Defining a minimal clinically important difference for endometriosis-associated pelvic pain measured on a visual analog scale: analyses of two placebo-controlled, randomized trials

Christoph Gerlinger, Ulrike Schumacher, Thomas Faustmann, Antje Colligs, Heinz Schmitz, Christian Seitz, Christoph Gerlinger, Ulrike Schumacher, Thomas Faustmann, Antje Colligs, Heinz Schmitz, Christian Seitz

Abstract

Background: When comparing active treatments, a non-inferiority (or one-sided equivalence) study design is often used. This design requires the definition of a non-inferiority margin, the threshold value of clinical relevance. In recent studies, a non-inferiority margin of 15 mm has been used for the change in endometriosis-associated pelvic pain (EAPP) on a visual analog scale (VAS). However, this value was derived from other chronic painful conditions and its validation in EAPP was lacking.

Methods: Data were analyzed from two placebo-controlled studies of active treatments in endometriosis, including 281 patients with laparoscopically-confirmed endometriosis and moderate-to-severe EAPP. Patients recorded EAPP on a VAS at baseline and the end of treatment. Patients also assessed their satisfaction with treatment on a modified Clinical Global Impression scale. Changes in VAS score were compared with patients' self-assessments to derive an empirically validated non-inferiority margin. This anchor-based value was compared to a non-inferiority margin derived using the conventional half standard deviation rule for minimal clinically important difference (MCID) in patient-reported outcomes.

Results: Anchor-based and distribution-based MCIDs were-7.8 mm and-8.6 mm, respectively.

Conclusions: An empirically validated non-inferiority margin of 10 mm for EAPP measured on a VAS is appropriate to compare treatments in endometriosis.

Figures

Figure 1
Figure 1
The VAS. Patients record the severity of their pain on a VAS score from 0 mm to 100 mm.
Figure 2
Figure 2
Change in VAS score categorized by patients' assessments on the modified CGI scale-global improvement item. Boxplots are drawn using the 10th and 90th percentiles as endpoints of the whiskers. Outlying observations are shown using a dot as the plot symbol.

References

    1. O'Shea RT, Jones WR. Danazol: objective assessment in the treatment of endometriosis. Clin Reprod Fertil. 1985;3:205–206.
    1. Salat-Baroux J, Giacomini P, Antoine JM. Laparoscopic control of danazol therapy on pelvic endometriosis. Hum Reprod. 1988;3:197–200.
    1. Bulletti C, Flamigni C, Polli V, Giacomucci E, Albonetti A, Negrini V, Galassi A, Morselli-Labate AM. The efficacy of drugs in the management of endometriosis. J Am Assoc Gynecol Laparosc. 1996;3:495–501. doi: 10.1016/S1074-3804(05)80157-4.
    1. Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2007;4:CD000068.
    1. American Fertility Society. Revised American Fertility Society classification of endometriosis: 1985. Fertil Steril. 1985;43:351–352.
    1. Vercellini P, Trespidi L, De Giorgi O, Cortesi I, Parazzini F, Crosignani PG. Endometriosis and pelvic pain: relation to disease stage and localization. Fertil Steril. 1996;65:299–304.
    1. Rodgers AK, Falcone T. Treatment strategies for endometriosis. Expert Opin Pharmacother. 2008;9:243–255. doi: 10.1517/14656566.9.2.243.
    1. Koninckx PR, Meuleman C, Demeyere S, Lesaffre E, Cornillie FJ. Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain. Fertil Steril. 1991;55:759–765.
    1. Tokushige N, Markham R, Russell P, Fraser IS. High density of small nerve fibres in the functional layer of the endometrium in women with endometriosis. Hum Reprod. 2006;21:782–787. doi: 10.1093/humrep/dei368.
    1. Koninckx PR, Oosterlynck D, D'Hooghe T, Meuleman C. Deeply infiltrating endometriosis is a disease whereas mild endometriosis could be considered a non-disease. Ann N Y Acad Sci. 1994;734:333–341. doi: 10.1111/j.1749-6632.1994.tb21763.x.
    1. American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67:817–821. doi: 10.1016/S0015-0282(97)81391-X.
    1. Kennedy S, Bergqvist A, Chapron C, D'Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A, Saridogan E. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005;20:2698–2704. doi: 10.1093/humrep/dei135.
    1. Mounsey AL, Wilgus A, Slawson DC. Diagnosis and management of endometriosis. Am Fam Physician. 2006;74:594–600.
    1. Sinaii N, Cleary SD, Younes N, Ballweg ML, Stratton P. Treatment utilization for endometriosis symptoms: a cross-sectional survey study of lifetime experience. Fertil Steril. 2007;87:1277–1286. doi: 10.1016/j.fertnstert.2006.11.051.
    1. Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani PG. Endometriosis: current therapies and new pharmacological developments. Drugs. 2009;69:649–675. doi: 10.2165/00003495-200969060-00002.
    1. Vincent K, Kennedy S, Stratton P. Pain scoring in endometriosis: entry criteria and outcome measures for clinical trials. Report from the Art and Science of Endometriosis meeting. Fertil Steril. 2010;93:62–67. doi: 10.1016/j.fertnstert.2008.09.056.
    1. Jones G, Jenkinson C, Kennedy S. Evaluating the responsiveness of the Endometriosis Health Profile Questionnaire: the EHP-30. Qual Life Res. 2004;13:705–713. doi: 10.1023/B:.
    1. Jones G, Jenkinson C, Taylor N, Mills A, Kennedy S. Measuring quality of life in women with endometriosis: tests of data quality, score reliability, response rate and scaling assumptions of the Endometriosis Health Profile Questionnaire. Hum Reprod. 2006;21:2686–2693. doi: 10.1093/humrep/del231.
    1. Schlaff WD, Carson SA, Luciano A, Ross D, Bergqvist A. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil Steril. 2006;85:314–325. doi: 10.1016/j.fertnstert.2005.07.1315.
    1. Crosignani PG, Luciano A, Ray A, Bergqvist A. Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Hum Reprod. 2006;21:248–256. doi: 10.1093/humrep/dei290.
    1. Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Hum Reprod. 2010;25:633–641. doi: 10.1093/humrep/dep469.
    1. ICH. International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH Harmonised Tripartite Guideline. Choice of control group and related issues in clinical trials. Recommended for adoption at step 4 of the ICH process on 20 July 2000 by the ICH steering committee. 2000. Accessed Nov 2010.
    1. Committee for Medicinal Products for Human Use (CHMP) Guideline on the Choice of the Non-Inferiority Margin. London, 27 July 2005. Doc ref EMEA/CPMP/EWP/2158/99. Accessed Nov 2010.
    1. Strowitzki T, Faustmann T, Gerlinger C, Seitz C. Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol. 2010;151:193–198. doi: 10.1016/j.ejogrb.2010.04.002.
    1. Guy W. ECDEU Assessment Manual for Psychopharmacology. Revised DHEW Pub. (ADM). Rockville, MD: National Institute for Mental Health; 1976. Clinical Global Impressions; pp. 218–222.
    1. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–174. doi: 10.2307/2529310.
    1. SAS Institute Inc. SAS/STAT® 9.1 User's Guide. Cary, NC.: SAS Institute Inc. 2004.
    1. SAS Institute Inc. SAS® 9.1 Software.
    1. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003;41:582–592. doi: 10.1097/00005650-200305000-00004.
    1. EMEA. European Agency for the Evaluation of Medicinal Products. Note for Guidance on Clinical Investigation of Medicinal Products for Treatment of Nociceptive Pain. EMEA/CPMP/EWP/612/00. London, 21 November, 2002. Accessed Nov 2010.
    1. Wells GA, Tugwell P, Kraag GR, Baker PRA, Groh J, Redelmeier DA. Minimum important difference between patients with rheumatoid arthritis; the patient's perspective. J Rheumatol. 1993;20:557–560.
    1. Todd KH, Funk JP. The minimum clinically important difference in physician-assigned visual analog pain scores. Acad Emerg Med. 1996;3:142–146. doi: 10.1111/j.1553-2712.1996.tb03402.x.
    1. Ostelo RW, de Vet HC. Clinically important outcomes in low back pain. Best Pract Res Clin Rheumatol. 2005;19:593–607. doi: 10.1016/j.berh.2005.03.003.
    1. Gallagher EJ, Liebman M, Bijur PE. Prospective validation of clinically important changes in pain severity measured on a visual analog scale. Ann Emerg Med. 2001;38:633–638. doi: 10.1067/mem.2001.118863.
    1. Gallagher EJ, Bijur PE, Latimer C, Silver W. Reliability and validity of a visual analog scale for acute abdominal pain in the ED. Am J Emerg Med. 2002;20:287–290. doi: 10.1053/ajem.2002.33778.
    1. Prentice A, Deary AJ, Goldbeck-Wood S, Farquhar C, Smith SK. Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev. 1999;2:CD000346.
    1. Prentice A, Deary AJ, Bland E. Progestagens and anti-progestagens for pain associated with endometriosis. Cochrane Database Syst Rev. 2000;2:CD002122.
    1. Cobellis L, Razzi S, De Simone S, Sartini A, Fava A, Danero S, Gioffrè W, Mazzini M, Petraglia F. The treatment with a COX-2 specific inhibitor is effective in the management of pain related to endometriosis. Eur J Obstet Gynecol Reprod Biol. 2004;116:100–102. doi: 10.1016/j.ejogrb.2004.02.007.
    1. Johnson NP, Farquhar CM, Crossley S, Yu Y, Van Peperstraten AM, Sprecher M, Suckling J. A double-blind randomised controlled trial of laparoscopic uterine nerve ablation for women with chronic pelvic pain. BJOG. 2004;111:950–959. doi: 10.1111/j.1471-0528.2004.00233.x.
    1. Petta CA, Ferriani RA, Abrao MS, Hassan D, Rosa E, Silva JC, Podgaec S, Bahamondes L. Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod. 2005;20:1993–1998. doi: 10.1093/humrep/deh869.
    1. Lockhat FB, Emembolu JO, Konje JC. The efficacy, side-effects and continuation rates in women with symptomatic endometriosis undergoing treatment with an intra-uterine administered progestogen (levonorgestrel): a 3 year follow-up. Hum Reprod. 2005;20:789–793. doi: 10.1093/humrep/deh650.
    1. Parker JD, Leondires M, Sinaii N, Premkumar A, Nieman LK, Stratton P. Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Fertil Steril. 2006;86:711–715. doi: 10.1016/j.fertnstert.2006.01.030.
    1. Parazzini F, Mais V, Cipriani S. Gruppo Italiano per lo Studio dell'Endometriosi. Adhesions and pain in women with first diagnosis of endometriosis: results from a cross-sectional study. J Minim Invasive Gynecol. 2006;13:49–54. doi: 10.1016/j.jmig.2005.10.002.
    1. Koninckx PR, Craessaerts M, Timmerman D, Cornillie F, Kennedy S. Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod. 2008;23:2017–2023. doi: 10.1093/humrep/den177.
    1. Sheng J, Zhang WY, Zhang JP, Lu D. The LNG-IUS study on adenomyosis: a 3-year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis. Contraception. 2009;79:189–193. doi: 10.1016/j.contraception.2008.11.004.
    1. Raber M, Hofmann S, Junge K, Momberger H, Kuhn D. Analgesic efficacy and tolerability of tramadol 100 mg sustained-release capsules in patients with moderate to severe chronic low back pain. Clin Drug lnvest. 1999;17:415–423. doi: 10.2165/00044011-199917060-00001.
    1. Wagenitz A, Mueller EA, Frentzel A, Cambon N. Comparative efficacy and tolerability of two sustained-release formulations of diclofenac: results of a double-blind, randomised study in patients with osteoarthritis and a reappraisal of diclofenac's use in this patient population. Curr Med Res Opin. 2007;23:1957–1966. doi: 10.1185/030079907X223251.
    1. Sieper J, Klopsch T, Richter M, Kapelle A, Rudwaleit M, Schwank S, Regourd E, May M. Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study. Ann Rheum Dis. 2008;67:323–329. doi: 10.1136/ard.2007.075309.

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