Every clinical trial should be based on a protocol—a document that details the study rationale, proposed methods, organisation, and ethical considerations.1
Trial investigators and staff 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 often lack information on important concepts relating to study design and dissemination plans.2
Guidelines for writing protocols can help improve their completeness, but existing guidelines vary extensively in their content and have limitations, including non-systematic methods of development, limited stakeholder involvement, and lack of citation of empirical evidence to support their recommendations.13
As a result, there is also variation in the precise definition and scope of a trial protocol, particularly in terms of its relation to other documents such as procedure manuals.14
Given the importance of trial protocols, an international group of stakeholders launched the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Initiative in 2007 with the primary aim of improving the content of trial protocols. The main outputs are the SPIRIT 2013 Statement,14
consisting of a 33 item checklist of minimum recommended protocol items (table 1) plus a diagram (fig1); and this accompanying Explanation and Elaboration (E&E) paper. Additional information and resources are also available on the SPIRIT website (www.spirit-statement.org
SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol and related documents*
Fig 1 Example template for the schedule of enrolment, interventions, and assessments (recommended content can be displayed using other schematic formats)
The SPIRIT 2013 Statement and E&E paper reflect the collaboration and input of 115 contributors, including trial investigators, healthcare professionals, methodologists, statisticians, trial coordinators, journal editors, as well as representatives from research ethics committees, industry and non-industry funders, and regulatory agencies. Details of the scope and methods have been published elsewhere.13
Briefly, three complementary methods were specified beforehand,
in line with current recommendations for development of reporting guidelines16
: 1) a Delphi consensus survey15
; 2) two systematic reviews to identify existing protocol guidelines and empirical evidence supporting the importance of specific checklist items; and 3) two face-to-face consensus meetings to finalise the SPIRIT 2013 checklist. Furthermore, the checklist was pilot tested by graduate course students, and an implementation strategy was developed at a stakeholder meeting.
The SPIRIT recommendations are intended as a guide for those preparing the full protocol for a clinical trial. A clinical trial is a prospective study in which one or more interventions are assigned to human participants in order to assess the effects on health related outcomes. The recommendations are not intended to prescribe how a trial should be designed or conducted. Rather, we call for a transparent and complete description of what is intended, regardless of the characteristics or quality of the plans. The SPIRIT 2013 Statement addresses the minimum content for interventional trials; additional concepts may be important to describe in protocols for trials of specific designs (eg, crossover trials) or in protocols intended for submission to specific groups (eg, funders, research ethics committees/institutional review boards). If information for a recommended item is not yet available when the protocol is being finalised (eg, funding sources), this should be explicitly stated and the protocol updated as new information is obtained. Formatting conventions such as a table of contents, glossary of non-standard or ambiguous terms (eg, randomisation phase or off-protocol), and list of abbreviations and references will facilitate understanding of the protocol.