for the CONSERVE Group 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 41 673 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.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Background COVID-19 frequently necessitates in-patient treatment and in-patient mortality is high. Less is known about the long-term outcomes in terms of mortality and readmissions following in-patient treatment. Aim The aim of this paper is to provide a detailed account of hospitalized COVID-19 patients up to 180 days after their initial hospital admission. Methods An observational study with claims data from the German Local Health Care Funds of adult patients hospitalized in Germany between February 1 and April 30, 2020, with PCR-confirmed COVID-19 and a related principal diagnosis, for whom 6-month all-cause mortality and readmission rates for 180 days after admission or until death were available. A multivariable logistic regression model identified independent risk factors for 180-day all-cause mortality in this cohort. Results Of the 8,679 patients with a median age of 72 years, 2,161 (24.9%) died during the index hospitalization. The 30-day all-cause mortality rate was 23.9% (2,073/8,679), the 90-day rate was 27.9% (2,425/8,679), and the 180-day rate, 29.6% (2,566/8,679). The latter was 52.3% (1,472/2,817) for patients aged ≥80 years 23.6% (1,621/6,865) if not ventilated during index hospitalization, but 53.0% in case of those ventilated invasively (853/1,608). Risk factors for the 180-day all-cause mortality included coagulopathy, BMI ≥ 40, and age, while the female sex was a protective factor beyond a fewer prevalence of comorbidities. Of the 6,235 patients discharged alive, 1,668 were readmitted a total of 2,551 times within 180 days, resulting in an overall readmission rate of 26.8%. Conclusions The 180-day follow-up data of hospitalized COVID-19 patients in a nationwide cohort representing almost one-third of the German population show significant long-term, all-cause mortality and readmission rates, especially among patients with coagulopathy, whereas women have a profoundly better and long-lasting clinical outcome compared to men.

No abstract