Reporting Bleeding Outcomes in Adult and Pediatric Studies of Primary Immune Thrombocytopenia: A Systematic Review

Bleeding is arguably the most clinically meaningful outcome in ITP clinical studies since it impacts morbidity, mortality and quality of life. Yet, the measurement of bleeding is not standardized, and its prevalence as a study outcome has not been well characterized.

We performed a systematic review of all English language, prospective clinical studies enrolling 20 or more adults or children with primary ITP to determine if and how bleeding data were reported. In duplicate and independently, we searched MEDLINE, EMBASE, Cochrane and Cinahl databases until January 2012. Titles were screened for relevance and abstracts and full text articles were reviewed in duplicate for eligibility. Study selection and data abstraction were performed in duplicate. Patient demographics, use of a bleeding measurement tool and frequency of bleeding were collected from all studies.

We identified 167 prospective studies, including 29 (33%) randomized trials enrolling 13,976 patients with primary ITP (including 3,723 adults; 9,730 children; and 523 combined adults and children). Of 167 studies, 87 (52.1%) reported bleeding either as an efficacy endpoint (n=77), a safety endpoint (n=5) or both (n=5). Of the 87 studies that reported bleeding, 17 (19.5%) used an ITP-specific bleeding measurement tool. Such a tool was used in 4 of the 29 randomized trials. Less common were the Common Terminology Criteria for Adverse Events score (n=4) and the World Health Organization score (n=4); but the majority of studies did not use a predefined tool to measure bleeding. Bleeding was reported as present or absent (n=8 studies, 9.1%); by anatomical site only (n=39, 44%); by severity only (n=1, 1.1%); or by severity and anatomical site (n=29, 33%). Ten (29.8%) studies did not specify how bleeding was measured. Forty-three studies reported some association between platelet count and bleeding; however, none provided a statistical association with severity of thrombocytopenia.

This study represents a summative description of the English-language world literature on bleeding outcomes in ITP studies. Of all studies, just over half (52.1%) reported bleeding outcomes. Only 20% of studies used a bleeding measurement tool that was specific for ITP patients. A standardized approach to bleeding and other patient-centered outcomes will help direct future research in ITP.

Funding support from the McMaster Division of Hematology & Thromboembolism.

Arnold:Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hoffman-LaRoche: Research Funding.