Please take a moment to review and comment on the measures for sickle cell disease research
related to Neurology, Quality of Life, and Health Services proposed for the PhenX Toolkit
below. We welcome your feedback on this important initiative.
The PhenX (consensus measures for Phenotypes and eXposures) Toolkit
(www.phenxtoolkit.org) provides investigators with access to well-established, low burden,
standardized measures to incorporate into new or existing biomedical studies involving human
subjects. The goal of the Toolkit is to encourage use of common measures to help researchers
effectively collaborate and share data.
The 17 measures proposed by the PhenX Sickle Cell Disease Neurology, Quality of Life, and
Health Services Working Group (WG) are shown in the table below. A limited number of the
measures in this table can be added to the PhenX Toolkit, and the Working Group requests your
feedback to help guide decisions. The measures currently in the PhenX Toolkit relevant for
sickle cell disease research related to Neurology, Quality of Life, and Health Services are listed
after the table.
Co-Chairs Dr. Robert Adams, Medical University of South Carolina, and Dr. Julie Panepinto,
Medical College of Wisconsin, thank you on behalf of the Sickle Cell Disease Neurology, Quality
of Life, and Health Services WG.
For each measure, put a Y in the last column if the measure is useful or an N if the measure is
not useful. You may also respond with general comments. Please email your response to
feedback@phenx.org by May 18, 2015. (Collected responses are confidential. E-mail addresses
are not shared or used for any other purpose.)
To review measure details, please click this link: Sickle Cell Disease Working Group Measures
for Review
Proposed Sickle Cell Disease Neurology, Quality of Life, and Health Services Measures
Please Review:
Measure
1. Quality of Care
2. Quality of Life
Profile
Description of Measurement Protocol
a. Adult: The Adult Sickle Cell Quality of Life Measurement Information
System (ASCQ-Me) Quality of Care Module is a set of 27 questions
administered to adults with sickle cell disease (SCD) to determine the
quality of care that they have received from health care providers.
b. Pediatric: The Consumer Assessment of Healthcare Providers and
Systems (CAHPS®) Health Plan Survey 4.0 Child Medicaid Questionnaire
includes general questions about access to care and quality of care and
additional questions about the services provided to children with chronic
conditions. Items CC1-CC38 of the questionnaire are version 4.0 of the
Children with Chronic Conditions Item Set.
a. Adult: This protocol includes 10 self-administered general health
questions from the PROMIS® Global Health item bank for adults and 29
Respond
Here:
Y/N
self-administered quality-of-life questions from the PROMIS® Profile 29
for adults. The quality-of-life questions include physical function, anxiety,
depression, fatigue, sleep disturbance, ability to participate in social
roles and activities, and pain intensity over the past seven days. Each
question, except for the pain questions, is measured on a five-point
scale.
b. Pediatric: This protocol includes seven self-administered from the
PROMIS® Pediatric Global Health item bank.
a. Adult: This protocol includes 30 self-administered questions from the
short form of the Adult Sickle Cell Quality of Life Measurement
Information System (ASCQ-Me). Domains covered include emotional
impact (5 items), social functioning impact (5 items), sleep impact (5
items), stiffness impact (5 items), pain episode (5 items), and pain
frequency (5 items).
b. Pediatric: The PedsQL™ Sickle Cell Disease Module includes 43 items
from 9 subscales: Pain and Hurt (9 items); Pain Impact (10 items); Pain
Management and Control (2 items); Worry (5 items); Worry II (2 items);
Emotions (2 items); Treatment (7 items); Communication I (3 items); and
Communication II (3 items). For all ages, each item asks how much of a
3. Quality of Life in problem there has been in the past month. There are self- or parentSickle Cell Disease reported forms for ages 8 to 18, and responses are scored on a five-point
Likert-style scale (0 = never a problem; 1 = almost never a problem; 2 =
sometimes a problem; 3 = often a problem; 4 = almost always a
problem). Forms for children ages 5 to 7 are interviewer-administered,
and responses include a three-point Likert-style scale (0 = not at all a
problem; 2 = sometimes a problem; 4 = a lot of a problem). Items are
reversed-scored and converted to a 100-point scale (0 = 100, 1 = 75, 2 =
50, 3 = 25, 4 = 0) with higher scores indicating better quality of life.
Scores for individual subscales are the sum of items divided by the total
number or items answered. The total score for the PedsQL™ Sickle Cell
Disease Module is the sum of the items divided by the number of items
answered.
The Sickle Cell Disease Self-Efficacy Scale is a nine-item, selfadministered questionnaire that measures disease-specific perceptions
of the ability to manage day-to-day issues resulting from sickle cell
4. Self-Efficacy in
disease (SCD). Items are scores according to a five-point scale ranging
Sickle Cell Disease
from "1 - Not sure at all" to "5 - Very sure." Responses from individual
items are summed to give an overall score with higher scores indicating
greater self-efficacy.
a. Birth to 3 ½ yrs.: The Bayley Scales of Infant and Toddler
Development®, Third Edition (Bayley-III®) is a standardized tool designed
to assess a child’s development as compared to same-age peers. The
Bayley-III® has components that involve both direct observation and
5. Intelligence Scale
interaction with a child as well as caregiver questionnaires. The BayleyIII® is a proprietary instrument and is available online from Pearson at
http://www.pearsonclinical.com/.
b. 2yrs 6 months to 7 yrs 7months: Wechsler Preschool and Primary
Scale of Intelligence™-Fourth Edition (WPPSI™-IV) is a standardized tool
designed to assess the cognitive development in preschool and young
children (up to age 7 years and 7 months). The WPPSI™-IV consists of a
battery of tests that allow an investigator to conduct a comprehensive
evaluation of IQ. The WPPSI™-IV is a proprietary instrument and is
available online from Pearson at http://www.pearsonclinical.com/.
c. 6 to 16 yrs: Wechsler Intelligence Scale for Children®-Fifth Edition
(WISC®-V) consists of a battery of tests that allow an investigator to
conduct a comprehensive evaluation of a child or adolescent’s cognitive
ability. The WISC®-V is a proprietary instrument and is available online
from Pearson at http://www.pearsonclinical.com/
d. 16 to 90 yrs.: Wechsler Adult Intelligence Scale®, Fourth Edition
(WAIS®-IV), is a standardized tool designed to assess an individual’s
cognitive abilities. The WAIS®-IV consists of a battery of tests that allow
an investigator to conduct a comprehensive cognitive evaluation of IQ.
The WAIS®-IV is a proprietary instrument and is available online from
Pearson at http://www.pearsonclinical.com/.
The Vineland Adaptive Behavior Scales, Second Edition (Vineland#8482II) is a parent or caregiver questionnaire administered as part of a
6. Adaptive
structured interview that measures day-to-day performance on
Behavior/Adaptive communication, daily living, socialization, and motor skills. Standard
Function
scores can be derived for communication, daily living, socialization, and
motor skills subtests or combined to create an Adaptive Behavior
Composite (ABC).
a. Adult: The Stroke Impact Scale (SIS) includes 59 proxy- or self-report
items in eight domains that assess multidimensional stroke outcomes.
Items 1(a-d) measure strength. Items 2(a-g) measure memory and
thinking. Items 3(a-I) measure emotions. Items 4(a-g) measure ease or
difficulty of communication. Items 5(a-j) measure activities of daily
living/instrumental activities of daily living (ADL/IADL). Items 6(a-I)
measure mobility. Items 7(a-e) measure hand function. Items 8(a-h)
measure participation/role function. Item responses are scored on a fivepoint Likert-style scale. A score of 1 = an inability to complete the item
and a score of 5 = no difficulty experienced at all. A standardized score
ranging from 0 to 100 is calculated for all domains, with higher scores
7. Functionality
indicating a higher quality of life. An extra question on stroke recovery
after Stroke
asks that the client rate on a scale from 0 to 100 how much the client
feels that he/she has recovered from his/her stroke, where 0 = "no
recovery" and 100 = "full recovery."
b. Pediatric: The Recovery and Recurrence Questionnaire (RRQ) includes
seven questions completed by a parent about their child. Questions 1A
to 1D capture problems with strength, coordination, or sensation,
problems with expression, problems with understanding, and problems
with thoughts or behaviors. Questions 2 to 7 capture difficulties with
day-to-day activities, recurrence of stroke, occurrence of headaches or
seizures, other medical problems, medications, and treatments.
Responses from questions 1A to 1D are summed to give a total score,
8. Stroke
Impact/Outcome
9. Brain
Morphology
with higher scores indicating greater functional impairment.
a. Adult: The NIH Stroke Scale (NIHSS) is a physical assessment of the
various symptoms associated with a stroke and consists of 11 categories.
For each category, the test administrator asks the respondent to
perform an activity or respond to stimuli. Respondents receive a score
for each category based upon their ability to complete the activity or
respond to the action. Each score typically ranges from 0 to 3. Each
category of the NIHSS is designed to determine the respondent’s level of
consciousness (LOC), visual, motor, or language ability.
b. Pediatric: The Pediatric NIH Stroke Scale (PedNIHSS) is a physical
assessment of the various symptoms associated with a stroke and
consists of 11 categories. The PedNIHSS was developed by a panel of
pediatric and adult stroke experts and is a modification of the adult NIH
stroke scale (NIHSS). Modifications were made to allow individuals age
18 or younger to be assessed and are identified in the PedNIHSS by bold
italic text. For each category of the PedNIHSS, the examiner asks the
respondent to perform an activity or respond to an action by the
provider. Respondents receive a score for each category based upon
their ability to complete the activity or respond to the action. Each score
typically ranges from 0 to 3. Each category of the PedNIHSS is designed
to determine the respondent’s level of consciousness (LOC), visual,
motor, or language ability.
a. CT: Noncontrast Computed Tomography (CT) of the brain is a
noninvasive radiological assessment that produces cross-sectional
images due to X-ray absorption by specific tissues. The American College
of Radiology-American Society of Neuroradiology (ACR-ASNR) Practice
Parameter for the Performance of Computed Tomography of the Brain
(Amended 2014, Resolution 39) outlines principles for performing highquality CT imaging of the brains of adult and pediatric participants.
Topics covered include indications for CT of the brain, qualifications and
responsibilities of personnel, specifications of the examination,
documentation, equipment specifications, radiation safety, and quality
control and improvement, safety, infection control, and patient
education.
b. MRI: Magnetic resonance imaging (MRI) of the brain is a noninvasive
imaging assessment that produces cross-sectional images due to
inherent contrast differences of tissues as a result of variable magnetic
relaxation properties and magnetic susceptibilities. The American
College of Radiology-American Society of Neuroradiology-Society for
Pediatric Radiology (ACR-ASNR-SPR) Practice Parameter for the
Performance and Interpretation of Magnetic Resonance Imaging (MRI) of
the Brain (Amended 2014, Resolution 39) outlines principles for
performing high-quality MRI of the brains of adult and pediatric
participants. Topics covered include indications for MRI of the brain,
qualifications and responsibilities of personnel, specifications of the
examination, documentation, equipment specifications, quality control
and improvement, safety, infection control, and patient education.
a. TCD: Transcranial Doppler (TCD) ultrasonography is a non-imaging
technique that measures the blood flow velocity in large intracranial
arteries. This TCD protocol covers how to identify relevant intracranial
10. Stroke Risk in
landmarks and how to record and score TCD results.
Children with Sickle
b. TCDi: Imaging Transcranial Doppler (TCDi) ultrasonography is an
Cell Disease
imaging technique that measures the blood flow velocity in large
intracranial arteries. This TCDi protocol covers how to identify relevant
intracranial landmarks and how to record and score TCDi results.
This protocol includes the American College of Radiology-American
Society of Neuroradiology-Society of Neurointerventional SurgerySociety for Pediatric Radiology (ACR-ASNR-SNIS-SPR) Practice Parameter
for the Performance of Cervicocerebral Magnetic Resonance Angiogram
(MRA) (Amended 2014, Resolution 39). Cervicocerebral MRA includes
several MRA techniques used to evaluate, determine the severity of, and
11. Brain Arterial
follow-up on vascular diseases of the cervicocerebral system. This
Blood Supply
practice parameter outlines principles for performing high-quality MRA
of the cervicocerebral system of adult and pediatric participants. Topics
covered include indications for MRA, qualifications and responsibilities
of personnel, specifications of the examination, documentation,
equipment specifications, quality control and improvement, safety,
infection control, and patient education.
Pediatric: The Conners Continuous Performance Test 3rd Edition™
(Conners CPT 3™) is a computerized test for the assessment of visual
attention problems in individuals’ ages 8 years old and older.
Respondents press the spacebar (or click the mouse) when any letter of
the alphabet (except "X") appears on the screen. Commission errors
occur when the spacebar is pressed when an "X" is presented. Omission
12. Sustained and
errors occur when the spacebar is not pressed when a letter besides “X”
Selective Attention
is presented on the screen. Reaction time is the interval between the
appearance of the letter on the screen and the response, e.g., pressing
the spacebar. The Conners CPT 3™ uses both standardized and raw
scores to measure overall visual attention as well as specific aspects of
attention in the areas of inattentiveness, impulsivity, sustained attention
and vigilance.
Pediatric: The Behavior Rating Inventory of Executive Function® (BRIEF®)
is a detailed questionnaire designed to assess executive function
13. Executive
behaviors of children and adolescents in the school and home
Function
environments. The BRIEF® is completed by parents and teachers and is a
proprietary instrument available online from PAR® at
http://www4.parinc.com
Pediatric: Working Memory subtests of the Children’s Memory Scale®
assesses a range of memory function in children and includes short and
long-term visual and verbal working memory and executive working
14. Working
memory tasks. The verbal working memory subtest includes recall of two
Memory
stories read by an examiner. The respondent is given credit for correctly
recalled themes and verbatim story blocks. The executive working
memory includes a forward and backward digit span and sequence (e.g.,
alphabet, days of the week) tasks.
Pediatric: Visual Memory subtests of the Children’s Memory Scale®
assesses a range of memory function in children and includes short and
long-term visual and verbal working memory and executive working
15. Visual Memory memory tasks. The visual working memory tasks including the ability to
remember and recognize faces, remember position and location of
people in a series of photographs, and remember the locations of
pictures within a rectangle.
Pediatric: The Pediatric Migraine Disability Assessment (PedMIDAS)
headache disability questionnaire is completed by the patient and
his/her parent and is reviewed with the clinician or study staff. It
captures the impact of headaches on school performance (three
questions), activities at home (one question on homework or chores),
16. Migraine
and social and/or sports functions (two questions). The PedMIDAS is
scored by summing the answers across the six questions. If a range is
provided as an answer, either use the high end of the range or prompt
for a single answer. The frequency and severity are not scored but can
be used for clinical reference.
Pediatric: The Adolescent Pediatric Pain Tool (APPT) is a
multidimensional self-administered pain assessment tool. The APPT is
used with children and adolescents to evaluate pain intensity, location,
17. Pain (Type and and quality (including sensory, temporal, affective, and evaluative). The
Intensity)
APPT can be used with individuals experiencing pain for various reasons,
such as sickle cell disease (SCD), postoperative pain, allergy testing,
orthopedic, traumatic injury, and cancer. The APPT was modeled after
the McGill Pain Questionnaire and is available in English and Spanish.
The PhenX Toolkit already contains the following measures that may be relevant for sickle cell
disease research related to Neurology, Quality of Life, and Health Services:















Pain
Pain, Type and Intensity
History of Stroke - Ischemic Infarction and Hemorrhage
Executive Function (for adults)
Migraine (for adults)
Verbal Memory (for adults)
Visual Memory (for adults)
Working Memory (for adults)
Gross Motor Function
Motor and Attentional Impulsivity (Immediate and Delayed Memory Task) (for adults)
Disability Due to Mental Health Symptoms
General Well-being
Physical, Social, and Mental Health Functioning (SF-36v2®)
Health Quality Index for Economic Evaluations
Current Quality of Life













Impairment
Medications (Current and Past Use of Pain Relievers, Statins, and Steroids)
Medication Inventory
Service Utilization and Cost
Epilepsy Screener
Alcohol - Lifetime Use
Alcohol - Lifetime Abuse and Dependence
Screening and Severity of Substance Use Problems
Substance Abuse and Dependence - Past Year
Substances - Lifetime Use
Substances - 30-Day Frequency
Substances - Lifetime Abuse and Dependence
Screening and Severity of Substance Use Problems
PhenX Measures for Sickle Cell Disease (SCD) Research Project
The PhenX Measures for Sickle Cell Disease (SCD) Research project is funded by the National
Heart, Lung, and Blood Institute (Ellen Werner, Project Scientist) and the National Human
Genome Research Institute (Erin Ramos, Project Scientist), and led by RTI International (Carol
Hamilton, Principle Investigator). The overall direction and guidance to the PhenX Measures for
the Sickle Cell Disease Research Project is provided by the Sickle Cell Disease Research and
Scientific Panel (SRSP), co-chaired by James Eckman and Kathryn Hassell.