Developing a guideline for clinical trial protocol content: Delphi consensus survey

Tetzlaff et al. Trials 2012, 13:176 http://www.trialsjournal.com/content/13/1/176 TRIALS RESEARCH Open Access Developing a guideline for clinical trial protocol content: Delphi consensus survey Jennifer Marie Tetzlaff1*, David Moher1,2 and An-Wen Chan3 Abstract Background: Recent evidence has highlighted deficiencies in clinical trial protocols, having implications for many groups. Existing guidelines for randomized clinical trial (RCT) protocol content vary substantially and most do not describe systematic methodology for their development. As one of three prespecified steps for the systematic development of a guideline for trial protocol content, the objective of this study was to conduct a three-round Delphi consensus survey to develop and refine minimum content for RCT protocols. Methods: Panellists were identified using a multistep iterative approach, met prespecified minimum criteria and represented key stakeholders who develop or use clinical trial protocols. They were asked to rate concepts for importance in a minimum set of items for RCT protocols. The main outcome measures were degree of importance (scale of 1 to 10; higher scores indicating higher importance) and level of consensus for items. Results were presented as medians, interquartile ranges, counts and percentages. Results: Ninety-six expert panellists participated in the Delphi consensus survey including trial investigators, methodologists, research ethics board members, funders, industry, regulators and journal editors. Response rates were between 88 and 93% per round. Overall, panellists rated 63 of 88 concepts of high importance (of which 50 had a 25th percentile rating of 8 or greater), 13 of moderate importance (median 6 or 7) and 12 of low importance (median less than or equal to 5) for minimum trial protocol content. General and item-specific comments and subgroup results provided valuable insight for further discussions. Conclusions: This Delphi process achieved consensus from a large panel of experts from diverse stakeholder groups on essential content for RCT protocols. It also highlights areas of divergence. These results, complemented by other empirical research and consensus meetings, are helping guide the development of a guideline for protocol content. Keywords: Randomized controlled trials, Delphi consensus survey, SPIRIT Initiative, Protocols, Clinical trials, Reporting guideline Background The protocol of a randomized clinical trial (RCT) serves many purposes. Protocols provide investigators with a document to guide trial conduct; trial participants with a detailed description of trial methodology; research ethics committees/institutional review boards (REC/IRBs) with a foreknowledge of predefined safeguards to protect participants’ interests and safety; research funders with a means of assessing proposed methods; and systematic * Correspondence: 1 Ottawa Methods Centre, Clinical Epidemiology Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada Full list of author information is available at the end of the article reviewers and others with a description of prespecified methods to evaluate potential biases [1-8]. To fulfill these purposes, protocols must be clear, detailed and transparent. Unfortunately, many protocols do not adequately describe important methodological details such as allocation concealment (59%) [9], primary outcomes (25%) [1], power calculations (27%) [3] and sponsor and investigators’ roles in aspects of trial conduct [10] - all of which have been associated with exaggerated effect sizes and potential bias in trials. The lack of transparency and incomplete description of methods makes critical assessment of trials difficult. © 2012 Tetzlaff et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tetzlaff et al. Trials 2012, 13:176 http://www.trialsjournal.com/content/13/1/176 Reporting guidelines have been developed to help improve deficiencies in research reports [11-18]. A recent systematic review examined 40 guidelines for trial protocols; only 20% included any description of their methodological development process. Of those reporting consensus methods, none described formal processes for achieving consensus among stakeholders (for example Nominal consensus technique, Delphi consensus) and none described a systematic consideration of empirical evidence for guideline development [19]. Additionally, recommendations differed considerably across guidelines and many did not include concepts supported by empirical evidence. These inconsistencies and deficiencies have implications for those preparing, using, and reviewing clinical trial protocols. An international group of researchers launched the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Initiative in 2007, with the primary aim of increasing the transparency and completeness of trial protocols. The main product of this initiative is a checklist of key items to address in protocols of clinical trials. This guideline is being developed with systematic and transparent methodology. In line with current recommendations [20], three complementary methods were specified a priori to develop the SPIRIT checklist: 1) a Delphi consensus survey involving key expert stakeholders in the development and use of clinical trial protocols; 2) a systematic review of empirical evidence supporting the importance of specific checklist items; and 3) face-to-face consensus meetings to develop and finalize the SPIRIT Statement and its associated explanatory document. This paper describes in detail the first component of this research. Methods The objective of this study was to develop and refine minimum content for RCT protocols by expert consensus. We conducted a three-round electronic Delphi survey. Ethics approval was obtained through the Children’s Hospital of Eastern Ontario. Selection of participants Invited expert panellists represented the main stakeholders involved in clinical trials: investigators, methodologists, statisticians and senior study coordinators from academia, pharmaceutical industry and government; REC/IRB members; members of funding and regulatory agencies; and major healthcare journal editors. Experts had to meet the following predefined criteria [21]: relevant knowledge and experience; capacity, willingness and sufficient time to participate; and ability to communicate effectively in English. Participants were selected based on expertise and, where possible, were ranked and selected according to objective criteria Page 2 of 10 (trialists were required to be an author on a minimum of five English-language RCT publications over the past 10 years). We identified potential panellists us (...truncated)