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Clinical Development Programs for Drugs, Devices, and Biological Products for the Treatment of Rheumatoid Arthritis (RA)

FinalCenter for Biologics Evaluation and Research Center for Devices and Radiological Health Center for Drug Evaluation and Research02/17/1999

Description

This guidance is intended to assist developers of drugs, biological products, and medical devices intended for the treatment of rheumatoid arthritis (RA). The document discusses the types of label claims that can be considered for such products and provides guidance on the clinical development programs to support those claims.

Scope & Applicability

Product Classes

10
Drugs

Clinical investigations of drugs, including human drugs and biological products

Biotechnology-Derived Pharmaceuticals

Assessment of embryo-fetal developmental toxicity; Small molecules, biotechnology-derived products, and related compounds

Corticosteroids

used for JRA and JRA subsets

Medical Devices

Medical devices intended for human use; Approved or cleared medical devices

Antibiotics

evaluated by the Division of Anti-Infective Drug Products

Biologics

Products for which batch/lot information is particularly important

Devices

Clinical investigations of medical devices

Biological Products

Requires analytical comparability per ICH Q5E

Combination Product

Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.

NSAIDs

drugs currently used to treat RA patients; currently approved traditional cyclooxygenase inhibitors

Stakeholders

6
Healthy volunteers

Possible to conduct the FIH trial in healthy volunteers

Patients

Primary source of experience data

Pediatric rheumatologists

Involved in assessing global disease activity in JRA trials

Dropouts

Dropouts are patients who, after a certain period of time in a trial, fail to provide clinical efficacy data.

Sponsor

Entity responsible for submitting applications under section 524B

Agency staff

FDA personnel to be consulted during planning stages.

Regulatory Context

Attributes

10
Six months' duration

Standard trial duration to establish efficacy for signs and symptoms

Response Rates

Measured at the end of the trial based on different definitions of improvement

Biological plausibility

basis for applying the pediatric rule to support labeling

Sample size

Determined during the planning of a research study

Composite endpoint

Efficacy variables can be combined within patients (composite endpoint).

Type I error rates

Statistical parameter to be controlled when handling multiplicity issues

Confidence intervals

sponsors should include confidence intervals on all reported results

Level of significance

Information such as hypotheses tested, parameters estimated, assumptions made, level of significance

Secondary efficacy variables

Secondary efficacy variables are those that support the validity of the primary variables.

Primary efficacy variables

Primary efficacy variables are critical to the identification of the effectiveness of the product.

Identified Hazards

Hazards

6
Antibody formation

Potential for products to elicit antibodies which may block efficacy

Neutralizing antibodies

May interfere with efficacy of biological agents over time

Immunogenicity

Safety concern if product heterogeneity is inconsistent

Bias

mitigate potential unwanted bias in learning or performance estimation

Opportunistic infections

Serious dose-related adverse reactions associated with RA drug products.

Malignancies

Risk from disruption of critical host genes or activation of proto-oncogenes

Related CFR Sections (1)

See Also (8)