Open Access Open Access  Restricted Access Subscription or Fee Access

Patient-relevant outcomes and health-related quality of life in patients with chronic, severe, noncancer pain treated with tapentadol prolonged release—Using criteria of health technology assessment

Johannes FX Hofmann, PhD, Arun Lal, MSc, MBA, Maike Steffens, Robert Boettger


Objective: To perform a systematic comparison of tapentadol prolonged release (PR) and oxycodone controlled release (CR) using patient-relevant endpoints of efficacy, safety, and health-related quality of life (HRQoL) according to criteria used in health technology assessment. To derive a minimal important difference (MID) for the EQ-5D from three pivotal trials to measure patient-relevant changes in HRQoL.

Design: Randomized, double-blind, placebo and active controlled.

Setting: Outpatient primary care.

Participants: Patients with severe chronic osteoarthritis pain (two pivotal studies) and severe lower-back pain (one pivotal study) were enrolled. The intent-to-treat population of the three studies comprised a total of 2,968 patients (tapentadol PR arms: 978, oxycodone CR arms: 999, and in the placebo arms: 991).

Interventions: Tapentadol PR (100-250 mg bid), oxydodone CR (20-50 mg bid), or placebo over a period of 15 weeks (3 weeks titration plus 12 weeks maintenance).

Outcome Measures: Patient-relevant endpoints of efficacy, safety, tolerability, and HRQoL.

Results: Tapentadol PR demonstrated significant added benefits as compared to oxycodone CR in meta-analyses of the patient-relevant outcomes 30 percent pain relief (Realtive risk [RR]: 0.80 [0.75, 0.87]), treatment discontinuations (RR: 0.55 [0.363, 0.825]), safety (RR: 0.652 [0.599, 0.710]), and HRQoL (RR: 0.78 [0.64, 0.96]) based on a MID derived for the EQ-5D summary index.

Conclusions: Added benefit of tapentadol in all endpoint categories suggests that it may be beneficial to initiate treatment of chronic severe nonmalignant pain with tapentadol rather than oxycodone.


tapentadol, chronic nonmalignant pain, evidence-based medicine, health-related quality of life

Full Text:



Breivik H, Collett B, Ventafridda V, et al.: Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. Eur J Pain Lond Engl. 2006; 10(4): 287-333.

Tzschentke TM, Christoph T, Kögel B, et al.: (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther. 2007; 323(1): 265-276.

Sánchez Del Águila MJ, Schenk M, Kern K-U, et al.: Practical considerations for the use of tapentadol prolonged release for the management of severe chronic pain. Clin Ther. 2015; 37(1): 94-113.

Institute for Quality and Efficiency in Health Care: General methods—Version 4.1. 2013. Available at Accessed August 7, 2015.

Devulder J, Richarz U, Nataraja SH: Impact of long-term use of opioids on quality of life in patients with chronic, non-malignant pain. Curr Med Res Opin. 2005; 21(10): 1555-1568.

Noble M, Treadwell JR, Tregear SJ, et al.: Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev. 2010; (1): CD006605.

Whittle SL, Richards BL, Husni E, et al.: Opioid therapy for treating rheumatoid arthritis pain. Cochrane Database Syst Rev. 2011; (11): CD003113.

Becker N, Bondegaard Thomsen A, Olsen AK, et al.: Pain epidemiology and health related quality of life in chronic nonmalignant pain patients referred to a Danish multidisciplinary pain center. Pain. 1997; 73(3): 393-400.

Schünemann HJ, Guyatt GH: Commentary—Goodbye M(C) ID! Hello MID, Where Do You Come From? Health Serv Res. 2005; 40(2): 593-597.

Food and Drug Administration: Guidance for Industry. Patient-Reported Outcome Measures: Use in Medical Product Development to support Labeling Claims. 2009. Available at Accessed June 12, 2014.

European Medicines Agency: Reflection paper on the regulatory guidance for the use of Health Related Quality of Life (HRQoL) measures in the evaluation of medicinal products. EMEA/CHMP/EWP/139391/2004. 2005. Available at Accessed June 12, 2014.

Crosby RD, Kolotkin RL, Williams GR: Defining clinically meaningful change in health-related quality of life. J Clin Epidemiol. 2003; 56(5): 395-407.

de Vet HCW, Ostelo RWJG, Terwee CB, et al.: Minimally important change determined by a visual method integrating an anchor-based and a distribution-based approach. Qual Life Res. 2007; 16(1): 131-142.

Afilalo M, Etropolski MS, Kuperwasser B, et al.: Efficacy and safety of Tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: A randomized, double-blind, placebo- and active-controlled phase III study. Clin Drug Investig. 2010; 30(8): 489-505.

Afilalo M, Morlion B: Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician. 2013; 16(1): 27-40.

Buynak R, Shapiro DY, Okamoto A, et al.: Efficacy and safety of tapentadol extended release for the management of chronic low back pain: Results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study. Expert Opin Pharmacother. 2010; 11(11): 1787-1804.

Lange B, Kuperwasser B, Okamoto A, et al.: Efficacy and safety of tapentadol prolonged release for chronic osteoarthritis pain and low back pain. Adv Ther. 2010; 27(6): 381-399.

Brazier J, Roberts J, Tsuchiya A, et al.: A comparison of the EQ-5D and SF-6D across seven patient groups. Health Econ. 2004; 13(9): 873-884.

Obradovic M, Lal A, Liedgens H: Validity and responsiveness of EuroQol-5 dimension (EQ-5D) versus Short Form-6 dimension (SF-6D) questionnaire in chronic pain. Health Qual Life Outcomes. 2013; 11: 110.

Goldsmith CH, Boers M, Bombardier C, et al.: Criteria for clinically important changes in outcomes: Development, scoring and evaluation of rheumatoid arthritis patient and trial profiles. OMERACT Committee. J Rheumatol. 1993; 20(3): 561-565.

Jenkinson C, Peto V, Coulter A: Measuring change over time: A comparison of results from a global single item of health status and the multi-dimensional SF-36 health status survey questionnaire in patients presenting with menorrhagia. Qual Life Res. 1994; 3(5): 317-321.

Juniper EF, Guyatt GH, Willan A, et al.: Determining a minimal important change in a disease-specific Quality of Life Questionnaire. J Clin Epidemiol. 1994; 47(1): 81-87.

Buchbinder R, Bombardier C, Yeung M, et al.: Which outcome measures should be used in rheumatoid arthritis clinical trials?. Clinical and quality-of-life measures’ responsiveness to treatment in a randomized controlled trial. Arthritis Rheum. 1995; 38(11): 1568-1580.

Ward MM, Marx AS, Barry NN: Identification of clinically important changes in health status using receiver operating characteristic curves. J Clin Epidemiol. 2000; 53(3): 279-284.

Turner D, Schünemann HJ, Griffith LE, et al.: Using the entire cohort in the receiver operating characteristic analysis maximizes precision of the minimal important difference. J Clin Epidemiol. 2009; 62(4): 374-379.

Wyrwich KW, Bullinger M, Aaronson N, et al.: Estimating clinically significant differences in quality of life outcomes. Qual Life Res. 2005; 14(2): 285-295.

Guyatt GH, Oxman AD, Kunz R, et al.: GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol. 2011; 64(4): 395-400.

Farrar JT, Young JP, LaMoreaux L, et al.: Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001; 94(2): 149-158.

Nelson AD, Camilleri M: Chronic opioid induced constipation in patients with nonmalignant pain: Challenges and opportunities. Ther Adv Gastroenterol. 2015; 8(4): 206-220.

Le QA, Doctor JN, Zoellner LA, et al.: Minimal clinically important differences for the EQ-5D and QWB-SA in Posttraumatic Stress Disorder (PTSD): Results from a Doubly Randomized Preference Trial (DRPT). Health Qual Life Outcomes. 2013; 11: 59.

Fransen M, Edmonds J: Reliability and validity of the EuroQol in patients with osteoarthritis of the knee. Rheumatol Oxf Engl. 1999; 38(9): 807-813.

Ravens-Sieberer U, Wille N, Badia X, et al.: Feasibility, reliability, and validity of the EQ-5D-Y: Results from a multinational study. Qual Life Res. 2010; 19(6): 887-897.



  • There are currently no refbacks.