Adverse event reporting in the recent study by Imanaka et al. describing the efficacy and safety of tapentadol extended release for tumor-related pain

Dear Editor

This letter is intended to provide additional clarification for your readers regarding the potentially confusing issue of adverse event vs serious adverse event reporting in a recently published phase 3 study of tapentadol extended release (ER) for malignant tumor-related pain.

The results of a randomized, double-blind, phase 3 study evaluating the efficacy and safety of tapentadol ER for the management of moderate-to-severe, chronic malignant tumor-related pain were published in this journal in October 2013 in our article entitled, ‘Efficacy and safety of oral tapentadol extended release in Japanese and Korean patients with moderate-to-severe, chronic malignant tumor-related pain’1.

According to our company’s policy and in accordance with guidance from the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, all treatment-emergent adverse events (TEAEs) were recorded throughout the double-blind treatment and for 3 days after the last dose of the study drug (based on the half-life of tapentadol ER), while any spontaneously reported serious AEs were recorded for up to 30 days after the last dose of the study drug. This difference in the time periods for collecting and reporting of TEAEs vs serious AEs resulted in an apparent discrepancy in the percentage of patients experiencing disease progression. The incidence of disease progression reported in Table 4 (which lists the most common [incidence ≥5%] TEAEs overall) was 21.4% (36/168) with tapentadol ER and 19.2% (33/172) with oxycodone controlled release (CR), while the incidence of disease progression given in the first full paragraph beneath Table 4, which was based on serious AE reporting (which included an additional 30 day reporting period after the last dose of study drug), was 23.8% (40/168) with tapentadol ER and 20.9% (36/172) with oxycodone CR.

Transparency

Declaration of funding

This letter was not funded.

Declaration of financial/other relationships

Keiichiro Imanaka is an employee of Janssen Japan and a Johnson & Johnson stockholder. Yushin Tominaga, Masaki Ohsaka, Mikio Wanibe, Keiichiro Hirose, and Taka Matsumura are employees of Janssen Japan. Mila Etropolski and Ilse Van Hove are employees of Janssen Research & Development, LLC, and Johnson & Johnson stockholders.