ORCID Profile
0000-0002-1227-4303
Current Organisation
The University of Auckland
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Publisher: Oxford University Press (OUP)
Date: 18-05-2022
Abstract: Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. In idual participant data meta-analysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate reporting of in idual studies by obtaining the IPD, and allows analyses on treatment–covariate interactions to identify couples who benefit most from a particular treatment. We performed this IPD-MA to compare the effectiveness and safety of ovarian stimulation with gonadotrophins, letrozole and CC and to explore treatment–covariate interactions for important baseline characteristics in couples undergoing IUI. We searched electronic databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO from their inception to 28 June 2021. We included randomized controlled trials (RCTs) comparing IUI-OS with gonadotrophins, letrozole and CC among couples with unexplained infertility. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA Collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Secondary outcomes were other reproductive outcomes, including time to conception leading to live birth. We performed a one-stage random effects IPD-MA. Seven of 22 (31.8%) eligible RCTs provided IPD of 2495 couples (62.4% of the 3997 couples participating in 22 RCTs), of which 2411 had unexplained infertility and were included in this IPD-MA. Six RCTs (n = 1511) compared gonadotrophins with CC, and one (n = 900) compared gonadotrophins, letrozole and CC. Moderate-certainty evidence showed that gonadotrophins increased the live birth rate compared to CC (6 RCTs, 2058 women, RR 1.30, 95% CI 1.12–1.51, I2 = 26%). Low-certainty evidence showed that gonadotrophins may also increase the multiple pregnancy rate compared to CC (6 RCTs, 2058 women, RR 2.17, 95% CI 1.33–3.54, I2 = 69%). Heterogeneity on multiple pregnancy could be explained by differences in gonadotrophin starting dose and choice of cancellation criteria. Post-hoc sensitivity analysis on RCTs with a low starting dose of gonadotrophins (≤75 IU) confirmed increased live birth rates compared to CC (5 RCTs, 1457 women, RR 1.26, 95% CI 1.05–1.51), but analysis on only RCTs with stricter cancellation criteria showed inconclusive evidence on live birth (4 RCTs, 1238 women, RR 1.15, 95% CI 0.94–1.41). For multiple pregnancy, both sensitivity analyses showed inconclusive findings between gonadotrophins and CC (RR 0.94, 95% CI 0.45–1.96 RR 0.81, 95% CI 0.32–2.03, respectively). Moderate certainty evidence showed that gonadotrophins reduced the time to conception leading to a live birth when compared to CC (6 RCTs, 2058 women, HR 1.37, 95% CI 1.15–1.63, I2 = 22%). No strong evidence on the treatment–covariate (female age, BMI or primary versus secondary infertility) interactions was found. In couples with unexplained infertility undergoing IUI-OS, gonadotrophins increased the chance of a live birth and reduced the time to conception compared to CC, at the cost of a higher multiple pregnancy rate, when not differentiating strategies on cancellation criteria or the starting dose. The treatment effects did not seem to differ in women of different age, BMI or primary versus secondary infertility. In a modern practice where a lower starting dose and stricter cancellation criteria are in place, effectiveness and safety of different agents seem both acceptable, and therefore intervention availability, cost and patients’ preferences should factor in the clinical decision-making. As the evidence for comparisons to letrozole is based on one RCT providing IPD, further RCTs comparing letrozole and other interventions for unexplained infertility are needed.
Publisher: Oxford University Press (OUP)
Date: 24-02-2022
Abstract: Infertility randomized controlled trials (RCTs) are often too small to detect realistic treatment effects. Large observational studies have been proposed as a solution. However, this strategy threatens to weaken the evidence base further, because non-random assignment to treatments makes it impossible to distinguish effects of treatment from confounding factors. Alternative solutions are required. Power in an RCT can be increased by adjusting for prespecified, prognostic covariates when performing statistical analysis, and if stratified randomization or minimization has been used, it is essential to adjust in order to get the correct answer. We present data showing that this simple, free and frequently necessary strategy for increasing power is seldom employed, even in trials appearing in leading journals. We use this article to motivate a pedagogical discussion and provide a worked ex le. While covariate adjustment cannot solve the problem of underpowered trials outright, there is an imperative to use sound methodology to maximize the information each trial yields.
Publisher: BMJ
Date: 05-2023
DOI: 10.1136/BMJOPEN-2023-072446
Abstract: To evaluate the reporting of results from the projects and programmes funded by the Health Research Council (HRC) New Zealand. A cross-sectional analysis. Research projects and programmes funded by the HRC New Zealand from 2006 to 2014. Publicly available data provided by the HRC. The number and proportion with evidence of publication and dissemination of a research output from HRC grants and the time taken to disseminate the results. Of the 374 HRC grants from 2006 to 2014, there was no evidence of publication or reporting of any research output for 48 studies (13%). Of the 326 (87%) grants with research outputs, there was a mean dissemination time of 4.73 years (SD 2.37). The total funding provided by the HRC was NZ$471 663 336, while the 48 grants with no evidence of dissemination represented NZ$47 095 727 (10%). Thirteen per cent of the HRC projects and programmes from 2006 to 2014 have not contributed to the healthcare evidence as their results remain unknown.
Publisher: Public Library of Science (PLoS)
Date: 05-01-2023
DOI: 10.1371/JOURNAL.PONE.0279926
Abstract: Timely publication of clinical trials is critical to ensure the dissemination and implementation of high-quality healthcare evidence. This study investigates the publication rate and time to publication of randomized controlled trials (RCTs) registered in the Australian New Zealand Clinical Trials Registry (ANZCTR). We conducted a cross-sectional study of RCTs registered with the ANZCTR in 2007, 2009, and 2011. Multiple bibliographic databases were searched until October 2021 to identify trial publications. We then calculated publication rates, proportions, and the time to publish calculated from the date of first participation enrolment to publication date. Of 1,970 trial registrations, 541 (27%) remained unpublished 10 to 14 years later, and the proportion of trials published decreased by 7% from 2007 to 2011. The average time to publish was 4.63 years. The prospective trial registration rate for 2007, 2009 and 2011 was 48% (952 trials) and over this time there was an increase of 19% (280 prospective trials). Trials funded by non-Industry organizations were more likely to be published (74%, 1204/1625 trials) than the industry-funded trials (61%, 224/345 trials). Larger trials with at least 1000 participants were published at a rate of 88% (85/97 trials) and on average took 5.4 years to be published. Smaller trials with less than 100 participants were published at a lower rate with 67% (687/1024 trials) published and these trials took 4.31 years on average to publish. Just over a quarter of all trials on the ANZCTR for 2007, 2009, and 2011 remain unpublished over a decade later. The average time to publication of nearly five years may reflect the larger trials which will have taken longer to recruit participants. Over half of study s le trials were retrospectively registered, but prospective registration improved over time, highlighting the role of mandating trial registration.
No related grants have been discovered for Marian Showell.