (95)
Employment	619		383
Full-time		62 (10)		138 (36)
Part-time		23 (4)		46 (12)
On disability		241 (39)		4 (1)
Retired		253 (41)		127 (33)
Unemployed		17 (3)		32 (8)
Other		23 (4)		36 (9)
Insurance^a	620		NR	NR
Affordable Care Act		13 (2)
Medicaid		34 (5)
Medicare		414 (67)
Private		304 (49)
Veterans		101 (16)
Other		80 (13)
Unsure		5 (1)
Living Situation	880		632
Patient lives independently		251 (29)		70 (11)
Patient lives at home with a separate caregiver		256 (29)		79 (12)
Patient and caregiver share a home		301 (34)		389 (62)
In a facility		17 (2)		19 (3)
Other		55 (6)		75 (12)

*Not all respondents completed the every question in the survey, and therefore the total responding to each item is shown in the above table.

^a Only asked of PALS; Respondents could select more than one type.

NR: not reported, information was not collected.

Living with ALS

A total of 764 PALS, 378 C-LPALS, and 153 C-DPALS responded to questions about symptom frequency in the 2 weeks preceding the survey. Responses are shown in Figure 1. The most common ALS symptoms noted by both PALS and C-LPALS were weakness and fatigue. In comparison to PALS, C-LPALS perceived significantly higher rates of all PALS symptoms except for pain and weakness (Table 2).

Figure 1 Comparison of perceived symptoms by people with ALS (PALS), current caregivers (C-LPALS), and prior caregivers (C-DPALS) over the last 2 weeks. *C-DPALS were asked to report perceived symptoms over the last 2 weeks of the patient’s life

Table 2 Percent of people with ALS (PALS) with given symptom in the preceding 2 weeks as reported by PALS and current caregivers (C-LPALS).

Symptom	PALS (%) n = 764	C-LPALS (%) n = 378	p-Value
Weakness	91	91	0.899
Fatigue	76	87	<0.001
Speech problems	52	62	0.002
Shortness of breath	45	59	<0.001
Pain	40	44	0.162
Difficulty sleeping	39	49	0.001
Depression	29	46	<0.001
Cognitive changes	19	26	0.014

End-of-life care

Significantly higher percentages of C-DPALS reported shortness of breath (72 vs 45%, p < 0.001), speech changes (72 vs 52%, p < 0.001), cognitive difficulty (38 vs 19%, p < 0.001), depression (46 vs 29%, p < 0.001), and difficulty sleeping (52 vs 39%, p = 0.004) in the last 2 weeks of PALS lives compared with PALS reporting symptoms over the prior 2 weeks. C-DPALS were less likely to report weakness (79 vs 91%, p < 0.001) in the last 2 weeks of life compared with PALS reporting over the prior 2 weeks. C-DPALS were less likely to report weakness (79 vs 91%, p < 0.001) and fatigue (75 vs 86%, p < 0.001) and more likely to report shortness of breath (72 vs 59%, p = 0.007), speech problems (72 vs 62%, p = 0.033), and cognitive difficulty (38 vs 26%, p = 0.007) in the last 2 weeks of life compared to C-LPALS reporting over the prior 2 weeks, but otherwise reported similar levels of pain, sleeping difficulty, and depression.

Caregiver and PALS stress

Overall, caregivers (C-LPALS and C-DPALS) reported higher stress levels than PALS (p < 0.001);(Figure 2). Most PALS and caregivers had fears about the future (PALS 68%; C-LPALS 67%; C-DPALS 73%). The most common fears were shared across PALS and all caregivers and included fears of leaving family too soon, dying from respiratory failure, and spending savings on medical care. There was no significant difference between frequency of fears reported by C-LPALS and PALS. C-DPALS were more worried about choking in the last 2 weeks of life than PALS (45 vs 31%, p = 0.007) but less worried than C-LPALS (45 vs 31%, p = 0.025). C-DPALS were less worried about falls (3 vs 16%, p < 0.001) and savings (31 vs 47%, p = 0.002) in the last 2 weeks of life than PALS and less worried about falls (3 vs 12%, p = 0.012) and savings (31 vs 44%, p = 0.027) than C-LPALS.

Figure 2 Self-reporting of stress level over the last 2 weeks from people with ALS (PALS) and caregivers (C-LPALS and C-DPALS).

A total of 383 caregivers responded to questions about financial security and their own health. Twelve percent (47/383) of caregivers felt that their financial security was unaffected by ALS, while 35% (135/383) reported a devastating or near-devastating financial impact of the disease. Finally, caregivers felt their own health had gotten much worse (53/383, 14%) or somewhat worse (194/383, 51%) more often than it had stayed the same (128/383, 33%) or improved (8/383, 2%).

Approaches to treating ALS

Ninety-seven percent (1082/1116) of all respondents (PALS and caregivers) noted at least some lifestyle changes since being diagnosed with ALS. PALS reported less time since their diagnosis doing household chores (84%), traveling (79%), working or school (78%), socializing (73%) and engaging in their favorite activity (75%). Fifty-one percent of PALS noted an increase in internet usage since their diagnosis.

Eleven percent (71/676) of PALS and 9% (38/435) of caregivers were uncertain how well they felt current treatments manage symptoms, 14% (92/676) of PALS and 19% (81/435) of caregivers felt treatments did not manage symptoms at all, 39% (267/676) of PALS and 45% (197/435) of caregivers felt they managed symptoms somewhat, and 36% (246/676) of PALS and 27% (119/435) of caregivers felt they managed symptoms “a lot” or “significantly.” Overall, caregivers were significantly less likely to report a positive response to treatment in comparison to PALS (p < 0.001).

When asked to select their top hopes for future ALS research, the three most frequently selected goals by caregivers were therapeutics aimed at breathing function, stopping disease progression, and speaking. The three most frequently selected goals selected by PALs were stopping disease progression, muscle weakness, and breathing function (Supplemental Table 1).

The most common barriers and challenges to current treatment options reported by PALS and caregivers were travel, cost of treatments or lack of insurance coverage for treatments, and time. Almost half reported having no substantial downsides to current treatment options (Supplemental Table 2).

Discussion

We conducted a large-scale survey of PALS and caregivers to provide perspective on the patient and caregiver experience with ALS. Demographics of our survey participants were similar to those in the ALS National Registry (18) suggesting that the respondents are broadly representative of the PALS population in the United States.

These results create a more complex narrative than the standard scientific perspective on ALS, which describes ALS as marked by a degeneration of motor neurons whose main symptom is progressive weakness. Certainly, weakness is a central feature of the disease, yet fatigue, speech problems, dyspnea, difficulty sleeping and pain were common problems perceived by both PALS and their caregivers. Our results support prior studies which have cited fatigue, difficulty speaking, and mobility limitations/weakness as top concerns for PALS (19–21). Our study adds to this work, demonstrating that while caregivers also note similar symptoms, they perceive them at higher rates than PALS. Prior studies have also indicated that caregivers may rate disease impact higher than PALS, particularly with regards to psychosocial symptoms, a finding which has also been seen in other patient populations, such as patients with cancer (22,23).

Pain appears to continue to be an uncontrolled symptom for many PALS, in keeping with prior studies suggesting this is an under recognized and undertreated symptom (24–26). Fatigue was also noted by a large percentage of caregivers and PALS and available treatments for this symptom are limited and of unclear efficacy (27,28). Quality of life assessment instruments exist which incorporate evaluation of these diverse, impactful symptoms (29–33). We would recommend that comprehensive quality of life scales be used for clinical care, and that future research studies carefully consider the diverse constructs assessed by various quality of life instruments when choosing the most appropriate one for a specific study.

Efforts are also needed in the functional, rehabilitation medicine, and augmentative communication support for PALS. PALS and caregivers clearly indicated that there are roles beyond stopping disease progression that they wish future therapies would address, such as communication, swallowing, and breathing support. Depression and cognitive changes were also frequently noted by both PALS and caregivers. Increased attention to these symptoms in research studies and in our clinics is warranted, and has been recommended in other recent work (28,34).

The survey results also highlight a desire for improvements in palliative care for PALS and in support of their caregivers, particularly around end of life. Prior reports have also highlighted this as an area of need in the care of PALS (35,36). PALS and caregivers expressed specific fears including dying an uncomfortable death from respiratory failure or choking. These fears should prompt pro-active palliative care education and goals of care conversations. In some instances, partnerships with palliative care physicians to provide ALS-specific palliative care can be highly beneficial (37–39), and some models have explored embedding a palliative care provider in the ALS multidisciplinary clinic (40).

We observed that C-DPALS reported high rates of untreated symptoms in the last 2 weeks of life. Nuedert et al. previously interviewed relatives of patients with ALS about symptoms in the last 24hrs of life and found that most patients’ symptoms were well controlled (41). In contrast, our study suggests that caregivers perceive untreated symptoms in the last 2 weeks of life. Future studies to examine the timing of hospice referral and impact of hospice on symptom management may provide more clarity on symptoms and perceived symptoms at end of life.

Barriers to accessing care included the burden of time, cost and travel. Telemedicine has begun to offer an ideal opportunity to address PALS’ symptoms while reducing burden on PALS and caregivers (42,43). Having met with notable successes in the clinical venue (44,45), ALS clinicians and researchers are now moving to include mobile digital outcome measures in newer studies to ease the same burdens experienced in clinical research and trials (46).

Perhaps unsurprisingly, ALS has a profound impact on caregivers. Financial, medical and psychological distress was high in caregivers, as demonstrated in other studies (47–49). It is also notable that PALS, themselves, report lower levels of stress than caregivers. This seeming paradox deserves further attention. At least one study has shown that caregiving time increases significantly over the course of disease (50), and this may have an effect on stress and perception of symptoms. Caregivers for PALS with cognitive and behavioral impairment have also been shown to have higher levels of burden and anxiety (51). Prior research has attempted to assess the degree to which caregiver characteristics and patient characteristics contribute to caregiver quality of life and resiliency (13,52–54), but the best approach to supporting caregivers requires further study.

There are several limitations to this study. Not all respondents completed every question of the survey, possibly due to the length of the survey itself. As a result, some questions earlier in the survey, such as questions about living situation, had more respondents, while other demographic data, which was later in the survey, was missing responses. This limited the ability to perform additional analyses examining the extent to which demographics affected symptoms of interest. It is also possible that more symptomatic patients/caregivers had increased motivation to complete the survey. However, this still provides meaningful data about the types and relative frequency of symptoms for a large number of patients. Future studies should aim to include a more diverse group of patients and caregivers, as the majority of our respondents were white. Additionally, this survey required use of the internet, which may have led to an under-representation of patients and caregivers with limited economic resources. Internet-based surveys also make it difficult to assure that PALS were responding for themselves and that cognitive dysfunction did not affect responses. For this survey, we were unable to use more sophisticated methods to track IP addresses or cookies to ensure non-duplicative entries. These are tools covered in the Checklist for Reporting Results of Internet Surveys (CHERRIES) checklist and validated instruments. These may be helpful tools in the development of future iterations of this work to help ensure highest quality responses (55). Lastly, data was not available regarding the nature of the caregiver-patient relationship (i.e. spouse, parent, child, friend, other). In future studies, it will be interesting to examine how the caregiver-patient relationship affects perception of PALS symptoms and caregiver strain.

Conclusions

This study sampled a large population of patients and caregivers and provides insight into the perspectives of people with ALS and their caregivers. Effects of the disease extend far beyond the physical weakness and mobility issues commonly associated with ALS. Caregivers report high levels of stress and perceived symptoms of the people they care for and may benefit from targeted interventions. Future research and therapeutic approaches in ALS alleviating the myriad of symptoms in ALS may have benefit to both patients and caregivers.

Declaration of interest

Kate T. Brizzi and John Bridges report no conflict of interest. Jill Yersak, Calaneet Balas, and Neil Thakur are employees of The ALS Association. Miriam Galvin reports no conflict of interest. Orla Hardiman is Editor in Chief of the ALS and Frontotemporal Degeneration Journal. She has been a consultant for Cytokinetics, Alexion, AveXis, Biogen, and Novartis. Chad Heatwole, MD, MS-CI. Chad Heatwole receives royalties for the use of multiple disease specific instruments. He has provided consultation to Biogen Idec, Ionis Pharmaceuticals, aTyr Pharma, AMO Pharma, Acceleron Pharma, Cytokinetics, Expansion Therapeutics, Harmony Biosciences, Regeneron Pharmaceuticals, Astellas Pharmaceuticals, AveXis and the Marigold Foundation. He receives grant support from Duchenne UK, Parent Project Muscular Dystrophy, Recursion Pharmaceuticals, the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Foundation, the Friedreich’s Ataxia Research Alliance, Cure Spinal Muscular Atrophy, and the Amyotrophic Lateral Sclerosis Association. John Ravits reports no conflict of interest. Zachary Simmons has received consulting fees from Cytokinetics and Biohaven, research support from Cytokinetics, Biohaven, Biogen, and Mallinckrodt, and a stipend from Wiley for duties as Editor of Muscle & Nerve. Lucie Bruijn has been a consultant to Ossianix, AveXis, Biohaven, Orthogonal, and Takeda. James Chan reports no conflicts of interest. Richard Bedlack has received research support from the ALS Association, Cytokinetics, Orion, and Ultragenyx. He has received consulting fees from the ALS Association, Biohaven, Biogen, Brainstorm, ITF Pharma, Mallinkrodt, MT Pharma, New Biotic, Woolsey Pharma. James D. Berry has been a consultant for Alexion Therapeutics and Denali Therapeutics. He has received research funding from Amylyx Therapeutics, Anelixis Therapeutics, Biogen, Brainstorm, Cytokinetics, Genentech, ALS Association, Muscular Dystrophy Association, ALS Finding A Cure, and ALS One. He has also been a consultant to CLEAN Nanomedicine.

Acknowledgements

We would like to acknowledge all of the people with ALS and caregivers of people with ALS who participated in this study. We would like to acknowledge the contributions of the following people to the design and/or interpretation of the study: Brian Kennedy (Caregiver Representative), Madeline Kennedy, RN, MSN, PhD (PALS Representative), Allison Martin (Consultant, Faegre Baker Daniels Consulting), James Valentine (Hyman, Phelps, & McNamara, PC), David Zook (Faegre Baker Daniels Consulting), Kristina Bowyer (Industry Partner, Ionis), Bonnie Charpentier (Industry Partner, Cytokinetics), Amy Laverdiere (Industry Partner, Cytokinetics), Lasair O’ Callaghan (Industry Partner, Biogen).

Additional information

Funding

This work was supported by The ALS Association.