Efficacy and safety of a combined oral contraceptive containing estradiol valerate/dienogest: results from a clinical study conducted in North America.

BACKGROUND: This study investigated the efficacy and safety of a combined oral contraceptive (COC) containing estradiol valerate/dienogest (E2V/DNG). METHODS: This was a multicenter, noncomparative, 13-cycle (extended to 28 cycles) study conducted in the United States and Canada. Contraceptive efficacy was calculated as a Pearl Index for 13 cycles, based on all on-treatment pregnancies; bleeding patterns were calculated based on bleeding and spotting information recorded daily in diary cards. Safety events during a 16-month extension study were added to the 1-year data. RESULTS: In total, 499 women, aged 18-35 years, were enrolled, and 490 of them were included in the full analysis set for contraceptive efficacy. Five pregnancies occurred in the first year (unadjusted Pearl Index=1.64). In cycles 1-12, an average 23.5% of women had absent scheduled (withdrawal) bleeding. Among women with scheduled (withdrawal) bleeding, bleeding started after a median of 2 days after intake of the last DNG-containing pill. For safety, data included from 147 women followed over an additional 16 months were added to the original 13-cycle data set. Treatment-related adverse events (AEs) occurred in 51.8% of women; 14.9% discontinued because of AEs over the entire 28-month study period. CONCLUSION: A COC with E2V and DNG was shown to provide effective contraception in women aged 18-35 years in North America.

Clinical trials in pulmonary hypertension: Time for a consortium.

Current and past clinical trials in pulmonary hypertension, while valuable, are limited by the absence of mechanistic aims, by dissatisfaction with endpoints and the inability to share data. Clinical studies in pulmonary hypertension might be enhanced by a consortium approach that utilizes the expertise of academic medicine, the treatment initiatives of the pharmaceutical industry and study design from funding agencies interested in biological mechanisms. A meeting of interested parties, the Pulmonary Hypertension Academic Research Consortium (PHARC), was held from 30 April to 1 May 2012 in Bethesda, Maryland. Members at the conference were from the USA Federal Drug Administration (FDA); pharmaceutical industry (Pfizer, Novartis, Bayer and Gilead); USA National Institutes of Health (NHLBI); the Pulmonary Vascular Research Institute (PVRI), a non-governmental organization (NGO); and research and clinical members of pulmonary hypertension programs of international scope. A recommendation to develop a clinical trials consortium was the product of the working group on academic standards in clinical trials. The working group concluded that clinical trials hold immense promise to move the field of pulmonary hypertension forward if the trials are designed by a consortium with input from multiple groups. This would result in study design, conduct and analysis determined by consortium members with a high degree of independent function. The components of a well-balanced consortium that give it scientific effectiveness are: (1) the consortium can work with multiple companies simultaneously; (2) sponsors with special interests, such as testing biological mechanisms, can add investigations to a study at lower cost than with present granting strategies; (3) data handling including archiving, analysis and future sharing would be improved; (4) ancillary studies supported by the collection and dissemination of tissues and fluids would generate a broader approach to discovery than is now possible; and (5) development of improved endpoints in consultation with regulatory agencies, industry and academia would be possible.

Retrospective analysis of variation in heavy menstrual bleeding treatments by age and underlying cause.

OBJECTIVE: To describe treatment patterns associated with heavy menstrual bleeding (HMB) in US practice. STUDY DESIGN: A retrospective claims-based analysis of organic (ICD-9 codes 218.x, 621.0, 622.7, 219.x, and bleeding disorders) or idiopathic (no underlying condition identified) HMB treatment patterns among newly diagnosed, commercially insured women who were enrolled in a large US health plan. First HMB claim (index date; ICD-9-CM 626.2 and 627.0), second HMB claim within 180 days of index date, and continuous enrollment ≥6 months prior to (pre-index period) and 18 months following (post-index period) index date were required. RESULTS: The database included 13,579 organic and 21,362 idiopathic HMB patients. More organic HMB patients received only one treatment type (64% vs 58%; p < 0.001) or two treatments types (14% vs 11%; p < 0.001) compared to idiopathic HMB patients. During the 18 month post-index period, fewer organic HMB patients had no observed treatment compared to idiopathic HMB patients (21% vs 31%; p < 0.001). The idiopathic cohort had significantly higher rates (p < 0.001) of medication use and endometrial ablation, whereas the organic HMB cohort had a higher rate of hysterectomy (p < 0.001). Women <35 years were more frequently prescribed medical treatments (p ≤ 0.037), while women aged >35 years utilized significantly more surgical approaches (p < 0.001). CONCLUSIONS: Among organic and idiopathic HMB patients, considerable variation was observed in the medications and procedures used to treat HMB. Current treatment pattern awareness may improve HMB management. Future research is needed to understand factors that influence women's treatment choices (including newer medications LNG-IUS and tranexamic acid) and age in relation to child-bearing preference.

Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel.

OBJECTIVES: The safety and efficacy of a single-rod implantable contraceptive containing etonogestrel (Implanontrade mark) were investigated in a multicenter clinical trial. STUDY DESIGN: Sexually active American women (N=330) with apparently normal menstrual cycles used the implant for up to 2 years. All subjects recorded bleeding and/or spotting daily in a diary. Safety was assessed through adverse experiences (AEs), laboratory tests and physical and gynecologic examinations. RESULTS: Total exposure was 474 woman-years (6186 cycles), and 68% of subjects had at least 1 year of exposure. No pregnancies occurred. The most common bleeding pattern observed throughout the study was infrequent bleeding, defined as less than three episodes of bleeding in a reference period (excluding amenorrhea). The least common pattern was frequent bleeding, defined as more than five episodes of bleeding in a reference period. Infrequent, prolonged and frequent bleeding patterns were most common early in the study and declined thereafter. During the 3-month Reference Periods 2-8 (Months 4-24), the incidence of amenorrhea ranged from 14% to 20%. Forty-three subjects (13%) withdrew from the study because of bleeding pattern changes and 76 subjects (23%) discontinued because of other AEs. Other common AEs leading to discontinuation, besides bleeding irregularities, were emotional lability (6.1%), weight increase (3.3%), depression (2.4%) and acne (1.5%). Use of Implanon (etonogestrel subdermal implant, referred to herein as ENG implant) for up to 2 years had no clinically significant effects on laboratory parameters, physical and pelvic examinations, vital signs or body mass index. The average length of time required for ENG implant insertion and that for removal were 0.5 and 3.5 min, respectively, and all the procedures were uncomplicated. The return to normal menstrual cycles and fertility was rapid after removal. CONCLUSIONS: Implanon is a safe, highly effective and rapidly reversible new method of contraception.

Why consider vaginal drug administration?

OBJECTIVE: To review the anatomy and physiology of the vagina, the merits of vaginal drug administration, and the currently available vaginal drug-administration systems. DESIGN: Review of basic and clinical research. RESULT(S): Although clinicians commonly use topically administered drugs in the vagina, this route for systemic drug administration is somewhat novel. Experience with a variety of products demonstrates that the vagina is a highly effective site for drug delivery, particularly in women's health. The vagina is often an ideal route for drug administration because it allows for the administration of lower doses, steady drug levels, and less frequent administration than the oral route. With vaginal drug administration, absorption is unaffected by gastrointestinal disturbances, there is no first-pass effect, and use is discreet. Knowledge of anatomy, physiology, histology, and immunology of the vagina should allow clinicians to reassure their patients concerning this mode of delivery. Greater understanding and experience by clinicians should lead to increased use and acceptance of the vagina as a route for drug administration. CONCLUSION(S): The safety and efficacy of vaginal administration have been well established. The vaginal route of drug delivery is acceptable and may even be a preferable route of administration for many drugs, particularly hormones, whether for contraception or postmenopausal estrogen therapy.