Open access Protocol Complex multidisciplinary intervention to improve Initial Medication Adherence to cardiovascular disease and diabetes treatments in primary care (the IMA-­cRCT study): mixed-­methods process evaluation protocol Carmen Corral-­Partearroyo,1,2 Alba Sánchez-­Viñas,1,3 Montserrat Gil-­Girbau ‍ ‍,1,4 Maria Teresa Peñarrubia-­María,1,5 Ignacio Aznar-­Lou,1,6 Carmen Gallardo-­González,1,5 María del Carmen Olmos-­Palenzuela,7 Maria Rubio-­Valera1,6 To cite: Corral-­Partearroyo C, ABSTRACT Sánchez-­Viñas A, Gil-­Girbau M, Introduction Medication non-­initiation, or primary non-­ STRENGTHS AND LIMITATIONS OF THIS STUDY et al. Complex multidisciplinary adherence, is a persistent public health problem that ⇒ This process evaluation will explain how the in- intervention to improve Initial tervention was implemented, how different com- increases the risk of adverse clinical outcomes. The initial Medication Adherence to ponents interact and work and how they influence cardiovascular disease and medication adherence (IMA) intervention is a complex multidisciplinary intervention to improve adherence to outcomes. diabetes treatments in primary care (the IMA-­cRCT study): cardiovascular and diabetes treatments in primary care ⇒ This study includes a wide range of quantitative mixed-­methods process by empowering the patient and promoting informed and qualitative research methods; it is logistically evaluation protocol. BMJ Open prescriptions based on shared decision-­making. This paper challenging and time consuming. A multidisciplinary 2022;12:e067468. doi:10.1136/ presents the development and implementation strategy of research team has been involved. bmjopen-2022-067468 the IMA intervention and the process evaluation protocol ⇒ The flexible and pragmatic design will be crucial embedded in a cluster randomised controlled trial (the to react to changes and adapt the intervention to ► Prepublication history for this paper is available online. IMA-­cRCT) to understand and interpret the outcomes of emerging contextual factors. To view these files, please visit the trial and comprehend the extent of implementation ⇒ Data collection methods have been designed to the journal online (http://dx.doi.​ and fidelity, the active mechanisms of the IMA intervention adapt to the participants in what we anticipate org/10.1136/bmjopen-2022-​ and in what context the intervention is implemented and might be an overloaded and difficult time due to the 067468). works. persisting COVID-­19 pandemic. Methods and analysis We present the protocol for a ⇒ There is a risk of response bias among profession- Received 16 August 2022 als that answer questionnaires and agree to partic- mixed-­methods process evaluation including quantitative and Accepted 10 October 2022 ipate in the qualitative evaluation as they may have qualitative methods to measure implementation and fidelity and to explore the active mechanisms and the interactions engaged more with the intervention. Additionally, between the intervention, participants and its context. patients will be recruited by professionals and this The process evaluation will be conducted in primary care might bias their responses and the decision of the centres and community pharmacies from the IMA-­cRCT, patient towards filling the prescription. and participants include healthcare professionals (general practitioners, nurses and community pharmacists) as well as patients. Quantitative data collection methods include data Trial registration number NCT05026775. extraction from the intervention operative records, patient clinical records and participant feedback questionnaires, INTRODUCTION whereas qualitative data collection involves semistructured Medication non-­ initiation, or primary non-­ © Author(s) (or their interviews, focus groups and field diaries. Quantitative and employer(s)) 2022. Re-­use adherence, is defined as not initiating the qualitative data will be analysed separately and triangulated permitted under CC BY. prescribed pharmacological treatment.1 to produce deeper insights and robust results. Published by BMJ. In recent years, there has been an increase Ethics and dissemination Ethical approval has been For numbered affiliations see obtained from the Research Ethics Comittee (CEIm) at in evidence regarding non-­ initiation.2–5 It end of article. is subject to patients’ characteristics and IDIAP Jordi Gol (codeCEIm 21/051 P). Findings will be Correspondence to disseminated through publications and conferences, as motivations, the pharmacological treatment Dr Montserrat Gil-­Girbau; well as presentations to healthcare professionals and prescribed and the context,4 6 7 and for some ​mariamontserrat.​gil@​sjd.​es stakeholders from healthcare organisations. treatments, it reaches a prevalence of 40%.3 Corral-­Partearroyo C, et al. BMJ Open 2022;12:e067468. doi:10.1136/bmjopen-2022-067468 1 Open access Adherence to long-­ term medications has been shown of SDM interventions on adherence to pharmacological to be crucial to the prevention of further complica- treatments.23–26 29 tions.8 Low adherence to cardiovascular disease (CVD) and diabetes treatments worsens patients’ clinical The non-initiation project outcomes9–12 and increases direct and indirect costs to The non-­ initiation project is based on the framework healthcare systems,10 13 14 highlighting the need for inter- for developing and evaluating complex interventions ventions to prevent it. proposed by the Medical Research Council (MRC)30 31 and In the past, some studies evaluated the effectiveness of aims to develop and evaluate an intervention to decrease interventions to improve non-­initiation, focused mainly non-­initiation. Figure 1 summarises the project phases. on CVD medications.15–20 The majority were based on In phase I, or the development phase, the prevalence patients’ reminders: two on automated messages,15 19 two and explanatory factors of non-­initiation were explored. on phone calls performed by professionals17 18 and one Overall prevalence of non-­initiation in primary care (PC) in Catalonia (Spain) was found to be 18% and between on both automated and professional’s phone calls.16 Only 6% and 9% for treatments for CVD and diabetes.5 32 two of these studies reported a significant decrease in non-­ Predictors of non-­initiation included patient characteris- initiation,15 19 and most showed a high overall risk of bias. tics (such as being younger), the treatment (such as cost) Hawthorne effect and desirability bias was high overall and the system (such as receiving the prescription from due to lack of blinding of participants and the charac- a substitute or resident general practitioner (GP)).5 32 teristics of the outcome under study15–18 20; most studies The patients’ reasons for non-­initiation were explored used medicine acquisition as a proxy for initiation with by carrying out qualitative research with patients and no further follow-­up, and false-­positive initiation could professionals.7 33 Based on the results of these studies, occur when patients know they are being observed.21 22 the Initial Medication Adherence (IMA) intervention, a None of the interventions tested was described as being complex, multidisciplinary intervention to improve initi- founded on a health behaviour change theory. ation and adherence to CVD and diabetes treatments, was In the last decade, there has been growing interest modelled. To increase the acceptability of the interven- in behavioural interventions based on shared decision-­ tion, discussion groups were conducted with GPs, nurses, making (SDM) to improve adherence.23–26 SDM is a pharmacists, social workers, cardiologists, endocrinol- process whereby the professional and the patient jointly ogists and internists, who made suggestions for refine- decide on a treatment or healthcare choice.27 Both share ment, described its limitations and anticipated barriers to their knowledge, and the patient is invited to express its implementation. their preferences and consider all options to achieve a To assess the feasibility of the IMA intervention and the mutual agreement.27 28 This respects patient autonomy evaluation design, a pilot trial with an embedded process yet offers guidance to the patient by involving them in evaluation was conducted as part of phase II, or feasi- the decision at their preferred level.27 By involving the bility phase (​ClinicalTrials.​gov, NCT05094986). Detailed patient in the decision process, SDM increases patients’ methods and results of the pilot study are presented else- health literacy and satisfaction.23–26 29 However, there is where.34 The intervention components and implementa- not sufficient evidence for an effect of SDM-­based inter- tion strategies were considered feasible and acceptable. ventions on medication adherence, and there is a lack of However, barriers to the engagement of professionals, standardised outcomes in studies evaluating the impact training for professionals and intervention decision aids Figure 1 IMA intervention phases: development, feasibility, evaluation and implementation. cRCT, cluster randomised controlled trial; IMA, initial medication adherence; PC, primary care. 2 Corral-­Partearroyo C, et al. BMJ Open 2022;12:e067468. doi:10.1136/bmjopen-2022-067468 Open access were identified. These results were used to refine the IMA necessary, the decision is delayed to offer the patient intervention prior to the definitive cluster-­randomised the opportunity to reflect on it, obtain complementary controlled trial (cRCT). information (reliable decision aids are recommended The process evaluation outlined in this paper is inte- as sources of information) and/or discuss the decision grated into the IMA-­cRCT, phase III or evaluation phase: with others (including nurses and pharmacists). When a pragmatic cRCT with two parallel groups that aims to consulted by patients, nurses and pharmacists explore evaluate the effectiveness, cost-­effectiveness and under- patients’ queries regarding new CVD or diabetes medi- stand the impact of the IMA intervention. Detailed cation prescriptions, or those of patients considering cRCT methods (​ ClinicalTrials.​ gov, NCT05026775) are the use of medication, and use decision aids to provide described elsewhere.35 The trial is being conducted in information support, standardising the message from all 24 PC centres in Catalonia (May 2022–September 2023), healthcare professionals and improving interdisciplinary randomised to the control (usual care) or the interven- collaboration. In the case that the patient changes their tion group (the IMA intervention), as well as community mind about the use of medication, nurses and pharma- pharmacies in the area covered by PC centres of the inter- cists refer them back to the GP. The IMA intervention is vention group. Professionals in the intervention group a one-­shot intervention at the time of a new prescription. were trained on the IMA intervention and will apply it to The dosage, or times the intervention has been applied all patients receiving a new prescription for lipid-­lowering to the same patient, varies on the healthcare professionals medication, antihypertensive medication, antiplatelet (GPs, nurses and pharmacists) consulted during and after medication and/or antidiabetic medication during the a new prescription and whether they are participating in study period (7 months).35 The primary outcome of the the trial, with the minimum dose being one time (when trial is the rate of initiation. Secondary outcomes include the prescription is issued). other measures of adherence (implementation and The logic model illustrated in figure 2 shows how the persistence), clinical outcomes and cost-­effectiveness. intervention would primarily influence the adequate use of treatment (primary and secondary adherence) and The IMA intervention ultimately impact the health outcomes of the population The IMA intervention is founded on the theoretical under study, as well as influence the interdisciplinary model for non-­ initiation.7 33 According to this model, collaboration between professionals and patient–health- the decision to initiate pharmacological treatments is care professional interaction. The IMA intervention multifactorial, and it is influenced by the patients’ beliefs has three main inputs as part of the implementation about the disease and treatment options, the existence strategy (figure 2). First, professional engagement increases of non-­pharmacological measures, the interaction with professionals’ interest and promotes participation. PC healthcare professionals (GPs, nurses and pharmacists) and pharmacy stakeholders, including scientific organ- and the context, cultural factors and health literacy isations, healthcare quality agencies, official colleges, of the patient.7 33 The model suggests that an interven- and managers and directors of PC centres were first tion that improves health literacy, helping the patient to contacted and informed. Thereafter, professionals were understand the risks of the disease and the benefits and informed at PC centres, community pharmacies and offi- risks of treatment options and involves the patient in the cial colleges. Second, the IMA intervention training was decision-­making process could improve initiation and provided to professionals (GPs, nurses and pharmacists) long-­term adherence.7 33 The model also highlights the in two sessions of 3 hours each. Professionals were trained influence of healthcare professionals and the importance together to promote standardisation and mutual under- of multidisciplinary recommendations when a new phar- standing of each other’s role and to generate bonds. The macological treatment is prescribed. first session covers the basics of the intervention: the As illustrated by the non-­ initiation model, the IMA evidence on non-­initiation, the practical aspects of the intervention is expected to work at the intrapersonal level intervention, the role of each professional and the inter- by increasing patients’ health literacy and empowerment vention decision aids. The second session was designed and the interpersonal level by promoting SDM through by an SDM expert and focuses on SDM and communi- the interaction between the patient and healthcare cation skills. Third, the IMA intervention decision aids professionals and supporting the standardisation of clin- promote discussion of all relevant topics with the patient ical practice among all the PC professionals that interact and SDM (increasing adherence to the intervention and with the patient (GPs, nurses and pharmacists). standardisation of practice). Leaflets (one for each phar- During a consultation, the GP applies the principles of macotherapeutic group) contain information on the risks SDM.27 28 They define the problem and decision at hand of the disease, the risks and benefits of pharmacological by providing information about the disease and treat- and non-­pharmacological treatments and key messages ment options and exploring the patient’s perspectives, to encourage the patients to express their opinions concerns and expectations supported by decision aids. and share their uncertainties with the professional, as Both the GP and patient have coresponsibility to nego- well as other reliable sources of information (including tiate a decision before the prescription of a new CVD other healthcare professionals and a website). The or diabetes pharmacological treatment is issued. When website www.iniciadores.es is divided into pathologies and Corral-­Partearroyo C, et al. BMJ Open 2022;12:e067468. doi:10.1136/bmjopen-2022-067468 3 Open access Figure 2 IMA intervention logic model. CVD, cardiovascular disease; GP, general practitioner; HCP, healthcare professional; IMA, Initial Medication Adherence. pharmacological treatments, with extended information and sustain an intervention, provides decision makers on the disease, treatments and additional links to other with relevant information when evaluating the translation reliable websites (such as those run by the national health of the intervention into routine clinical practice.38 system). The content of the leaflets and website are reli- able and are endorsed by public healthcare organisations. Aims and objectives This process evaluation aims to understand the imple- The IMA intervention in the context of the COVID-19 mentation and mechanism of action of the IMA inter- In the case of a COVID-­19 outbreak, when a new treat- vention and how the context affects them and therefore ment is recommended during a telephone consultation, understand and explain the results of the cRCT in terms the doctor sends the leaflet through email and refers the of effectiveness and cost-­effectiveness, refine the IMA patient to the website (where leaflets are also available). intervention and provide information on replicability Additionally, the patient can collect the leaflet from and generalisability to other contexts. participating pharmacies when collecting the medica- The objectives of the study are to: tion. In this case, a follow-­up telephone consultation (GP 1. Assess the extent to which the IMA intervention was or nurse) is recommended a week after the prescription implemented as intended (fidelity) and understand is issued to explore patients’ queries and concerns. how the IMA intervention becomes integrated into routine healthcare practice (implementation). Process evaluation 2. Identify and understand the active mechanisms of the Randomised controlled trials (RCTs) have been presented IMA intervention (mechanisms of impact). as the gold standard for evaluating effectiveness and effi- 3. Understand the context where the IMA intervention ciency of complex interventions.36 Complex interventions is implemented and identify factors that can influence combine multiple components that interact with each the IMA intervention’s active mechanisms (context). other, involve several stakeholders and generally require a 4. Assess the cost of implementing the IMA intervention. behavioural change by those that implement and receive the intervention.30 31 36 However, RCTs typically have rigid designs, tend to focus mainly on outcome effect and fail METHODS AND ANALYSIS to explain how the intervention was implemented and in Study design and framework of the process evaluation what context, what the active components were and for A mixed-­methods process evaluation study will be under- whom it worked.30 31 Process evaluations embedded in taken, involving analysis of real-­world practice evidence, pragmatic RCTs are needed to understand how the inter- data collection forms, field diaries and interviews with vention was delivered, how different components interact professionals and patients. The MRC guideline for and work, how they influence the intervention’s primary process evaluations of complex interventions was used to and secondary outcomes and its effectiveness.37 guide the design of this evaluation.37 It focuses on three Ultimately, some very efficient interventions can be domains that interact with each other: (1) the implemen- difficult to translate into routine practice, especially when tation of the intervention; (2) the mechanisms of the the intervention cost is high because it requires organi- intervention that affect the outcomes; and (3) the char- sational and behavioural changes. Assessing the cost of acteristics of the contexts that can influence the previous implementation, costs of the strategies to put in practice domains in the intervention group and control group 4 Corral-­Partearroyo C, et al. BMJ Open 2022;12:e067468. doi:10.1136/bmjopen-2022-067468 Open access CONTEXT Realist evaluation (Pawson and Tilley, 1997)39 The IMA intervention Logic model of the IMA IMPLEMENTATION MECHANISMS OF IMPACT intervention: Normalisation process theory Realist evaluation (Pawson Inputs: (May et al. 2007)40 and Tilley, 1997)39 • Professional Indicators: Indicators: engagement • Coherence • Participants’ experiences • Training for • Cognitive participation OUTCOMES • Intended and unintended professionals • Collective action pathways and • Decision aids consequences • Reflexive monitoring Main processes: Other indicators: fidelity and • Shared decision-making adaptation (GP) • Support from other health care professionals (nurse and pharmacist) Figure 3 Domains and theoretical framework of the IMA-­cRCT process evaluation (adapted from Moore et al37). GP, generalpractitioner; IMA, Initial Medication Adherence. contextual factors that could influence the outcomes of monitor and prescribe treatments and nurses follow-­up the cRCT. the patient. Medications are electronically prescribed, Figure 3 shows the interaction between the three and patients can fill them only at community pharma- domains and the theoretical frameworks used to eval- cies where the pharmacist can check the prescription uate them.39 40 Implementation will be assessed through directly through the electronic prescription system.44 the normalisation process theory,41 42 which explains A warning appears when a new platelet aggregation how an intervention becomes routinely integrated into inhibitors excluding heparin and insulin is going to be everyday healthcare practice by assessing four indicators: dispensed. Full details on the cRCT setting are provided coherence, cognitive participation, collective action and elsewhere.35 reflexive monitoring.42 The evaluation of the mecha- The IMA-­cRCT will recruit 24 PC centres, around 300 nisms of impact and the context of the intervention will professionals and 4000 patients.35 The sampling strategy be assessed following the recommendations of realist eval- of the process evaluation is conditioned by the cluster uation39 to explain how active mechanisms of the inter- sampling design of the cRCT and is detailed below. vention generate an effect, for whom and under what circumstances.37 39 It takes into account the expected and Intervention group unexpected consequences that may result from the acti- Professionals vation of different hypothesised mechanisms in different GPs, nurses and pharmacists from all PC centres will have contexts and end up generating different effects.37 39 feedback questionnaires sent to them, but only profes- Additionally, the Stages of Implementation Completion sionals from six to eight PC centres will be recruited to framework will be used, and the Cost of Implementing participate in the qualitative research due to time restric- New Strategies tool will be adapted to the IMA interven- tions. The recruitment will be based on a theoretical tion43 to assess the costs of implementation when trans- sampling strategy according to the type of PC centre (size lating the IMA intervention into other settings. and location) and taking into account predictors of non-­ The process evaluation will be conducted by the IMA-­ initiation (socioeconomic level of the area, rurality and cRCT research team. This is a multidisciplinary team the proportion of immigrant population). Professionals formed by researchers with expertise in quantitative from the recruited PC centres will be invited to partici- and qualitative research and PC professionals. The main pate in the interviews by phone calls following maximum components of the intervention are not expected to be variation sampling according to role and type of contract, adapted during the trial, although the dynamic approach of this pragmatic evaluation gives the design the flexibility years of experience in PC, sex and age, nationality and to react to changes if needed. owner or not of the pharmacy. Each PC centre will have a study coordinator, a GP or Setting and participants nurse. The coordinator will be the link with the research The IMA intervention will be implemented in PC centres team, promoting the implementation of the intervention, and community pharmacies in Catalonia (Spain). PC is coordinating the distribution of intervention materials the gateway to the healthcare system and where the vast and informing the research team of external events that majority of the prescriptions for long-­term treatments may influence the correct implementation of the inter- are issued.44 Patients have an assigned GP and nurse. GPs vention and development of the trial. Corral-­Partearroyo C, et al. BMJ Open 2022;12:e067468. doi:10.1136/bmjopen-2022-067468 5 Open access Patients attitudes and interdisciplinary collaboration, changes The coordinator of the PC centres will identify patients to patients’ knowledge, behaviour and interaction that were prescribed a new treatment for CVD or diabetes with professionals and any expected or unexpected during the study period and invite them to participate consequences. in an interview. They will be asked to follow a varia- tion sampling strategy based on medication prescribed Context and treatment being initiated or not. In addition, we Data on the context of both the intervention and control will follow a maximum variation criterion based on the groups will be collected (table 3). Demographic data previous aspects, educational and socioeconomic level, from the PC centres will be extracted from Catalan sex and age. Once patients agree to participate, the health system records. Interviews will be carry out with research team will contact them by phone calls to provide professionals and patients to explore the context of the further information about the study. PC centre and examine in which circumstances mecha- nisms of impact work and therefore influence the study Control group outcomes. The coordinator from the control group PC centres will be contacted and interviewed by phone calls to explore any external events and contextual factors that could Cost of implementation have influenced outcomes on the usual care groups and, To assess the cost of implementing the intervention, all therefore, the results of the cRCT. human and material resources used in each stage of the implementation process to put the IMA intervention into Data collection practice will be collected and taken into account. The specific objectives and research questions, as well as the data collection method used to assess the first three Data collection methods domains are presented in table 1 (implementation), Quantitative methods table 2 (mechanisms of impact) and table 3 (context). Monitoring data Specific quantitative and qualitative methods used to Data will be collected from the operative records, website meet the process evaluation aims and objectives are records and clinical records from real-­world databases in described for each domain. the public PC system in Catalonia (System for the Devel- Implementation opment of Research in Primary Care).45 Data will be Data will be collected on intervention fidelity to identify structured and descriptively summarised to assess fidelity, how consistent the implementation of the intervention context and cost of implementation through: ► Professional engagement: number of PC centres and was with the initial plan and if it required any adapta- tions during the trial, as well as assess the implementation professionals that decline to participate after the into routine practice (table 1). Fidelity will be assessed information session. ► Training attendance rate. through quantitative data on professional interaction and the intervention implementation plan (PC centres ► Intervention tools usage rate: website indicators and professional engagement, training attendance, use of (number of views, percentage of rebound, mean view intervention tools and follow-­up consultations). Adapta- time and depth) and number of times the leaflet was tions will be assessed using quantitative data from profes- downloaded. sionals’ feedback questionnaires and qualitative data ► Follow-­up consultation rate at the PC centre after a from the coordinator’s field diary. new prescription. Additionally, qualitative methods will be used to eval- ► Demographic records: PC centre size and location, uate the implementation of the IMA intervention into number of professionals, socioeconomic level of the routine PC centre practice. Interviews with professionals area, rurality, average age of the population and the will assess the perceived need and adequacy of the IMA proportion of the immigrant population. intervention as well as measures used to appraise it. ► Implementation costs: human resources based on Professionals’ feedback questionnaires will collect data time invested and professional category, and consum- on professionals’ attitudes towards the IMA intervention able materials based on units used. before and after the trial and how it is operationalised Professionals’ questionnaires and integrated into routine practice. Professionals will be asked to complete post-­ training Mechanisms of impact questionnaires to evaluate the quality of the training and Qualitative methods will be used to identify and under- professionals’ understanding of SDM. Furthermore, ques- stand the active mechanisms of the IMA intervention tionnaires will be sent by email to professionals during that bring about any effects and explains the interven- and after the cRCT. These will provide measures about tion’s logic (table 2). Interviews with professionals and adaptation and implementation, as well as professionals’ patients will explore their perspectives and experiences attitudes towards the intervention and its usefulness in with the intervention, potential changes to professionals’ clinical practice. 6 Corral-­Partearroyo C, et al. BMJ Open 2022;12:e067468. doi:10.1136/bmjopen-2022-067468 Open access Table 1 Implementation domain: specific objectives, research questions and data sources and collection methods Implementation Specific objectives Research questions Data source Data collection Fidelity and Understand the 1.1. How consistent is the Operative records, Monitoring data adaptation extent to which the intervention implementation website records and extraction and IMA intervention plan? real-­world databases questionnaires. was implemented as (patients’ clinical intended. records). 1. How is the 1.2. Did the IMA intervention Professionals. Questionnaires and field IMA intervention require any adaptations diaries. implemented? during the cRCT? Coherence Understand how 2.1. How is the IMA Professionals. Interviews. professionals make intervention conceptualised sense of the IMA by professionals? intervention. 2.2. What are the Professionals. Questionnaires and 2. What is the IMA professionals’ perspectives interviews. intervention for and attitudes towards the use professionals? and usefulness of the IMA intervention? Cognitive Understand how 3.1. How do professionals Professionals. Questionnaires and participation professionals engage engage and commit with the interviews. and commit with the IMA intervention? IMA intervention. 3.2. What factors promote Professionals. Interviews. 3. Who implements the or inhibit professionals’ IMA intervention? participation and commitment? Collective action Understand how 4.1. How are the resources Professionals. Questionnaires and professionals make of the IMA intervention interviews. use and execute the structured and used? intervention as part of 4.2. To what extend and why Professionals. Questionnaires and their clinical practice. have professionals integrated interviews. 4. How is the the intervention into their IMA intervention clinical practice? operationalised? 4.3. To what extent and why Professionals. Questionnaires and do participants enact the IMA interviews. intervention? Reflexive monitoring Understand how 5.1. How the professionals Professionals. Interviews and professionals assess appraise the IMA intervention questionnaires. and comprehend the and its effects? effect of the intervention 5.2. How the professionals Professionals. Interviews and on their clinical practice. value the IMA intervention in questionnaires. 5. How is the comparison with standard IMA intervention practice? understood? Professionals: GPs, nurses and pharmacists. cRCT, cluster-­randomised controlled trial; GPs, general practitioners; IMA, Initial Medication Adherence. Qualitative methods Interviews Field diary Individual semistructured interviews will be conducted A field diary will be completed by a member of the during and after the cRCT with professionals to explore research team. It will contain field notes from periodic their perspectives and experiences after implementing calls (every 2 weeks the first month, and monthly until the IMA intervention and with patients to determine the study finishes) to the PC centre coordinators. Addi- their experience with the IMA intervention and SDM tionally, field diaries will be completed by each PC centre and its impact on their behaviour in relation to the treat- coordinator. These will include data on any barriers, facil- ment. Approximately 30–40 interviews will be carried itators or thoughts concerning the organisation and oper- out with professionals and 20–30 with patients to ensure ation of the PC centre or pharmacy and the intervention. representativeness. Focus groups will be conducted with Corral-­Partearroyo C, et al. BMJ Open 2022;12:e067468. doi:10.1136/bmjopen-2022-067468 7 Open access Table 2 Mechanisms of impact domain: specific objectives, research questions and data sources and collection methods Mechanisms of impact Specific objectives Research questions Data sources Data collection Participants’ experiences Understanding the 1. What are the experiences of the Professionals Interviews. mechanism of the participants (professionals and and patients. IMA intervention that patients) with the intervention? influences the outcomes 2. What attitude and behaviour Professionals Interviews. and explains its logic. changes have occurred because of and patients. the intervention? Intended and unintended Understanding anticipated 3. Did the intervention lead Professionals Interviews and consequences and unanticipated to anticipated pathways or and patients. field diary. consequences of the IMA consequences? intervention and its effects 4. Did the intervention lead to on the outcomes. any unanticipated pathways or consequences? Professionals: GPs, nurses and pharmacists. GPs, general practitioners; IMA, Initial Medication Adherence. professionals after the cRCT to understand the interven- Analysis tion’s impact mechanisms and explore professionals’ The analysis of process evaluation data will be performed opinions of the IMA intervention and its integration into throughout the study and at the end. Quantitative data the PC centre and pharmacy practice. Moreover, we will will be analysed using descriptive statistics (ie, counts, explore the perceived barriers and facilitators to imple- proportions and means) and regression models using mentation and continuity of the intervention in PC and Stata V.17 to describe how the intervention was imple- in particular those related to COVID-­19 outbreaks. About mented overall and explore variations between PC centres three to four focus groups will be conducted with profes- and pharmacies. sionals from varying PC centres. Interviews and focus Qualitative data will be analysed using the principles of groups will be recorded, anonymised and transcribed by framework analysis by qualitative researchers.46 47 This will the research team before analysis. help researchers to organise large amounts of data system- Different types of data will be collected at different atically and focus the analysis as a group (PC centres) time points: before, during, and after the trial to account and as individuals (professional and patient). Field notes for the intervention dynamics and to comprehend how (from diaries) and transcripts from the interviews will be the context and the intervention adapt to one another included as narrative data. After a process of familiarisa- (figure 4). tion with the data (listening to recordings and reading Table 3 Context domain: specific objectives, research questions and data sources and collection methods Context Specific objectives Research questions Data sources Data collection Intervention Understanding the 1. What is the context of the PC centres? Professionals, Questionnaires group conditions in which patients, and monitoring the intervention is demographic data extraction. implemented that records. can be relevant 2. What mechanisms of the IMA intervention and Professionals Interviews and to the process of consequences change depending on the context, and patients. field diary. the intervention and what can explain these differences? mechanisms. 3. Was there any contextual factor related to the Professionals. Interviews. community, PC centre, professional or patient that could have influenced the outcomes of the cRCT? Control group Evaluate contextual and 4. Was there any contextual factor related to the Professionals. Interviews. organisational changes, community, PC centre, professional or patient and understand the that could have influenced the outcomes of the factors that could cRCT? influence the process. Professionals: GPs, nurses and pharmacists. cRCT, cluster-­randomised controlled trial; GPs, general practitioners; IMA, Initial Medication Adherence; PC, primary care. 8 Corral-­Partearroyo C, et al. BMJ Open 2022;12:e067468. doi:10.1136/bmjopen-2022-067468 Open access ETHICS AND DISSEMINATION The IMA-­ cRCT and its integrated process evaluation were approved by the Research Ethics Comittee (Comitè Ètic d'Investigació amb medicaments (CEIm)) at IDIAP Jordi Gol, code CEIm 21/051 P. The IMA-­ cRCT is a low-­intensity intervention clinical trial where groups of subjects are allocated to the intervention and control groups. Informed consent from patients participating in the clinical trial will be obtained by simplified means, and it fulfils the conditions described in Regulation (EU) No 536/201451 and the Real Decreto 1090/2015.52 Details of how informed consent will be obtained by simplified means are described somewhere else.35 Participation in the process evaluation is entirely voluntary. As approved by the CEIm, all healthcare professionals participating Figure 4 Process evaluation timeline. *Pretrial: September in the process evaluation will have signed an informed 2021 until February 2022; trial: March 2022 until September consent prior to the trial commencement agreeing to 2022; Post-­trial: September 2022 until December 2022. have feedback questionnaires sent by mail and to take cRCT, cluster randomised controlled trial. part in an interview if invited to do so towards the end of the trial. Patients participating in the process evaluation will sign an informed consent after the recruitment and field notes), the researchers will use thematic content prior to the beginning of interviews. All participants have analysis48 to generate a coding framework following a the right to refuse to participate and to withdraw from the mixed-­method approach: deductive and inductive. The coding frameworks generated by the researchers will be study at any time. put in common until a final one is created and applied Findings will be disseminated through publications and to all the data. Data will be organised by cases and cate- conferences, as well as presentations to healthcare profes- gories and will be compared within cases (PC centres) sionals and stakeholders from healthcare organisations in and between cases (professionals and patients) while Catalonia. Full details of the dissemination strategy are mapping and interpreting it. NVivo software will be used outlined in the main trial protocol.35 to manage the data. Author affiliations 1 Health Technology Assessment in Primary Care and Mental Health (PRISMA) Triangulation of results Research Group, Parc Sanitari Sant Joan de Deu, Institut de Recerca Sant Joan de Quantitative and qualitative data from the process evalu- Deu, St Boi de Llobregat, Catalunya, Spain ation will be analysed separately and then interpreted in 2 Department of Paediatrics, Obstetrics, Gynaecology and Preventive Medicine, combination.49 50 First, two researchers will combine and Universitat Autonoma de Barcelona, Bellaterra, Catalunya, Spain 3 compare the results of both, quantitative and qualitative, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Catalunya, Spain analyses independently. Then, a final summary of key 4 Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), findings will be produced jointly by the two researchers, Barcelona, Spain and if there are any unresolved disagreements, another 5 Unitat de Suport a la Recerca Regió Metropolitana Sud, Fundació Institut researcher will be involved. The final summary of key Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina findings will be presented to the rest of the research team (IDIAPJGol), Barcelona, Catalunya, Spain 6 Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública for review and clarification. The combined interpretation (CIBERESP), Madrid, Comunidad de Madrid, Spain of results will allow us to generate deeper insights than 7 Primary Care Centre Bartomeu Fabrés Anglada, Institut Català de la Salut Gerència use of either of the methods alone. Territorial Metropolitana Sud, Barcelona, Catalunya, Spain Additionally, process and effectiveness evaluation results will be integrated. Analyses will be performed Acknowledgements This work has been carried out within the framework of the separately, and once both analyses are done, the results PhD programme in Methodology of Biomedical Research and Public Health at the Universitat Autònoma de Barcelona. will be combined. Combining process and effectiveness Contributors MR-­V obtained financing for this study and, together with CC-­P, led results will facilitate better understanding and interpreta- the design, conduct and monitoring of the process evaluation. MG-­G and MTP-­M tion of the IMA-­cRCT outcomes. supported the design of the process evaluation. All authors will have a role in collecting and analysing process evaluation data as per their field of expertise. CC-­ Patient and public involvement P wrote the first draft of the manuscript and AS-­V, MG-­G, MTP-­M, CG-­G, MdCO-­P, Patient and public were not involved in setting the IA-­L and MR-­V added to and approved the final manuscript. research questions and outcomes of the no-­ initiation Funding This project has received funding from the European Research project, yet they have been closely involved in the devel- Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 948973). IA-­L has a CIBERESP contract (CIBER opment and design of the IMA intervention and its in Epidemiology and Public Health, CB16/02/00322). MTP-­M has the '16th ICS support tools and will be informed of the results through support for the promotion of group research strategies through the intensification the project website suitable for a non-­specialist audience. of researchers' (7Z20/028), from the IDIAP Jordi Gol. CG-­G has the '17th ICS Corral-­Partearroyo C, et al. BMJ Open 2022;12:e067468. doi:10.1136/bmjopen-2022-067468 9 Open access support for the promotion of group research strategies through the intensification of 17 Fischer MA, Jones JB, Wright E, et al. A randomized telephone researchers' (7Z21/019), from the IDIAP Jordi Gol. intervention trial to reduce primary medication nonadherence. J Manag Care Spec Pharm 2015;21:124–31. Competing interests None declared. 18 O'Connor PJ, Schmittdiel JA, Pathak RD, et al. Randomized trial of Patient and public involvement Patients and/or the public were involved in the telephone outreach to improve medication adherence and metabolic control in adults with diabetes. Diabetes Care 2014;37:3317–24. design, or conduct, or reporting, or dissemination plans of this research. Refer to 19 Kerner DE, Knezevich EL. Use of communication tool within the Methods section for further details. electronic medical record to improve primary nonadherence. J Am Patient consent for publication Not applicable. 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