How personalized are benefit and harm results of randomized trials? A systematic review.

OBJECTIVES: This study aimed to review the degree of personalization of benefit and harm in the reporting of recent high-profile randomized controlled trials (RCTs) involving pharmacological interventions. STUDY DESIGN AND SETTING: This study is a systematic review of RCTs published between 2012 and 2017 with at least one intervention evaluating drug therapy and meeting the "high-profile" threshold in a premier academic literature abstraction service. Our primary outcome was the proportion of trials reporting subgroup analyses of a combined benefit-harm outcome. Secondary outcomes included the proportion of trials reporting subgroup analyses or clinical prediction guide for benefits or harms. We assessed the quality of the subgroup analyses using a modified version of previously published credibility criteria. RESULTS: Of 296 eligible RCTs, nine studies (3%) reported a combined benefit-harm endpoint. We found subgroup analyses of a combined benefit-harm endpoint in three studies (1%), a benefit endpoint in 167 studies (56.4%), and a harm endpoint in 18 studies (6.1%). The overall quality of the subgroup analyses was poor. Only one study reported a clinical prediction guide for an outcome. CONCLUSION: Despite great interest in the personalization of therapies, it is rarely reported in high-profile trials. Lack of rigorous and widely accepted methods may be the major barrier.

The quality of clinical practice guidelines for management of pediatric type 2 diabetes mellitus: a systematic review using the AGREE II instrument.

AIMS: Pediatric type 2 diabetes mellitus (T2DM) is a relatively new disease with increasing incidence corresponding to the obesity epidemic among youth. It is important for clinicians to have access to high-quality clinical practice guidelines (CPGs) for appropriate management of pediatric patients with T2DM. The objective of this systematic review was to evaluate overall quality of CPGs for the management of pediatric T2DM using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. METHODS: We searched MEDLINE, Embase, CINAHL, Trip, National Guideline Clearinghouse, and grey literature to identify eligible CPGs. We also searched the webpages of national and international diabetes and pediatric organizations globally. We included CPGs from national and international diabetes and pediatric associations that were published as standalone guidelines for T2DM in children and adolescents (2-18 years of age). We also included pediatric and adult guidelines for type 1 diabetes if they included a section addressing T2DM management in children and adolescents. We retrieved the two most recent guidelines from each organization when available to assess change in quality over time. We excluded individual studies and systematic reviews that made treatment recommendations as well as CPGs that were developed for a single institution. RESULTS: We included 21 unique CPGs in this systematic review. Of the included guidelines, 12 were developed or updated between 2012 and 2014. Five of all included CPGs were specific to pediatric populations. The analysis revealed that "Rigour of Development" (mean 45%, SD 28.68) and "Editorial Independence" (mean 45%, SD 35.19) were the lowest scoring domains on the AGREE II for the majority of guidelines, whereas "Clarity of Presentation" was the highest scoring domain (mean 72%, SD 18.89). CONCLUSIONS: Overall, two thirds of the pediatric T2DM guidelines were moderate to low quality and the remaining third ranked higher in quality. Low quality was especially due to the scores for the "Rigour of Development" domain, which directly measures guideline development methodology. It is important that future guidelines and updates of existing guidelines improve the methodology of development and quality of reporting in order to appropriately guide physicians managing children and adolescents with T2DM. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016034187.