We obtained research ethics approval from the ethics committees at the clinical institution at which the research is taking place (University Health Network, UHN REB 24–5397). For the survey part of the Objective 2’s priority setting process, research participants will provide an informed consent (S4 File), confirming that they: (1) understood the essential elements of the research, including risks and benefits, and (2) consent to participate. The ethics board waived the requirement for a signed consent form. For more details on the informed consent process, please refer to the priority setting process section of the protocol.

We will register this study on Open Science Framework (OSF) [24], a research project management tool to promote transparency in the research process. Our previously published systematic reviews [12, 13] are registered on PROSPERO (CRD42017055309, CRD42018098697). We created new registries for the updated reviews to reflect the substantial shift of focus to incorporate PROGRESS-Plus parameters in the present study. Protocols were registered on PROSPERO on May 17, 2024 (CRD42024547415, CRD42024547456). Reporting of this protocol followed PRISMA-P guidelines (S1 File).

We will follow the FAIR Guiding Principles [25], which state that research should be Findable, Accessible, Interoperable, and Reusable, to support replicability and transparency of the research process and maximize opportunity for further applications of data and data templates. To reduce costs and streamline our research process, we are exploring implementation of crowdsourcing [26], natural language processing and machine learning [27], and research/project management tools, such as the systematic review management tool Covidence [28].

This protocol was informed by input from patient and public representatives. We will follow best practices for patient and public involvement in research [29], enabling equitable and shared decision-making with people with lived experience and the public. We collaborated with partner organizations and people with lived experience during grant development and will continue to do so throughout the entire research process. Applying a knowledge-user feedback framework [29], current scientific evidence, and the team’s expertise, all concepts and ideas emerging in the research process will be documented and incorporated.

People with lived experience who are part of our research team (Table 1) will participate in bi-monthly team meetings, contributing to the research process and end-of-grant knowledge translation. Individuals with lived experience will present their unique perspectives and preferences, which we expect will facilitate operationalization of person-specific PROGRESS-Plus components and tailoring of knowledge translation materials for knowledge users. For the purposes of this research, a knowledge user is defined as “an individual who is likely to be able to use research results to make informed decisions about health policies, programs and/or practices” [30].

To incorporate a PROGRESS-Plus lens to the knowledge synthesis on TBI-induced cognitive changes and brain health outcomes, we will develop 1) metadata configurations; 2) templates to standardize data collection; and 3) protocols for data curation and upload. Our two previous systematic reviews on cognitive changes [12] and health- and function-related outcomes of persons with TBI of various injury severities [13] featured 36 and 58 studies, respectively. We will perform a full-text review of these studies to determine to what extent PROGRESS-Plus variables were considered by the authors. We will aggregate data with emphasis on PROGRESS-specific variables and organize the data in a repository that will serve as a template to facilitate further analysis (e.g., machine learning analyses, including classical and Bayesian meta-analysis, multi-level modeling, and AI-driven approaches).

The process of study selection, data management, extraction and synthesis, risk of bias assessment, and reporting will follow the methodology of our previous systematic reviews [12, 13] outlined in detail in the published protocols [31, 32]. Briefly, for the systematic review of cognitive changes [12], we included peer-reviewed, English language studies that assessed cognition by clinical diagnosis or standardized measure, targeted adult patients with a TBI determined by clinical evaluation, and followed them for any period of time. We excluded treated cohorts from studies of intervention efficacy for cognitive performance, utilizing data from untreated cohorts only. For the systematic review on health- and function-related outcomes [13], we included original peer-reviewed English language studies of all designs that (1) included adults with TBI diagnosis made by clinicians or specialists; (2) adequately described at least three key characteristics of their participants: age, sex, and severity of TBI; and (3) provided sex/gender-stratified results, taking into account at least age and TBI severity; or (4) included sex/gender or an interaction between sex and other variable(s) as a covariate in their statistical analysis of any TBI outcome, along with at least age and TBI severity; or (5) qualitatively discussed implications of sex/gender on TBI outcomes, considering age and injury severity. For this systematic review, we excluded studies that (1) did not specify how a TBI diagnosis was made; (2) focused on TBI itself as an outcome; (3) compared TBI samples with other clinical populations without evaluating the effect of sex/gender in TBI separately; or (4) focused on sports-related concussion. We excluded studies on sports-related concussion to avoid redundancy due to other published systematic reviews on the topic [33–35]. Case reports, paediatric studies, dissertations, articles with no primary data, single-sex studies, studies that did not consider TBI severity and age were excluded from both systematic reviews.

In our previous review on cognitive changes, we focused on five domains of cognitive functioning: recent memory, language, visuo-spatial ability, executive function, and information processing speed. For the update, we will include an additional category of social cognition [36]. For the review on health- and function-related outcomes, we considered the following categories: mortality, structural/physiological, care, medical, psychiatric disorders, sleep-related, cognitive functioning, functional outcome, disability, social participation, work-related, and life satisfaction. For the update on the reviews, we will exclude categories that do not fall within the construct of brain health, as defined by global organizations [7] and subsequently rated by research team members. The working definition of brain health prioritized by the team is “state of brain function across cognitive, sensory, socio-emotional, behavioural, and motor domains” [37] (S1 Table and S1 Fig). Thus, outcomes concerning mortality and care will be excluded. The scope of the systematic reviews is summarized in Table 2.

We repeated searches on the two systematic reviews in March and April 2024 (S2 and S3 Files). Two independent researchers will screen for eligibility and inclusion, and any disagreements will be resolved through discussions with the senior author. For the update on the systematic reviews, the following data will be extracted using templates developed in previous reviews [12, 13]: (1) study information (i.e., authors, publication year, country, Gender Inequality Index (GII) of country of study origin, objectives, design, sample size, outcomes assessed and measures used, and whether effect of PROGRESS-Plus variables was investigated); (2) participant TBI-related variables (i.e., injury severity, external cause of injury, time since injury/stage post injury, outcomes concerning brain health, etc.); and (3) participant social equity information (i.e., PROGRESS-Plus variables) (Table 3). In case of unclear data, authors of the original study will be contacted.

The data extraction process will consist of three phases. In the first phase, we will extract all PROGRESS-Plus variables from included studies, along with data type and profile (structure, format, unique values, etc.). In the second phase, we will create a separate matrix for each PROGRESS-Plus variable. The columns will represent each extracted variable and its measure, while the rows will represent the included publications that considered this variable. We will use crosses to indicate similar measures used and color to mark studies concerning similar brain injury and brain health outcomes. In the final phase, we will identify the frequency order of the considered PROGRESS-Plus variables for each injury severity and brain health related outcomes separately. For this, we will replace the crosses of the matrix with ascending numbers.

Next, we will discuss data transformation and harmonization. We expect the data harmonization process to follow the steps proposed by Kumar et al [41], but is subject to change based on the results of data extraction. We will summarize data extraction results, by PROGRESS-Plus parameter, for cognition and brain health outcomes by injury severity and phase of assessment after the injury, if data permit. We will organize results according to the approach taken to investigate the association between PROGRESS-Plus variables and studied outcomes. In situations where sufficient homogeneity is achieved, we will pool the data for similar outcomes stratified by subgroups of sex/gender, injury severity, and phase of assessment after the injury in meta-regression following methodologies suggested by Cochrane [42]. If pooling is not possible, we will use analytical approaches to data analysis as suggested by Slavin [43].

A Round Robin activity [47, 48] will be conducted with internal stakeholders (i.e., team members) to discuss knowledge mobilization and translation initiatives that reflect users’ priorities, preferences, and needs expressed in the online survey. This is essential since knowledge communicated in peer-reviewed journals might not reach individuals living with TBI, their family members and friends, brain health advocates, clinicians, and policymakers. We will continue to work alongside relevant stakeholders including individuals with TBI for this objective, integrating their insights on the knowledge synthesis results to develop the content for our knowledge mobilization products (Fig 2).