Keywords
haemophilia - clinical scoring tool - real-world evidence - joint health - assessment
Introduction
Haemophilia is a rare genetic disorder characterized by a deficiency in coagulation
factor VIII (haemophilia A) or IX (haemophilia B), leading to spontaneous bleeds or
excessive bleeding as a result of trauma, commonly in the muscles and joints.[1] Despite advances in treatment, joint bleeds may still occur in people with haemophilia
(PwH) on prophylactic regimens; they can also be silent, and could result in arthropathy
and reduced functional mobility.[1]
[2]
[3]
[4]
[5] Recurrent bleeding in PwH is not uncommon after even one instance of haemarthrosis
and although prophylaxis decreases bleeding episodes, arthropathy can still occur
during the lifetime of a PwH.[6]
[7] Monitoring joint status to detect early functional damage is therefore critical
for the clinical management of severe, moderate, and mild haemophilia alike; this
allows for timely adjustments within prophylactic regimens in order to maintain joint
health and minimize joint destruction.[1] According to the current World Federation of Hemophilia (WFH) guidelines, the musculoskeletal
health of each patient should be assessed and documented at least annually.[1]
In order to gain insight into the impact haemophilia has on the daily lives of PwH,
patient-reported outcomes (PROs) are being increasingly considered, alongside standard
clinical outcomes such as factor levels and annual bleed rates. Furthermore, PROs
are becoming critical in assessing efficacy of new treatments,[8]
[9] and as a complementary measure to other objective measures, such as Haemophilia
Joint Health Score (HJHS)[10] and also Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US).[11]
The HJHS is the current standard used for joint examination in PwH.[1] Administering the HJHS requires training and experience[12] and takes 45 to 60 minutes to complete, limiting its regular use in clinical practice.[13] However, time to completion may vary depending on the experience of the clinician.
This has led to calls for new, less time-consuming tools to evaluate joint health.[13] The Hemophilia Functional Ability Scoring Tool (Hemo-FAST) is a simple scoring system
designed to quickly assess functional mobility in PwH.[14]
[15] By relying on routine physical examinations, Hemo-FAST is intended to be a fast
and effective alternative to HJHS.
Hemo-FAST development was based on assessment of relevant items identified in an extensive
literature review of existing tools for diseases that involve functionally damaged
joints or affect mobility, such as rheumatoid arthritis and multiple sclerosis. The
tool was subsequently developed with clinical input, patient testing, and refinement
following cognitive interviews during the initial phase of the project.[14]
[15] The Hemo-FAST tool comprises a PRO part and a clinician-reported outcome (ClinRO)
part, with a score of 0 indicating the best possible joint health status and a score
of 100 as the worst.[15]
The purpose of this study (NCT04731701) was to validate the psychometric properties
of Hemo-FAST for assessment of joint health in adult PwH,[16] with the ultimate intention of using Hemo-FAST in routine clinical practice and
research settings.[14]
Methods
Study Design
This was a low interventional study, with minimal risk, conducted in adults with haemophilia
A or B of all severities across multiple centres in France. The study consisted of
one visit, during which time PwH were asked to complete the PRO part of Hemo-FAST
at both the beginning (test) and end (retest) of the visit. PwH also completed the
short-form 36 health survey (SF-36) questionnaire and the patient global impression
of severity (PGI-S) questionnaire. Clinicians were asked to complete both the ClinRO
part of Hemo-FAST and version 2.1 of the HJHS questionnaire.[a] Hemo-FAST is available through registration at Mapi Research Trust (https://eprovide.mapi-trust.org/instruments/hemophilia-functional-ability-scoring-tool).
To test inter-rater reliability, two qualified clinicians completed the ClinRO part
of Hemo-FAST independently for the same patient during the study visit, with both
raters blinded to the other's findings. The first 50 PwH consecutively enrolled at
sites who agreed to have two raters took part.
Population
Eligible people were aged ≥18 years, had a diagnosis of haemophilia A or B, and the
ability to complete the PRO questionnaire in French and provide a signed informed
consent form. The study exclusion criteria included: joint replacement within the
last 6 months, a non-resolved joint or muscle bleeding events ≤7 days prior to the
enrolment visit, comorbid illnesses or other illness that may have independently affected
the HJHS and Hemo-FAST score and/or limited ability of the patient to participate
in the study as determined by the investigator, and adults under guardianship or curatorship.
Data Collection
The age, sex, body weight, height, medical history (including joint surgery and relevant
comorbidities), haemophilia history (including haemophilia type, severity, joint bleeds
treated in the last 12 months, and treatment regimen), and history of inhibitors in
PwH were collected at the study visit.
The components of the Hemo-FAST questionnaire are summarized in [Fig. 1]. Before validation, the PRO part of the Hemo-FAST tool comprised 17 questions. This
was redefined as 15 questions during validation, with the removal of two questions.
This was due to lack of variation in response to one question, whilst the second excluded
question was considered redundant following reliability assessments of the initial
Hemo-FAST tool. All of the results reported here are based on the validated tool that
includes the 15-item PRO part (assessing mobility level, walking and bending, hand
and finger function, arm function, self-care, household tasks, pain, and support from
family and friends) and the 9-item ClinRO part (covering muscular atrophy, lameness,
and range of motion) except the completion time, which was assessed for the pre-validation
PRO part. The PRO questions were scored on a 4-point Likert scale or as a dichotomized
score (apart from one question that was scored on a scale of 0–10). The ClinRO items
in the Hemo-FAST tool were scored as a dichotomized score (except for one question
scored on a 3-point Likert scale). Scores were transformed to represent the percentage
of the total possible score for ease of interpretation, with a score of 0 indicating
the best possible joint health whilst a score of 100 indicates the worst joint health.
Hemo-FAST total scores were not calculated if more than 10% of questions were unanswered.
Fig. 1 Hemophilia Functional Ability Scoring Tool (Hemo-FAST) components. The pre-validation
Hemo-FAST comprised 17 items in the patient-reported outcome (PRO) part whereas, following
validation, the final Hemo-FAST PRO scores were calculated based on 15 questions.
Time to complete the clinician-reported outcome (ClinRO) part of Hemo-FAST was not
assessed in the study.
The HJHS version 2.1 comprised assessment of six joints and global gait, as described
previously.[17] The total score, scaled 0 to 124, was calculated by adding together the score for
each joint (out of 20) and the gait (out of 4). A high score indicates a worse outcome.
When one or more items were missing, the total joint score was not calculated. Normalized
HJHS total score, scaled 0 to 1, was computed by adding all non-missing item scores
and dividing them by the maximum possible sum for those item scores.
The SF-36 version 1.0 comprises a 36-item, patient-reported survey across eight health
domains: physical functioning (10 items), physical role functioning (four items),
bodily pain (two items), general health perceptions (five items), vitality/energy/fatigue
(four items), social functioning (two items), emotional role well-being (five items),
and mental health (four items) over the past 4 weeks.[18]
[19] SF-36 consists of a physical component and a mental component score; these can be
further sub-divided into eight domains.
The PGI-S is a single self-reported item used to assess haemophilia-related symptom
severity. In this study, PGI-S was worded, ‘When thinking about all of the symptoms
and physical consequences related to haemophilia that you may have experienced during
the past week, please indicate the one option that best described how your symptoms
overall have been: no symptoms, mild symptoms, moderate symptoms, or severe symptoms.’[20]
Analyses
Test, Retest, and Completion Times
The data collated from the pre-validation PRO part of the Hemo-FAST questionnaire
were utilized to calculate the average time interval between the test and retest,
and the total time required to complete the pre-validation PRO part of Hemo-FAST.
Reliability Assessments
Test–retest reliability was assessed according to the intraclass correlation coefficient
(ICC) for the Hemo-FAST PRO score between test and retest. ICC values <0.50 indicated
poor reliability, values between 0.50 and <0.70 moderate reliability, and values ≥0.70
good reliability.[21]
[22]
[23]
Inter-rater reliability was assessed according to the ICC for the Hemo-FAST ClinRO
score between two raters. A positive rating for reliability was given for an ICC of
≥0.70.
Internal consistency, which assessed intercorrelations across the items of Hemo-FAST,
was analyzed according to Cronbach's alpha correlation. A value of 0.70 to 0.95 was
considered acceptable,[22]
[24]
[25] whilst a value of >0.95 indicated high correlations among the items in the scale,
suggesting redundancy of one or more items.[24] Inter-item correlations allow determination of whether the hypothesis that Hemo-FAST
measured one overarching domain is valid, or if sub-domains should be considered.
Inter-item correlation coefficients <0.20 indicates no correlation, whilst >0.70 indicates
an item is redundant.[26] Item-to-factor correlation (also called item-to-total correlation) allows determination
of whether the item contributed to the construct measurement, with values >0.30 indicating
correlation.[23]
[27]
Construct Validity Assessments
Construct validity was assessed according to the Pearson's correlation coefficient
(r) between the Hemo-FAST score and those of HJHS and SF-36, to examine whether different
measures of distinct but related concepts converged in the same direction. Convergent
validity (the extent to which two measures relate) criteria were met if r was >0.50.[22]
[28]
Known-groups validity assessed the extent to which Hemo-FAST scores were distinguishable
between groups of PwH with different characteristics (e.g., haemophilia type, haemophilia
severity, HJHS score, and PGI-S score) by t-tests or analysis of covariance. Additionally,
three multivariate linear regression models were used to examine whether differences
between groups were still present when adjusting for covariates.
Structural Validity Assessments
Floor and ceiling effect was assessed according to the proportion of PwH who achieved
the lowest score/floor effect or the highest score/ceiling effect. Floor or ceiling
effects were considered present if >15% of PwH achieved the lowest or highest possible
scores, respectively.[29] Acceptability and data completeness were assessed according to the percentage of
missing responses to analyze the extent to which the total score could be calculated.
Statistical Analysis
The full analysis set (FAS) consisted of all PwH enrolled in the study. A sensitivity
analysis set was determined for the test–retest reliability assessment, excluding
all PwH with an interval of <30 minutes between test and retest.
The psychometric evaluation was performed using R® environment (R Core Team, 2013;
version 4.2.1). Other statistical evaluations were performed using the statistical
analysis system (SAS) software package version 9.4 (SAS Institute Inc., Cary NC, USA).
It is generally recommended to include at least 10 patients for each scale item.[30] As the pre-validated Hemo-FAST PRO part was based on 17 questions, approximately
180 PwH were planned to be enrolled to allow for approximately 5% missing data and
patient dropout.
Results
Population Characteristics and Demographics
The study enrolled 180 PwH A or B from 14 haemophilia treatment centres across France.
Of the 180 enrolled PwH, 83% had haemophilia A and 17% had haemophilia B. No PwH withdrew
from the study. The median (range) age of the population was 38.0 years (18.0–78.0)
(n = 180) with a median (range) body mass index (BMI) of 24.7 kg/m2 (15.4–41.8) (n = 161); one patient was female. Based on factor VIII or IX levels, haemophilia severity
was rated as severe for 64%, moderate for 17%, and mild for 19% of PwH ([Table 1]). Of those people with severe haemophilia (n = 115), 96 (84%) and 19 (17%) were receiving prophylaxis and on-demand treatment,
respectively.
Table 1
Population demographics and clinical characteristics at baseline (overall population)
|
Characteristic
|
All PwH, n = 180[a]
|
|
Male/female, n (%)
|
179 (99)/1 (1)
|
|
Age, median (range)
|
38.0 (18.0–78.0)
|
|
BMI (kg/m2), median (range)
|
24.7 (15.4–41.8)[b]
|
|
Haemophilia A/haemophilia B, n (%)
|
149 (83)/31 (17)
|
|
Severity of haemophilia, n (%)
|
|
|
Severe (<1% basal factor VIII or IX)
|
115 (64)
|
|
Moderate (1–5% basal factor VIII or IX)
|
30 (17)
|
|
Mild (>5%– < 40% basal factor VIII or IX)
|
35 (19)
|
|
Current treatment regimen, n (%)
|
|
|
Prophylaxis
|
111 (62)
|
|
On-demand
|
69 (38)
|
|
Type of prophylaxis, n (%)[c]
|
|
|
Primary
|
11 (10)
|
|
Secondary
|
68 (61)
|
|
Tertiary
|
30 (27)
|
|
Unknown
|
2 (2)
|
|
Number of joint bleeds in the 12 months prior to enrolment, n (%)
|
|
|
No bleeds
|
107 (59)
|
|
1–5 bleeds
|
52 (29)
|
|
≥6 bleeds
|
6 (3)
|
|
Unknown
|
15 (8)
|
|
PwH with at least one comorbidity (liver disease, renal disease, CVD, respiratory
disease, or GID), n (%)
|
57 (32)
|
|
PwH with at least one surgery in ankles, elbows, knees, shoulders, or hips, n (%)
|
69 (38)
|
|
Inhibitors, n (%)
|
|
|
Inhibitors at the time of the study
|
9 (5)
|
|
A history of inhibitors
|
11 (6)
|
|
No inhibitors and no history of inhibitors
|
159 (88)
|
|
Unknown
|
1 (1)
|
Abbreviations: BMI, body mass index; CVD, cardiovascular disease; GID, gastrointestinal
disease; PwH, people with haemophilia.
Notes: aOne PwH did not provide sufficient responses and was excluded from validation.
b
n = 161.
c
n = 111.
All PwH completed the Hemo-FAST PRO part (excluding one PwH who did not answer enough
questions for his responses to be included). The Hemo-FAST PRO retest was subsequently
completed by 175/180 PwH, whilst the SF-36 and PGI-S questionnaires were completed
by 178 and 177 PwH, respectively. The Hemo-FAST ClinRO part was completed for all
PwH and HJHS total score was evaluable for 158 PwH.
Clinical Characteristics
For the PwH who completed the SF-36 (n = 178), mean (standard deviation [SD]) physical and mental component summary scores
were 70.3 (20.4) and 72.6 (19.1), respectively. Among the PwH who rated their symptoms
via the PGI-S (n = 177), 31% had no haemophilia symptoms, while 41% had mild, 22% had moderate, and
7% had severe symptoms. The mean (SD) HJHS total score was 13.3 (15.8) and the median
(range) was 8.0 (0.0–82.0) for 158 PwH; 22 PwH had non-evaluable HJHS scores (for
1 patient all HJHS questions were non-evaluable, with the remaining 21 PwH having
one or more non-evaluable joints). To account for this a mean (SD) normalized HJHS
total score of 0.13 (0.14; n = 179) was calculated, based on non-missing data.
Completion Time
The PRO part of the pre-validation Hemo-FAST questionnaire was completed by PwH (n = 146) at first test in a mean (SD) of 5.2 (6.1) minutes. The total mean time taken
to complete the PRO part of the questionnaire was divided by 17 (as per 17 questions
in the pre-validation PRO part), and then multiplied by 15 (as per 15 questions in
the validated questionnaire) to give an estimated completion time of mean (SD) 4.6
(5.4) minutes for the validated PRO part of Hemo-FAST.
Reliability Assessments
Test–Retest Reliability
At first test (n = 179), mean (SD) Hemo-FAST total and Hemo-FAST PRO scores were 25.1 (23.0) and 24.1
(22.2), respectively ([Fig. 2A]). These scores were similar at retest (n = 175), when mean (SD) Hemo-FAST total and PRO scores were 24.8 (22.6) and 23.7 (21.5),
respectively. The results for the final Hemo-FAST total score at test, by subgroup,
are presented in [Table 2].
Fig. 2 Hemophilia Functional Ability Scoring Tool (Hemo-FAST) scores at test and retest
in the overall population and subgroups. (A) Total score and patient-reported outcome (PRO) score in the overall population (n = 180). (B) Total score by severity of haemophilia. (C) Total score by treatment regimen. (D) Total score by type of haemophilia. Scores were not calculated if more than 10% of
the questions were unanswered. A score of 0 indicated the best possible joint health
status and 100 indicated the worst joint health. SD, standard deviation.
Table 2
Results for the Hemo-FAST total score at test, overall, and by subgroup
|
Total final Hemo-FAST score at test
|
|
n
|
Mean (SD)
|
Median
|
Min; Max
|
|
Overall
|
|
(n = 180)
|
179
|
25.1 (23.0)
|
18.8
|
0.0; 84.0
|
|
By age group
|
|
18–29 (n = 60)
|
60
|
10.3 (14.0)
|
4.2
|
0.0; 50.7
|
|
30–44 (n = 51)
|
50
|
28.1 (21.2)
|
20.6
|
0.0; 84.0
|
|
≥45 (n = 69)
|
69
|
35.8 (24.0)
|
38.9
|
0.0; 80.6
|
|
By severity of haemophilia
|
|
Severe (n = 115)
|
114
|
32.1 (23.6)
|
33.7
|
0.0; 84.0
|
|
Moderate (n = 30)
|
30
|
17.9 (20.0)
|
10.8
|
0.0; 77.8
|
|
Mild (n = 35)
|
35
|
8.6 (9.7)
|
4.9
|
0.0; 36.1
|
|
By type of haemophilia
|
|
Haemophilia A
(n = 149)
|
148
|
26.0 (23.1)
|
19.8
|
0.0; 84.0
|
|
Haemophilia B
(n = 31)
|
31
|
20.8 (22.4)
|
8.3
|
0.0; 72.2
|
|
By current regimen
|
|
On-demand (n = 69)
|
69
|
14.5 (17.8)
|
6.9
|
0.0; 65.3
|
|
Prophylactic (n = 111)
|
110
|
31.7 (23.5)
|
31.6
|
0.0; 84.0
|
|
Unknown (n = 0)
|
0
|
–
|
–
|
–
|
|
By occurrence of joint bleeding
|
|
No bleeding (n = 107)
|
106
|
22.6 (23.6)
|
14.9
|
0.0; 84.0
|
|
1 to 5 bleeding(s)
(n = 52)
|
52
|
24.9 (20.3)
|
20.1
|
0.0; 77.8
|
|
≥6 bleedings
(n = 6)
|
6
|
42.8 (18.6)
|
45.8
|
7.6; 61.6
|
|
Unknown (n = 15)
|
15
|
36.7 (24.6)
|
39.1
|
0.7; 70.8
|
Abbreviations: Hemo-FAST, Hemophilia Functional Ability Scoring Tool; Max, maximum;
Min, minimum; n, number of people with haemophilia; SD, standard deviation.
The Hemo-FAST PRO questionnaire showed good test–retest reliability in both the FAS
(ICC: 0.76–0.97) and sensitivity analysis (ICC: 0.78–0.97) sets ([Fig. 3]). The mean (SD) time between test and retest for the pre-validation Hemo-FAST was
44.7 (28.3) minutes (n = 144). The sensitivity analysis excluded PwH who had an interval of <30 minutes
between test and retest (n = 95).
Fig. 3 Test–retest reliability of Hemophilia Functional Ability Scoring Tool (Hemo-FAST)
patient-reported outcome (PRO) per question. *The sensitivity analysis set included
people with haemophilia (PwH) who started the retest of Hemo-FAST PRO more than 30 minutes
(and up to 169 minutes) after completing the first test. Q14 and Q17 are not shown
because they were removed from the PRO part of the questionnaire following validation.
Intraclass correlation coefficient (ICC) values <0.50 indicated poor reliability,
values between 0.50 and <0.70 moderate reliability, and values ≥0.70 good reliability.
Inter-rater Reliability
Inter-rater values for the ClinRO questions, assessed according to the ICC, were over
0.7 for seven of the nine questions, indicating good reliability. There were two ClinRO
questions with inter-rater values <0.7 at 0.67 and 0.44, indicating moderate-to-high
and poor-to-moderate reliability, respectively. The ClinRO part was subsequently revised
with additional instructions for all movement assessments, to provide further clarity
for clinicians completing the questionnaire and to ensure a consistent approach to
the physical examination.
Internal Consistency
Intercorrelation assessment across all items of Hemo-FAST resulted in a Cronbach's
coefficient alpha of 0.97 for the entire questionnaire. This demonstrates a high level
of internal consistency between the 24 questions, suggesting some redundancy of one
or more items. However, inter-item correlations were similar for each question, ranging
from 0.53 to 0.55, confirming good internal consistency and no redundancy for any
of the specific 24 assessed questions. Item-to-factor correlation coefficients ranged
from 0.37 to 0.86. This indicates that all questions are considered acceptable to
reliably assess the overall construct evaluated by the Hemo-FAST questionnaire, albeit
to different degrees.
Construct Validity Assessments
Construct Validity
The Hemo-FAST questionnaire demonstrated convergent construct validity with the HJHS
total scores and with individual SF-36 domains assessing physical health ([Fig. 4]). The study also demonstrated discriminant construct validity of the Hemo-FAST total
score regarding mental health with the SF-36 mental health component.
Fig. 4 Construct validity—correlation of Hemophilia Functional Ability Scoring Tool (Hemo-FAST)
with Haemophilia Joint Health Score (HJHS) and short-form 36 health survey (SF-36)—presented
using Pearson's correlation coefficient. Convergent validity criteria were met if
r > 0.50.
Known-groups Validity
At both test and retest the total Hemo-FAST scores approximately doubled between ‘mild’
and ‘moderate’ and between ‘moderate’ and ‘severe’ haemophilia severity ratings ([Fig. 2B]). This was similarly seen with individual PRO and ClinRO scores (data not shown).
Also, at test and retest, the Hemo-FAST total scores for PwH under prophylactic treatment
were more than double to those measured for PwH treated on-demand, regardless of the
severity of the disease ([Fig. 2C]). Similar Hemo-FAST total scores were obtained at test and retest for PwH, regardless
of whether they had haemophilia A or B ([Fig. 2D]). The PRO score of the Hemo-FAST tool increased with age, haemophilia severity,
and for PwH under prophylactic treatment.
Hemo-FAST scores also discriminated between subgroups of PwH with known differences
in characteristics when stratified by HJHS scores and haemophilia severity, although
there was no statistical difference between Hemo-FAST total scores for PwH A and B
(p = 0.25, data not shown). Hemo-FAST total scores were significantly higher for PwH
with abnormal HJHS scores (>3 for PwH ≤50 years old and >8 for PwH >50 years old)
compared with PwH with normal HJHS scores (≤3 for PwH ≤50 years old and ≤8 for PwH
>50 years old[17]) (p < 0.0001) ([Fig. 5A]). Hemo-FAST total scores were overall statistically different for the mild, moderate,
and severe haemophilia subgroups (p < 0.0001) ([Fig. 5B]).
Fig. 5 Construct validity of the Hemophilia Functional Ability Scoring Tool (Hemo-FAST)
scale. (A) Hemo-FAST score stratified by Haemophilia Joint Health Score (HJHS) scores. (B) Distribution of Hemo-FAST score according to haemophilia severity. Boxplots showing
means (squares), medians (bars inside each box), interquartile ranges (box limits),
and minimum and maximum (bars) excluding outliers (triangles). An outlier was defined
as a value more than 1.5 times of the interquartile range below the first quartile
or above the third quartile. (A) Changes in joint health according to HJHS score were defined as: normal HJHS ≤3
(abnormal >3) for people with haemophilia (PwH) ≤50 years old; normal HJHS ≤8 (abnormal
>8) for PwH >50 years old.[17] (B) Mild haemophilia was defined as PwH with >5% to <40% basal factor VIII or IX; moderate
haemophilia was defined as PwH with 1 to 5% basal factor VIII or IX; severe haemophilia
was defined as PwH with <1% basal factor VIII or IX. F-statistic is the ratio of the
variation between sample means and the variation within samples. F, F-statistic.
An adjusted multivariable linear regression model of the Hemo-FAST score demonstrated
that Hemo-FAST scores increased with haemophilia severity for people with moderate
(p = 0.005) or severe (p < 0.001) haemophilia, compared to people with mild haemophilia. Covariates that contributed
significantly to this regression model included age (p < 0.001) and joint surgery status (PwH who had one or more joint surgeries compared
with no surgeries) (p = 0.014). Covariates that did not have a significant impact on this regression model
included BMI, at least one comorbidity, and number of joint bleeds within the past
12 months. In a separate adjusted regression model, the Hemo-FAST scores did not discriminate
between patients with haemophilia A and B. Age had a significant impact also in this
regression model (p = 0.003), as did joint surgery status (p < 0.001) and the presence of ≥6 joint bleeds within the past 12 months (p = 0.023).
Structure Validity Assessments
Floor and Ceiling Effects
There was no floor or ceiling effect. No Hemo-FAST total score reached the worst possible
value of 100, indicating no ceiling effect. Fewer than 15% of PwH (12%) presented
the best possible score of 0, indicating no floor effect.
Acceptability and Data Completeness
The acceptability and data completeness analysis showed around 1% or less of the Hemo-FAST
PRO questions were unanswered (99% completion by all PwH). The Hemo-FAST total score
could not be calculated for 1/180 participants.
Discussion
Monitoring joint status in PwH is critical to adjust treatment modalities for the
maintenance of joint health.[1] Although the HJHS is currently the standard measure used to examine joint health
in haemophilia in clinical studies,[1]
[12] it is time consuming in daily routine and is entirely clinician-assessed.[13]
[17] A simpler tool is therefore needed for use by both PwH and clinicians, with the
use of a combined objective joint assessment and PRO to assess outcomes advocated
in the literature.[10] Hemo-FAST was developed with the aim of providing a simple, convenient, and reliable
tool for assessing joint health that captures clinician and patient perspectives.[14]
[15] Hemo-FAST contains both clinician-reported assessments of muscular atrophy, lameness
and range of motion, and PROs relating to mobility in their daily lives. Overall,
the presented results successfully validate Hemo-FAST as a rapid and reliable tool
to assess joint health in PwH.
The study cohort (n = 180) was expected to be comparable to the population assessed for the international
validation of the HJHS in adult PwH (n = 192)[17]; in both studies, the ratio of PwH A to B was approximately 5:1, which is in agreement
with the WFH-reported prevalence estimate of 80 to 85% and 15 to 20% of all haemophilia
cases, respectively.[1] The proportions of severe, moderate, and mild haemophilia were comparable across
the two studies. However, the proportion of those on prophylaxis treatment was slightly
lower in the HJHS validation study when compared with the current validation study
(56% vs. 62%).[17] In both studies, the proportion of PwH with severe versus moderate/mild haemophilia
may be higher compared with the wider haemophilia population since those with less
severe disease are less likely to regularly attend clinics or be recruited into studies.
Notably, median HJHS total score in our study was lower than in the HJHS validation
study.[17] This may be due to slight differences in the study populations or due to the HJHS
score not being calculated for 22 PwH in the current study, with all but 3 of them
classified as severe. An additional factor may be that, in our study, PwH with a history
of joint replacement within the last 6 months were excluded; this has the potential
to favour those with low HJHS scores.
Hemo-FAST was designed to be quick to complete in order to overcome the limitation
of existing, time-consuming tools: the PRO part of the validated Hemo-FAST questionnaire
(15 questions) will take approximately 5 minutes or less to complete. This would allow
for frequent evaluation of how joint health affects the daily lives of PwH. The completion
time of the recently validated ACTIVLIM-Hemo measure, which assesses the perceived
difficulty of PwH in completing certain activities, is also reported to be similar
at within 5 minutes.[31] However, this measure was developed as an alternative to the Haemophilia Activity
List, includes assessment of non-daily activities (such as skiing, sprinting, and
playing a racquet sport), and contains no clinician part; so it can be considered
complementary to Hemo-FAST in assessing the overall health of PwH. The Functional
Independence Score in Haemophilia (FISH) is a performance-based instrument also developed
to assess functional independence in PwH.[32] However, it utilizes a different rating system compared with Hemo-FAST, involves
no full self-report by the patient, and was developed and validated in a group of
patients who have significant arthropathy. Consequently, FISH is a useful tool for
use in adolescents and adult patients who have not had access to prophylaxis, whilst
Hemo-FAST was validated across a study population with a high percentage of patients
on prophylaxis.[32]
The Hemo-FAST questionnaire demonstrated strong reproducibility: at the first test
and retest, mean total score was 25.1 versus 24.8, and mean PRO score was 24.1 versus
23.7, respectively. The Hemo-FAST total score at test and retest was also similar
between PwH A and B, and increased according to haemophilia severity. This is in agreement
with the recent HJHS validation study for adults, which demonstrated that the HJHS
also differentiates between haemophilia severity.[17]
Overall, the total score was higher for adult PwH receiving prophylactic treatment
compared with on-demand treatment, as also confirmed by test and retest. This is likely
due to a higher proportion of people with severe haemophilia being on prophylactic
treatment compared with the overall study population (84% vs. 62%), rather than a
reflection of the treatment regimen. Indeed, of this overall adult population receiving
prophylaxis, more patients were receiving secondary or tertiary prophylaxis, which
are initiated following two or more joint bleeds or the onset of joint disease, respectively,[33] rather than primary prophylaxis. Furthermore, in the 1980s, adoption of prophylaxis
was delayed due to the risk of transmission of blood-borne diseases; this has likely
impacted joint health in patients with haemophilia born around this time, despite
now being on prophylaxis.[34]
[35]
The Hemo-FAST score showed high internal consistency. The overall Cronbach's coefficient
alpha of >0.95 suggested a degree of redundancy; however, removing one question at
a time did not identify any individual question to exclude. Moreover, the inter-item
correlation coefficients, which were all <0.70, did not indicate redundancy for any
of the PRO or ClinRO Hemo-FAST items.
Convergent validity with total HJHS and the physical component of SF-36 demonstrated
that Hemo-FAST captures the functional aspect of haemophilia. Conversely, Hemo-FAST
showed discriminant construct validity with the mental component of SF-36, suggesting
only functional and not mental impacts of haemophilia are captured. Although changes
in joint health do have a direct impact on the mental health of PwH,[36] Hemo-FAST was developed to assess physical joint health, so this was to be expected.
The structural validity of Hemo-FAST was also demonstrated, with no floor or ceiling
effect and almost all questions answered by all PwH (99%).
The study has a number of potential limitations. Although the time taken to complete
the PRO part of Hemo-FAST was collected, the time taken to complete the ClinRO part
of the questionnaire was not recorded; therefore, the time required to complete Hemo-FAST
in its entirety is currently not available. However, since the ClinRO part of Hemo-FAST
consists of nine questions, based around standard physical examinations performed
during routine follow-up of a PwH, it was not found to be time consuming by the clinicians.
The mean interval between test and retest was relatively short, which could potentially
bias the results in favour of test–retest reliability. However, a sensitivity analysis
excluding all PwH with a test–retest interval of <30 minutes was performed to address
this and confirm test–retest reliability. A factor analysis was not undertaken, and
no statistical analysis was performed to consider the value of prophylactic treatment
(as a covariate) on the Hemo-FAST score; comparison of Hemo-FAST scores between the
on-demand and prophylactically treated patient groups would require a higher number
of PwH. Given the low number of people with severe haemophilia (n = 19) undergoing on-demand treatment, it was not possible to compare Hemo-FAST scores
with those undergoing prophylaxis treatment. Furthermore, although Hemo-FAST provides
a functional and physical examination of joint health, detection of early changes
in joint status may only be possible using certain imaging techniques, such as ultrasound
or MRI.[1]
[37] The objective of Hemo-FAST was not to replace ultrasound to assess joint health,
but rather to provide clinicians with a fast, reliable tool that would bring meaningful
information on joint structure and function during an outpatient visit. In this complementary
role, patient's functional capabilities and joint health assessment could trigger
an additional structural evaluation with imaging technologies such as ultrasound examination.
A prospective longitudinal study would be required to assess whether Hemo-FAST may
also be an appropriate tool to detect early signs of joint deterioration.
Future investigations could assess the sensitivity of Hemo-FAST to treatment effects
over time. The strong psychometric properties and the sensitivity of Hemo-FAST across
clinically distinct categories, particularly in differentiating between the mild,
moderate, and severe groups, suggest that Hemo-FAST may be able to capture clinical
changes that occur over time, whether negative or positive.
Although Hemo-FAST was validated in a population of PwH in France, which is likely
to be representative of middle- and high-income countries, it may not be as representative
of lower-income countries. To help address this, official translations of the Hemo-FAST
questionnaire to cover multiple languages will be released in the future. This will
allow Hemo-FAST to be an accessible tool for PwH, their caregivers, and clinicians
across different geographies.
Conclusion
The psychometric validation of Hemo-FAST supports its use as a rapid and reliable
tool for the functional assessment of joint health in adults with haemophilia A and
B, both in routine clinical practice and clinical research settings. To the best of
our knowledge, this is the first score that evaluates joint health in daily practice
both quickly and easily. The short completion time allows the test to be taken frequently,
thus improving patients' experience by enabling them to have regular evaluations of
their joint health. This in turn provides insight into how their joint health affects
their daily life over time and allows for adaptation of treatment modalities. Overall,
Hemo-FAST offers a practical and complete assessment of joint health and functionality
as it captures both the patient and clinician perspectives through the use of a PRO
and physical exam; its validation could establish Hemo-FAST as a new standard scoring
system for use both in clinical practice and clinical research settings.
What is known about this topic?
-
Monitoring joint health status in people with haemophilia (PwH) is essential to detect
functional damage.
-
Current tools utilized for monitoring joint health status, such as the Haemophilia
Joint Health Score, are time consuming and completed solely by a clinician or physiotherapist.
Subsequently, there is a need for patient-focused tools that are both quick and easy
to implement.
What does this paper add?
-
Here we describe the validation of the Hemophilia Functional Ability Scoring Tool
(Hemo-FAST) questionnaire, a new scoring system designed to quickly and effectively
assess functional mobility in PwH.
-
The questionnaire combines a patient-reported outcome part, to capture the patient
perspective, and a clinician-reported outcome part, comprising a physical examination.
-
Hemo-FAST is a validated, rapid, and reliable tool that allows for more frequent and
longitudinal assessment of joint health in routine clinical practice and in research
settings. This tool puts both the patient and clinician perspective at the front and
centre of the assessment, and allows for adaptation of treatment modalities in response
to detected changes in functional mobility.
