SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials

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Abstract

High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol.

This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available ( www.spirit-statement.org).

The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders.

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Long Term Outcomes Following Hospital Admission for Sepsis Using Relative Survival Analysis: A Prospective Cohort Study of 1,092 Patients with 5 Year Follow Up

Joshua Davis, Vincent He, Nicholas Anstey … (2014)

Background Sepsis is a leading cause of death in intensive care units and is increasing in incidence. Current trials of novel therapeutic approaches for sepsis focus on 28-day mortality as the primary outcome measure, but excess mortality may extend well beyond this time period. Methods We used relative survival analysis to examine excess mortality in a cohort of 1,028 patients admitted to a tertiary referral hospital with sepsis during 2007–2008, over the first 5 years of follow up. Expected survival was estimated using the Ederer II method, using Australian life tables as the reference population. Cumulative and interval specific relative survival were estimated by age group, sex, sepsis severity and Indigenous status. Results Patients were followed for a median of 4.5 years (range 0–5.2). Of the 1028 patients, the mean age was 46.9 years, 52% were male, 228 (22.2%) had severe sepsis and 218 (21%) died during the follow up period. Mortality based on cumulative relative survival exceeded that of the reference population for the first 2 years post admission in the whole cohort and for the first 3 years in the subgroup with severe sepsis. Independent predictors of mortality over the whole follow up period were male sex, Indigenous Australian ethnicity, older age, higher Charlson Comorbidity Index, and sepsis-related organ dysfunction at presentation. Conclusions The mortality rate of patients hospitalised with sepsis exceeds that of the general population until 2 years post admission. Efforts to improve outcomes from sepsis should examine longer term outcomes than the traditional primary endpoints of 28-day and 90-day mortality.

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Preparation of Artificial Plasma Membrane Mimicking Vesicles with Lipid Asymmetry

Qingqing Lin, Erwin London (2014)

Lipid asymmetry, the difference in lipid distribution across the lipid bilayer, is one of the most important features of eukaryotic cellular membranes. However, commonly used model membrane vesicles cannot provide control of lipid distribution between inner and outer leaflets. We recently developed methods to prepare asymmetric model membrane vesicles, but facile incorporation of a highly controlled level of cholesterol was not possible. In this study, using hydroxypropyl-α-cyclodextrin based lipid exchange, a simple method was devised to prepare large unilamellar model membrane vesicles that closely resemble mammalian plasma membranes in terms of their lipid composition and asymmetry (sphingomyelin (SM) and/or phosphatidylcholine (PC) outside/phosphatidylethanolamine (PE) and phosphatidylserine (PS) inside), and in which cholesterol content can be readily varied between 0 and 50 mol%. We call these model membranes “artificial plasma membrane mimicking” (“PMm”) vesicles. Asymmetry was confirmed by both chemical labeling and measurement of the amount of externally-exposed anionic lipid. These vesicles should be superior and more realistic model membranes for studies of lipid-lipid and lipid-protein interaction in a lipid environment that resembles that of mammalian plasma membranes.

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Outcomes in Patients with Acute and Stable Coronary Syndromes; Insights from the Prospective NOBORI-2 Study

Farzin Fath-Ordoubadi, Erik Spaepen, Magdi El-Omar … (2014)

Background Contemporary data remains limited regarding mortality and major adverse cardiac events (MACE) outcomes in patients undergoing PCI for different manifestations of coronary artery disease. Objectives We evaluated mortality and MACE outcomes in patients treated with PCI for STEMI (ST-elevation myocardial infarction), NSTEMI (non ST-elevation myocardial infarction) and stable angina through analysis of data derived from the Nobori-2 study. Methods Clinical endpoints were cardiac mortality and MACE (a composite of cardiac death, myocardial infarction and target vessel revascularization). Results 1909 patients who underwent PCI were studied; 1332 with stable angina, 248 with STEMI and 329 with NSTEMI. Age-adjusted Charlson co-morbidity index was greatest in the NSTEMI cohort (3.78±1.91) and lowest in the stable angina cohort (3.00±1.69); P<0.0001. Following Cox multivariate analysis cardiac mortality was independently worse in the NSTEMI vs the stable angina cohort (HR 2.31 (1.10–4.87), p = 0.028) but not significantly different for STEMI vs stable angina cohort (HR 0.72 (0.16–3.19), p = 0.67). Similar observations were recorded for MACE (<180 days) (NSTEMI vs stable angina: HR 2.34 (1.21–4.55), p = 0.012; STEMI vs stable angina: HR 2.19 (0.97–4.98), p = 0.061. Conclusions The longer-term Cardiac mortality and MACE were significantly worse for patients following PCI for NSTEMI even after adjustment of clinical demographics and Charlson co-morbidity index whilst the longer-term prognosis of patients following PCI STEMI was favorable, with similar outcomes as those patients with stable angina following PCI.

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Author and article information

Contributors

: Role: Phelan scientist

: Role: research coordinator

: Role: professor and director

: Role: programme associate

: Role: vice president, epidemiology

: Role: professor and director

: Role: senior researcher

: Role: distinguished scientist

: Role: associate professor

: Role: adjunct professor

: Role: professor

: Role: senior scientist

Journal

Journal ID (nlm-ta): BMJ

Journal ID (iso-abbrev): BMJ

Journal ID (publisher-id): bmj

Title: BMJ : British Medical Journal

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1756-1833

Publication date Collection: 2013

Publication date (Print): 2013

Publication date (Electronic): 9 January 2013

Volume: 346

Electronic Location Identifier: e7586

Affiliations

[1 ]Women’s College Research Institute at Women’s College Hospital, Department of Medicine, University of Toronto, Toronto, Canada, M5G 1N8

[2 ]Ottawa Methods Centre, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada

[3 ]Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark

[4 ]Centre for Statistics in Medicine, University of Oxford, Oxford, UK

[5 ]Division of Medical Ethics and Humanities, University of Utah School of Medicine, Salt Lake City, USA

[6 ]Janssen Research and Development, Titusville, USA

[7 ]Center for Clinical Trials, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA

[8 ]Quantitative Sciences, FHI 360, Research Triangle Park, USA

[9 ]NCIC Clinical Trials Group, Cancer Research Institute, Queen’s University, Kingston, Canada

[10 ]Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada

[11 ]Keenan Research Centre at the Li Ka Shing Knowledge Institute of St Michael’s Hospital, Faculty of Medicine, University of Toronto, Toronto, Canada

Author notes

Correspondence to: A-W Chan anwen.chan@ 123456utoronto.ca

Article

Publisher ID: chaa006386

DOI: 10.1136/bmj.e7586

PMC ID: 3541470

PubMed ID: 23303884

SO-VID: 39a34178-1f45-4b3b-8693-117e84b39f15

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

History

Date accepted : 04 October 2012

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SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials

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JMIR: Research Protocols

Most cited references 294

Long Term Outcomes Following Hospital Admission for Sepsis Using Relative Survival Analysis: A Prospective Cohort Study of 1,092 Patients with 5 Year Follow Up

Preparation of Artificial Plasma Membrane Mimicking Vesicles with Lipid Asymmetry

Outcomes in Patients with Acute and Stable Coronary Syndromes; Insights from the Prospective NOBORI-2 Study

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