Survey of Osteoarthritis Real World Therapies (SORT)

1.0 PROTOCOL SYNOPSIS
PRODUCT(s): None, This is an observational, prospective, single-cohort study
and will include subjects being treated during usual clinical care with oral or
topical analgesics used to relieve symptoms of osteoarthritis of the knee,
according to standard medical guidelines or clinical practice standards of the
investigating physician.

PROTOCOL TITLE: Survey of Osteoarthritis Real World Therapies (SORT)

US IND No: Not applicable

Clinical Phase: NA

OBJECTIVE:
Primary Objective:
Among patients with symptomatic osteoarthritis of the knee(s) who are
prescribed oral or topical analgesics for their symptoms, characterize over a
12-month follow-up period the clinical care and outcomes of patients who report
inadequate pain relief (as defined by BPI *Average Pain* score) at baseline.

Secondary Objectives:
• Among patients with symptomatic knee OA who are prescribed oral or topical
analgesics, characterize over a 12-month follow-up period the clinical care and
outcomes of patients who report inadequate relief from joint stiffness or
limitations in physical functioning (as defined by WOMAC Scores) at baseline.

• Among the entire study population of patients with symptomatic knee OA who
are prescribed oral or topical analgesics (with and without adequate
pain/symptom relief), describe or characterize at baseline and over the
12-month follow-up period:

• Demographic and clinical characteristics including comorbidities.
• Prescription and non-prescription medication and ancillary treatment used to
treat symptoms of knee osteoarthritis
• Quality of life (QOL) related to knee osteoarthritis as measured by the SF-12.
• Pain as measured by items from the Brief Pain Inventory (BPI)
• Health resource utilization as measured by Healthcare Resource Utilization
Questionnaire.
• Work productivity loss due to knee osteoarthritis as measured by the Work
Productivity Activity Index (WPAI).
• Pain, joint stiffness and disability in the knee measured by the Western
Ontario McMaster University Osteoarthritis Index (WOMAC) Questionnaire.
• Satisfaction with symptomatic treatment for knee OA as measured by treatment
satisfaction questionnaire.
• Patient Response to Therapy as measured by the PGART (Patient Global
Assessment of Response to Therapy) Questionnaire.
• Investigator Assessment of Response to Therapy as measured by the IGART
(Investigator Global Assessment of Response to Therapy) Questionnaire.


HYPOTHESES
This is an observational study conducted for the purposes of descriptive
analysis and hypothesis generation. No pre-specified hypothesis will be tested
due to the exploratory nature of the study.

STUDY DESIGN AND DURATION:
This is an observational, prospective single-cohort study designed to
characterize the course of clinical care and outcomes of subjects with
symptomatic osteoarthritis of the knee(s) who are using oral or topical
analgesics for their symptoms. The primary objective of the study is focused
upon the subset of all patients who report inadequate pain relief at entry into
the study. A scheduled clinic visit will be performed at study enrollment and
at Month 12, and subjects will be treated throughout the study according to
usual clinical practice as determined by the attending physician. Any clinic
visits that occur after Baseline and before Month 12 will be captured as an
Unscheduled Visit. Treatment for knee OA, quality of life, pain, physical
functioning related to knee OA, joint stiffness, treatment satisfaction,
response to OA treatment, health care resource utilization and productivity
will be measured by questionnaires completed at Months 0 (Baseline), 1, 3, 6, 9
and 12. Study entry and exit questionnaires will be performed during the
scheduled clinic visits, and subjects will be provided with the questionnaires
with instructions for completion and business reply envelopes for submission of
those completed at Months 1, 3, 6 and 9.

This study will be conducted in seven countries (United Kingdom, France,
Germany, Italy, Spain, the Netherlands and Portugal). Enrollment will be
competitive within each country, with approximately 5 sites in each country
(total approximately 35 sites), and a total of approximately 1400 subjects
enrolled. Competitive enrollment means that within one particular country if
the subject recruitment rate is lower than expected at one study site and
higher than expected at another site, planned allocation numbers will be
transferred from the site with low subject recruitment to a site with high
recruitment. This will be done to ensure that subject enrollment within a given
country is completed as planned. Additional participating countries and/or
sites may be added during the study as required. Recruitment is expected to
extend over a period of approximately 6 months, and each subject will be
followed for twelve months.

SUBJECT SAMPLE:
This study will enroll male and female patients >= 50 years of age who have a
clinical diagnosis of osteoarthritis of the knee(s). Subjects must be presently
receiving prescribed (at the direction of a physician) oral or topical
analgesics which commenced at least two weeks prior to enrollment.

DOSAGE / DOSAGE FORM, ROUTE and DOSE REGIMEN:
No investigational or approved medication will be provided. All subjects will
be treated according to standard medical guidelines or clinical practice
standards of the investigating physician.

SAFETY MEASURES:
This is an observational study conducted under conditions of normal clinical
practice, and no therapeutic agents are provided under this protocol.
Investigators will be responsible for adverse events reporting according to
local, national, international and SPONSOR guidelines governing AE reporting.

DATA ANALYSIS:

PRIMARY ANALYSIS
The primary analysis for this study will be a general descriptive
characterization of the clinical care of subjects with osteoarthritis of the
knee(s). The primary objective of the study is focused upon the subset of all
patients who do not have adequate pain relief with their OA treatment at entry
into the study.

The analysis will include descriptive characterizations of the following
parameters at baseline, at Months 1, 3, 6, 9 and 12 and any unscheduled visit:
• Subject demographic and defined clinical characteristics at study entry,
including comorbidities
• Prescription and non-prescription, and other ancillary/complementary
medications used for treatment of knee OA
o Use of nonprescription, herbal, and other ancillary/complementary medications
used for the treatment of symptomatic knee osteoarthritis during the
observation period
o Non-medicinal therapeutic interventions including diathermy, transcutaneous
electrical nerve stimulation, topical applications, acupuncture, physical
therapy, massage and surgery
• Quality of life (QOL) related to knee OA as measured by the SF-12.
• Pain as measured by items from the Brief Pain Inventory (BPI).
• Health resource utilization as measured by Healthcare Resource Utilization
Questionnaire.
• Work productivity loss due to knee osteoarthritis as measured by the Work
Productivity Activity Index (WPAI).
• Pain, joint stiffness and disability in the knee measured by the Western
Ontario McMaster University Osteoarthritis Index (WOMAC) Questionnaire.
• Satisfaction with symptomatic treatment for knee OA as measured by treatment
satisfaction questionnaire.
• Patient Response to Therapy as measured by the PGART (Patient Global
Assessment of Response to Therapy) Questionnaire.
• Investigator Assessment of Response to Therapy as measured by the IGART
(Investigator Global Assessment of Response to Therapy) Questionnaire.

The analysis will also evaluate longitudinally throughout the duration of study
the following:
• Patterns of change in prescription treatment during the period of observation
including
o Prescription treatment for knee osteoarthritis
o Time to discontinuation of baseline analgesic medication
o Time to commencement of another analgesic medication
o Change in dose and/or frequency of baseline or new analgesic treatments
o Time to commencement of complementary medication
o Time to discontinuation of complementary medication
o Change in dose and/or frequency of complementary medication
• Use of nonprescription, herbal, and other ancillary/complementary medications
used for the treatment of symptomatic knee osteoarthritis during the
observation period
• Non-medicinal therapeutic interventions including diathermy, transcutaneous
electrical nerve stimulation, topical applications, acupuncture, physical
therapy, massage and surgery
• Quality of life (QOL) related to knee OA as measured by the SF-12.
• Pain as measured by items from the Brief Pain Inventory (BPI)
• Health resource utilization as measured by Healthcare Resource Utilization
Questionnaire.
• Work productivity loss due to knee osteoarthritis as measured by the Work
Productivity Activity Index (WPAI).
• Pain, joint stiffness and disability in the knee measured by the Western
Ontario McMaster University Osteoarthritis Index (WOMAC) Questionnaire.
• Satisfaction with symptomatic treatment for knee OA as measured by treatment
satisfaction questionnaire.
• Patient Response to Therapy as measured by the PGART (Patient Global
Assessment of Response to Therapy) Questionnaire.
• Investigator Assessment of Response to Therapy as measured by the IGART
(Investigator Global Assessment of Response to Therapy) Questionnaire

All data will be summarized using standard descriptive statistics (numerical
variables: n, mean, median, standard deviation, minimum and maximum;
categorical variables: n, percent). Time to event variables will be summarized
using Kaplan-Meier estimates.

The incidence and intensity of adverse events will be tabulated for all
subjects enrolled, grouped by MedDRA SOC and Preferred Terms . The incidence
of the use concomitant medications will be summarized similarly, grouped by WHO
ATC Classes and Preferred Terms.

All descriptive analyses will be performed overall ("All Countries") and by
country (*Country Specific*). Interpretation of the findings will be based on
the "All Countries" results unless there is evidence of important variation in
the "Country Specific" analysis. Judgement as to whether important variation
is seen will be based on both reasoned judgement and p-values associated with
the observed differences. In general, all analytical results will be
interpreted descriptively, as hypothesis-generating rather than confirmatory,
and will be presented as such in any dissemination of the study results.
Differences and ratio measures comparing groups will be presented with 95%
confidence intervals. P-value thresholds may be used in the construction
multivariate regression model for purposes of deciding which variables to
include or drop from the model.

OBJECTIVE:
Primary Objective:
Among patients with symptomatic osteoarthritis of the knee(s) who are
prescribed oral or topical analgesics for their symptoms, characterize over a
12-month follow-up period the clinical care and outcomes of patients who report
inadequate pain relief (as defined by BPI *Average Pain* score) at baseline.

Secondary Objectives:
• Among patients with symptomatic knee OA who are prescribed oral or topical
analgesics, characterize over a 12-month follow-up period the clinical care and
outcomes of patients who report inadequate relief from joint stiffness or
limitations in physical functioning (as defined by WOMAC Scores) at baseline.

• Among the entire study population of patients with symptomatic knee OA who
are prescribed oral or topical analgesics (with and without adequate
pain/symptom relief), describe or characterize at baseline and over the
12-month follow-up period:

• Demographic and clinical characteristics including comorbidities.
• Prescription and non-prescription medication and ancillary treatment used to
treat symptoms of knee osteoarthritis
• Quality of life (QOL) related to knee osteoarthritis as measured by the SF-12.
• Pain as measured by items from the Brief Pain Inventory (BPI)
• Health resource utilization as measured by Healthcare Resource Utilization
Questionnaire.
• Work productivity loss due to knee osteoarthritis as measured by the Work
Productivity Activity Index (WPAI).
• Pain, joint stiffness and disability in the knee measured by the Western
Ontario McMaster University Osteoarthritis Index (WOMAC) Questionnaire.
• Satisfaction with symptomatic treatment for knee OA as measured by treatment
satisfaction questionnaire.
• Patient Response to Therapy as measured by the PGART (Patient Global
Assessment of Response to Therapy) Questionnaire.
• Investigator Assessment of Response to Therapy as measured by the IGART
(Investigator Global Assessment of Response to Therapy) Questionnaire.

STUDY DESIGN AND DURATION:
This is an observational, prospective single-cohort study designed to
characterize the course of clinical care and outcomes of subjects with
symptomatic osteoarthritis of the knee(s) who are using oral or topical
analgesics for their symptoms. The primary objective of the study is focused
upon the subset of all patients who report inadequate pain relief at entry into
the study. A scheduled clinic visit will be performed at study enrollment and
at Month 12, and subjects will be treated throughout the study according to
usual clinical practice as determined by the attending physician. Any clinic
visits that occur after Baseline and before Month 12 will be captured as an
Unscheduled Visit. Treatment for knee OA, quality of life, pain, physical
functioning related to knee OA, joint stiffness, treatment satisfaction,
response to OA treatment, health care resource utilization and productivity
will be measured by questionnaires completed at Months 0 (Baseline), 1, 3, 6, 9
and 12. Study entry and exit questionnaires will be performed during the
scheduled clinic visits, and subjects will be provided with the questionnaires
with instructions for completion and business reply envelopes for submission of
those completed at Months 1, 3, 6 and 9.

This study will be conducted in seven countries (United Kingdom, France,
Germany, Italy, Spain, the Netherlands and Portugal). Enrollment will be
competitive within each country, with approximately 5 sites in each country
(total approximately 35 sites), and a total of approximately 1400 subjects
enrolled. Competitive enrollment means that within one particular country if
the subject recruitment rate is lower than expected at one study site and
higher than expected at another site, planned allocation numbers will be
transferred from the site with low subject recruitment to a site with high
recruitment. This will be done to ensure that subject enrollment within a given
country is completed as planned. Additional participating countries and/or
sites may be added during the study as required. Recruitment is expected to
extend over a period of approximately 6 months, and each subject will be
followed for twelve months.

No risks; the patient will receive regular treatment for his osteoarthritis of
the knee and will fill out on 6 timepoints osteoarthritis questionaires.
Patient will be filling out these questionaires, which may take up to half an
hour per occasion. Total amount of time will be 3-4 hours during the
participation in this trial.

Patients will not directly benefit, however from filling out the questionaires
the patient may be obtaining a better understanding in the development of his
osteoarthritis of the knee. From the knowledge gained in this trial patients
may benefit in the future.