Construct and Content Validity of Instruments Used in Clinical Trials of Psoriatic Arthritis
PI: Alexis Ogdie, MD MSCE
Supplemental Table: Variables to be requested. The following variables, when available, will be
requested for the baseline visit and study completion.
Trial specific
Treated or placebo
Measures of Peripheral Arthritis
Tender joint count (0-28)
Activity*
Swollen joint count (0-28)
Tender joint count (0-68)
Swollen joint count (0-66)
Tender joint count (0-78)
Swollen joint count (0-76)
Measures of Radiographic
Modified Total Sharp-van der Heijde Score
Damage
Erosion subscore
Joint space narrowing subscore
Laboratory Measures of
CRP (both mg/L and mg/dL)
Inflammation
ESR
Physician Assessment
Physician Arthritis Global VAS
Physician Disease Global VAS
Enthesitis
Leeds Enthesitis Index
MASES (0-13)
Modified MASES (0-15)
4-point enthesitis Index
SPARCC
Dactylitis
Dactylitis Count
Dactylitis Severity score
Leeds Dactylitis Index
Spondylitis
Bath ankylosing spondylitis disease activity index (BASDAI)
Bath ankylosing spondylitis functional index (BASFI)
Bath ankylosing spondylitis metrology index (BASMI)
Psoriasis
Psoriasis Area Severity Index (PASI)
Physician Global Assessment (PGA)
Body Surface Area (BSA)
Nails
Nail Global Assessment VAS
Nail Psoriasis Severity Index (NAPSI)
Modified Nail Psoriasis Severity Index (mNAPSI)
Patient reported outcomes
Global Assessment (arthritis and
Patient assessment of skin (VAS)
skin) (VAS)
Patient assessment of arthritis (VAS)
Patient global assessment of disease activity (VAS)
Stiffness
Stiffness VAS
Duration
Depression
Beck Depression Inventory
CES-D Depression Scale
Columbia Suicide Severity Rating Scale (C-SSRS)
Hospital Anxiety and Depression Scale
Other depression or suicidality scales
Pain
Patient assessment of pain (VAS)
Fatigue
Fatigue Assessment Scale
Functional Assessment of Chronic Illness Therapy (FACIT)
Fatigue score
SF-36 Vitality domain
Sleep
Pittsburgh Sleep Quality Index (PSQI)
MOS Sleep Scale
HRQOL
Psoriatic Arthritis Quality of Life Index (PsAQOL)
Short Form 36 (SF36) total score
SF36 Physical Component Summary
SF36 Mental Component Summary
Individual SF36 domains:
 physical function, role physical, bodily pain, general health,
vitality, social functioning, role emotional, mental health
EQ5D
SF-6D derived from mean changes across all 8 domains of SF-36
AsQoL
Skin
Dermatology Life Quality Index (DLQI)
Psoriasis Symptom Inventory (PSI)
Itch VAS
Function
Health Assessment Questionnaire-Disability Index (HAQ-DI)
SF-36 Physical Function Domain
Work/Productivity
Work Limitations Questionnaire
Work Productivity Survey (WPS)
Valuation of Lost Productivity (VOLP) questionnaire
Work Productivity and Activity Impairment (WPAI)
questionnaire
We recognize that many of these variables will not be available for individual clinical trial but these
instruments will be examined whenever available.
Joint counts may be provided as the joints recorded and then AO can create variables for the 28-,
66/68- and 76/78- joint counts or alternatively, the individual scores may be provided.
Supplemental Methods/Analysis: Data analysis will be performed by Dr. Ogdie (the study PI) in
Stata 13.0 (College Station, TX).
Descriptive Reporting: We will first descriptively report the number and category of instruments
in each clinical trial. Note that all clinical trials will be de-identified and labeled as “A”, “B”, and
so on. This will be reported in Table 1 of the manuscript. Patient level data will not be reported
(although patient-level data is required for analysis).
Mapping of outcome measures to domains: All outcome measures will be mapped to one or
more domains. For instruments with multiple domains, their individual domains and summary
component scores will be analyzed separately.
Construct validity: The concept of construct validity is that an instrument measures what it is
supposed to measure. We will establish construct validity by assessing convergent and
divergent relationships of similar and dissimilar instruments pretreatment and post treatment
separately. We will create a correlation matrix containing all of the outcome measures (change
in measures over the course of the study). Pearson’s or Spearman’s correlation coefficients will
be calculated for each cell of the matrix (depending on the parametric or non-parametric
distribution of the measure respectively). Intra-domain and inter-domain correlations will then
be compared. Intra-domain correlation should be higher than inter-domain correlation for an
individual outcome measure. We will examine therapy categories to ensure that the correlation
direction is the same for all measures but will report mean correlations among all trials included.
Responsiveness is also a part of construct validity. Responsiveness is the ability of an outcome
measure to detect change over time. Correlation among change in the response measures will
similarly be calculated as described above. In addition, we will calculate standardized response
means over all of the treatment groups (not comparing among therapies but combining all
therapies). Confidence intervals will be generated using a bootstrapping method (1000 samples
with replacement).
Content validity: Content validity is the ability of an outcome measure (or set of outcome
measures) to represent all facets of a condition. The PsA working group aims to measure as fully
as possible patient response using available outcomes measures. We aim to determine the
most complimentary group of outcome measures to best explain “response”. Thus, we will
examine two different parameters for response: 1) achievement of minimal disease activity
(MDA) and 2) patient global assessment of disease at study completion. MDA is defined as
defined as meeting 5 of the 7 criteria: Patient Pain VAS(1-100)<15, Patient Disease Global (1100)<20, Modified Health Assessment Questionnaire (0-3)<0.5, Tender joint count (1-68)<1,
Swollen joint count (1-66)<1, Psoriasis Area Severity Index (0-72)<1 OR %BSA<3, Enthesitis sites
(1-13, MASES) <1. The use of the patient global assessment as one of the outcomes addresses
the patient perspective and the patient reported outcome domain but is not the sole measure
for treatment response. The transition question of SF-36 “compared to one year ago, how are
you feeling today?,” the EQ-5D and the Guyatt feeling thermometer will be examined as
alternative model outcomes when available.
We will perform multivariable logistic and linear regression analyses with 1) the binary outcome
of MDA and separately, 2) the continuous outcome of last visit patient global assessment as the
outcomes. The predictor variables will be the individual outcome measures at the final visit
(same visit during which MDA and patient global assessment are assessed). Outcome measures
with the highest correlation coefficient with change in patient global will be selected from each
domain for inclusion in the model. Variance inflation factors will be used to assess for the
degree of collinearity among outcome measures included in the models. Clustering by trial
and/or medication will be accounted for in the models. The R squared value will be used to
identify the best model for overall improvement. The R squared value represents the goodness
of fit (or total explained variation) in linear regression and ranges from 0-100%. If there is
sufficient missing data (or non-overlap of outcome measures), modeling will be performed in
each study separately and compared across studies.
Two examples of studies using the methods outlined for a similar purpose in fibromyalgia and
rheumatoid arthritis are shown below. Dr. Mease, one of the co-investigators, was involved in
both studies. Dr. Vibeke Strand, while she will not have access to the data, will be available to
answer methodologic questions and will assist in interpretation of the data from this study.
 Choy EH, Arnold LM, Clauw DJ, Crofford LJ, Glass JM, Simon LS, et al. Content and criterion
validity of the preliminary core dataset for clinical trials in fibromyalgia syndrome. J
Rheumatol 2009; 36(10): 2330-4
 Strand V, Smolen JS, van Vollenhoven RF, Mease P, Burmester GR, Hiepe F, et al.
Certolizumab pegol plus methotrexate provides broad relief from the burden of rheumatoid
arthritis: analysis of patient-reported outcomes from the RAPID2 trial. Ann Rheum Dis 2011;
70(6): 996-1002