Centchroman Regresses Mastalgia: A Randomized Comparison with Danazol

Abstract

We conducted a randomized trial to evaluate effectiveness of Centchroman in control of mastalgia and compared it with Danazol. Research Question- Is proportion of pain relief achieved by Centchroman similar to or inferior to that achieved by Danazol? In a randomized controlled trial of Centchroman vs. Danazol in mastalgia, 81 patients with mastalgia were studied. Thirty-nine patients were randomized to Danazol arm and 42 in Centchroman arm. The treatment was given for 12 weeks, followed by observation for 12 weeks. The pain was measured by visual analogue scale (VAS) of 0–10. At 12 weeks 89.7% women achieved reduction in pain score to ≤3 in Centchroman group (pvalue 0.001). In Danazol group 69.44% women achieved reduction in pain score to ≤ 3 (p = 0.001). Three months after stopping therapy, Centchroman was more effective in pain score reduction at 24 weeks as compared to Danazol (p = 0.019). Centchroman is an effective, safe and inexpensive alternative to Danazol for treatment of mastalgia.

Appendix

Sample Size Consideration

We put forth the assumption that, Centchroman therapy would achieve pain relief similar to or slightly less than that achieved by Danazol. Hence in this calculation one tailed hypothesis was considered. The clinically meaningful difference in the proportion of cases getting pain relief in between the two arms is represented by delta-(δ) which is the non-inferiority margin in calculating the sample size with the following null hypothesis (H₀).

• H₀: ε ≤ δ, and alternative hypothesis H_A: ε > δ , where ε is the difference in the proportion of success between two therapies. (ε = p1–p2 ; where p1 = pain response proportion with Centchroman therapy,

• p2 = pain response proportion with Danazol therapy).

Allowing the 15% of difference between results of two therapies as the clinically meaningful difference, the value of δ has been chosen as 0.15.

• Assuming: p1 = 50% .

• The literature showed that 60% cases get benefit in mastalgia by Danazol therapy, hence value of p2 = 60% or 0.6.

• The values of other factors were taken as follows:-Z_œ = 1.645 for œ = 0.05 for one tailed hypothesis

• Z_β = 0.84 for power = 80% for one or two tailed hypothesis

With all these values the formula used in calculation of sample size for one group was as follows: -

$$ N = {({Z_\alpha } + {Z_\beta })^2}[p1(1 - p1) + p2(1 - p2)]/{[(p1 - p2) - \delta ]^2} $$

$$ {\hbox{N}} = {({1}.{645} + 0.{84})^2}\left[ {0.{5(1} - 0.{5)} + 0.{6(1} - 0.{6)}} \right]/{\left[ {0.{1} - 0.{15}} \right]^2} $$

The value of N (i.e. the sample size for one group) was calculated to be 48. Expecting 10% of withdrawal of the volunteers from the groups, the total numbers of patients to participate were considered 110. The study presents the result on 81 subjects.

Method of Randomization

Block randomization with a block size of 4 was employed to generate a list of random numbers on web site www.randomization.com. The sealed numbered opaque brown envelopes were prepared with the label of case number e.g “ case 1” . The envelopes were opened after ensuring inclusion criteria and signing the consent form. The envelope contained a folded slip of paper stating the assigned treatment, i.e Centchroman or Danazol. The assigned treatment was given to the patient. No randomization violation or contamination occurred.