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Review
. 2018 Jul 11;16(1):45.
doi: 10.1186/s12969-018-0261-x.

Pediatric Rheumatology Collaborative Study Group - over four decades of pivotal clinical drug research in pediatric rheumatology

Hermine I Brunner  1 , Lisa G Rider  2 , Daniel J Kingsbury  3 , Dominic Co  4 , Rayfel Schneider  5 , Ellen Goldmuntz  6 , Karen B Onel  7 , Edward H Giannini  8 , Daniel J Lovell  8 ; PRCSG Advisory Council
Collaborators, Affiliations
Review

Pediatric Rheumatology Collaborative Study Group - over four decades of pivotal clinical drug research in pediatric rheumatology

Hermine I Brunner et al. Pediatr Rheumatol Online J. .

Abstract

Importance: Specialized research networks are essential to achieve drug approvals for rare pediatric diseases. Such networks help realize the potential of global legislation enacted upon the recognition that most children are treated with drugs whose most beneficial dose and regimen have not been established in pediatric patients. The Pediatric Rheumatology Collaborative Study Group (PRCSG) is a North American clinical trials network that is specialized in the performance of clinical trials of new therapies for pediatric populations with rheumatic diseases. This review provides an overview of the strategies employed by this research network to achieve drug and biologic approvals for children with pediatric rheumatic diseases, particularly juvenile idiopathic arthritis.

Observations: Clinical trial conduct in rare pediatric diseases has required global recruitment. Supported or led by the PRCSG, highly responsive, validated, composite measures have been established to assess drug efficacy. For pediatric orphan diseases with high disease burdens, specialized investigative sites and study designs are needed to complete adequately powered trials at the high standard necessary to enable drug labeling by regulatory agencies. Novel trial designs have been utilized for more efficient testing of innovative drug candidates. All these have been developed or co-developed by the PRCSG research network.

Conclusions and relevance: Specialized research networks in pediatric rheumatology, such as the PRCSG, have changed the landscape of available therapies and improved overall disease outcomes for children with pediatric rheumatic diseases.

Keywords: Clinical trials; Drug approvals; JIA; Networks; PRCSG; Pediatrics.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable. This research review does not report on human participants, human data or human or animal experiments.

Consent for publication

Not applicable.

Competing interests

Dr. Lovell is Chairman of the PRCSG, Dr. Brunner is the Scientific Director of the PRCSG. All other named authors are members of the PRCSG Advisory Council. Drs. Yim and Peng are also members of the Advisory Council and reviewed the manuscript but deemed their contributions to the manuscript not significant enough to be included as named authors.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Basic design of Randomized Withdrawal Design. A randomized withdrawal design (RWD) study consists of three parts. During Part 1 and Part 3 all study participants receive open-label active study drug. Participants who show a clinically meaningful response to study drug by the end of Part 1 are randomized to the double-blinded placebo-controlled Part 2. Participants move from Part 2 to Part 3 if there is a flare event during Part 2 or upon completion of all Part 2 visits, whichever comes first. Patients for whom study drug may be beneficial, but who did not meet criteria for a meaningful improvement during Part 1, may be allowed to enter Part 3. The primary endpoint of a RWD trial is ‘the time to disease flare or the occurrence of a flare event during Part 2. The participant’s disease status at the end of Part 1 is used as the baseline to assess whether disease worsening (flare) has occurred during Part 2. Secondary RWD study endpoints can be measured throughout the duration of the entire RWD trial (Part 1 through 3) and include achievement of inactive disease, success in tapering certain background medications and change in patient reported outcomes
Fig. 2
Fig. 2
The PRCSG is a productive collaborative research network with focus on medication studies in pediatric rheumatic diseases. The PRCSG network has been continuously active with the number of studies active or in development markedly increasing since the passage of FDA Safety and Innovation Act (FDASIA) in 2012
See this image and copyright information in PMC

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