On 2017 Aug 15, Andrea Messori commented:

Pearl-I trial: incremental benefit between patients treated with ulipristal 5 mg/day and those receiving placebo

Andrea Messori, HTA Unit, Regional Health Service, 50100 Firenze, Italy

In the Pearl-I trial [1], women with symptomatic fibroids, excessive uterine bleeding (PBAC score>100) and anemia were randomized to receive oral ulipristal (dose: 5 mg/day for 13 weeks) or placebo (48 women). A third arm received 10 mg/day of ulipristal. In the comparison between ulipristal 5 mg/day and placebo, the end point of controlled uterine bleeding (PBAC score<75) was achieved by 91% of the patients in the treatment group vs 19% in the controls receiving placebo. Figure 2 (Panel A) of the article by Donnez et al.[1] shows the time-to-event curve for treated patients and controls. Nagy et al.[2] have estimated that the value of utility is around 0.83 for patients with mild-to-moderate bleeding vs 0.72 for patients with severe bleeding (see Table 3 of Nagy’s article). We have carried out an analysis of the results of the Pearl-I trial in order to estimate the magnitude of the incremental benefit between patients treated with ulipristal 5 mg/day and those receiving placebo by expressing this benefit in quality-adjusted life years (QALYs). For this purpose, we employed a statistical tool (WebPlotDigitizer program) with which we analyzed the time-to-event curves reported in Figure 2 Panel A of the Pearl-I trial (time interval: from 0 to 100 days). As regards the ulipristal group, this statistical program estimated an average of 77.38 days per patient after achievement of the end-point vs 22.62 days per patient without achievement of the end-point. Likewise, in the control group there were on average 13.30 days per patient after achievement of the end-point vs 86.70 days per patient without achievement of the end-point. Using the two values of utility previously mentioned, these figures generated the following estimates of quality-adjusted survival: 80.51 quality adjusted days per patient in the treatment group (i.e. 0.22058 QALYs) and 73.46 quality adjusted days per patient in the control group (i.e. 0.20127 QALYs). The difference between these two QALY values yields 0.01931 QALYs per patient (around 7 quality-adjusted days per patient), which represents the incremental benefit between patients treated with ulipristal 5 mg/day and those receiving placebo.

References

[1] Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, Ugocsai G, Mara M, Jilla MP, Bestel E, Terrill P, Osterloh I, Loumaye E; PEARL I Study Group. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012 Feb 2;366(5):409-20.

[2] Nagy B, Timár G, Józwiak-Hagymásy J, Kovács G, Merész G, Vámossy I, Ágh T, László Á, Vokó Z, Kaló Z. The cost-effectiveness of ulipristal acetate tablets in treating patients with moderate to severe symptoms of uterine fibroids. Eur J Obstet Gynecol Reprod Biol. 2014 Apr;175:75-81.

[3] Rohatgi A. WebPlotDigitizer, Version: 3.12, Austin, Texas, available at http://arohatgi.info/WebPlotDigitizer, last accessed 15 August 2017

On 2017 Aug 15, Andrea Messori commented:

Pearl-I trial: incremental benefit between patients treated with ulipristal 5 mg/day and those receiving placebo

Andrea Messori, HTA Unit, Regional Health Service, 50100 Firenze, Italy

In the Pearl-I trial [1], women with symptomatic fibroids, excessive uterine bleeding (PBAC score>100) and anemia were randomized to receive oral ulipristal (dose: 5 mg/day for 13 weeks) or placebo (48 women). A third arm received 10 mg/day of ulipristal. In the comparison between ulipristal 5 mg/day and placebo, the end point of controlled uterine bleeding (PBAC score<75) was achieved by 91% of the patients in the treatment group vs 19% in the controls receiving placebo. Figure 2 (Panel A) of the article by Donnez et al.[1] shows the time-to-event curve for treated patients and controls. Nagy et al.[2] have estimated that the value of utility is around 0.83 for patients with mild-to-moderate bleeding vs 0.72 for patients with severe bleeding (see Table 3 of Nagy’s article). We have carried out an analysis of the results of the Pearl-I trial in order to estimate the magnitude of the incremental benefit between patients treated with ulipristal 5 mg/day and those receiving placebo by expressing this benefit in quality-adjusted life years (QALYs). For this purpose, we employed a statistical tool (WebPlotDigitizer program) with which we analyzed the time-to-event curves reported in Figure 2 Panel A of the Pearl-I trial (time interval: from 0 to 100 days). As regards the ulipristal group, this statistical program estimated an average of 77.38 days per patient after achievement of the end-point vs 22.62 days per patient without achievement of the end-point. Likewise, in the control group there were on average 13.30 days per patient after achievement of the end-point vs 86.70 days per patient without achievement of the end-point. Using the two values of utility previously mentioned, these figures generated the following estimates of quality-adjusted survival: 80.51 quality adjusted days per patient in the treatment group (i.e. 0.22058 QALYs) and 73.46 quality adjusted days per patient in the control group (i.e. 0.20127 QALYs). The difference between these two QALY values yields 0.01931 QALYs per patient (around 7 quality-adjusted days per patient), which represents the incremental benefit between patients treated with ulipristal 5 mg/day and those receiving placebo.

References

[1] Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, Ugocsai G, Mara M, Jilla MP, Bestel E, Terrill P, Osterloh I, Loumaye E; PEARL I Study Group. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012 Feb 2;366(5):409-20.

[2] Nagy B, Timár G, Józwiak-Hagymásy J, Kovács G, Merész G, Vámossy I, Ágh T, László Á, Vokó Z, Kaló Z. The cost-effectiveness of ulipristal acetate tablets in treating patients with moderate to severe symptoms of uterine fibroids. Eur J Obstet Gynecol Reprod Biol. 2014 Apr;175:75-81.

[3] Rohatgi A. WebPlotDigitizer, Version: 3.12, Austin, Texas, available at http://arohatgi.info/WebPlotDigitizer, last accessed 15 August 2017