Standardising outcome reporting for clinical trials of interventions for heavy menstrual bleeding: Development of a core outcome set

OBJECTIVE: To develop a core outcome set for heavy menstrual bleeding (HMB). DESIGN: Core outcome set (COS) development methodology described by the COMET initiative. SETTING: University hospital gynaecology department, online international survey and web-based international consensus meetings. POPULATION OR SAMPLE: Phase 1: Systematic review of previously reported outcomes to identify potential core outcomes. Phase 2: Qualitative studies with patients to identify outcomes most important to them. Phase 3: Online two-round Delphi survey to achieve consensus about which outcomes are most important. Phase 4: A consensus meeting to finalise the COS. METHODS: Phase 1: Systematic review of previously reported outcomes to identify potential core outcomes. Phase 2: Qualitative studies with patients to identify outcomes most important to them. Phase 3: Online two-round Delphi survey to achieve consensus about which outcomes are most important. Phase 4: A consensus meeting to finalise the COS. MAIN OUTCOME MEASURES: Outcome importance was assessed in the Delphi survey on a 9-point scale. RESULTS: From the ‘long list’ of 114, 10 outcomes were included in the final COS: subjective blood loss; flooding; menstrual cycle metrics; severity of dysmenorrhoea; number of days with dysmenorrhoea; quality of life; adverse events; patient satisfaction; number of patients going on to have further treatment for HMB and haemoglobin level. CONCLUSIONS: The final COS includes variables that are feasible for use in clinical trials in all resource settings and apply to all known underlying causes of the symptom of HMB. These outcomes should be reported in all future trials of interventions, their systematic reviews, and clinical guidelines to underpin policy

Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides

The potential use of antisense and siRNA oligonucleotides as therapeutic agents has elicited a great deal of interest. However, a major issue for oligonucleotide-based therapeutics involves effective intracellular delivery of the active molecules. In this Survey and Summary, we review recent reports on delivery strategies, including conjugates of oligonucleotides with various ligands, as well as use of nanocarrier approaches. These are discussed in the context of intracellular trafficking pathways and issues regarding in vivo biodistribution of molecules and nanoparticles. Molecular-sized chemical conjugates and supramolecular nanocarriers each display advantages and disadvantages in terms of effective and nontoxic delivery. Thus, choice of an optimal delivery modality will likely depend on the therapeutic context

The FAST-EU trial: 12-month clinical outcomes of women after intrauterine sonography-guided transcervical radiofrequency ablation of uterine fibroids: Gynecological Surgery

The FAST-EU Trial was designed to establish the effectiveness and confirm the safety of transcervical intrauterine sonography-guided radiofrequency ablation with the VizAblate (TM) System in the treatment of symptomatic uterine fibroids. This was a multicenter, prospective, single-arm trial involving academic and community hospitals in the United Kingdom, the Netherlands, and Mexico. Women with qualifying uterine fibroids and heavy menstrual bleeding underwent intrauterine sonography-guided transcervical radiofrequency ablation (RFA) with the VizAblate System; anesthesia was individualized. Patients were required to have up to five fibroids from 1 to 5 cm in diameter. The primary trial endpoint was the percentage change in perfused fibroid volume, as assessed by contrast-enhanced MRI at 3 months by an independent core laboratory. Secondary endpoints, evaluated at 6 and 12 months, included safety, percentage reductions in the Menstrual Pictogram (MP) score, and the Symptom Severity Score (SSS) subscale of the Uterine Fibroid Symptom-Quality of Life (UFS-QOL) questionnaire, along with the rate of surgical reintervention for abnormal uterine bleeding and the mean number of days to return to normal activity. Additional assessments included the Health-Related Quality of Life (HRQOL) subscale of the UFS-QOL, nonsurgical reintervention for abnormal uterine bleeding, anesthesia regimen, patient satisfaction, and pain during the recovery period. An additional MRI study was performed at 12 months on a subgroup of patients. Fifty patients (89 fibroids) underwent transcervical radiofrequency ablation with the VizAblate System. At 3 and 12 months, perfused fibroid volumes were reduced from baseline by an average of 68.1 +/- 28.6 and 67.4 +/- 31.9 %, respectively, while total fibroid volumes were reduced from baseline by an average of 54.7 +/- 37.4 and 66.6 +/- 32.1 %, respectively (all P <.001 compared with baseline; Wilcoxon signed-rank test). At 12 months, mean MP score and SSS decreased by 53.8 +/- 50.5 and 55.1 +/- 41.0 %, respectively; the mean HRQOL score increased by 277 +/- 483 %. There were four surgical reinterventions (8 %) within 12 months. This is the first report of the 12-month follow-up for patients in the FAST-EU Trial. In concert with previously reported 3- and 6-month endpoint data, the 12-month results of the FAST-EU Trial suggest that in addition to substantially reducing the perfused and total volume of targeted uterine fibroids, the VizAblate System is safe and effective through 12 months in providing relief of abnormal uterine bleeding associated with submucous, intramural, and transmural fibroids

Correlation of Reductions in Perfused Fibroid Volume With Subsequent Reductions in Total Fibroid Volume After Transcervical Radiofrequency Ablation

Study Objective To determine if the extent of fibroid ablation, as reflected in a decrease in perfused fibroid volume three months after treatment, correlates with a reduction in total fibroid volume at 12 months. Design Prospective, longitudinal, multicenter, single-arm trial. Setting Academic and community hospitals in the United Kingdom, The Netherlands and Mexico. Patients 27 women with heavy menstrual bleeding secondary to fibroids. Intervention Radiofrequency ablation guided by built-in intrauterine sonography (the Sonata™ System). Measurements and Main Results The 27 patients had a total of 42 fibroids that were ablated. Contrast-enhanced MRI was used to determine the perfused and total fibroid volumes at baseline, at 3 months post-treatment and again at 12 months post-treatment. All MRI measurements were performed at a single core laboratory (MedQIA, Los Angeles, USA). Using a least squares method for linear regression, the change in total fibroid volume at 12 months as a function of the change in perfused fibroid volume at 3 months was found to have a correlation coefficient (R2) of 0.7518. The linear equation describing this relationship was y = 0.9919x + 0.0052. Conclusion There is a positive correlation between the reduction in perfused fibroid volume noted on contrast-enhanced MRI at 3 months after transcervical radiofrequency ablation and the reduction in total fibroid volume at 12 months. Thus, as larger portions of a fibroid are ablated, there will tend to be a greater reduction in total fibroid volume at 1 year

Correlation of Reductions in Perfused Fibroid Volume With Subsequent Reductions in Total Fibroid Volume After Transcervical Radiofrequency Ablation

Study Objective To determine if the extent of fibroid ablation, as reflected in a decrease in perfused fibroid volume three months after treatment, correlates with a reduction in total fibroid volume at 12 months. Design Prospective, longitudinal, multicenter, single-arm trial. Setting Academic and community hospitals in the United Kingdom, The Netherlands and Mexico. Patients 27 women with heavy menstrual bleeding secondary to fibroids. Intervention Radiofrequency ablation guided by built-in intrauterine sonography (the Sonata™ System). Measurements and Main Results The 27 patients had a total of 42 fibroids that were ablated. Contrast-enhanced MRI was used to determine the perfused and total fibroid volumes at baseline, at 3 months post-treatment and again at 12 months post-treatment. All MRI measurements were performed at a single core laboratory (MedQIA, Los Angeles, USA). Using a least squares method for linear regression, the change in total fibroid volume at 12 months as a function of the change in perfused fibroid volume at 3 months was found to have a correlation coefficient (R2) of 0.7518. The linear equation describing this relationship was y = 0.9919x + 0.0052. Conclusion There is a positive correlation between the reduction in perfused fibroid volume noted on contrast-enhanced MRI at 3 months after transcervical radiofrequency ablation and the reduction in total fibroid volume at 12 months. Thus, as larger portions of a fibroid are ablated, there will tend to be a greater reduction in total fibroid volume at 1 year