Final Research Report
View this project's final research report.
Article Highlight: Clinicians and patients have been uncertain about the optimal time to start biologics for polyarticular juvenile idiopathic arthritis (pJIA). However, results from this PCORI-funded study, published in Arthritis & Rheumatology, provide useful new evidence about first-line treatment options for this disease. Researchers compared the effectiveness of three treatment approaches among 400 children with pJIA. The approaches included starting patients on a non-biologic disease-modifying antirheumatic drug (DMARD) only, starting patients with a DMARD and a biologic medication, and starting patients with a biologic only. After one year, the approaches did not differ significantly in achieving clinically inactive disease without the use of glucorticoids, and patients reported decreased pain interference levels and increased mobility with all three approaches.
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Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers questioned the researchers’ handling of missing data. They posited that the problem of missing data was greater in this observational study compared to what would be expected in a randomized controlled trial (RCT) because of limited active follow-up in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry as opposed to a more robust follow-up plan that would be expected in an RCT. The researchers acknowledged this point and noted it in their study limitations section. They also noted that they did not report on recommended multiple imputation techniques to account for missing data for patient-reported outcomes, where the missing data rate was especially high. The researchers explained that multiple imputation requires the assumption that the patient-reported outcome data are missing at random, but the researchers could not verify this fact in their dataset.
- The reviewers asked why the researchers stated that RCTs were less feasible than cohort studies for a rare condition. The researchers explained that their statement was specifically about the resources available to them for studying juvenile idiopathic arthritis (JIA) through the CARRA Registry. Given the registry’s existing agreements with patients, no additional institutional review board (IRB) approval was needed to conduct this study, so the study could be rolled out quickly across all CARRA sites. An RCT would have required additional IRB approval and contracting, which would have made the study no longer feasible in the time frame required, particularly given the low incidence of JIA. Also, not all insurance plans would allow the use of all the medications tested, further reducing the pool of eligible participants for an RCT. Finally, the researchers noted, families and physicians may not have been as likely to participate in the study if patients were randomly assigned medications rather than allowed to choose their own treatment regimens in consultation with their physicians.
- The reviewers said it would have been helpful if the researchers had reported results according to more specific diagnoses than JIA, since that is a broad category of conditions. The researchers agreed that it is reasonable to ask whether specific treatments work better for specific diagnoses, but the study did not have enough statistical power to detect differences among different categories of JIA. However, the researchers said that exploratory analyses are underway to assess whether individual patient trajectories demonstrate specific phenotypes that could predict treatment outcomes.
- The reviewers asked whether the researchers looked at outcomes based on the actual treatments that patients received, rather than only comparing patient outcomes based on the consensus treatment plans. The researchers said they did follow up on the treatments that patients received and grouped patients into three categories: patient received treatment as planned, patient did not receive treatment as planned, and patient treatment status was uncertain. The researchers populated these categories based on a review of whether and when patients received biologics or disease-modifying antirheumatic drugs, or both treatments. This review allowed the researchers to determine which consensus treatment plan each patient actually received and rerun analyses based on this information. The researchers noted that because there was very close alignment between the planned treatment and the executed treatment, the results of the as-treated analyses were similar to the results of the intent-to-treat analyses.
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