Stakeholders’ perspectives and experiences of patient and public involvement (PPI) in clinical trials in maternal and neonatal healthcare: protocol for a qualitative evidence synthesis

Background: Patient and public involvement (PPI) has the potential to improve the relevance of trial outcomes and improve participant recruitment within clinical trials. However, the literature on PPI approaches, outcomes, and attitudes towards PPI in specific clinical research areas is limited. We are interested to know the current approaches to and views of PPI within maternal and neonatal clinical trials, from the perspective and experience of involved stakeholders. Methods: A qualitative evidence synthesis (QES) of stakeholders’ perspectives and experiences of PPI will be conducted. Stakeholders will include any individual involved in maternal or neonatal clinical trials with experience of PPI in the area or who expresses their views on PPI. The electronic bibliographic databases CINAHL, MEDLINE, PsycINFO, EMBASE, Web of Science and the Maternity and Infant Care (OVID) will be searched from inception. Qualitative studies, mixed-methods studies where the qualitative data can be extracted independently, and surveys with open-ended qualitative questions, will be included. Aims: The QES seeks to explore stakeholders’, including PPI contributors, trial participants and guardians, and trial researchers, perspectives and experiences of PPI in maternal and neonatal clinical trials. Discussion: THE QES will provide an understanding of how PPI is understood, operationalised and experienced by stakeholders in maternal and neonatal clinical trials, with the aim of identifying good practice and areas for improvement. PROSPERO registration: CRD42023383878 (2 nd March 2023)


Introduction
'Patient and public involvement' (PPI) is defined as research being conducted with and by patients or members of the public, as opposed to research being solely conducted on these groups (Dudley et al., 2015b;Staley, 2009).The terminology of 'PPI' varies across countries, sometimes being referred to, for example, as 'consumer engagement' or 'public participation' (Dudley et al., 2015a;Molloy et al., 2019).
The inclusion of PPI in research is advocated for on pragmatic and ethical grounds (Bagley et al., 2016); pragmatically in that PPI has the potential to produce more relevant research (Bagley et al., 2016) and ethically by the belief that those affected by a condition or disease should be involved in research that impacts them (Crocker et al., 2015).Involving patients, their families, or other members of the public, can help identify critical gaps in the research (EFCNI, 2017), leading to improvements in what type of research is conducted and how.
While PPI is increasingly encouraged by health research funders (Dudley et al., 2015b;HRB, 2022), discrepancies can arise between the PPI activities detailed within funding applications and its actual implementation (Buck et al., 2014).Involvement can be tokenistic, particularly if PPI inclusion is viewed solely as a means to secure grant funding (Dudley et al., 2015b).This qualitative evidence synthesis (QES) is being conducted as part of a doctoral study on PPI activity within maternal and neonatal clinical trials.While studies have been conducted on public contributors' and researchers' experiences of PPI within clinical trials (Selman et al., 2021;South et al., 2016), to our knowledge, a QES specifically on stakeholders' perspectives of PPI within maternal or neonatal clinical trials has not been conducted.The objective of this QES is to synthesise the evidence of stakeholders' perceptions of PPI in maternal and neonatal clinical trials.

Inclusion criteria
The SPIDER tool was used to define the inclusion criteria for this QES (Cooke et al., 2012).
-Sample: Stakeholders in maternal or neonatal clinical trials who have experience of PPI or have expressed their views on PPI.These may include, although not necessarily limited to, trial participants, PPI contributors, and any member of the trial research team (e.g., principal investigators, research midwives/nurses, trial managers, and statisticians).
-Phenomenon of Interest: PPI recruitment and PPI activity at any stage of a maternal or neonatal clinical trial.
-Design: Published and unpublished primary qualitative research of any design.
-Evaluation: Themes representative of stakeholders' perceptions and experiences of PPI in maternal and neonatal clinical trials. -

Search strategy
With the assistance of a subject librarian, a search strategy of index terms and keywords was developed from two key concepts; clinical trials in maternal and neonatal health, and patient and public involvement (Table 1).The electronic bibliographic databases CINAHL, MEDLINE, PsycINFO, EMBASE, Web of Science, and Maternity and Infant Care (OVID) will be searched, with the search terms adapted for each database.Grey literature sources, such as GreyNet, will also be searched.
No restrictions on language or date will be applied; that is the databases will be searched from their date of inception to the date of the search.Although studies in any language will be included in the search, only English language studies will be

Amendments from Version 1
We made amendments to the protocol following helpful suggestions from two peer reviewers.In our inclusion criteria, we updated the definition of 'PPI contributor' to reflect a wider variety of people who are engaged in PPI.We updated information about our screening of retrieved citations to state we will conduct a pilot screening to ensure the inclusion criteria is concise and consistently applied.Two reviewers will assess a sample of title and abstracts in order to identify and resolve any differences between the reviewers' interpretations of the inclusion criteria before continuing the screening process.
We updated our section on data extraction for clarity about the extent of information we plan to extract from included studies, which will include any and all information relating to the individuals involved as PPI contributors, such as who was involved as a PPI contributor (for instance, whether the individual is a service user or a person with lived experience of a condition, etc.), the number of PPI contributors involved, at what stage PPI was conducted, types of involvement, and any other PPI information provided.
Any further responses from the reviewers can be found at the end of the article included in the QES.Searching all languages, however, will enable the reviewers to determine how many studies may be excluded based on language, and thus assess the extent of language bias as a potential limitation of the QES.
All retrieved citations will be exported to Endnote (version 20.5) where duplicates will be removed before the citations are transferred to Covidence for screening.Two reviewers will conduct a pilot of the screening process.A sample of titles and abstracts will be reviewed by both reviewers, who will then discuss with each other their interpretation of the inclusion criteria.This process will be conducted in order to ensure a shared understanding of the inclusion criteria when screening.Once the reviewers have reached agreement on the interpretation of the inclusion criteria, full screening of retrieved citations will commence.Screening will take place in two stages; title and abstract screening, and full text review.First, title and abstracts will be screened against the inclusion criteria by one reviewer (KH).A second reviewer (VS or DD) will screen 20% of the records on title and abstract, and the reviewers' assessments will be crosschecked for congruency.If reviewer congruency is <80%, based on AMSTAR 2's recommendation that at least 80% agreement should be achieved (Shea et al., 2007), all citations will be screened independently by two reviewers.Full text of records will be sourced and each record will be screened for inclusion/exclusion by at least two reviewers working independently.Any disagreements will be resolved through discussion until consensus is achieved.A record will be retained of reasons for exclusion of papers at full text review and reported in the final QES in a PRISMA flow diagram (Page et al., 2021).

Data extraction and analysis
One reviewer will extract data from all included studies, which a second reviewer will corroborate.A purposively designed data extraction form will be developed.Data extracted will include study design, aim of study, location and setting, year study was conducted, participant demographics, information on PPI and impact on trial design and outcomes (as described by stakeholders), and findings of experiences and views of PPI.The information on PPI that will be extracted will include information such as who was involved as a PPI contributor, the number of PPI contributors involved, stage and types of involvement, and any other information provided.
A thematic analysis will be undertaken, following the approach described by Thomas and Harden ( 2008) unless another method is more appropriate once the raw data have been assessed.This approach will involve generating codes from study findings (i.e., authors' interpretations and study participant verbatim quotes) extracted from the included studies.These codes will then be grouped into descriptive categories, followed by the researchers generating new analytical themes from these descriptive categories (Thomas & Harden, 2008).In order to enhance the trustworthiness of the findings (Barrett et al., 2020), a reflexive approach will be undertaken throughout this QES.Research diaries will be used to document the process and formation of themes, as well as regular discussions between all three reviewers.

Methodological quality assessment
The twelve-item assessment criteria checklist by Thomas et al. (2003) will be used to assess the methodological quality of the included studies.The tool is widely used for assessing the methodological quality of qualitative research.Two reviewers will independently assess the quality of each included study.Consensus will be reached through discussion or through assessment by a third reviewer, if required.Studies will not be excluded from the review based on judgements of low methodological quality, rather this information will be reported in the findings and highlighted in the discussion, as appropriate.
In addition to a quality assessment, the GRIPP2 short form checklist (GRIPP2-SF) will be utilised to evaluate the reporting of PPI in included studies (Staniszewska et al., 2017).The GRIPP2 checklists, available in both long-and short-form versions, were developed to strengthen the quality of PPI reporting (Staniszewska et al., 2017).

Assessing the findings
The GRADE-CERQual (Confidence in the Evidence from Review of Qualitative Research) assessment will be used to assess and summarise confidence in the review findings (Lewin et al., 2018).

Study status
The protocol has been registered on PROSPERO, and the search strategy developed (Table 1).The search strategy will be implemented on publication and approval of this protocol.

Discussion
To our knowledge, this is the first QES on stakeholders' experiences and perceptions of PPI within clinical trials in neonatal and maternal healthcare.First, I suggest the authors consider the variety of people who might be part of PPI: individuals who can reflect on their own experience or expectations; and advocates who are well informed by networks of patients and/ or the wider public about a variety of experiences and expectations.I would anticipate the involvement of these different groups suiting different specific purposes and methods for involvement.

Sandy Oliver
Second, I suggest the authors revisit the procedures for screening search outputs.Their current plans for one reviewer to screen titles and abstracts, followed by a second reviewer screening 20% of titles and abstracts suits the purpose of checking accuracy -the usual purpose for this exercise in effectiveness reviews.However, much of this work involves interpretation.I recommend both reviewers screening independently a small set of titles and abstracts then comparing and discussing any discrepancies so they can understand how they have interpreted the text differently.Taking those different interpretations into account, the definitions and screening guidelines can then be refined to more accurate reflect the concepts of interest in the eligibility criteria.This can be repeated with another small set of titles and abstracts until the reviewers are satisfied that they have clearly expressed and consistently applied their eligibility criteria.
At the data extraction stage, I recommend extracting data about the types of individuals involved in the role of patients or the public.
The protocol states that 'The GRADE-CERQual (Confidence in the Evidence from Review of Qualitative Research) assessment will be used to assess and summarise confidence in the review findings'.This statement would be clearer if 'findings' were replaced by 'analytical themes' or 'synthesis statements'.
Generally the authors make good use of standardised tools for research synthesis.
I look forward to reading the resulting synthesis.
Is the rationale for, and objectives of, the study clearly described?Yes

Is the study design appropriate for the research question? Yes
Are sufficient details of the methods provided to allow replication by others?Yes Are the datasets clearly presented in a useable and accessible format?
Is the rationale for, and objectives of, the study clearly described?Yes

Is the study design appropriate for the research question? Yes
Are sufficient details of the methods provided to allow replication by others?Yes Are the datasets clearly presented in a useable and accessible format?

Not applicable
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Maternal nutrition and health, including PPI with service users and midwives.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
Social Research Institute, University College London, London, England, UK This planned qualitative evidence synthesis (QES) will address the important topic of stakeholders' perspectives and experiences of PPI.The key concepts (stakeholders and PPI) are clearly defined.The methods proposed are well established.I have a couple of suggestions to strengthen the work.