RESUMEN
Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete. Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances. Evidence: A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders. Findings: The rapid review yielded 41â¯673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses. Conclusions and Relevance: CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.
Asunto(s)
COVID-19 , Guías como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Informe de Investigación/normas , Protocolos Clínicos , Técnica Delphi , Humanos , Edición/normas , Encuestas y CuestionariosRESUMEN
Repeated stimulation of the laryngeal mucosa occurs during speech. Single stimuli, however, can elicit the laryngeal adductor response (LAR). Our hypothesis was that the LAR to repeated rapid air pressure stimuli is centrally suppressed in humans. Hooked-wire electrodes were inserted into the thyroarytenoid and cricothyroid muscles on both sides and into the posterior cricoarytenoid muscle on one side. Pairs of air puff stimuli were presented to the mucosa over the arytenoids at pressure levels three times threshold with interstimulus intervals from 250 to 5,000 ms. Bilateral thyroarytenoid responses occurred at around 150 ms to more than 70% of the initial stimuli. With repeated presentation at intervals of 2 seconds or less, the percent occurrence decreased to less than 40% and response amplitudes were reduced by 50%. Central suppression of adductor responses to repeated air puff stimuli may allow speakers to produce voice without eliciting reflexive spasms that could disrupt speech.