Table 2.
Table of contents and resources
| SPIRIT-PRO item no. | Item title | SPIRIT-PRO extension or elaboration item description | Page number of example/explanation |
| 5a | SPIRIT5a-PRO Elaboration | Specify the individual(s) responsible for the PRO content of the trial protocol. | 11–12 |
| 6a | SPIRIT6a-PRO Extension | Describe the PRO-specific research question and rationale for PRO assessment and summarise PRO findings in relevant studies. | 12 |
| 7 | SPIRIT7-PRO Extension | State-specific PRO objectives or hypotheses (including relevant PRO concepts/domains). | 12–14 |
| 10 | SPIRIT10-PRO Extension | Specify any PRO-specific eligibility criteria (eg, language/reading requirements or prerandomisation completion of PRO). If PROs will not be collected from the entire study sample, provide a rationale and describe the method for obtaining the PRO subsample. | 14 |
| 12 | SPIRIT12-PRO Extension | Specify the PRO concepts/domains used to evaluate the intervention (eg, overall health-related quality of life, specific domain, specific symptom) and, for each one, the analysis metric (eg, change from baseline, final value, time to event) and the principal timepoint or period of interest. | 14–16 |
| 13 | SPIRIT13-PRO Extension | Include a schedule of PRO assessments, providing a rationale for the timepoints and justifying if the initial assessment is not prerandomisation. Specify time-windows, whether PRO collection is prior to clinical assessments, and, if using multiple questionnaires, whether order of administration will be standardised. | 16–17 |
| 14 | SPIRIT14-PRO Elaboration | When a PRO is the primary endpoint, state the required sample size (and how it was determined) and recruitment target (accounting for expected loss to follow-up). If sample size is not established based on the PRO endpoint, then discuss the power of the principal PRO analyses. | 17–19 |
| 18a | SPIRIT-18a (i)-PRO Extension | Justify the PRO instrument to be used and describe domains, number of items, recall period and instrument scaling and scoring (eg, range and direction of scores indicating a good or poor outcome). Evidence of PRO instrument measurement properties, interpretation guidelines and patient acceptability and burden should be provided or cited if available, ideally in the population of interest. State whether the measure will be used in accordance with any user manual and specify and justify deviations if planned. | 19–20 |
| SPIRIT-18a (ii)-PRO Extension | Include a data collection plan outlining the permitted mode(s) of administration (eg, paper, telephone, electronic, other) and setting (eg, clinic, home, other). | 20–21 | |
| SPIRIT-18a (iii)-PRO Extension | Specify whether more than one language version will be used and state whether translated versions have been developed using currently recommended methods. | 21–22 | |
| SPIRIT-18a (iv)-PRO Extension | When the trial context requires someone other than a trial participant to answer on his or her behalf (a proxy-reported outcome), state and justify the use of a proxy respondent. Provide or cite evidence of the validity of proxy assessment if available. | 22–23 | |
| 18b | SPIRIT-18b (i)-PRO Extension | Specify PRO data collection and management strategies for minimising avoidable missing data. | 23–24 |
| SPIRIT-18b (ii)-PRO Elaboration | Describe the process of PRO assessment for participants who discontinue or deviate from the assigned intervention protocol. | 24–25 | |
| 20a | SPIRIT-20a-PRO Elaboration | State PRO analysis methods, including any plans for addressing multiplicity/type I (α) error. | 25–26 |
| 20c | SPIRIT-20c-PRO Elaboration | State how missing data will be described and outline the methods for handling missing items or entire assessments (eg, approach to imputation and sensitivity analyses). | 26–27 |
| 22 | SPIRIT-22-PRO Extension | State whether or not PRO data will be monitored during the study to inform the clinical care of individual trial participants and, if so, how this will be managed in a standardised way. Describe how this process will be explained to participants; for example, in the participant information sheet and consent form. | 27–29 |
| Additional resources | |||
| Table 1. SPIRIT 2013 and SPIRIT-PRO Extension checklist: recommended items to address in a clinical trial protocol | 3–8 | ||
| Glossary of terms | 10–11 | ||
| Protocol template | Online supplemental file 2 | ||
PRO, patient-reported outcome; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials.