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Open-label Studies Preferable to Double-blind Parallel Trials for Childhood SLE Treatments
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To increase the speed with which new treatments for childhood-onset systemic lupus erythematosus are studied, researchers should look to specialized networks and trial designs successfully used in other rare diseases, according to a review published in the Annals of the Rheumatic Diseases.
In addition, the researchers concluded that open-label pharmacokinetic-pharmacodynamic studies, rather than double-blind parallel designs, are preferred by pediatric rheumatology investigators for childhood-onset SLE trials.
“There are no drugs that have been approved by either FDA or [European Medicines Agency] for childhood-onset SLE , that is, children and adolescents with SLE with disease onset prior to age 18 years,” Hermine I. Brunner, MD, MSc, MBA, of the Cincinnati Children’s Hospital Medical Center, and colleagues wrote. “Lack of approved drugs for [childhood-onset] SLE leads to delays in providing proper care in a time where physicians are restricted in prescribing off-label medications, especially if their price is high.”
To review the current regulatory framework governing medication approval and describe the barriers to conducting a clinical trial, and to propose strategies to improve access to childhood-onset SLE treatments, Brunner and colleagues reviewed methodological aspects and epidemiological data. In addition, they evaluated various study designs and outcome measures.
The researchers also designed and distributed a survey among 289 pediatric rheumatology investigators in the Pediatric Rheumatology Collaborative Study Group (PRCSG), and to 462 investigators in the Pediatric Rheumatology International Trials Organization (PRINTO). In all, 161 members of the PRCSG and 192 investigators in PRINTO responded to the poll.
According to the researchers, current laws and regulations in the United States and Europe require novel medicines to be studied among pediatric populations if adults with similar or identical diseases have been found to benefit from them. In addition, regulatory agencies consider childhood-onset SLE the pediatric form of SLE found in adults. However, extrapolating strategies for medicines that have been found safe and effective in adult SLE can limit the number and complexity of studies needed to support the labelling of these treatments for use in younger patients.
To help remedy this, Brunner and colleagues recommended seeking out specialized research networks, validated outcome measures, stakeholder input, study designs and statistical methods that have already been successfully used for other uncommon diseases. In addition, the researchers found that 79% of respondents from PRCSG, and 70% from PRINTO, preferred open-label pharmacokinetic-pharmacodynamic studies, compared with the 21% and 30%, respectively, who favored double-blind parallel designs.
“Based on prior experience, specialized pediatric research networks that offer experience in clinical trial design and execution have coordinating centers that are proficient in overseeing clinical trial operations and are familiar with the validated assessments will be essential for the successful completion of [childhood-onset] SLE trials,” Brunner and colleagues wrote. “Blinded studies should omit traditional parallel-arm placebo designs. It is noted that use of extrapolation plan including data from other sources, particularly from adult trials, together with open-label and innovative design studies will be more expedient in providing children with [childhood-onset] SLE access to new medications.” – by Jason Laday
Disclosure: Brunner reports consulting fees from AbbVie, Ablynx, Amgen, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, MedImmune, Novartis, Pfizer, R-Pharm, Roche, Sanofi, Servier and Takeda; speaking fees from Genentech and Novartis; grant support from Pfizer and Bristol-Myers Squibb; and contributions from Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis and Pfizer for the coordination activity of the PRCSG network . Please see the study for all other authors’ relevant financial disclosures.
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