| Methods |
Randomized controlled trial without blinding. The method of randomization is not described. Reports notes stratification using investigational site as the stratification variable. Communication with the investigators revealed no extra information. |
| Participants |
387 women at 11 sites in the USA. 65 women did not start the study after randomization. Inclusion criteria were healthy women aged 18 to 35 years for smokers and no upper age limit for non‐smokers with regular menstrual cycles (25 to 31 days) for the 3 months before enrollment who were at risk of becoming pregnant. Exclusion criteria were the standard contraindications for oral contraceptive studies listed in product class labeling, use of oral contraceptives within the previous 3 cycles before enrollment, use of an IUD or injectable or implantable estrogens, progestins or androgens during the 6 months before enrollment and smoking of more than 15 cigarettes per day. |
| Interventions |
Triphasic norethindrone/ethinylestradiol (500‐750‐1000 μg NET and 35 μg ethinylestradiol in a 7/7/7 days regimen and 7 days of placebo tablets, N=195) [Ortho‐Novum 7/7/7; TriNovum] versus
monophasic levonorgestrel/ethinylestradiol (100 μg LNG and 20 μg ethinylestradiol for 21 days and 7 days of placebo tablets, N=192) [Alesse;Loette]. |
| Outcomes |
Principal outcome measures are: pregnancy; side effects during treatment and after discontinuation; cycle control; discontinuation and reasons for discontinuation; metabolic outcomes. Use of diary cards to collect data on pill intake, cycle control, side effects and concomitant medication. The report describes the results of 4 cycles of exposure. Spotting was defined as a light flow that did not necessitate sanitary protection; breakthrough bleeding as a heavier flow, similar to normal menstrual flow, that did necessitate sanitary protection; withdrawal bleeding as bleeding or spotting that began during the drug‐free interval and stopped by day 4 of the next cycle; intermenstrual bleeding as all other bleeding or spotting; and an amenorrheic cycle as one with neither withdrawal bleeding nor intermenstrual bleeding. |
| Notes |
The report provides an adequate sample size calculation. Study duration: 4 cycles. 77 women in the triphasic group and 90 women in the monophasic group discontinued early. Reasons for discontinuation are described. 28 women in the triphasic group and 37 women in the monophasic group did not take the oral contraceptives. 20 women in the triphasic group and 19 women in the monophasic group were lost to follow up. 6 women in both groups were withdrawn because of protocol violations. Analysis not according to intention‐to‐treat principle. Breakthrough bleeding includes breakthrough bleeding and spotting in this meta‐analysis. The trial was sponsored by the manufacturer of the monophasic levonorgestrel/ethinylestradiol pill (Wyeth‐Ayerst). |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment (selection bias) |
Low risk |
Allocation concealment by sequentially‐numbered, sealed envelopes opened at the time of admission. |
