Patient-Perceived Outcomes and Quality of Life in ALS
Neurotherapeutics
Patient-Perceived Outcomes and Quality of Life in ALS
Zachary Simmons 0
Introduction: Why Patient-Perceived Outcomes Matter 0
0 Z. Simmons (
1 ) Department of Neurology, Penn State Hershey Medical Center , EC 037, Hershey, PA 17033 , USA
A variety of outcome measures are used in clinical practice and in research to assess patients with amyotrophic lateral sclerosis (ALS). However, there may be discordance between traditional outcome measures such as strength and physical function, and patient-perceived measures of wellbeing. One such self-perceived measure, reflecting the patient's view, is quality of life (QOL). QOL in patients with severe medical disorder is often underestimated by others. Patients with ALS often have high QOL, and this may persist throughout the disease due to shifting expectations and to reprioritization of factors contributing to QOL. QOL instruments can measure health-related QOL (HRQOL) or global QOL, and can be generic or disease-specific. HRQOL refers primarily to physical and mental health. Global QOL is much broader, and is also determined by non-health-related factors. The choice of a QOL instrument depends on whether the setting is routine patient care or clinical research, whether or not the outcome of a specific intervention is being assessed, and upon the expected efficacy or toxicity of the intervention. Global QOL instruments are best for individual clinical patient care or for comparing groups. HRQOL or a combination of HRQOL and global QOL instruments are most appropriate for assessing specific interventions.
Amyotrophic lateral sclerosis; Quality of life; Health-related quality of life; Psychological health; Outcome measures
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Published online: 11 December 2014
# The American Society for Experimental NeuroTherapeutics, Inc. 2014
A variety of outcome measures are used to assess patients with
ALS in clinical practice and in research. Common measures in
routine clinical care include limb strength as measured by
manual muscle testing or hand-held dynamometry, physical
function as measured by the ALS Functional Rating Scale
(ALSFRS) and its revised version (ALSFRS-R) [
1, 2
], and
respiratory parameters such as forced vital capacity, maximum
inspiratory pressure and sniff nasal inspiratory force. Research
outcome measures have varied widely, due to the lack of a
specific biomarker to measure ALS disease progression. The
most common have been survival, rate of change in strength,
and rate of change in function [3]. However, there is not
always concordance between traditional outcome measures
and patient-perceived measures of well-being. This is not
unique to ALS, but has been found in many neurological
and non-neurological diseases [
4–7
].
To date, only one drug, riluzole, has been shown to be
effective in altering the natural history of ALS [
8, 9
], and it is
not clear if the very modest average benefit conferred by
riluzole is perceived by patients as being meaningful. As the
field moves forward, it will be important to determine whether
the benefits of new therapies are meaningful to patients. A
cure for ALS would, of course, be meaningful to the
individuals being treated. But current drug trials for ALS are geared
toward extending survival, slowing rate of progression of
weakness, or slowing loss of function. The concept of
“clinically meaningful” changes in ALS measures is just beginning
to be studied [10]. A different, or at least complementary, way
to assess the perceived value of a new therapy is to measure its
impact on quality of life (QOL), as perceived by the patient.
For drug trials, a critical question is whether the benefits
outweigh the costs. Ignoring the economic implications, the
costs can be thought of primarily as being of two types: 1)
adverse effects of medications, and 2) the physical and
psychological costs of remaining alive longer with a
progressive, degenerative neurological condition. One can imagine
scenarios in which an experimental drug prolonged survival or
slowed rate of disease progression, but with profound fatigue,
or persistent nausea, or an increase in pain and cramping.
Using “objective” clinical trial endpoints such as survival or
rate of change in strength and function, such a treatment
would be considered successful. However, from the patient’s
perspective, the treatment might be considered a failure if they
deemed their QOL to be poorer and if this led them to question
the value of the added survival time.
QOL must be considered not only in the context of
therapeutic trials, but in standard clinical care as well.
Noninvestigational clinical care measures for ALS are currently
palliative, including the optimization of mobility and activities
of daily living, nutrition, communication, respiratory function,
psychological well-being, pseudobulbar affect, sialorrhea,
pain, cramps, spasticity, fatigue, sleep, and end-of-life
decisions [
11, 12
]. It is important to assess whether our standard
clinical m (...truncated)