Individuals with intellectual disabilities (ID) are at high risk for high levels of sedentary behaviour. To inform the development of programmes to reduce sedentary behaviour, insight into the correlates is needed. Therefore, the aim of this study is to review the evidence on correlates of sedentary behaviour in adults with ID. We performed a systematic literature search in Ovid Medline, Ovid Embase, Web of Science and Google Scholar up to 19 January 2018, resulting in nine included studies that were published from 2011 to 2018. Correlates were categorized according to the ecological model. Studies predominantly focused on individual level correlates. Of those correlates studied in more than one study, having epilepsy was associated with less sedentary behaviour and inconsistent results were found for sex, genetic syndromes, weight status, physical health, mobility, level of ID, and mental health. Of the few interpersonal and environmental factors studied, only living arrangements were studied in more than one study, with inconsistent results. To date, we have limited and inconclusive evidence about correlates of sedentary behaviour in adults with ID. Only when future studies unravel correlates and determinants, across all domains of the ecological model, will the potential opportunities to improve health by reducing sedentary behaviour come within reach. Sedentary Behaviour Research Network defines sedentary behaviour as any waking behaviour with an energy expenditure ≤ 1.5 metabolic equivalents (MET), while in a sitting, reclining or lying posture [Reducing sedentary behaviour is one of the new promising strategies to promote a healthy lifestyle and improve health ,2,3. The posture . Prolong posture ,7.Individuals with intellectual disabilities (ID) are a population particularly at risk for the health consequences of high levels of sedentary behaviour. An intellectual disability is defined by a significant limitation in both intellectual functioning and adaptive behavior, originating before the age of 18 . Even thA recent review showed that adults with ID are at increased risk for high levels of sedentary behaviour than the general population . It alsoSedentary behaviour is not the same as insufficient physical activity behaviour, which is termed physical inactivity. Compared to physical inactivity, the efforts to reduce sedentary behaviour may take place in different settings, and a different set of correlates may be important to address ,15. In tA review on sedentary behaviour in older adults who did not have ID also identified that included studies focused mostly on individual correlates, such as sex and age . BecauseSuch knowledge is key to informing current and future research on this topic, and to identify the gaps of knowledge required to design effective interventions that are adapted to the specific living and working circumstances of adults with ID. However, for adults with ID, no systematic evaluation of the existing evidence is currently available. The aim of the current paper is therefore to provide a systematic review of the evidence on individual, interpersonal, and environmental correlates of sedentary behaviour in adults with ID.We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to structure this review  see Tab. Our revOn 19 January 2018, we searched in the databases Ovid Medline, Ovid Embase, Web of Science and Google Scholar. Our search strategy was developed with the help of a biomedical information specialist and search terms on the following topics were included: (a) intellectual disabilities, (b) sedentary behaviour and synonyms , and (c) types of sedentary behaviour , experimental  and qualitative study design were all eligible for inclusion.(a)Study sample with participants with ID.(b)Study sample with participants aged ≥18 years. For studies that also included individuals under 18 years, at least 80% of the total sample had to be ≥18 years.(c)In study samples with mixed developmental disabilities and data only presented for the sample as a whole, at least 50% of the sample had to have an ID. Studies were excluded if they did not report the proportion of participants with ID.(d)Sedentary behaviour was measured with objective and/or subjective methods.(e)Correlates of sedentary behaviour are reported.(f)Studies are published in English.(g)Studies are published after 1 January 1990.Studies had to meet the following inclusion criteria:(a)It was a conference abstract.(b)It was a lab-based study e.g., to calibrate accelerometer cut-offs.(c)The term sedentary was used to describe a lack of physical activity e.g., <5000 steps per day.Studies were excluded if:After the database search, studies were screened for inclusion with the inclusion and exclusion criteria. First, the first and last author (AO and CM) independently screened the title and abstracts of all identified records, with 98.6% agreement and a Cohen’s kappa of 0.81. Disagreement about inclusion and exclusion was resolved through a consensus discussion. Second, the first and last author (AO and CM) independently read the full text and completed inclusion and exclusion checklists for each paper. Again, disagreement was resolved through a consensus discussion. There was 99.1% agreement and a Cohen’s kappa of 0.94.Data was extracted with an adapted version of the data extraction form we previously developed for our review regarding sedentary behaviour in adults with ID . We extrData were synthesized based on the ecological model of sedentary behaviour , as has The Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields was used to assess the quality of the included articles . This toThe study selection process is shown in Eight of the nine included studies used a cross-sectional design, with three studies reporting findings from population-based samples in the UK  and the Four studies used an objective measure of total sedentary behaviour, using an accelerometer ,25,28 orAll nine studies examined one or more of the 22 individual level correlates of sedentary behaviour, which fitted into physical, biological and genetic , behavioural  and socioeconomic status  categories of the ecological model . None ofNone of the 17 factors were examined as a correlate of sedentary behaviour in all nine studies. Age was not correlated with sedentary behaviour in any of the four studies that included it as a variable in the analyses ,26,27,28Three of the five studies that assessed the association between sex and sedentary behaviour reported a statistically significant correlation ,26,27. OWeight status was the most commonly examined health indicator investigated as a potential correlate of sedentary behaviour. Three studies found that individuals with obesity had higher levels of sedentary behaviour ,26,27. HBoth studies that used data on screen time/TV viewing from population-based samples of adults with ID found that individuals with epilepsy were less sedentary than individuals without epilepsy ,27. ThesOf the three correlates  assessed from these levels of the ecological model, only living arrangements  were found to be correlated with sedentary behaviour in one study . HoweverThis systematic review is the first to investigate the evidence on correlates of sedentary behaviour in adults with ID. Very few studies have investigated factors associated with sedentary behaviour, and therefore to date we have minimal understanding of the correlates of sedentary behaviour in adults with ID. The nine included studies focused predominantly on correlates related to the individual level. Of the individual correlates studied in more than one study, having epilepsy was associated with lower levels of sedentary behaviour. Inconsistent results were found for sex, genetic syndromes, weight status, physical health, mobility, level of ID, and mental health. Of the few interpersonal and environmental factors studied, only living arrangements were studied in more than one study, with inconsistent results.The focus on research on individual factors is in stark contrast with the importance and with recent emphasis on interpersonal and environmental factors in research in the general population . To be aNone of the studies found a correlation with age in contrast to studies in the general population often showing increasing sedentary behaviour with increasing age . It may Weight status was most commonly examined as a potential correlate of sedentary behaviour. This may be explained by the high prevalence of obesity in adults with ID, even among Special Olympics athletes, and specifically in females ,35. AddiHowever, we found inconsistent results regarding the correlation between weight status and sedentary behaviour across studies. Three studies found obese individuals to be more sedentary ,26,27, oUnexpectedly, having epilepsy was found to be associated with being less sedentary ,27. HoweMore severe ID was also associated with being less sedentary ,27, whilFew studies have looked at interpersonal and environmental factors correlated with sedentary behaviour of adults with ID. However, because adults with ID experience their environment differently than the general population, it is especially important to get more knowledge about the influence of interpersonal and environmental factors on sedentary behaviour, specific to this population. The studies included in this review only looked at living arrangements , social participation  and residential location , which is a very limited set of interpersonal and environmental factors. To be able to develop successful interventions to decrease sedentary behaviour in adults with ID more studies are needed on the influence of additional interpersonal and environmental factors on sedentary behaviour, as well as on their interaction.Additionally, even though the association between individual factors has been studied more widely than the interpersonal and environmental factors, we still have limited knowledge on which individual factors are correlated with sedentary behaviour because we see contradicting results across studies. A better understanding of the influence of individual factors on sedentary behaviour is needed to be able to tailor interventions to individual characteristics. For example, we have limited knowledge on the influence of genetic syndromes on sedentary behaviour, and comorbidities often seen in individuals with ID, such as physical impairments, medication use, and mental health problems.Strengths of this review were closely following the PRISMA guidelines, and performing the process of inclusion of papers and data extraction in duplicate to maximize reliability. The studies included had fairly large sample sizes, and some were population based samples. However, generalizability of the results is limited because of the few studies included and the inconsistency of results.This review is a continuation on a previous review performed by the same group ) regarding definitions, measurements and prevalence of sedentary behaviour in adults with intellectual disabilities . The curIn a review on correlates of sedentary behaviour in the general population, the associations differed depending on whether sub-domains or total sedentary behaviour time were used . For exaLarge-scale epidemiological studies are needed to examine possible correlates and determinants of sedentary behaviour and develop the necessary understanding to develop successful interventions to improve the health of individuals with ID. The focus should be on all the domains of the ecological model, and the complex interplay between individual, interpersonal and environmental factors.There is only fragmented information available on correlates of sedentary behaviour in adults with ID, and therefore there is very limited and inconclusive evidence about relationships between correlates and sedentary behaviour. Only when future studies unravel correlates and determinants of sedentary behaviour will the potential opportunities to improve health by reducing sedentary behaviour in this vulnerable group come within reach.


The Peer Engagement and Evaluation Project (PEEP) aimed to engage, inspire, and learn from peer leaders who represented voices of people who use or have used illicit substances, through active membership on the ‘Peeps’ research team. Given the lack of critical reflection in the literature about the process of engaging people who have used illicit substances in participatory and community-based research processes, we provide a detailed description of how one project, PEEP, engaged peers in a province-wide research project.By applying the Peer Engagement Process Evaluation Framework, we critically analyze the intentions, strategies employed, and outcomes of the process utilized in the PEEP project and discuss the implications for capacity building and empowerment among the peer researchers. This process included: the formation of the PEEP team; capacity building; peer-facilitated data collection; collaborative data analysis; and, strengths-based approach to outputs.Several lessons were learned from applying the Peer Engagement Process Evaluation Framework to the PEEP process. These lessons fall into themes of: recruiting and hiring; fair compensation; role and project expectations; communication; connection and collaboration; mentorship; and peer-facilitated research.This project offers a unique approach to engaging people who use illicit substances and demonstrates how participation is an important endeavor that improves the relevance, capacity, and quality of research. Lessons learned in this project can be applied to future community-based research with people who use illicit substances or other marginalized groups and/or participatory settings. Community based participatory research (CBPR) is an increasingly popular methodology due to its potential to improve research relevance, validity, and reliability through the participation of the community the emphasis on action as part of the research process –5. CBPR People who use illicit substances (PWUS) who use that experience to inform their professional work, commonly referred to (herein) as ‘peers,’ are increasingly participating in research, practice, and policy processes. Involving peers in this work can democratize knowledge and promote social change when power and control are distributed equitably among team members , 9. For The roles of community members involved in the research process can vary widely in terms of responsibilities, decision-making power, and length or depth of involvement. Peers’ can be engaged as research partners or leaders, or be limited to roles similar to others involved in research (i.e. assistants), or participate as consultants in research advisory groups . Each ofWithin Canada, peer engagement has been gaining traction as a best practice approach to designing health and harm reduction solutions and is widely endorsed in principle –14. ReseThis identified need was the impetus for the creation of the Peer Engagement and Evaluation Project (PEEP) at the BCCDC . The BCCThe goal of this paper is to critically and reflexively evaluate the methodological and pragmatic considerations that arise when engaging peers in CBPR through reflections on the PEEP research process Fig. . This paPeeps”. The structure of the Peeps and their relation to the BCHRSS committee who initiated the project can be found in Fig. A diverse group of PWUS were sought to work as research assistants and advisors (RAAs) on the PEEP project. First, a description of the RAA position was developed and reviewed by peers engaged with other BCCDC projects. Then, BCCDC researchers approached peer-based organizations (in regions where they existed) or distributed the description to harm reduction service providers known to work with peers. The individuals hired represented a diversity of backgrounds, ethnicities, ages, and regions . This group of five peers (herein referred to as “the RAAs”) participated as peer researchers and the advisory committee for PEEP. The RAAsTo initiate the project, the Peeps came together for an interactive, three-day orientation and training in July 2015. The non-peer researchers delivered a visual and interactive “Research 101” training through PowerPoints, printed material in binders, and flip charts. The training covered basic research concepts and approaches, with a focus on qualitative research methods. The objectives of PEEP were reviewed and discussed in detail. The Peeps then developed more concrete research questions, a focus group recruitment strategy, question guides, and travel plans for their regions. The team often broke into smaller groups and discussed these strategies in greater detail, reporting back to the larger group.During this meeting the Peeps developed a Memorandum of Understanding which aimed to establish expectations including project goals, team member goals, recognition of the personal risks of participation, responding unmet expectations or disagreement in perspectives, crediting members of the team, and disseminating the findings to community partners. This document also included how each Peep would contribute to decisions, the length and scope of the project, resources, training, support, communication, confidentiality and disclosure, compensation, and what happens at project end. This Memorandum was revisited annually.Following the training in July 2015, smaller groups of the Peep team (one RAA and two coordinators) traveled throughout each region of BC, holding focus groups with local PWUS. From July to October 2015, thirteen focus groups were held with 83 PWUS across rural and urban communities. In addition to the training provided at the July meeting, the RAAs were supported through individual coaching prior to the focus groups to ensure they felt prepared and comfortable in facilitating, and team members provided support during the focus groups where needed. Each focus group was followed by a debrief with the participating team members to discuss challenges and identify the emerging themes. Every two weeks during this time, the team also held a phone call to provide support to each other and to share their experiences. For instance, the RAAs found the question guide to be too wordy and included technical language which some PWUS did not understand. In keeping with the flexible nature of PEEP, the question guide was adapted to include language more acceptable to the community.To organize and focus the abundance of qualitative data collected, an independent data coder thematically coded the data in NVivo using three preliminary themes. These initial themes were inductively developed by three of the BCCDC non-peer researchers by working with the data coder and synthesized the focus group field notes, and read transcripts meeting minutes, and field notes. These themes were provisional as it was important to gather RAA input. Later, the themes were modified after discussing the input from RAAs (described herein).Data analysis was an opportunity to build the RAAs research skills further. In the fall of 2015, the RAAs were sent a training manual and copies of a focus group transcript of which they had facilitated. Each manual described the goals and steps of qualitative analysis through visuals and plain language. This training was discussed during the team phone meetings as well as individually until the RAAs felt equipped. Codes that the RAAs developed were added to NVivo and used to revise the primary codes into four more specific themes. Several subthemes were highlighted and salient quotes the RAAs highlighted were extracted.After this coding process, the entire team met again in Vancouver in February 2016. Here, one full day was spent validating data using a method adapted from Bogdan and Biklen’s ‘cut-up-and-put-in-folders’ approach , PEEP inThe Peeps were encouraged and supported to participate in various knowledge translation activities. Participation varied per the level of comfort of each RAA. Some felt confident with public speaking, while others participated in community events or outreach locally. The Peeps shared their experiences and supported others on the team regularly, which was promoted through weekly or bi-weekly calls, as well as financial resources and training. To date, the RAAs and other Peeps have attended and presented at various conferences, co-created knowledge translation tools, and engaged in other policy and programming initiatives. The Peeps have also co-authored several community and academic publications and a series of case studies to engage health care providers to consider their own engagement practice.BMC Public Health in 2016. The framework consists of four process goals: supportive environment; equitable participation; capacity building and empowerment; improved programming and policy  conflicting understanding of what constitutes legitimate research, competing agendas, and power inequities” . CBPR reThe roles and relationships of the peers and providers expanded beyond our expectations as the project unfolded. First, the capacity and tenacity of the RAAs on the project was far greater than anticipated. This was particularly evident during periods of crisis and the ability of the group to adapt. We learned that we each face and struggle with crises in our lives. In other work settings, colleagues may not disclose challenges occurring outside the work place, but for us it was important in order to support where each of us were at  in the project at different times. Also, our learning was reciprocal – peer and non-peer researchers grew throughout the project. Communication, support, and reflexivity were key to our growth. We learned that in this work it is important to have a safe space to share with others – whether that be with other peers or staff who can support them both professionally and personally. By using reflexivity individually and as a team throughout the project, we continually recognized, understood, and adapted our dynamics and expectations. This process diffused power dynamics and made for a more meaningful experience overall.These experiences highlight the transformative nature of CBPR in terms of social change and social justice, which have broader social implications that are embedded within the wider context of the marginalization and stigmatization of PWUS. As a marginalized and stigmatized group , PWUS arOur findings add to a small but growing body of literature that examines the roles of PWUS in CBPR. Past research has focused on the ethics of engaging PWUS, which has problematized and drew attention to how participation can be disempowering or exclusionary , 29–31. before engaging with the community. Participants may have other priorities and interests than those described in funding applications, which can cause frustration and conflict amongst the team. Conversely, there are ethical concerns in asking for support and increasing expectations of the community by developing funding proposals with them which later may not be granted. Alternatively, rather than engaging with the community as part of discrete projects, researchers could forge ongoing relationships and engagement as a process that develops with the community or peer-based organizations over time [While PEEP was participatory in many aspects, it would not be considered ‘true’ CBPR. We had engaged the community before PEEP was funded by doing interviews and focus groups to identify issues that were important. However, as seen in other CBPR, this information gathering process and grant writing stage was not participatory as resources available were limited . The PEEver time – an apprand advised much of the research process alongside other researchers. By examining this model, we add to the conversation and support involvement of peers in CBPR [Many CBPR projects use a community advisory committee that oversees all aspects of the research . These r in CBPR .and the community. As well, the amount of reciprocal learning and growth was profound; we saw tremendous personal and professional growth among the RAAs and other researchers alike. Furthermore, the outcomes of the PEEP project have community benefit – the peer engagement best practice guidelines will promote the inclusion of PWUS internationally. In these ways, PEEP has held its integrity in its participatory process.PEEP performed other aspects of CBPR. In theory, CBPR has been described as an “orientation to research” that focuses on relationships between the Peeps, with goals of societal or social change rather than a using specific set of techniques . CBPR reThe lessons in this paper are not limited to research settings; the practices of engaging with peers can be applied to other community settings such as in drug policy and service provision. Internationally, peer involvement has been incorporated in a range of projects in the drugs research and policy field. For instance, several projects have focused on user involvement in treatment settings in Australia , 39 or tSeveral limitations to this paper should be acknowledged. We reviewed evidence from internal meeting minutes, field notes, and reflections from the Peeps against the Peer Engagement Process Evaluation Framework . HoweverBy critically reflecting on the process of engaging the peers as research assistants and advisors to the research, we have shown that participation of the community in research is an important and worthy endeavour that improves the relevance, capacity, and quality of the research. The PEEP project successfully supported capacity development across all members of the Peeps, and empowered PWUS to take on leadership roles. By recruiting and fostering a team of peers, we have enriched the validity and applicability of the PEEP project outcomes and have ensured that this research process will promote change. The methods developed in this project provide important insights for future researchers engaging PWUS in their work and provides an example of how one might engage peers in future qualitative and participatory research projects.


Today, the majority of young persons living with chronic conditions in high-income countries survive into adulthood and will need life-long medical follow-up. Therefore, transition programmes have been developed to facilitate transfer to adult care, and to support self-management and independence during adulthood. The Swedish Transition Effects Project Supporting Teenagers with chrONic mEdical conditionS (STEPSTONES) project aims to evaluate the effectiveness of a person-centred transition programme for empowering adolescents with congenital heart disease in transition to adulthood. To understand how the transition programme causes change and how outcomes are created, process evaluation is imperative to assess implementation, context and mechanisms of impact. This protocol aims to describe the process evaluation of the STEPSTONES transition programme.Medical Research Council guidance for process evaluation of complex interventions will be the guiding framework for this mixed-method study. The combination of qualitative and quantitative data will capture different aspects of programme delivery. The sample will consist of participants in the STEPSTONES randomised controlled trial (RCT), persons implementing the programme and healthcare professionals. Quantitative data will consist of protocols and routine monitoring documents from the RCT, data collected from patient registries and sociodemographic data to assess the implementation of the intervention. This data will be analysed with quantitative content analysis, along with descriptive and inferential statistics. Qualitative data will consist of participatory observations, logbooks and interviews with persons implementing the programme, participants and healthcare professionals. Analyses will be performed using qualitative content analysis to investigate mechanism of impact, context and delivery. Quantitative and qualitative data will be integrated in the final stage by using a triangulation protocol according to mixed-method guidelines.The study is approved by the Regional Ethical Review Board in Gothenburg, Sweden. Results will be presented in open access, peer-reviewed journals and at international scientific conferences. This is the first process evaluation study of a transition programme for adolescents with congenital heart disease. Therefore, the study is expected to fill a gap in current knowledge on how transition programmes produce change.The use of multiple data sources, both quantitative and qualitative, strengthens the quality of the findings by triangulation between data sources.Quantitative data in this study rely heavily on routine monitoring documents from the randomised controlled trial, which may affect the trustworthiness of the process evaluation results.Process evaluation data will be reported separately from the results from the effectiveness evaluation.Today, the majority of young persons living with chronic conditions (CC) in high-income countries survive into adulthood and need life-long follow-up.Transition programmes are complex interventions, comprising numerous interacting ingredients. When the effectiveness of a complex intervention is evaluated, the active ingredients producing the outcome are generally unknown. Process evaluation is therefore indispensable in understanding which these active ingredients are and therefore help explain the mechanism of impact and causal pathways.The study in focus of the process evaluation reported here is the STEPSTONES project, which is a person-centred transition programme for adolescents (age 16–18.5 years) with CHD. The programme was developed from a brief transition intervention previously tested in Belgium.The STEPSTONES programme is evaluated through a hybrid RCT, where a longitudinal observational study is embedded within the RCT . The stuThe primary outcome of patient empowerment is measured using the Gothenburg Young Persons Empowerment Scale (GYPES). GYPES has been psychometrically tested and proven to be valid for the study population.In accordance with the Medical Research Council’s (MRC) guidance on the process evaluation of complex interventions, key aspects of this evaluation are centred on the logic model of the intervention, the implementation, mechanism of impact and context.The concept of implementation within this model focuses on how successful delivery of the intervention is accomplished and what is actually being delivered . Fidelity is described as ‘the degree to which the clinical intervention was delivered as it was intended’ and is assessed by evaluating adherence, dose and reach of each component of the intervention.The concept of mechanism of impact refers to how the activities performed within the intervention produce intended or unintended effects,Finally, context includes factors external to the intervention, which influences implementation, or whether the mechanisms of impact act as intended within the context in which the intervention is being delivered.A mixed-method embedded design will be used, including collection, analysis and integration of quantitative and qualitative data.For the quantitative assessment, participants (n=70) and participating parents in the intervention group will be included. In addition, the TCs at the intervention centres, as well as a sample of physicians and nurses at all participating centres will be asked to participate. For the qualitative assessment, we will use a purposive subsample since it is not considered feasible to include all participants in the intervention group (n=70) in the qualitative data collection. Specifically, we will strive for variability of the participants’ characteristics in order to capture a breadth of experiences.Data will consist of a range of sources in order to capture different perspectives of key process variables. Quantitative and qualitative data collection will be carried out simultaneously and synthesised in the final analysis.The enrolment form is based on the five delivery steps of the intervention see . The datEnrolment formThis form will be filled out by the TC after each individual patient encounter, whether in person, by telephone, text message or email. This form contains the components of the intervention, for example, information and education about the health condition, treatment and health behaviour, and information about the adult care follow-up. It also gives information about topics covered, supportive activities and recommendations given, providing an indication about adherence, and dose delivered of the intervention to the patients. The data source will also give information on which communication channel is primarily used for contact between the TC and patients.Intervention implementation formThe occurrence of AEs will give an indication of potential attrition from the study.Adverse event (AE) reportEach patient in the intervention receives a transition plan in which the care is documented. An analysis of this plan will be undertaken to understand what the main objectives were in the transition of individual patients. This analysis will estimate which components of the intervention have been delivered, the outcomes of these and how this is documented. The data from these sources will give information about the possible mechanism of impact, adherence, dose and the potential effects of moderating factors on fidelity such as patient characteristics.Transition plansAge, sex, education level, diagnosis and pharmacotherapy, comorbidities, geographic location, living situation, country of birth, parental marital status and employment situation will be retrieved from the Swedish registry of CHD (Swedcon) and the questionnaires used in the RCT. These data will be used to examine the characteristics of participants who engage with and continue participation in the intervention, and those who do not , and how this affects the reach of the programme.Sociodemographic dataIn this form, the TCs register how much time is spent on performing different tasks of the transition programme, such as the preparation of visits, patient contacts, administration and contacts with other healthcare professionals. Time spent on study-related tasks  is excluded from this form. By collecting data on time management, differences in intervention delivery between the two centres will be visible, also giving valuable information to a future implementation scenario.Time-management formThe following data sources will be used to collect quantitative data on process measures:Throughout the course of the trial, pair interviewsPair interviews with TCReflective diary notes are requested from the TCs, describing their experiences of implementing the transition programme, barriers and facilitators and contextual factors they perceive to have affected the intervention.Diary notes written by the TCObservations of outpatient visits will be performed to investigate how the transition programme is being implemented in practice and the responsiveness and engagement of the participants. The observations will provide data on several process variables such as fidelity, adaptations, dose and participants engagement. Both a structured observation protocol and field notes will be used. The protocol includes components from the intervention implementation form and, in addition, practical applications of how the intervention is intended to be delivered, for example, use of materials and methods to deliver the behavioural change techniques and application of person-centered care. Informal interviews will be conducted with the TCs and participants in connection with the observations as a way of ensuring trustworthiness.Observations of an information day for adolescents and their parents will be held between the second and third outpatient visit in the transition programme. During the information day, adolescents and their parents will get the opportunity to meet their peers, receive information about the adult care and discuss issues regarding transfer and transition. Participatory observations of these meetings will be performed, including informal interviews with the participants about their experiences of the day.Participatory observationsParticipants and their parents will be interviewed about their experiences 1 month after completion of the transition programme. The interviews will give increased understanding of the dose received by the participants, potential moderating factors on intervention delivery, acceptability of the intervention and potential improvements for a future implementation of the transition programme into current practice.Semistructured interviews with adolescents and parentsFocus group interviews will be held with interdisciplinary teams from the intervention centres. The aim is to explore what contextual factors on a local and organisational level are perceived to affect implementation and what prerequisites that are needed for a future implementation of the transition programme. The sample will consist of physicians and nurses from both paediatric cardiology and adult care with experiences of young persons with CHD.Focus group interviews with the healthcare teamThroughout the course of the trial, the assessment of the usual care in the control and comparison groups will be undertaken through participatory observations of outpatient visits and interviews with healthcare professionals. The objective is to assess current practices, barriers and facilitators for future implementation and identify possible contamination between study sites.Usual care assessmentThe qualitative data will be used to answer questions on how implementation is achieved, possible moderating factors and how the participants experience and engage with the intervention. Qualitative data will be collected and analysed by a researcher (MS) that is not involved in the RCT study, to ensure trustworthiness of the data.The process variables  retrieved from the enrolment form, intervention implementation form and sociodemographic data will be entered into a database and analysed in the Statistical Package for the Social Sciences by using descriptive statistics with frequency distributions, proportions, variability over time and means. The effect on process variables of intervention centres’ characteristics and patients’ sociodemographic factors will be analysed by regression analysis, as will data from the time management form, to explain potential moderators on fidelity. The reach of the intervention  will be assessed by comparing participants versus non-participants of the RCT with sociodemographic data and clinical data . The MRC guidance recommends reporting results of the process evaluation separately from the effectiveness evaluation to avoid biased interpretation of effectiveness results.The data from the transition plans will be analysed using descriptive statistics along with quantitative content analysisDesign, sampling, analysis and reporting of the qualitative findings will follow the Consolidated Criteria for Reporting Qualitative research.Analysis and reporting of the mixed-method study will follow the Good Reporting of A Mixed Methods Study framework.The STEPSTONES project was developed with the support of an advisory board and panel of international experts consisting of stakeholders, that is, young adults with CHD, parents, clinicians, researchers and representatives from the patient organisation. Patients will not be involved in the recruitment of this study; however, young adults with CHD will be involved during the adolescent day sharing their experiences of the transfer to adult care and transition to adulthood, acting as role models and providing peer support. Dissemination of results to study participants will be delivered through the patient organisation and social media.Adolescents, parents and healthcare professionals in the RCT have consented to participation after receiving written and oral information about the study. Written consent to participate in the qualitative data collection will be requested after additional written and oral information about the study. Ethical approval for the study was received from the Regional Ethical Review Board in Gothenburg, Sweden (No. 931-15), and the study will be performed in accordance to the Declaration of Helsinki.Process evaluation studies have been increasing in recent years and are imperative to explaining how complex interventions produce the desired outcomes. Furthermore, such evaluation studies are arguably more important when interventions fail to produce the intended outcomes. Since its release in 2015, MRC guidance has been used in process evaluation studies, providing extensive data on important aspects of interventions delivery.The proposed study has several strengths. First, solid funding of the process evaluation has allowed us to employ adequate number of research staff to handle logistics regarding recruitment, data collection and analysis. Furthermore, the documentation of process variables is digital and can be followed up continuously from the main research site.Second, when implementing a complex intervention, a clear description of the intervention is beneficial, as a benchmark for evaluators and for those delivering the intervention. Previous studies show that complex interventions with clear descriptions have a greater chance of being implemented with high adherence.Third, the planned extent of data sources, methods and scope of data collection have, to the best of our knowledge, not been applied in previous process evaluation studies. This is beneficial for many reasons. The use of various sources can strengthen understanding of how different factors interact in creating outcomes. A recent review concluded that only one quarter of all studies measuring fidelity and engagement in interventions used multiple data collection methods such as observations and self-reported measures.Finally, the findings of the process evaluation will be reported separately from the effectiveness evaluation, avoiding biased interpretations of results and therefore strengthening the validity of the findings.However, some challenges and limitations of this process evaluation study have to be considered. Factors affecting recruitment are not directly included in the qualitative data collection. In Steckler and Linnan’sTransfer of care for adolescents living with CCs is a timely issue, and the effectiveness and causal assumptions of transition programmes are yet to be proven. It is therefore imperative to conduct high-quality process evaluation studies to understand how the programmes are delivered, for whom they are delivered and under what circumstances. The effect of contextual factors and possible moderating factors on intervention fidelity and participant engagement may also increase transferability of findings and can thus inform the implementation of transition programmes in other settings.


More than 50 years ago, the first concepts for gastroretentive drug delivery systems were developed. Despite extensive research in this field, there is no single formulation concept for which reliable gastroretention has been demonstrated under different prandial conditions. Thus, gastroretention remains the holy grail of oral drug delivery. One of the major reasons for the various setbacks in this field is the lack of predictive in vitro and in vivo test methods used during preclinical development. In most cases, human gastrointestinal physiology is not properly considered, which leads to the application of inappropriate in vitro and animal models. Moreover, conditions in the stomach are often not fully understood. Important aspects such as the kinetics of fluid volumes, gastric pH or mechanical stresses have to be considered in a realistic manner, otherwise, the gastroretentive potential as well as drug release of novel formulations cannot be assessed correctly in preclinical studies. This review, therefore, highlights the most important aspects of human gastrointestinal physiology and discusses their potential implications for the evaluation of gastroretentive drug delivery systems. The development of concepts for the prolongation of the gastric residence time of dosage forms has been the focus of pharmaceutical scientists for more than half a century . The proThe benefits of gastroretentive dosage forms (GRDFs) were nicely demonstrated by Levy  already Despite the overwhelming potential benefits for oral drug application, the number of gastroretentive systems marketed so far remains small . The lacOn the other hand, there is a lack of simple in vitro methods, which allow the early evaluation of the gastroretentive properties of new approaches. Expensive and complex clinical studies with humans are still the gold standard to confirm the gastroretentive potential of novel formulations. However, it should be the aim of pharmaceutical scientists to provide meaningful in vitro methods to test gastroretention early in development in order to support formulation development. In vivo studies should only be performed with highly promising concepts. Unfortunately, in vivo studies can also have many pitfalls that need to be considered if a qualitative statement about the actual extent of gastroretention of a system shall be made. This also requires thorough background knowledge of the most relevant physiological processes in the stomach in order to be able to correctly interpret clinical data and to draw the right conclusions for further development. This review gives a detailed overview of the physiological processes relevant for gastroretentive dosage forms and describes their implications for in vitro and in vivo investigations of gastroretentive systems.The profound comprehension of gastric physiology in humans and laboratory animals is mandatory to understand and correctly interpret the outcome of in vivo studies on GRDFs, but also to develop new approaches for GRDFs. Since the 1970s, when the first concepts for GRDFs were developed, our knowledge about gastric physiology has dramatically increased. Modern diagnostic tools such as scintigraphy, high-resolution manometry, telemetric capsule systems, and magnetic resonance imaging (MRI) have emerged and advanced. The data obtained with these technologies already provide a very comprehensive picture of the conditions inside the GI tract. Nowadays, many factors are known to have a decisive influence on drug release and the gastric transit behavior of oral dosage forms. In this section, the most important physiological aspects will be described in more detail.In general, the biggest hurdle for gastroretentive systems are the so-called housekeeping waves . These aAfter the ingestion of caloric drinks and food, the conditions within the stomach change substantially . Once em® study .,33.32,33In the case of the high-caloric, high-fat standard meal recommended by the FDA and EMA for food-effect studies and fed-state bioequivalence studies, the pH value drops from about pH 4.6 to baseline values of pH 1 almost linearly within 4 h  23]. Si. Si23]. Pharmaceutics.Over the last decades, several gastroretentive drug delivery systems were developed to overcome the physiologic hurdles present in the stomach. The majority of these systems can be assigned to at least one of the following approaches: flotation, sedimentation, expansion or mucoadhesion . The folThe very first steps towards gastroretention were made with floating systems . This apAlmost 90 years ago, Hoelzel  already The rapid expansion of a drug delivery system is often regarded as one of the most promising concepts to achieve proper gastroretention ,47,48. TProlonging the gastric residence time with the aid of mucoadhesive systems is the most recent approach, which was developed already 35 years ago . The ideExamples in the literature show that although our knowledge in the field of gastrointestinal physiology markedly increased, the outcome of the studies performed with novel concepts of GRDFs is somewhat disillusioning. The fact that there is still not a single gastroretentive system on the market that works reliably and independently from the prandial status suggests that the approaches followed so far are not able to overcome the complex gastric environment. However, besides the concepts mentioned above, the first steps towards more innovative solutions have been made. For instance, Verma and colleagues  recentlyOf course, this system cannot be administered without the help of medical staff, but it nicely illustrates the awareness that more sophisticated approaches are needed in the future to reach the goal of reproducible gastroretention.Currently, clinical studies with humans are still the gold standard for the investigation of the performance of new gastroretentive systems. Due to the high costs associated with in vivo studies as well due to the various pitfalls that may affect the interpretation of in vivo data, powerful in vitro methods are needed for the early evaluation of the behavior of new gastroretentive concepts. The following sections give an overview of the most frequently used in vitro methods and shall enable the reader to critically evaluate data obtained with these methods. In vitro assessment of drug release behavior;In vitro and ex vivo assessment of gastroretentive properties;In vivo assessment of gastroretentive properties.The different in vitro and in vivo methods used to characterize GRDFs can be roughly divided into three groups depending on the investigated parameter:One of the most widely studied parameters of GRDFs is their drug release behavior, preferably under biorelevant conditions. However, the poor predictability in terms of later in vivo drug release is one of the most neglected facts in this context. Interestingly, the vast majority of scientists actually rely on compendial dissolution test apparatuses, which are usually applied for the investigation of drug release from common oral dosage forms. However, it is generally accepted that gastric conditions strongly influence the drug release behavior even for common oral dosage forms. Considering the physiological situation in the human stomach, the compendial methods are at best applicable for quality control purposes, but generally not suitable to study drug release of GRDFs ,54. NoneIn particular, for low-density and, thus, floating GRDFs, dissolution testing in compendial apparatuses can be problematic, as a relatively large surface area of the system is not in contact with the dissolution medium . SeveralAnother very simple approach was recently demonstrated by Kong et al.  who usedEberle and colleagues  proposedParikh and colleagues  identifiIn contrast to floating dosage forms, drug release testing of mucoadhesive systems using compendial dissolution test methods seems to be less complicated. Therefore, in many cases, the paddle apparatus and rotating basket apparatus are used for this purpose. However, since mucoadhesive systems are designed to stick to the gastric mucosa, it would be misleading to study drug release if the dissolution medium is in full contact with the entire surface. Consequently, drug release may be overestimated. In a study by Llabot and colleagues , cyanoacA step towards a more physiological dissolution test of novel GRDFs was made by Nakagawa and colleagues . They usA similar observation was recently observed through the use of the so-called dissolution stress test device . This deBesides the dissolution stress test device, there have been recent developments towards a more physiologically relevant testing of dosage forms. Among the most prominent in vitro models to simulate gastric physiology are TNO’s TIM-1 system, the human gastric simulator (HGS), and the dynamic gastric model (DGM) ,72,73,74The aim of in vitro investigations on the gastroretentive properties of GRDF is to predict the actual gastric transit behavior and, thus, to identify potentially gastroretentive formulations during formulation development. These investigations are usually based on the gastroretentive concepts presented above, i.e., floating, mucoadhesive or expanding. Therefore, they typically focus on certain parameters that are believed to play a key role in vivo later. Despite various efforts in the field of gastroretentive formulation, the in vitro test methods for the assessment of gastroretentive properties have barely advanced and are still almost where they were 40 years ago. However, the development of models dedicated to the investigation of gastroretention would be very helpful for the design of novel formulation approaches.Although simple parameters like tablet density or porosity can be used to obtain a first impression of the floating properties, these tests do not account for the dynamic changes that occur within the human gastrointestinal tract. Processes such as swelling and erosion as well as dynamically changing media may alter the in vivo floating properties of low-density systems over time. Therefore, more sophisticated methods are necessary to characterize such formulations in a physiologically relevant manner.One step towards a more thorough characterization of the floating properties is the determination of the floating lag time and total floating time  ,75. The In contrast to low-density systems with inherent floating properties, gas generating systems may exhibit a short time of non-flotation directly after submersion, due to the more or less slow starting reaction . This soThe tests described above are easy to perform but it should be considered that the tested system may more or less interact with the test medium, which in turn may result in reduced buoyancy force. Already 30 years ago, Timmermans and colleagues  proposedThey used a balance to measure the resultant weight, which is necessary to keep the dosage form fully submerged . NowadayIn vivo, a clearly changed situation is expected compared to the commonly applied in vitro conditions. Besides a dynamically changing pH value, viscosity is certainly one of the major factors that has an impact on floating. So far, it has been largely neglected. In addition, the gastric emptying of the chyme and, thus, the position of the dosage form within the stomach play major roles. The time by which digestion and emptying are almost complete is certainly the most critical time for the functionality of floating systems, as by this time, the volume for flotation and the distance to the pylorus are clearly reduced. Moreover, the dosage form will be exposed to higher stresses if it is located in the distal part of the stomach. The mentioned tests may be useful to get a first impression of the floating properties but in vivo, floating depends on far more complex processes.In general, the same factors that are important for the performance of floating dosage forms are also relevant for sinking systems. These include the viscosity of the medium or changes in the total density due to the presence of swelling. Since the number of studies on sinking systems is extremely limited, data on characterizing their gastroretentive properties in vitro are lacking too. However, compared to floating dosage forms, the performed tests seem somewhat easier. Among these are the theoretical calculation of the density, the density determination via air comparison pycnometry, and the visual determination of the settling kinetics ,44,77,83The simplest way to investigate expanding dosage forms is to perform a measurement of the system before and after expansion. For instance, Gröning and colleagues  measureds(t) refers to the mass determined for the swollen system at time t and m(i) equals the initial mass of the system. The obtained data can also be used to determine the equilibrium swelling time, i.e., the time until complete swelling and size increase [d(t)) so that the mass loss referred to the initial weight can be used to describe the extent of erosion (E) that took place [Furthermore, they investigated the water uptake  of their formulations, which is the most widely performed test for such systems ,86,87,88increase . Some auA major problem with the methods described is the stress that occurs during the removal of the formulation from the media. Similar to hydrogel matrix tablets, expanding formulations based on hydrophilic polymers can be pressure sensitive and, thus, the destruction of the gel may occur within the human GIT. However, it should be noted that the gastric contents are not described correctly by the use of aqueous media. The swelling properties of these systems in more complex media  may be significantly different. One method, mainly applied to superporous hydrogels, is the investigation of the systems’ transparency. Omidian and colleagues defined the Tcore as the time at which the swelling system changes from opaque to transparent appearance . HoweverS is the area of the dosage form before folding and, therefore, describes the maximum expectable value.The exposed size parameter was introduced by Klausner et al.  who wantThis method provides a non-invasive measurement of the size increase but is mostly restricted to systems that unfold and that can sufficiently be described by only two dimensions. Although, originally developed for the in vivo assessment of the size increase, Wang et al.  used thiThe gastroretentive properties of mucoadhesive systems depend mainly on the strength of the interaction between the surface of the dosage form and the gastric mucosa. Therefore, the most widely used method to determine the mucoadhesive properties of GRDFs is the measurement of the tensile strength ,95,96,97For optimal adhesion, the mucoadhesive formulation should obtain close contact with the tissue in the dry state . HoweverA nearly forceless assessment of the mucoadhesive properties of such systems can be done with the gut sac test ,101,102.Another widely accepted test to assess the mucoadhesive properties of multi-particulates is the wash-off test ,104,105.A comparable setup was described by Prajapati and colleagues  who usedCompared to the ex vivo situation, the in vivo adhesion of GRDFs to gastric mucosa is likely to be reduced because of high turnover rates of the mucus, especially after food intake . It is nIn a review by Omidian and colleagues , they deChen and colleagues  developeA novel approach was also chosen by Neumann and colleagues , who triIn general, it is complicated to simulate the complex conditions that are present in the human stomach. Although various approaches over the last years are heading in the right direction, it is still not possible to correctly predict the actual transit behavior of a gastroretentive system. This is also due to the fact that we are not yet aware of the exact properties necessary to reproducibly increase gastric residence time.It should be clear by now that the current in vitro methods are, at best, useful only for initial statements about the gastroretentive properties of new formulations in terms of the respective principle used to provide gastroretention. However, in most cases, the in vivo transit behavior cannot be predicted. Therefore, in vivo investigation remains the only possibility of checking whether a supposedly gastroretentive formulation actually exhibits the desired transit behavior or not.During the early development of novel dosage forms, animal studies are widely used and often not replaceable. For first tests regarding the functionality of a gastroretentive concept, especially multi-particulate mucoadhesive or floating systems, smaller species such as rats or rabbits are used . AlthougIn order to administer dosage forms that were initially developed for humans , larger species like dogs and pigs are used. In this respect, the beagle dog is still the standard . HoweverThe pig is often claimed to be an alternative to the dog, especially because of the length of the small intestine as well as the comparable microbiota of the colon with respect to humans . A recenA study in human subjects remains the gold standard. However, if not performed with the critical pitfalls in mind, this cost-intensive type of study may also result in misleading data. Therefore, the major issues that must be taken into consideration will be addressed in the following sections.The greatest influence on gastric residence time is certainly the intake of caloric food components. As was described above, the greatest risk of early gastric emptying is present in fasted state due to the action of housekeeper waves . Since nWhen testing GRDFs, a good recommendation is to administer a light meal of up to 250 kcal in order to keep the influence of the food on the prolongation of the gastric transit time as low as possible. The gastric residence time then strongly depends on the onset of fasted state motility, especially IMMC phase III. It is possible to estimate the expectable gastric residence time (EGRT) of a non-gastroretentive dosage form via the following rule of thumb:Based on the above stated rule of thumb, the postprandial intake of a large, non-disintegrating dosage form after the ingestion of the American breakfast  would lead to expected gastric residence times of 3.75–10.5 h. Of course, these values can be considered as rare extremes. However, when one looks at the graph in On the basis of the recommendation to administer a 250 kcal meal, the maximum expectable gastric residence time for a larger, non-disintegrating dosage form would be approximately 5 h. A true GRDF should clearly exceed this time. Further food intake may artificially prolong the postprandial status of the subjects and should be avoided until the desired gastric residence time is reached or the system is emptied from the stomach . In geneThere are several examples in the literature where choosing none or the wrong control formulation has led to a misinterpretation of the in vivo data ,127,128.max or AUC may be determined. However, the problem with this procedure is that an appropriate model drug has to be selected in order to be able to draw the right conclusions from the study. Theophylline, for instance, is a good example for a rather poor model drug, since it is well absorbed along the whole GIT. In this case, it is hardly possible to state whether the dosage form is still in the stomach and releases its drug locally. A model drug, at best, exhibits an absorption window in the upper GIT, such as riboflavin [In order to verify the gastroretentive properties, certain pharmacokinetic parameters such as tboflavin ,12,48. ANovel imaging techniques such as magnetic resonance imaging or scintigraphy have dramatically enhanced our possibilities regarding non-invasive dosage form visualization and in vivo tracking. The following section will briefly describe commonly applied in vivo methods used to describe the in vivo transit behavior of GRDF.113mIn-labeled raft-forming system was studied under varying body postures. For the first time, visual evidence was presented that floating systems are more rapidly emptied from the stomach if subjects are lying on the left side, in which case, the antral region represents the highest point [99mTc, was administered to delineate the contour of the stomach. A second radionuclide with a longer half-life was then used to label the dosage form [Scintigraphy is often referred to as the gold standard of dosage form tracking. A high temporal resolution in combination with sufficient spatial resolution are certainly strong arguments in favor of this technique. One of the first studies to highlight the value of scintigraphy in determining the performance of a formulation claimed gastroretentive was done by Bennett, Hardy, and Wilson  in 1984.st point . Howeverst point  chose anage form . Recentlage form  successfThe use of X-ray for dosage form tracking raises the same issues as scintigraphy, i.e., radiation exposure to healthy subjects. Besides the missing anatomical reference, the high radiation exposure for subjects remains one of the major drawbacks of this method, which explains why this method is rarely applied. For the evaluation of whole GI transit, several X-rays have to be gathered. However, confirming intragastric location could be done with a few X-rays after a certain time. Therefore, there have been some examples that highlight the potential value in locating gastroretentive systems. Klausner and colleagues  successfA comparable method was used by Sharma et al.  to visua−1. This can be further reduced if only the gastric location of the dosage form should be confirmed. Magnetic resonance imaging is probably the best example for a non-invasive measurement technique that provides anatomical reference data with sufficient spatial resolution. A great advantage of this technique is the clearly reduced risk of radiation exposure of the subjects. On the other hand, the temporal resolution of classical MRI measurements is comparatively low. Since body movement during an MRI scan leads to artifacts in the images, the subjects are usually advised to hold their breath, which reduces the feasible sampling rate. However, for the characterization of dosage form transit, it seems completely sufficient to apply a sampling rate of 0.5 minRecently, Curley and colleagues  could evThey also accounted for the effect of body posture on the floating and emptying behavior and conducted their study in an upright 0.5 T MRI scanner . Grimm aBy use of a magnetic dipole signal and appropriate sensors, it is possible to precisely track dosage forms in real-time and in three dimensions. The radiation exposure and risk of patients can be neglected in this connection. In the case of magnetic marker monitoring, extremely sensitive sensors are applied, which also require measurement inside a magnetically shielded room to reduce the noise of the Earth’s magnetic field ,139. AboA more straightforward but highly invasive way to confirm the intragastric localization of a dosage form is the visual examination via an endoscope . The anaAlthough ultrasonography suffers from comparatively low spatial resolution, its high temporal resolution along with the technological advancements over the past years provide a basis for potential use for localization of gastroretentive dosage forms. Novel systems are portable, wireless, and easy to use . The litGastroretention of dosage forms offers enormous potential. A platform technology in this area would substantially change the pharmacotherapy with orally administered drugs. However, over the past five decades, such a technology has yet to be developed. This is not only due to the lack of predictive power of the applied in vitro methods, but also the misinterpretation of in vivo data. In the development of such systems, well-known paths must be left, and less attention must be paid to the marketing of the system. With the help of novel developments in the field of diagnostics and in vitro testing, completely new possibilities are already available today. These should be applied in a smart and sophisticated way in order to reach the goal of reproducible gastroretention.


SITLESS is a randomised controlled trial determining whether exercise referral schemes can be enhanced by self-management strategies to reduce sedentary behaviour and increase physical activity in the long term, in community-dwelling older citizens. The intervention is complex and requires a process evaluation to understand how implementation, causal mechanisms and context shape outcomes. The specific aims are to assess fidelity and reach of the implementation, understand the contextual aspects of each intervention site, evaluate the mechanisms of impact, and explore perceived effects.Following the Medical Research Council guidance on complex interventions, a combination of qualitative and quantitative procedures is applied, including observational checklists and attendance registries, standardised scales  at baseline, postintervention and follow-up assessments, semistructured questionnaires gathering contextual characteristics, and participant observations of the sessions. Semistructured interviews and focus groups with the participants and trainers are conducted at postintervention and during the follow-up to explore their experiences. Outcomes from the standardised scales are analysed as moderators within the impact evaluation. Descriptive results on context and perceived effects complement results on impact. The qualitative and quantitative findings will help to refine the logic model to finally support the interpretation of the results on the effectiveness of the intervention.The study design was approved by the respective Ethical Committee of Ramon Llull University, Southern Denmark, Northern Ireland and Ulm University. Participation is voluntary, and all participants are asked to sign informed consent before starting the study. A dissemination plan operationalises how to achieve a social impact by reaching academic and non-academic stakeholders. A data management plan describes the specific data sets and regulates its deposition and curation. All publications will be open access.NCT02629666; Pre-results. Process evaluation is an essential part of the testing of the SITLESS complex intervention.et al., is used as a framework for conducting and reporting this process evaluation.The Medical Research Council guidance on ‘Process evaluation of complex interventions’, by Moore Mixed methods are used to address the specific aims, and each aim is addressed by several methodological procedures applied with a complementary purpose.Important information is identified about the differences and commonalities regarding implementation, context and mechanisms of impact of a complex intervention aimed at increasing physical activity and reducing sedentary behaviour across intervention sites in four European countries.Potential limitations are the reduced number of cases interviewed from the control arm and the lack of in-depth analysis of the experiences of participants with lower adherence to the intervention and of those dropping out of the study.Randomised controlled trials have been traditionally focused on outcome evaluations by linking cause and effect and have been criticised as oversimplistic for ignoring relevant aspects, such as the crucial role of context in shaping outcomes.2et al.,context comprises seven domains—geographical, epidemiological, sociocultural, socioeconomic, ethical, legal and political—whereas setting refers to the specific physical location in which the intervention is put into practice.The Medical Research Council (MRC) has recently proposed guidance to structure the process evaluation of clinical trials of complex interventions.In our current ageing societies, promoting physical activity has become one of the key healthcare policies for the prevention of age-related disability, risk reduction of non-communicable diseases and improvement of quality of life.The SITLESS intervention fulfils the definition of a complex intervention, mainly since it comprises different active components that allow for tailoring to the personal and local characteristics, it is aimed at changing behaviours, and has a wide potential range of short-term and long-term physical, social and psychological effects.In addition, for the SITLESS study, conducted in the European research framework Horizon 2020, it is a key issue to use the approach of Responsible Research and Innovation (RRI). RRI is understood as an approach that anticipates and assesses potential implications and societal expectations with regard to research and innovation, with the aim to foster the design of inclusive and sustainable research and innovation.Therefore, the SITLESS project has designed a process evaluation with the aim of understanding how implementation, causal mechanisms and the contextual factors shape the short-term and long-term outcomes. The primary outcomes of the trial include (1) sedentary behaviour as sitting time and time spent in activities which have been traditionally reported as requiring ≤1.5 Metabolic Equivalent of Task (MET), and (2) physical activity as daily counts-per-minute and intensity of exercise performed, both objectively measured by ActiGraph accelerometer. Furthermore, the secondary outcomes include other health-related aspects, quality of life, function and psychosocial outcomes at postintervention and at 12 and 18 months follow-up. The specific aims of the process evaluation are first to assess the implementation of the intervention in terms of (1) fidelity to the intervention design, variability of what was delivered and how between intervention sites; and (2) reach (adherence) of participants to the intervention. Second is to understand the role of context through the following: (1) exploring whether contextual factors regarding the characteristics of the setting, facilitator, the neighbourhood, healthcare system and other location-specific aspects affect implementation and outcomes; (2) assessing the variability and comparability between and within intervention sites; and (3) assessing the generalisability of the intervention’s effectiveness results. Third, the SITLESS project aims to understand the mechanisms of impact. Fourth and finally it aims to explore the perceived effects of the intervention.The specific research questions corresponding to each aim are shown in The process evaluation of the SITLESS project follows the guidance on ‘Process evaluation of complex interventions’ from the MRC.5A combination of quantitative and qualitative procedures will be applied. This process evaluation was planned prior to implementation of the intervention, except for the semistructured questionnaire on contextual data that was added more recently. Nevertheless, observational checklists, attendance registries and guidance for the qualitative procedures were tested with the first participants and improved accordingly to ease their use and capture the most relevant data.Quantitative procedures quantify the fidelity to the intervention manual and participants’ adherence to the intervention through observational checklists and attendance registries, respectively. They also involve standardised scales to assess the mediating factors ,Qualitative procedures address the same research questions but according to participants’ perceptions, trainers’ experiences and researchers’ observations. Qualitative procedures include participant observation, semistructured interviews and focus groups and are detailed in Qualitative methods require specific considerations regarding the research team, reflexivity and the study design.A multicountry and multidisciplinary research team including a variety of health professionals  will lead the analysis of the qualitative data gathered in Barcelona, Odense, Ulm and Belfast. All members of the team involved in the qualitative research will be encouraged to keep a research diary to record their reflexive notes, impressions of the data and thoughts about the analysis throughout the process. Researchers should remain flexible and adaptive throughout the process and not be attached to certainty to generate rich findings that could explain the complexity of social issues. Researchers with less experience in qualitative research will be trained to code, index and chart data and to think reflexively about how their identities and experience affect the analysis process in order to help to interpret with accuracy the meaning and significance of the data.We will apply purposeful sampling of participants with a maximum variation sampling method as a strategy to select a small number of cases that maximise the diversity relevant to the research question. By doing so, we aim to explore the differences and commonalities regarding gender, functional level, ethnicity and socioeconomic background, next to the type of intervention arm . Each qualitative procedure targets a specific purposeful sample of participants from each of the four intervention sites  according to the characteristics specified in Each aim is addressed by several methodological procedures applied with a complementary purpose as illustrated in After each session of all SMS and ERS groups, the trainer records the degree of fulfilment of each task and each aim. Hence, the observational checklist of the ERS sessions also covers the implementation characteristics that might vary across intervention sites or across sessions .All SMS, ERS and control group sessions have a corresponding attendance registry recorded by the trainer after each session. It contains each participant’s attendance, reasons for not attending and adverse events due to the intervention. The attendance is used to calculate the adherence as an equivalent concept of dose and considers the compliance with the intervention .Semistructured interviews and focus groups with participants will include questions about their perception of the implementation of the specific intervention elements. Focus groups with trainers will have specific questions on their perception of the implementation challenges. In addition, the participant observation of the SMS and ERS sessions by researchers will focus on the implementation of the intervention.The evaluation of this aim is addressed with a table with prespecified domains of context. Specifically, all intervention sites will provide information on the specific intervention setting and context. Setting characteristics will comprise neighbourhood socioeconomic level (low/medium/high), urban/semirural/rural area, type of centres involved with the recruitment, type of centres in which the ERS intervention, SMS intervention and the control group intervention are conducted and existing ERS in these settings. This information will be collected by researchers at each intervention site. Data on context will include those geographical, epidemiological, sociocultural, socioeconomic, ethical, legal and political information that might be relevant as a barrier or facilitator to the intervention implementation, or its effect, for instance existing national programmes on physical activity. These contextual data will be first collected by the leaders of each intervention site and complemented with the knowledge and views of the members of each local advisory board.Semistructured interviews and focus groups with participants and trainers include specific questions about the context. We will specifically explore the role of the physical environment and social context, with the latter comprising the personal circumstances, the personal network and the group dynamic of the SMS+ERS and ERS intervention arms.The MSEQ,22This will be used to get a better understanding of complex causal pathways and unexpected mechanisms between intervention and outcomes. Specifically, semistructured interviews with participants and focus groups with participants and trainers at the end of the intervention and at follow-up will include questions about perceived effects according to participants’ experiences and trainers’ observations. In addition, the participant observation of the SMS and ERS sessions by researchers will focus on how participants actively respond and interact with the intervention.This aim is addressed through semistructured interviews with participants and focus groups with participants and trainers at the end of the intervention and at follow-up. Perceived impacts will be considered as complementary to the results of the effectiveness evaluation assessed with standardised scales.13Within the RRI framework, the SITLESS process evaluation explores if there are differing responses to the intervention by disadvantage categories related with gender, disability, ethnicity and socioeconomic position. It also considers how these categories affect implementation and mechanisms of impact and, consequently, the effectiveness of the intervention.16Data from the process evaluation will be analysed according to two main procedures: quantitative and qualitative analyses.SITLESS observational checklists will be used to calculate the percentage of fidelity of the implementation regarding the tasks and aims of the SMS and ERS sessions in each intervention site. The adherence to the ERS, SMS and control group sessions will be calculated as a percentage of sessions attended with each respective attendance registry. In addition, this registry will allow estimating the frequency of reasons for not attending. Percentage of fidelity of the implementation and adherence will be compared across intervention sites to identify whether differences may exist between them. Comparison will be conducted applying analysis of variance models.Quantitative process evaluation data, recorded in the attendance registries and the observational checklists, will be used to conduct a descriptive analysis, overall and by intervention site. The Specific data will be entered in the main study database. This is the case for the variable fidelity and for adherence that will allow us to assess whether a better implemented intervention or a higher dose of the intervention is related with more effect, respectively. The potential mediator role of adherence/dose, the MSEQ, the PASR-12 and the LSNS on the effect of the intervention on physical activity and sedentary behaviour will be explored by covariance analyses, adding these scales as covariates to the mixed linear models testing the effect of the intervention. The statistical efficacy analysis of SITLESS has been described previously.The SITLESS qualitative data analysis will be based on the transcripts of the semistructured interviews and focus groups, and the trainers’ notes from the participant observation. The framework method will be applied to analyse these data.The analysis will be conducted following these steps: transcription, familiarisation with the interview, coding of the transcripts and diaries of the participant observation, developing a working analytical framework, applying the analytical framework, charting data into the framework matrix, and interpreting the data.The initial coding of the first four transcripts, one per intervention site, will be conducted by two independent researchers, adding coding labels, notes and ideas. As a next step, a working analytical framework will be developed by discussing codes assigned, similarities and differences to achieve an agreement on a set of codes to establish an initial analytical framework. This framework will be refined by coding of further manuscripts until no new codes are generated by two independent researchers. Next, the final analytical framework will be applied to the remaining transcripts. The use of a software to conduct the analysis will be discussed. Once all the data are coded, we will summarise the data in a matrix for each theme.As shown in SITLESS, as an RRI project, has considered in the study design and involved from its onset different types of stakeholders as primary, secondary and tertiary end users.Qualitative procedures undertaken in the trial include questions to assess whether participants perceive any burden due to the intervention and to their participation in the study.The dissemination plan comprises sharing the results of the trial at each healthcare, social or leisure centre involved in the recruitment and/or intervention to reach end users, health professionals and other relevant stakeholders. Further dissemination activities will be held to involve participants of each site as much as possible.The SITLESS dissemination plan operationalises the main dissemination goal, which is to achieve a social impact by reaching academic and non-academic stakeholders, that is, primary care and healthcare professionals, older adults, policymakers, professionals related to physical activity promotion and so on. Specifically, process evaluation results will enhance social impact by providing implementation details that might be of interest for policymakers. In addition, qualitative results  will support reaching non-academic stakeholders. A data management plan has been developed for the SITLESS study describing each specific data set in the study and regulating its deposition and curation.All publications from the SITLESS project, including those related with process evaluation, will be open access.The SITLESS project has developed a process evaluation to understand how implementation, causal mechanisms and the contextual factors shape the outcomes of a complex intervention that enhances ERS with SMS to reduce sedentary behaviour and increase physical activity among community-dwelling older adults of four European countries. Accordingly, this trial has the purpose of facilitating future intervention development by informing policymakers, practitioners and researchers about implementation, mechanisms of impact and contextual factors in detail. In case the intervention is proven as being effective and cost-effective, the information will be focused on the delivered intervention to allow replication in new contexts considering the relevant core components, context characteristics and implementation challenges. In case of being ineffective, process evaluation results will contribute to define whether the failure can be attributed to the intervention itself or to a poor implementation. Hence, process evaluation will provide useful data for systematic reviews to compare interventions considering their implementation and contextual characteristics.SITLESS started in May 2015. The feasibility study was conducted from December 2015 until June 2016. The recruitment for the trial started in July 2016. At the time of submission of this protocol, all 1390 participants have been included in the study. To date, follow-up assessments are being conducted and are planned to finish by September 2019.10.1136/bmjopen-2018-027073.supp1Supplementary Appendix 110.1136/bmjopen-2018-027073.supp2Supplementary Appendix 210.1136/bmjopen-2018-027073.supp3Supplementary Appendix 310.1136/bmjopen-2018-027073.supp4Supplementary Appendix 410.1136/bmjopen-2018-027073.supp5Supplementary Appendix 510.1136/bmjopen-2018-027073.supp6Supplementary Appendix 6