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Objectives: The objective of this study was to evaluate the extent, type, and severity of spin in randomized controlled trials (RCTs) in obstetrics and gynecology. Data Sources: The top five highest impact journals in obstetrics and gynecology were systematically searched for RCTs with non-significant primary outcomes published between January 1, 2019, and December 31, 2020. Methods: Study selection and data extraction assessment were conducted independently and in duplicate. The extent, type, and severity of spin was identified and reported with previously established methodology, and risk of bias was assessed with the Cochrane Risk-of-Bias 2 Tool independently and in duplicate. Fisher's exact tests were used to evaluate the association between study characteristics, risk of bias, and spin. Results: We identified 1475 publications, of which 59 met our inclusion criteria. Articles evaluated interventions in obstetrics (n = 37, 63%) and gynecology (n = 22, 37%). Spin was not detected in 28 (47%) of the articles: Three (5%) had one, 10 (17%) had two, and 18 (31%) had greater than two occurrences of spin. Compared with articles where no spin was detected, spin was associated with the Cochrane Risk-of-Bias domain pertaining to missing data (p < 0.05). No association was observed with the journal, funding source, number of authors, types of interventions, and whether the study involved gynecology or obstetrics. Conclusions: Spin was detected in nearly half of 1:1 parallel two-arm RCTs in obstetrics and gynecology, highlighting the need for caution in the interpretation of RCT findings, particularly when the primary outcome is nonsignificant.
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BACKGROUND: A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25 × 106 cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. METHODOLOGY/PRINCIPAL FINDINGS: Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 106 or 2.5 × 106 cells from 13 weeks of age. A third, pre-symptomatic, group received 106 cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 106 cells pre-symptomatically or 2.5 × 106 cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies.
