Comparison of two doses and two routes of administration of misoprostol after pre-treatment with mifepristone for early pregnancy termination

<p>Abstract</p> <p>Background</p> <p>It is not known whether a 400 μg dose of misoprostol has a similar efficacy as an 800 μg dose when administered sublingually or vaginally 24 hours after 200 mg mifepristone.</p> <p>Methods</p> <p>It is proposed to undertake a placebo-controlled, randomized, non-inferiority trial (3% margin of equivalence) of the two misoprostol doses when administered sublingually or vaginally using factorial design. A total of 3008 pregnant women (< 63 days of gestational age) who request legal termination of pregnancy will be recruited for the trial at 16 clinics in ten countries providing abortion services. Eligible women willing to join the study will be allocated randomly to one of the four treatment groups within each centre. Women in all treatment groups will first receive 200 mg mifepristone, followed 24 hours later by either 400 μg or 800 μg misoprostol, administered either sublingually or vaginally. The dose and route of administration of misoprostol will be blinded to women, each woman receiving four tablets vaginally and four tablets sublingually, two or four of which are 200 μg tablets of misoprostol and the rest are placebo tablets.</p> <p>The four treatment regimens will be compared in terms of: (i) their efficacy to induce complete abortion; (ii) induction-to-abortion interval when possible; (iii) the frequency of side effects; and (iv) women's perceptions. The initial judgment of the outcome of treatment is made at the follow-up visit on day 15 of the study and the final assessment four weeks later. It is estimated that the clinical phase will require 12–14 months for data collection.</p> <p>To compare the two routes and two doses, relative risks (RR) of failure to achieve a complete abortion and failure to terminate pregnancy and the two-sided 95% CIs will be calculated by standard methods, as well as risk differences and two-sided 95% CIs. The latter will be used to test the non-inferiority hypotheses (at 2.5% level of significance) for achieving complete abortion. The factorial structure will be taken into account in the analysis after testing the interaction.</p> <p>Trial registration</p> <p>ISRCTN87811512</p

The methodology for developing a prospective meta-analysis in the family planning community

<p>Abstract</p> <p>Background</p> <p>Prospective meta-analysis (PMA) is a collaborative research design in which individual sites perform randomized controlled trials (RCTs) and pool the data for meta-analysis. Members of the PMA collaboration agree upon specific research interventions and outcome measures, ideally before initiation but at least prior to any individual trial publishing results. This allows for uniform reporting of primary and secondary outcomes. With this approach, heterogeneity among trials contributing data for the final meta-analysis is minimized while each site maintains the freedom to design a specific trial. This paper describes the process of creating a PMA collaboration to evaluate the impact of misoprostol on ease of intrauterine device (IUD) insertion in nulliparous women.</p> <p>Methods</p> <p>After the principal investigator developed a preliminary PMA protocol, he identified potential collaborating investigators at other sites. One site already had a trial underway and another site was in the planning stages of a trial meeting PMA requirements. Investigators at six sites joined the PMA collaborative. Each site committed to enroll subjects to meet a pre-determined total sample size. A final common research plan and site responsibilities were developed and agreed upon through email and face-to-face meetings. Each site committed to contribute individual patient data to the PMA collaboration, and these data will be analyzed and prepared as a multi-site publication. Individual sites retain the ability to analyze and publish their site's independent findings.</p> <p>Results</p> <p>All six sites have obtained Institutional Review Board approval and each has obtained individual funding to meet the needs of that site's study. Sites have shared resources including study protocols and consents to decrease costs and improve study flow. This PMA protocol is registered with the Cochrane Collaboration and data will be analyzed according to Cochrane standards for meta-analysis.</p> <p>Conclusions</p> <p>PMA is a novel research method that improves meta-analysis by including several study sites, establishing uniform reporting of specific outcomes, and yet allowing some independence on the part of individual sites with respect to the conduct of research. The inclusion of several sites increases statistical power to address important clinical questions. Compared to multi-center trials, PMA methodology encourages collaboration, aids in the development of new investigators, decreases study costs, and decreases time to publication.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00613366">NCT00613366</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00886834">NCT00886834</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01001897">NCT01001897</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01147497">NCT01147497</a> and <a href="http://www.clinicaltrials.gov/ct2/show/NCT01307111">NCT01307111</a></p