Flow of participants through each stage
13(a) Flow of participants through each stage (a diagram is strongly recommended).
Specifically, for each group report the numbers of participants randomly assigned, receiving intended treatment, completing the study protocol, and analyzed for the primary outcome.
Examples
Figure 1 - Flow diagram of a multicentre trial comparing implantation of
heparin-coated stents with percutaneous transluminal angioplasty
(PTCA). The diagram includes detailed information on the interventions
received. CABG = coronary artery bypass grafting. Adapted from Serruys
et al. (144):
Figure 2 - Flow diagram of a trial of chiropractic manipulation of the cervical
spine for treatment of episodic tension-type headache. The diagram
includes the number of patients actively followed up at different times
during the trial. Adapted from Bove and Nilsson (145). 
Figure 3 - Flow diagram of a trial of the topoisomerase I inhibitor irinotecan
in patients with metastatic colorectal cancer in whom fluorouracil
chemotherapy had failed. The diagram includes the results for the main
outcome (overall survival). Adapted from Cunningham et al. (146).
Explanation
The design and execution of some RCTs is straightforward, and the flow of participants through each phase of the study can be described adequately in a few sentences.In more complex studies, it may be difficult for readers to discern whether and why some participants did not receive the treatment as allocated, were lost to follow up, or were excluded from the analysis (54). This information is crucial for several reasons. Participants who were excluded after allocation are unlikely to be representative of all participants in the study. For example, patients may not be available for follow-up evaluation because they experienced an acute exacerbation of their illness or severe side effects (32, 141).
Attrition as a result of loss to follow up, which is often unavoidable, needs to be distinguished from investigator-determined exclusion for such reasons as ineligibility, withdrawal from treatment, and poor adherence to the trial protocol. Erroneous conclusions can be reached if participants are excluded from analysis, and imbalances in such omissions between groups may be especially indicative of bias (141-143). Information about whether the investigators included in the analysis all participants who underwent randomization, in the groups to which they were originally allocated, (intention-to-treat analysis, see also item 16), is therefore of particular importance. Knowing the number of participants who did not receive the intervention as allocated or did not complete treatment permits the reader to assess to what extent the estimated efficacy of therapy might be underestimated under ideal circumstances. If available, the number of persons assessed for eligibility should also be reported. Although this number is relevant to external validity only, and arguably less important than the other counts (55), it is a useful indicator of whether trial participants were likely to be representative of all eligible participants.
A recent review of RCTs published in five leading general and internal medicine journals in 1998 found that reporting of the flow of participants was often incomplete, particularly with regard to the number of participants receiving the allocated intervention and the number lost to follow up (54). Even information as basic as the number of participants who underwent randomization and the number excluded from analyses were not available in up to 20% of articles (54). Reporting was considerably more thorough in articles that included a diagram of the flow of participants through a trial, as recommended by CONSORT. This study informed the design of the revised flow diagram in the revised CONSORT statement (56-58). The suggested template is shown in Figure 4 and the counts required are described in detail in Table 5.
Figure 4 - Revised template of the CONSORT (Consolidated Standards of Reporting
Trials) diagram showing the flow of participants through each stage of
a randomized trial (202).
Table 5. Information required to document the flow of participants through each stage of a randomized, controlled trial
| Stage | Number of people included | Number of people not included or excluded | Rationale |
|---|---|---|---|
| Enrollment | People evaluated for potential enrollment | People who did not meet the inclusion criteria People who met the inclusion criteria but declined to be enrolled | These counts indicate whether trial participants were likely to be representative of all patients seen; they are relevant to assessment of external validity only, and they are often not available. |
| Randomization | Participants randomly assigned | Crucial count for defining trial size and assessing whether a trial has been analyzed by intention to treat | |
| Treatment allocation | Participants who received treatment as allocated, by study group | Participants who did not receive treatment as allocated, by study group | Important counts for assessment of internal validity and interpretation of results; reasons for not receiving treatment as allocated should be given. |
| Follow-up | Participants who completed treatment as allocated, by study group.
Participants who completed follow-up as planned, by study group |
Participants who did not complete treatment as allocated, by study group
Participants who did not complete follow-up as planned, by study group |
Important counts for assessment of internal validity and interpretation of results; reasons for not completing treatment or follow-up should be given |
| Analysis | Participants included in main analysis, by study group | Participants excluded from main analysis, by study group | Crucial count for assessing whether a trial has been analyzed by intention to treat; reasons for excluding participants should be given. |
Some of the information, such as the number of persons assessed for eligibility, may not always be known (14), and depending on the nature of a trial, some counts may be more relevant than others. It will therefore often be useful or necessary to adapt the structure of the flow diagram to a particular trial. For example, a multicenter trial compared implantation of heparin-coated stents with standard percutaneous transluminal angioplasty in patients scheduled to undergo coronary angioplasty (144). The nature of the intervention meant that a relatively large number of patients did not receive the allocated intervention. In the flow diagram (Figure 2) the box describing treatment allocation had to be expanded to reflect this.
In some situations, other information may usefully be added. For example, the flow diagram of a trial of chiropractic manipulation of the cervical spine in the treatment of episodic tension-type headache (145) showed the number of patients actively followed up at different times during the study (Figure 3). The main results, such as the number of events for the primary outcome, may sometimes also be added to the flow diagram. For example, the flow diagram of a trial of the topoisomerase I inhibitor irinotecan in patients with metastatic colorectal cancer in whom fluorouracil chemotherapy had failed (146) included the number of deaths (Figure 4).
These examples illustrate that the exact form and content of the flow chart may be varied according to specific features of a trial. For example, for many trials of surgery or vaccination do not include the possibility of discontinuation. Although CONSORT strongly recommends this graphical device to communicate participant flow throughout the study, there is no specific, prescribed format. Inclusion of a diagram may be unnecessary for simple trials without losses to follow up or exclusions.
Page last edited: 17 July 2007
