For KQs 1–2

• Publication must be peer-reviewed (excludes editorials, letters to the editor, etc.).

For KQ 3

• Case reports published in non-peer-reviewed form (e.g., as letters) in academic journals are acceptable.
• Other types of studies must be peer-reviewed.

For All KQs

• The sample population must have juvenile idiopathic arthritis (JIA) according to the International League of Associations for Rheumatology (ILAR) criteria, or juvenile rheumatoid arthritis (JRA) according to the American College of Rheumatology (ACR) definition, or juvenile chronic arthritis (JCA) according to the European League Against Rheumatism (EULAR) criteria.
• Any subtype of JIA/JRA/JCA of any severity is acceptable.

Notes/Further Guidance

For All KQs

• Study sample must consist of children 18 years or younger. If the study includes adults, at least 80% of the sample must be children, or outcomes must be reported separately for the 18 years or younger subgroup.

For KQs 1 -4

• Study must include one of the DMARDs on our list (see table below) either:

  ◦

  Alone;

  ◦

  In combination with another DMARD on our list; or

  ◦

  In combination with conventional treatment.

Included DMARDs (Table 2 from project protocol). List of DMARDs, their mechanism of action, FDA approval status for JIA, and examples of significant warnings from the drug product label.

For KQ 1, Acceptable Comparators Are

• Conventional treatment, defined as “NSAIDs or intra-articular corticosteroids, with or without methotrexate” (see table below for acceptable NSAIDs and corticosteroids)

For KQ 2, Acceptable Comparators Are

• Any other DMARD on our list (see table above) either:

  ◦

  Alone;

  ◦

  In combination with another DMARD on our list; or

  ◦

  In combination with conventional treatment (defined as above).

For KQ 3, Acceptable Comparators Are

• None or any

Included NSAIDs and intra-articular corticosteroids (Table 1 from project protocol). List of intra-articular corticosteroids and NSAIDs FDA approval status for JIA, and examples of significant warnings from the drug product label.

Relevant Only to KQs 1-2

• Any prospective comparative study is acceptable. Studies evaluating a prospective treatment group vs. a historical control group are also acceptable.

For KQ 3

• Studies are not required to be prospective. For KQ3, any study design is acceptable (comparative or non-comparative, prospective or retrospective, any size [including case studies with n = 1]).

For KQs 1-2

• Study must include at least one of the following intermediate or long-term outcomes:

  ◦

  Intermediate outcomes include:

  ▪

  Laboratory measures of inflammation

  ▪

  Active joint count

  ▪

  Number of joints with limited range of motion

  ▪

  Radiographic evidence of progression of disease

  ▪

  Global assessment of current status

  ◦

  Long-term outcomes include:

  ▪

  Pain control

  ▪

  Clinical remission

  ▪

  Quality of life

  ▪

  Growth

  ▪

  Development

  ▪

  Joint function

  ▪

  Functional Ability

  ▪

  Mortality

For KQ 3

• Study must report adverse events
• We are especially (but not exclusively) interested in:

  ◦

  Mortality

  ◦

  Malignancy

  ◦

  Serious infection

  ◦

  Hepatitis

  ◦

  Bone marrow suppression

  ◦

  Nausea or vomiting

  ◦

  Risks to fetus or pregnant mother

Relevant Only to KQs 1-2

• Outcomes must be measured using an objective standard

Relevant Only to KQs 1-2

• Study duration must be ≥ 3 months.

For KQ 3

• Any study duration is acceptable.

For All KQs

• The sample population must have juvenile idiopathic arthritis (JIA) according to the International League of Associations for Rheumatology (ILAR) criteria, or juvenile rheumatoid arthritis (JRA) according to the American College of Rheumatology (ACR) definition, or juvenile chronic arthritis (JCA) according to the European League Against Rheumatism (EULAR) criteria.
• Any subtype of JIA/JRA/JCA of any severity is acceptable.

Notes/Further Guidance

For All KQs

• The study sample must consist of children 18 years or younger. If the study includes adults, at least 80% of the sample must be children, or outcomes must be reported separately for the 18 years or younger subgroup.

Notes/Further Guidance

The following list of specific measures/instruments was agreed on after discussions with the project's technical expert panel (TEP).

• Measures of disease activity:

  ◦

  Active joint count (AJC)

  ◦

  Physician global assessment of disease activity (PGA)

  ◦

  Parent/patient global assessment of well-being (PGW)

• Measure of functional status/disability:

  ◦

  Childhood Health Assessment Questionnaire (CHAQ)

• Measures of health-related quality of life:

  ◦

  Child Health Questionnaire (CHQ)

  ◦

  Pediatric Quality of Life Inventory (PedsQL) 4.0

  ◦

  Pediatric Quality of Life Inventory Rheumatology Module (PedsQL-RM)

• Composite measures of response to therapy and developing definitions of disease status:

  ◦

  American College of Rheumatology Pediatric Response Criteria (ACR Pediatric 30)

  ◦

  A consensus-based definition of remission

  ◦

  Flare

  ◦

  Minimal disease activity (MDA)