The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

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 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 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 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.Every clinical trial should be based on a protocol-a document that details the study rationale, proposed methods, organisation, and ethical considerations. Trial investigators and sta use protocols to document plans for study conduct at all stages from participant recruitment to results dissemination. Funding agencies, research ethics committees/institutional review boards, regulatory agencies, medical journals, systematic reviewers, and other groups rely on protocols to appraise the conduct and reporting of clinical trials.To meet the needs of these diverse stakeholders, protocols should adequately address key trial elements. However, protocols o en lack information on important concepts relating to study design and dissemination plans.-Guidelines for writing protocols can help improve their completeness, but existing guidelines vary extensively in their content and have limitations, including nonsystematic methods of development, limited stakeholder involvement, and lack of citation of empirical evidence to support their recommendations. As a result, there is also variation in the precise de nition and scope of a trial protocol, particularly in terms of its relation to other documents such as procedure manuals.Given the importance of trial protocols, an international group of stakeholders launched the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Initiative in with the primary aim of improving the content of trial protocols. The main outputs are the SPIRIT Statement, consisting of a item checklist of minimum recommended protocol items (table ) plus a diagram ( g ); and this accompanying Explanation and Elaboration (E&E) paper. Additional information and resources are also available on the SPIRIT website ( www.spirit-statement.org ).The SPIRIT Statement and E&E paper re ect the collaborat...

To our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.

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