Mansour 2012.
| Methods | Design: multicenter RCT Location: 95 practices in Europe, Asia, Australia Time frame: May 2006 to April 2008 Sample size calculation: based on precision of Pearl Index in women ≤ 35 years old, 80% power; used guidance of Committee for Medicinal Products for Human Use |
|
| Participants | 2152 healthy, sexually active women Inclusion criteria: aged 18 to 50 years; BMI 17 to 35 kg/m2; needed contraception and did not plan to use condoms Exclusion criteria: contraindication for contraceptive steroids; abnormal cervical smear at screening; clinically relevant abnormal laboratory result at screening; use of injectable hormonal contraception within 6 months if 3‐month duration, within 4 months if 2‐month duration, within 2 months if 1‐month duration; present use or use in past 2 months of phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole, sex steroids (except allowed contraceptive methods used before and after treatment period), or herbal remedies containing Hypericum perforatum (St John’s Wort) |
|
| Interventions | Group 1: Nomegestrol acetate (NOMAC) 2.5 mg + 17β‐estradiol (E2) 1.5 mg (24/4) (N = 1613)
Group 2: Drospirenone (DRSP) 3 mg + EE 30 μg (21/7) (N = 539) Duration: 13 treatment cycles |
|
| Outcomes | Pearl Index; percentage pregnant Other outcomes, including adherence, not examined by BMI Comparison groups: BMI < 18.5; 18.5 to < 25; 25 to < 30; ≥ 30 |
|
| Notes | Study funded by Merck Sharp & Dohme (MSD); 3 authors employed by MSD (Oss, the Netherlands) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | NRS: non‐randomized comparisons RCT information: computer‐generated randomization schedule with blocks of four; allocated 3:1 (NOMAC + E2: DRSP + EE); stratified by age (18 to 35 years; 36 to 50 years) |
| Allocation concealment (selection bias) | Unclear risk | NA for this analysis Interactive voice‐response system; central allocation in order of randomization call |
| NOS selection (NRS) | Unclear risk | Overweight or obese: participants in RCT of OCs (high risk) Not overweight or obese: same source (low risk) Exposure to intervention: counted dispensed and unused tablets and examined participants' records in electronic diaries (unclear risk) |
| NOS comparability (NRS) | High risk | Design: _ Analysis: no adjustment for potential confounding |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Not feasible to blind BMI or weight groups Open label for methods |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | No mention |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Loss to follow‐up: NOMAC 2.5%; DRSP 3.2% Loss overall (discontinuations, exclusions): NOMAC 471/1613 (29%); DRSP 129/539 (24%) Excluded those who did not take any study drug: NOMAC n = 22 (1.4%); DRSP n = 4 (0.7%) |
| Other bias | Unclear risk | Outcome assessment: no information regarding pregnancy or weight assessment |
| Sponsor | High risk | Merck provided funding for study Investigators: 3 from Merck; Oss, Netherlands |