Women and babies are dying from inertia: a collaborative framework for obstetrical drug development is urgently needed.

Obstetrical complications, often referred to as the "great obstetrical syndromes," are among the most common global causes of mortality and morbidity in young women and their infants. However, treatments for these syndromes are underdeveloped compared with other fields of medicine and are urgently needed. This current paucity of treatments for obstetrical complications is a reflection of the challenges of drug development in pregnancy.

Coordination and planning of clinical research on a national and global level.

In reproductive medicine, the needs and desires of infertility patients drive future research, with the most important outcome being live birth of a baby. Large, multicenter, randomized clinical trials are considered the best research tool to evaluate the effectiveness of medical interventions, but they can often take a long time to find definitive answers. Advances in individual participant data (IPD) and network meta-analysis have enabled research questions to be answered more quickly, but better planning could streamline this process further.

Peer review comments on drug trials submitted to medical journals differ depending on sponsorship, results and acceptance: a retrospective cohort study.

Objective: During peer review, submitted manuscripts are scrutinised by independent experts to assist journal editors in their decision-making and to help improve the quality of articles. In this retrospective cohort study, peer review comments for drug trials submitted to medical journals were analysed to investigate whether there is a relation between the content of these comments and sponsorship, direction of results and decision about acceptance.

Design/setting: Descriptive content analysis of reviewer comments made on manuscripts on drug trials submitted to eight medical journals (January 2010-April 2012).

Differences between information in registries and articles did not influence publication acceptance.

Objectives: To assess whether journals are more likely to reject manuscripts with differences between information in registries and articles. We compared differences by sponsorship and assessed whether selective reporting favored publication of significant outcomes.

Study Design And Setting: Drug trials submitted to eight journals (January 2010-April 2012) were included.

Shortcomings of protocols of drug trials in relation to sponsorship as identified by Research Ethics Committees: analysis of comments raised during ethical review.

Background: Submission of study protocols to research ethics committees (RECs) constitutes one of the earliest stages at which planned trials are documented in detail. Previous studies have investigated the amendments requested from researchers by RECs, but the type of issues raised during REC review have not been compared by sponsor type. The objective of this study was to identify recurring shortcomings in protocols of drug trials based on REC comments and to assess whether these were more common among industry-sponsored or non-industry trials.

Role of editorial and peer review processes in publication bias: analysis of drug trials submitted to eight medical journals.

Background: Publication bias is generally ascribed to authors and sponsors failing to submit studies with negative results, but may also occur after submission. We evaluated whether submitted manuscripts on randomized controlled trials (RCTs) with drugs are more likely to be accepted if they report positive results.

Methods: Manuscripts submitted from January 2010 through April 2012 to one general medical journal (BMJ) and seven specialty journals (Annals of the Rheumatic Diseases, British Journal of Ophthalmology, Gut, Heart, Thorax, Diabetologia, and Journal of Hepatology) were included, if at least one study arm assessed the efficacy or safety of a drug and a statistical test was used to evaluate treatment effects.

Recommendations for a uniform assessment of publication bias related to funding source.

Background: Numerous studies on publication bias in clinical drug research have been undertaken, particularly on the association between sponsorship and favourable outcomes. However, no standardized methodology for the classification of outcomes and sponsorship has been described. Dissimilarities and ambiguities in this assessment impede the ability to compare and summarize results of studies on publication bias.

Optimizing the gonadotrophin dose regimen.

The starting dose of gonadotrophin for controlled ovarian stimulation (COS) or ovulation induction (OI) must be individualized and has considerable impact on outcomes (pregnancy and adverse events). Five large randomized, controlled trials have compared fixed doses of recombinant follicle-stimulating hormone (rFSH) for COS for assisted reproductive technology (ART). Among young women, a fixed dosage of 200 IU/day (versus 100 IU/day) yielded more oocytes and more transferable embryos.

Recombinant follicle-stimulating hormone: gold standard or not?

Recombinant follicle stimulating hormone has been available now for almost 10 years and many couples have benefited from its use. Its clinical efficacy, purity and safety profile have been extensively documented in numerous publications. Because of growing public concerns on the safety of gonadotrophins extracted from human urine, the future will lie in the recombinant technology, which will also enable the design of more convenient tailor-made gonadotrophins.

A randomized, double-blind, multicentre clinical trial comparing starting doses of 150 and 200 IU of recombinant FSH in women treated with the GnRH antagonist ganirelix for assisted reproduction.

Background: Studies with the GnRH antagonist ganirelix in assisted reproduction have indicated that compared with traditional GnRH agonist downregulation protocols, slightly fewer oocytes are retrieved. In this study it was investigated whether an increase in the starting dose of recombinant FSH (rFSH) could compensate for this loss.

Methods: A randomized, double-blind, multicentre clinical trial comparing a starting dose of 150 and 200 IU of rFSH (follitropin beta), in women undergoing treatment with the GnRH antagonist ganirelix.

The gonadotrophin-releasing hormone antagonist ganirelix--history and introductory data.

The gonadotrophin-releasing hormone antagonist ganirelix has recently become available to clinicians. Its indication, prevention of premature luteinizing hormone surges in assisted reproduction programmes, has been investigated extensively in numerous studies. This article summarizes the major results from pharmacokinetics studies, a double-blind dose-finding trial and three large-scale phase III randomized clinical trials, comparing ganirelix and the most commonly used gonadotrophin-releasing hormone agonists, buserelin,leuprolide and triptorelin, in a long protocol.

The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

Background: The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG).

Methods: A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP.

A randomized, double-blind clinical trial using fixed daily doses of 100 or 200 IU of recombinant FSH in ICSI cycles.

The effect of 100 and 200 IU per day recombinant FSH (rFSH) on numbers of oocytes retrieved and the total dose used in ovarian stimulation before intracytoplasmic sperm injection was investigated in a double-blind, randomized multicentre trial. A total of 91 women was treated with a low-dose protocol and 88 with a high-dose regimen at five centres. For each started cycle, significantly more oocytes were retrieved in the 200 IU group than in 100 IU group (12.

Increasing the daily dose of recombinant follicle stimulating hormone (Puregon) does not compensate for the age-related decline in retrievable oocytes after ovarian stimulation.

A prospective, randomized, double-blind, multicentre (n = 6) study was conducted to compare the influence of either a 150 or 250 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH, Puregon) on the number of oocytes retrieved and the total dose used in down-regulated women between 30 and 39 years of age undergoing ovarian stimulation. In all, 138 women were treated with recombinant FSH, 67 with 150 IU and 71 with 250 IU. The number of oocytes retrieved in the low-dose group was 9.

A prospective, randomized, double-blind clinical trial to study the efficacy and efficiency of a fixed dose of recombinant follicle stimulating hormone (Puregon) in women undergoing ovarian stimulation.

A prospective, randomized, double-blind, multicentre (n = 5) study was conducted to compare the influence of either a 100 or 200 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH) on the number of oocytes retrieved and the total dose used in down-regulated women undergoing ovarian stimulation. Fertilization was done by intracytoplasmic sperm injection or conventional in-vitro fertilization. A total of 199 women were treated with FSH, 101 subjects with 100 IU and 98 subjects with 200 IU.

A prospective randomized clinical trial comparing recombinant follicle stimulating hormone (Puregon) and human menopausal gonadotrophins (Humegon) in non-down-regulated in-vitro fertilization patients.

A randomized clinical trial was performed comparing recombinant follicle stimulating hormone (rFSH, Puregon, n = 54) and human menopausal gonadotrophin (HMG, Humegon, n = 35) in infertile women undergoing in-vitro fertilization without the use of a gonadotrophin-releasing hormone (GnRH) agonist. Most patients had a tubal or idiopathic infertility, the latter always longer than 4 years' duration. Patients with sperm abnormalities were excluded.