Table 1

User-friendly version of the SPIRIT-PRO Extension guidance

SPIRIT-PRO item number and description	Questions for PPI partner(s) to consider	Key considerations for PPI partner(s)	Considerations for the lay summary	Considerations for participant information sheet and consent form
Administrative information
SPIRIT-5a-PRO Elaboration: specify the individual(s) responsible for the PRO content of the trial protocol	Are PPI partners being involved in the codesign of trials involving PROs? (Are they patients or carers; are there different considerations?)	PPI partners who have made a significant contribution to the trial protocol should be acknowledged.16
		Specify PPI partner role: coapplicant, trial management group or coproduction.
Introduction
SPIRIT-6a-PRO Elaboration: describe the PRO-specific research question and rationale for PRO assessment and summarise PRO findings in relevant studies	Is the research team collecting PROs? If not, why not?	PPI partners can help to prioritise research questions.	Has the research team looked at the literature around previous trials, qualitative work or COS (core outcome sets) on what matters to the patient (or carer)?	Describe the PRO specific research question and rationale for PRO assessment, and summarise PRO findings in relevant studies.
	If yes, do the team have a clear reason for assessing PROs in the trial?	What is the purpose of collecting the PRO data?
	Have the team specified their goals in assessing PROs?	Has the research team explained to you (and in the protocol) about the likely effect of treatment on participants’ symptoms, function and quality of life? If likely to be impacted by the intervention during the clinical trial.
		Can the clinical team draw a graph showing quality of life progression for standard care vs new treatment for the duration of the trial? Does this match your experience as patient (or carer)?
		What evidence do they have to support this?
SPIRIT-7-PRO Elaboration: state specific PRO objectives or hypotheses (including relevant PRO concepts/domains)	Has the research team clearly stated the purpose of the research?	How do they plan to use the PRO data that they collect during and at the end of the trial? For instance, to inform clinical practice, inform future patient care and inform NICE (National Institute for Health and Care Excellence) policy or health economics.	It is important that lay summary clearly describe the purpose of assessing PROs in the trial.	Include the purpose of assessing PROs in the trial.
Methods: participants, interventions and outcomes
SPIRIT-10-PRO Elaboration: 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	Are there any specific reasons why a participant might not be able to complete the PRO questionnaire?	PPI partners can provide advice to the research team on whether patients (or carers) are likely to be able to complete PROs in the trial. For example, some may be unable to complete them because of poor literacy, language, communication difficulties. Because their condition, or cultural or cognition considerations.		Has data protection been taken into consideration if proxy completion is a possibility?
		Consider whether these participants need to be excluded from the PRO study or trial. Try to be as inclusive as possible
		It is important to consider that proxy completion (report of the patient health status by his/her carer or clinician or parents reporting on behalf of children) can be an option in some cases—please see SPIRIT-PRO 18a(iv) below.
SPIRIT-12-PRO Elaboration: 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 time point or period of interest	Has the team specified exactly what is going to be measured? How and when do they plan to do this? For example, physical function, pain and/or HRQL, etc.	PPI partners can work with the broader research team to help determine which PROs (eg, symptoms, side effects, aspects of functioning or mental health) patients or carers should report on and how often these will be assessed.		Include what questionnaire(s) are going to be completed during the trial.
SPIRIT-13-PRO Elaboration: include a schedule of PRO assessments, providing a rationale for the time points, 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	How often will participants be asked to complete the questionnaire(s)?	PPI partners can help determine whether the frequency of PRO assessments is likely to be feasible for patients or carers. If it is frequent is this likely to be a burden, and if so, will it cause drop out or failure to respond?		How often are the participants going to be asked to complete the questionnaire(s), when and with what deadlines?
		Is the time between assessment too long and likely to miss important events that matter to patients or carers?
		PPI partners can provide feedback on the most important time-points to collect PROs based on their own experience of the condition or treatment.
		How long will participants have to return the questionnaire? Is the timeframe too short—will participants have time to complete the PRO? Does it need to include a weekend?
		Will it coincide with clinic visits or will it take place another time (eg, diaries)?
		If trial participants are having tests at clinic or may receive news, try to complete PRO questionnaire before.
SPIRIT-14-PRO Elaboration: when a PRO is the primary end point, 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 end point, then discuss the power of the principal PRO analyses	Is the required number of participants feasible to recruit based on the population being assessed?	PPI partners are not expected to assess whether the sample size is adequate, but you may have views on whether people are likely to be interested in participating in the PRO aspects of the trial.
	Are the exclusion criteria too restrictive (ie, they are excluding too many people)?	If you see something in the protocol that patients or carers might not like then please raise this with the trial team as it may affect whether they have big enough numbers for their study.
	Are there cultural/age related/geography/frailty/language condition/working status reasons why people may not participate or may drop-out?
Methods: data collections, management and analysis
SPIRIT-18a(i)-PRO Elaboration: Justify the PRO instrument to be used and describe domains, number of items, recall period, 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	How did they select the questionnaire (eg, literature, PPI session)?	How appropriate and acceptable are the questionnaires?		Include how long is going to take to complete the questionnaire.
	Which questionnaire(s) are they considering using?	How long will it take to complete the questionnaire? Trial team should ask PPI partners to complete it to give an estimate.		Are there any questions, such as sexual function, which patients may not wish to answer and may result in missing data?
	Does it cover patient priorities?	What burden/issues/symptoms/side-effects/aspects of functioning or mental health are relevant in the context of the trial? Are these addressed in the questionnaire?		Specify the estimated time to complete each assessment, and discuss feasibility of assessment for the population.
	Are the instructions for completion of the questionnaire clear?	Is the recall/remember period (eg, 1 month or 7 days) appropriate for the condition? For instance, are symptoms stable over time or fluctuating daily (which may require more frequent assessment)?
	Can you understand the scoring categories? Are they properly explained and do they make sense?
SPIRIT-18a(ii)-PRO Elaboration: include a data collection plan outlining the permitted mode(s) of administration (eg, paper, telephone, electronic, other) and setting (eg, clinic, home, other)	Where, when and how will the PRO questionnaire be completed?	PPI partners can help determine the most convenient/practical method to collect PRO data.		Include a data collection plan outlining the permitted mode(s) of administration (eg, paper, telephone, electronic, other) and setting (eg, clinic, home, other).
		Where is it going to be collected for example, in clinic at home?
		Can participants complete on paper/electronically or both?
		Will all participants be able to do this?
		Have the team got back up plans for those who cannot complete the PRO in a particular way?
SPIRIT-18a(iii)-PRO Elaboration: specify whether more than 1 language version will be used and state whether translated versions have been developed using currently recommended methods	What languages are the chosen questionnaire(s) available?	Researchers to make PPI partners aware of the availability of PRO measures in other languages.
	Have they got questionnaires available for trial population?	Are there groups of the population that require a translated version?
		Have they costed for it?
		Are they following translation guidelines?
		These are the responsibilities of the trial team but PPI partners may be able to suggest ways of widening inclusivity.
SPIRIT-18a(iv)-PRO Elaboration: 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	Has the research team made clear whether it is possible for someone other than the patient to complete the questionnaire from the patient’s point of view?	Generally, in a trial we prefer to collect PROs directly from the patient as we want to know their views but sometimes a patient cannot complete the questionnaire (eg, if they have memory problems or become too ill). If you think patients may not be able to complete PROs in the trial flag this to the broader research team.		If it is permissible for another person to help the study participant complete the PROM, describe what type and level of assistance is acceptable.
		Other things that should be considered: carer reported outcomes.
	How will the team ensure that data collected is complete? So that it can be used to inform patient care.	PPI partners can help provide input on how to collect PRO data and strategies to ensure that participants complete questionnaires as they are scheduled (eg, reminders for patients, training for staff/patients).
Ideally researchers should have plans in place to ensure that participants complete questionnaires as they are scheduled	Can you think of any other ideas that may help promote completion?	Important to provide guidance on PRO completion.
		State why we need as complete data as possible and how it will be used, and where it will be reported (eg, publication).
SPIRIT-18b(ii)-PRO Elaboration: describe the process of PRO assessment for participants who discontinue or deviate from the assigned intervention protocol	Is there a plan for collecting data provided by patients who stop receiving the treatment under study (discontinue), or receive the treatment in a way other than planned (deviation)?	PPI partners can provide input into developing a process for patients that stop receiving treatment or receive treatment in a way different to planned. This should be linked back to the trial research question.
		Consider burden to patients and whether PRO completion is ethical.
SPIRIT-20a-PRO Elaboration: state PRO analysis methods, including any plans for addressing multiplicity/type I (α) error	What method has the research team selected to analyse the PRO data?	PPI partners are not expected to contribute in the selection of methods for addressing multiple testing. However, they could ask the team to explain what PRO analysis method has been chosen and why.
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)	How is the research team going to analyse the PRO data?	PPI partners are not expected to plan how data will be analysed, but can question the trial team about the methods that will be used to handle missing data.
	How will the team deal with missing data?
Monitoring
SPIRIT-22-PRO Elaboration: 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	Will questionnaire data be reviewed by the research or clinical team? If so, when? What happens if the PRO indicates patient deterioration or distress? Have the research team explained what sorts of scores would indicate distress or deterioration?	PPI partners can help develop the participant information sheet and consent form and any other process used to inform patients about how PRO data will be monitored during the study to inform the clinical care of individual trial participants.		What measures are in place to ensure patient distress or deterioration is identified, communicated to patient and dealt with it?
	How will participants be informed of this process? (ie, in the participant information sheet and consent form).	PPI partners can question the team about their plan to manage concerning levels of psychological distress or physical symptoms that might require an immediate response.		If data will not be clinically reviewed, how concerns are going to be dealt with by the clinical research team. For instance, mobile phone to support (emergency number) and what resources are there to support participants.
				Include detailed plans for regular feedback to participants via letter/newsletter on PRO aspect of study.

HRQL, Health-related quality of life; PPI, patient and public involvement; PRO, patient-reported outcome; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials.