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Guidelines for randomized clinical trial protocol content: a systematic review

Jennifer M Tetzlaff1*, An-Wen Chan2, Jessica Kitchen2, Margaret Sampson3, Andrea C Tricco4 and David Moher1

Author Affiliations

1 Ottawa Methods Centre, Ottawa Hospital Research Institute, Smyth Road, Ottawa, Ontario, K1H 8L6, Canada

2 Department of Medicine, Women’s College Research Institute, University of Toronto, Bay Street, Toronto, Ontario, M5G 1N8, Canada

3 Library Services, Children's Hospital of Eastern Ontario, Smyth Road, Ottawa, Ontario, K1H 8L1, Canada

4 Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Bond Street, Toronto, Ontario, M5B 1W8, Canada

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Systematic Reviews 2012, 1:43  doi:10.1186/2046-4053-1-43

Published: 24 September 2012



All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations.


We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement.


Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a minority of guidelines.


Existing guidelines for RCT protocol content varied substantially in their recommendations. Few reports described the methods of guideline development, limiting comparisons of guideline validity. Given the importance of protocols to diverse stakeholders, we believe a systematically developed, evidence-informed guideline for clinical trial protocols is needed.

Randomized controlled trials; Systematic review; Protocols; Clinical trials; Reporting guideline; SPIRIT initiative