Selective validation of the WHO Bleeding Scale in patients with chronic immune thrombocytopenia

Abstract

Objective:

To evaluate the World Health Organization’s (WHO) Bleeding Scale in two studies of eltrombopag in adults with chronic immune thrombocytopenia (ITP).

Research design and methods:

Validated scales assessing bleeding in adults with ITP are lacking. Data from two long-term, phase 3 clinical trials (RAISE: NCT00370331; EXTEND: NCT00351468) that assessed eltrombopag in adults with chronic ITP were analyzed to evaluate the performance of the WHO Bleeding Scale.

Results:

In RAISE, effect size (0.71), standardized response (0.75), and responsiveness statistics (0.57) were moderate for bleeding and bruising assessments. In EXTEND, effect size (0.62) and responsiveness statistics (0.59) were moderate; the standardized response statistic was 0.487. Intraclass correlation for test–retest reliability was 0.75 in RAISE and 0.71 in EXTEND. A positive correlation was observed between the WHO Bleeding Scale and the ITP Bleeding Scale. Bleeding scores and quality-of-life measures were inversely correlated (p < 0.05 for all). Minimal important differences for the WHO Bleeding Scale were 0.33–0.40 at baseline and last on-treatment assessment in both studies.

Limitations:

The majority of bleeding in these studies was mild to moderate, so this analysis cannot provide strong evidence of the validity of the WHO Bleeding Scale in patients with more severe bleeding. Potential limitations to the WHO Bleeding Scale itself include dependence on clinician interpretation of patient recall, inability to distinguish among bleeding events occurring at different anatomical sites, and an inherent assumption of linear increases in severity of bleeding across the response categories.

Conclusions:

These findings suggest potential usefulness of the WHO Bleeding Scale in adult patients with chronic ITP for standardizing grading of bleeding across research studies and in clinical practice.

Key words::

• Bleeding
• Bruising
• Eltrombopag
• Immune thrombocytopenia
• Validation
• WHO Bleeding Scale

Transparency

Declaration of funding

This work was supported financially by GlaxoSmithKline.

Declaration of financial/other relationships

P.F.F.’s institution received research funding from GlaxoSmithKline. M.D.T. has received grants from Novo Nordisk, and honoraria for speaking engagements from Baxter, Novo Nordisk, Lundbeck, and Talecris. M.D.T. also provides noncommercial expert testimony, and all records of royalties and advisory boards are up to date. K.M.G. and A.B. are employees of GlaxoSmithKline and possess stock options as employees. J.S. declares no conflict of interest.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed any relevant financial relationships.

Acknowledgments

The authors would like to thank AOI Communications, L.P., for medical writing, editorial, and graphics assistance, and Kimberly Marino of GlaxoSmithKline for her critical review during the development of this manuscript.