Supporting GPs and people with hypertension to maximise medication use to control blood pressure: Protocol for a pilot cluster RCT of the MIAMI intervention

Background: Hypertension is one of the most important risk factors for stroke and heart disease. Recent international guidelines have stated that 'poor adherence to treatment – in addition to physician inertia - is the most important cause of poor blood pressure control'. The MaxImising Adherence, Minimising Inertia (MIAMI) intervention, which has been developed using a systematic, theoretical, user-centred approach, aims to support general practitioners (GPs) and people with hypertension to maximise medication use, through the facilitation of adequate information exchange within consultations about long-term antihypertensive medication use and adherence skill development. The aim of the MIAMI pilot cluster randomised controlled trial (RCT) is to gather and analyse feasibility data to allow us to (1) refine the intervention, and (2) determine the feasibility of a definitive RCT. Methods: GP practices (n = 6) will be recruited and randomised to the intervention arm (n = 3) or usual care control arm (n = 3). Each practice will recruit 10 patient participants. For a patient to be eligible they must have a diagnosis of hypertension, be on two or more anti-hypertensive medications, must not be achieving recommended blood pressure levels, and be over the age of 65 years. Participants in the intervention arm will meet their GP and receive the MIAMI intervention twice over three months. Quantitative data collection will take place at baseline and three month follow up. A pilot health economic analysis and a qualitative sub-study will also be incorporated into the study. Discussion: This pilot cluster RCT of the MIAMI intervention will allow us to gather valuable acceptability and feasibility data to further refine the intervention so it optimally designed for both GP and patient use. In particular, the qualitative component will provide an insight into GP and patient experiences of using the intervention.


Introduction
Hypertension is one of the most important risk factors for stroke and heart disease 1 .A landmark study of twelve high income countries from 1976-2017 concluded that hypertension 'control rates have plateaued in the past decade, at levels lower than those in high quality hypertension programmes' 1 .International comparisons suggests that in Ireland there are relatively low levels of awareness of hypertension and relatively poor levels of control and suboptimal treatment.For example, estimates from the same international study indicate that the proportion of Irish male patients with controlled blood pressure is 17%, while the comparable figure in Canada is 69% 1 .A parallel paper reviewing the state of hypertension care for 1.1 million adults in 44 low-and middle-income countries 2 identified countries in each world region that performed better than expected from their economic development.Many of these countries, which spend much less on healthcare than Ireland, significantly outperformed Ireland in hypertension awareness, treatment and control.
Recent international guidelines have stated that 'poor adherence to treatment -in addition to physician inertia -is the most important cause of poor blood pressure (BP) control' 3 .The adverse impact of poor adherence to anti-hypertensive medication has been recently shown in a Korean study 4 .This showed, in a random sample of 33,728 patients with hypertension, that poor medication adherence was associated with higher mortality and the development of key negative cardiovascular outcomes.For example, patients with poor medication adherence had, in comparison to those with good adherence, worse ischaemic heart disease mortality (hazard ratio [HR] 1.64; 95% confidence interval [CI] 1. 16-2.31)  and cerebral haemorrhage (HR 2.19; 95% CI 1. 28-3.77).Improving adherence to antihypertensive medication has the potential to quickly lower blood pressure and to reduce the related cardiovascular risk in most patients 3 .Gupta and colleagues in a non-randomised study of 238 UK patients with apparent resistant hypertension (high blood pressure that is not responsive to treatment) attending a tertiary referral centre utilised sequential biochemical urine screening for assessment of adherence 5 .The results of this testing were fed back to patients, with subsequent significant improvements in both adherence and blood pressure (systolic 32.6mmHg and diastolic 7.5mmHg).This approach, referred to as chemical adherence testing, may have some potential to enhance collaboration between patients and physicians in optimising the management of hypertension 6 .
Clinical inertia is largely seen as failure to advance therapy when appropriate to do so, and this is particularly relevant in the treatment of hypertension.Two Irish studies have confirmed that suboptimal dosing is a significant issue in Irish general practice populations of patients with resistant hypertension 7 and post stroke and/or transient ischaemic attack 8 .In 646 patients with apparent resistant hypertension from 16 independent centres, i.e., community-based general practice sites, 19% of patients had adequate dosing for each hypertensive medication according to the World Health Organisation defined daily dose guidelines 9 .However, in terms of the definition of 'clinical inertia,' it can be argued that failure to advance therapy when indicated is just one facet of a larger phenomenon.Khunti and Davis argue that 'clinical inertia' is not only related to escalation of therapy but is a much wider concept and encompasses failure to improve care at many levels of health care 10 .In the context of hypertension care, we know that conversations around medication adherence are often avoided.A recent survey of 200 hypertension specialists in 30 countries found that the topic of medication taking was under attended to, despite its importance 11 .A similar survey of healthcare professionals (n = 3196) working in primary care in Europe found that less than half of respondents ever asked their patients whether they have missed any doses of their medication 12 .It can be argued, therefore, that tackling clinical inertia in hypertension care involves addressing issues of medication adherence as well as optimal dosing.The 'MaxImising Adherence, Minimising Inertia' (MIAMI) intervention, which has been developed using a systematic, theoretical, user-centred approach, aims to support GPs and people with hypertension to maximise medication use.The Behaviour Change Wheel (BCW) 13 and Collective Intelligence (CI) methodology 14 were used in development and a detailed description of the process will be described elsewhere.In brief, we used evidence developed by the team 7,[15][16][17][18] , along with Public and Patient Involvement (PPI) input, to inform Phase 1 of the BCW, 'understanding the behaviour'.We then operationalised Phase 2 'identifying intervention options' and Phase 3 'identifying content and implementation options' through a CI workshop.Workshop attendees included people with backgrounds in GP, nursing, pharmacy, clinical pharmacology, health psychology, PPI contributors and lay people.Scenario-based design (informed by Phase 1 and relevant theory 19,20 ) was used to generate user needs, from both the GP and patient perspective.The outputs of the workshop were refined with guidance from the PPI panel.A full description of the intervention can be seen in Table 2.The MIAMI intervention specifically targets older patients (over 65 years of age), as they are at increased risk from both hypertension 3 and medication non-adherence, given the increased likelihood of Any further responses from the reviewers can be found at the end of the article multimorbidity and the related challenge of polypharmacy in older adulthood 21,22 .

Aims of the MIAMI cluster pilot RCT
The aim of the MIAMI pilot cluster randomised controlled trial (RCT) is to gather and analyse feasibility data to allow us to (1) refine the MIAMI intervention, and (2) determine the feasibility of a definitive RCT.
Specifically, the MIAMI pilot cluster RCT has the following objectives: 1. To investigate if the MIAMI intervention is acceptable to GPs and people with hypertension; 2. To assess the feasibility of recruitment and retention of both practices and patients; 3. To assess the feasibility of outcomes and measures used; 4. To conduct a pilot health economic assessment of the MIAMI intervention; 5. To inform the sample size calculation, including the optimal number of GP practices (clusters) and people with hypertension (participants), for a definitive cluster RCT; 6. To assess the feasibility of a 'Study Within A Trial' focused on the impact of an informational video on study retention levels This protocol has been registered on ISRCTN (registration number: ISRCTN85009436) and all study materials can be found as Extended data 23 .

Design
This is a pilot cluster RCT with an intervention arm and a control arm.The intervention arm is the MIAMI intervention and the control arm is usual care.

Inclusion and exclusion criteria
Please see Table 1 for inclusion and exclusion criteria.

Sample size calculations
As this is a pilot study, a formal sample size calculation is not warranted.One of the aims of the study is to generate the estimates needed for a sample size calculation for a future definitive trial.In order to generate the reliable estimates needed, it is proposed that six clusters (three in the intervention arm, three in the control arm) each containing 10 patient participants are recruited.Each cluster will be an independent GP practice, meeting the inclusion criteria laid out in Table 1.The number of clusters chosen is governed by pragmatism and to provide a representative sample (using best judgement) of the diversity in the population of clusters from which data in the definitive trial will be sampled.

GP practice recruitment
General practices affiliated with the HRB Primary Care Clinical Trials Network Ireland, who have previously expressed an interest in hypertension research and are within the catchment area of the biochemistry laboratory at University Hospital Galway, will be invited to participate.A detailed practice information sheet will be provided (see Extended data).
If invited practices express interest in taking part, research staff on the project will follow up with a telephone call to provide further details about the study.All participating practices will be offered €100 per recruited patient participant to cover the additional administration costs, as well as a right to keep a 24-hour ambulatory blood pressure monitor (ABPM) after the study has ended.

Patient participant recruitment
The practice administrator/manager, supported by the research team, will search the practice records using the inclusion and exclusion criteria to identify eligible patient participants.

Details Timing of delivery
Pre-consultation plan Short document containing • ' What do you want to talk about at your blood pressure appointment today' (to be filled in prior to consultation) • Textbox for BP reading and whether it is in target • Textbox for goal setting and action planning (to be used during consultation) Given at practice visit 2, prior to GP consultation.To be used at the beginning and during the consultation.
This is optional and patient participants can decide whether or not they want to use it.
Once identified, the practice will post a letter of invitation and information sheet to a random selection of 20 patients from each practice (this is based on a 50% recruitment rate as seen in a previous feasibility study 24 ).The random selection will be facilitated using random.org.These patients will be asked to contact the research team if interested in taking part.If there is no response after 10 days, the practice will contact eligible patients by phone and explain the information in the letters and offer an opportunity to ask questions.If the target of 10 participants is not met at that point, another 10-20 letters will be sent out, dependent on the response to date.This will continue until the target is met.All interested patients will receive a consent form in the post, which they will be asked to return to the team before the trial begins.All patient participants will be offered a €40 multi-store voucher to cover costs associated with their participation (e.g., travel to the practice for study visits).

Randomisation procedures
After all participants have been recruited, three GP practices will be randomised to the MIAMI intervention and three will be randomised to the usual care control.The code to generate the randomisation plan will be written in R (using a reproducible random generation seed) and implemented by an independent statistician.

Intervention procedures
The MIAMI intervention will be delivered at a minimum of one GP appointment during a three-month period.The intervention arm and control arm are described below.

MIAMI intervention arm
The MIAMI intervention is a structured set of supports for GPs and patients with hypertension to facilitate adequate information exchange within consultations about long-term antihypertensive medication use and adherence skill development.Full details are in Table 2.It will include the following, where indicated:

Patients
• Wearing an ABPM and providing a urine sample for a chemical urine test of adherence.
• Filling out a brief 'pre-consultation plan' before a GP consultation.

GPs
• Training in how to structure a consultation around adherence issues.This will be provided through online videos and will take a maximum of 30 minutes.
• A booklet with key takeaways from training videos and current guidance around blood pressure medication prescribing (from the European Society of Hypertension 3 and American College of Cardiology 25 ) • A drop down menu on GP software which will provide a reminder of consultation guide and a list of resources that can be recommended to the patient (e.g., medication reminders -dontforget.ieand BP information -croi.ie/health/heart-conditions/high-blood-pressure/) The patient flow through the intervention arm can be seen in Figure 1.

Control group
Participants in the control group will receive usual care.This would involve visits by patients to GPs where blood pressure would be measured manually via office-based sphygmomanometer or automated blood pressure device and management decision on how best to proceed would stem from this meeting, which is typically scheduled every 3-4 months for patients over 65.Blood pressure may also be assessed via out of office assessment if manual readings are high.Previous research  has demonstrated typical appointments between hypertensive patient and their GP does not often involve structured discussions about adherence 11,12 .
Patient flow through the control arm can be seen in Figure 2.

Data collection Participant quantitative data collection Patients
Patient data collection will occur at two time points during the trial.These include: T1) Baseline T2) Follow up (3 months later) Self-report questionnaires for T1 and T2 will be administered to participants at the GP practice.The questionnaire will be paper based and will include questions on demographics, outcome measures, and resource use (for health economic analysis).
For the blood pressure measurement outcomes, participants will be given an ABPM at T1 and T2.For the objective adherence outcome, participants will provide a urine sample which will undergo chemical adherence testing 6 .All other quantitative data will be taken from practice records by the lead researcher.
Please see Table 3 for description of outcome measures.

GPs
This data will be collected at T1 only.A questionnaire will gather demographic and personal information including: length of time working in primary care, employment basis (full-time, part-time, and other), practice location (urban/rural) and practice size.

Feasibility and acceptability data
The following will also be measured: 1. Recruitment of GP practices will be assessed by documenting the number of invitations sent, the number of refusals and number of acceptances.
2. Recruitment of patients will be assessed by documenting the number of invitations sent, the number of initial responses, the number of follow-up phone-calls required, the number of refusals and the number of acceptances.
3. Attrition of participants will be documented at every time-point.
4. Levels of missing data in returned questionnaires will be reported.
5. The comprehensibility and acceptability of all questionnaires will be measured by asking participants how the questionnaires might be improved, and how long they took to complete.

Qualitative evaluation of feasibility and acceptability
A descriptive qualitative approach 26 will be used to explore the perceptions and experiences of people with hypertension (n = 6) and GPs (n = 3) of participating in the MIAMI study and their views as to the acceptability of the intervention.
In the intervention arm, six patient participants will be invited to participate in one-to-one interviews at month 1 (post first GP visit) and again at month 3 (post follow up visit).These  *** Four of the five subscales -recent psychometric evaluation evidence that indicates that 'Follow-up/Coordination' subscale and item 10 is the least psychometrically robust and that a 14-item measure with an underlying four factor structure provides more psychometrically robust measurement than the original 20 item scale with a 5 factor structure 32 longitudinal interviews will give an insight into participants' views and changes in perceptions as they progress through the study.In addition, GPs delivering the intervention (n = 3) will be interviewed at month 3.These interviews will focus on their experiences of delivering the intervention and their views on its acceptability and feasibility in practice.
Patient participants (n = 6) and GPs (n = 3) in the control arm will be invited to one-to-one interviews at month 3.The focus of these interviews will be to acceptability of taking part in a pilot RCT in the control arm.The interview guides can be seen as Extended data.Thematic analysis as outlined by Braun & Clarke 33 will be used to analyse the data.Rigour will be maintained by adhering to the criteria described by Lincoln & Guba 34 and the computer software package NVivo will be used to assist the analysis process.

Fidelity
Fidelity assessment will provide valuable information on the feasibility of intervention implementation, as well as information on the acceptability and usefulness of the fidelity assessment procedures which may require adaptation for the definitive RCT.

MIAMI intervention training fidelity
Attendance by GPs in each practice at the initial training method will be recorded.Analytics such as the number of clicks and time spent on each page will also be available from the GP training website.
Analytics such as number of clicks and time spent on each page will be available from the GP training website.

MIAMI intervention delivery fidelity
A checklist embedded as a 'Drop-Down Menu' in the Socrates practice software system will be developed for the distinct components in the MIAMI intervention.This checklist will be completed by GP participants during each consultation and subsequently reviewed by the research team.
Fidelity will also be explored in the qualitative interviews with patient and GP participants.

Health economic analysis
A pilot health economic assessment of the MIAMI intervention will be conducted to provide preliminary cost effectiveness estimates and to inform the design of a future definitive economic evaluation.A healthcare perspective will be adopted with respect to costing.Data collection tools will be developed for the purposes of measuring data on resource use over the trial follow-up period.An exploratory process will be conducted to identify the resource use and costs associated with the delivery of the MIAMI intervention.Unit costs will be identified and applied to convert data on resource use to costs.For the pilot cost utility analysis, Quality Adjusted Life Years (QALYs) will be estimated using data collected using the EuroQol EQ-5D-5L instrument 35 and the ICECAP-O instrument 36 at baseline and follow up.A preliminary analysis will be undertaken to provide information on the incremental costs and incremental effects of the MIAMI intervention relative to the usual care control, and a range of techniques will be employed to address uncertainty.The pilot analysis is designed to determine the feasibility of the approaches adopted and not cost effectiveness.

Statistical analysis
Suitable summary statistics (e.g., mean, standard deviation, and frequency) will be provided for the main outcomes.These summary statistics will guide the sample size calculation needed for the future definitive two arm cluster RCT 37,38 .

Progression to a full RCT
The following pre-defined stop/go criteria in Table 4 will be used to inform the decision on whether to proceed to a full trial.
The Decision-making after Pilot and feasibility Trials (ADePT) process involves examining 14 methodological issues that are pertinent to feasibility research.We will use this process, as well as the progression criteria, findings from the qualitative research, and discussions with the study research team, Trial Management Group, Trial Steering Committee and the public and patient involvement (PPI) panel to make a decision on whether to progress to full RCT.

Study within a trial (SWAT)
A pilot SWAT (study within a trial) will be embedded within this pilot RCT.The objective of the SWAT will be to evaluate the effect of a video outlining the importance of the research on retention to the study.This is in line with objective 2 of the pilot RCT, and will provide additional data on the feasibility of retention to the study.Videos have been used in the past to improve recruitment to studies 39,40 and it is possible that this effect may also apply to retention.Half of the patient participants will be randomised to the intervention group.
Randomisation will be at the individual, rather than cluster level, meaning participants in all clusters will have an equal chance of receiving the intervention, regardless of pilot RCT arm allocation.Those in the SWAT intervention group will receive a text message with a link to the video at the mid-point of the study.The control group will not receive a text message and progress through the study as usual.The video will be less than five minutes long and contain information on the prevalence of high blood pressure, risks of high blood pressure, and justification for the current research.The primary outcome will be the number and proportion of participants who are retained in the study; however, as this is a pilot SWAT, we will not test for effectiveness.We will analyse the feasibility and acceptability of the SWAT through descriptive statistics, including the an adaptation of the Decision Making Questionnaire 41 and qualitative work.

Public and patient involvement (PPI)
The study team includes a public and patient involvement (PPI) panel of six people living with hypertension.This panel meets quarterly and contributes to tasks such as development of the protocol, patient materials and SWAT materials.Two members of the panel also attend and contribute to Trial Steering Committee meetings.

Ethics and dissemination
Ethical approval has been obtained for all intervention sites from the Irish College of General Practitioners on 23/8/22 (ICGP_REC_22_014).The results of this pilot cluster RCT will be published in a peer-reviewed journal.

Study status
Five GPs practices have been recruited.Patient participant recruitment began in November 2022.

Discussion
Supporting GPs and people living with hypertension to work together to maximise medication use has the potential to significantly lower blood pressure in primary care in Ireland.This pilot cluster RCT of the MIAMI intervention will allow us to gather valuable acceptability and feasibility data to further refine the intervention so it optimally designed for both GP and patient use.In particular, the qualitative component will provide an insight into GP and patient experiences of using the intervention.
The pilot cluster RCT will also allow us to the assess the potential feasibility issues involved in running a definitive RCT in the Irish primary care context.One possible difficulty that may arise are the logistics and safety of running such a study during flu season and the possibility of another wave of coronavirus disease 2019 (COVID-19) infection.As this pilot cluster RCT is due to begin in winter 2022, it should allow us to gain an insight into this context.
This project contains the following extended data: -

Peter Knapp
University of York, York, England, UK Hypertension is clearly a problem in Ireland but I think the authors overstate the extent of it.Their citation (1) has been referenced selectively.The data from those surveys show that the estimated prevalence of hypertension in Ireland was 43% in women and 56% in men.(The equivalent figures for Canada were 36% and 34%).The data for Ireland come from 2009-11 (since when the position may have improved) while the data for Canada are from 2016-17.Clearly there is a problem in Ireland (and the problem is relatively big compared to some other countries), but the issue has been reported selectively in the paper.
The details of the pilot trial design seem sensible, collecting both quantitative and qualitative data to inform the design of a further trial.However, I'm concerned by 2 of the design decisions: First, if clinical inertia is one source of problems, why is one of the patients' entry criteria taking at least two anti-hypertensives?Would an example of clinical inertia be not prescribing a 2nd medicine for patients whose hypertension was not responsive to the 1st medicine?Will this patient entry criterion potentially lead to exclusion of patients currently being treated with 'clinical inertia'?Second, the authors describe two main sources of hypertension in older patients: clinical inertia (ie under-treatment) and patient non-compliance.While that seems convincing, the design of the trial potentially conflates the two sources of problems and might not allow them to be differentiated if the intervention is ineffective or only partly effective.Suppose the intervention has an effect on GPs' prescribing patterns but not on patient medicine-taking behaviour: a null result for the trial would not be an accurate reflection of the effect of the intervention.Can the data collection and analysis allow the two problem sources to be separated?
Is the rationale for, and objectives of, the study clearly described?Yes

Is the study design appropriate for the research question? Partly
Introduction: I realize this isn't the point of the current study, but it should be noted that resistant hypertension has a more specific definition than is listed at the bottom of page 3, 1 st column.See article by Yaxley 1 In several places the language should be more precise, some examples: This statement is confusing: "19% of patients had adequate dosing … according to the World Health Organisation defined daily dose guidelines" Adequate dosing is defined by the BP level, not an arbitrary dose.
You state that "…conversations around medication adherence are often avoided."I disagree with that term-overlooked perhaps, but to say avoided implies intent that is not evidence-based.
You state that the MIAMI intervention has been developed "… to maximise medication use."I think you mean to optimize?
You state: "The MIAMI intervention specifically targets older patients … increased risk from both hypertension and medication non-adherence, given increased likelihood of multimorbidity…" Several studies Please explain what you mean by "Receive MIAMI intervention" under Baseline practice visit 3.
The bullets on the previous page say the patient MIAMI intervention consists of wearing the ABPM and filling out the pre-consultation plan, which are already done at visits 1 and 2, respectively.This visit sounds like a scheduled HTN-focused visit with their GP.If that is part of the intervention, it should be included as an additional bullet in the methods description.
Page 9 1 st column, this text: "Analytics such as number of clicks and time spent…" is repeated twice.
Is the rationale for, and objectives of, the study clearly described?Yes

Are sufficient details of the methods provided to allow replication by others? Partly
Are the datasets clearly presented in a useable and accessible format?

Not applicable
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: population health, especially involving chronic disease management for hypertension, diabetes, osteopososis.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Buna Bhandari
University of New South Wales, Sydney, New South Wales, Australia

MIAMI study
This is an interesting study to address the non-adherence to antihypertensive medication and prevent further complications.I have added some comments for the improvement of the quality of the article.Objectives need revision, e.g.objectives 2,3, and 5 do not require "to collect quantitative and qualitative data".Author can directly write "to assess the feasibility outcomes" and how those objectives will be assessed, "Data collection process" can be detailed in the methods section.Rather it's better to mention what are those feasibility outcomes if possible. 1.
The protocol should be registered in a clinical trial registry such as ISRCTN, and the registration number should be provided in the paper.I noticed it is under process, so please provide the number once registered.

2.
Methods -please provide little details about the characteristics of the study cluster.In addition, it's not compulsory to have power calculation for the sample size in the pilot study, but it is worth mentioning how those 6 clusters and 10 participants in each cluster were decided.Please also specify whether these 10 include only patients or patients and GPs.
There is a mismatch in the information provided in the manuscript.

3.
I am not clear why the acceptability interview with the control arm is needed; what were the objectives of this interview?Please specify.

4.
Table 2 provides details about the MIAMI intervention, which is clear.However, the author has indicated in the background that Behavior change and Collective Intelligence methodologies were used to design the intervention, so it is unclear how those models/theories were used and how the intervention was designed.Though the author plans to discuss that in a separate paper, it is very important to provide some details about the intervention design process (MIAMI booklet, Computer guide development etc.) to ensure the robustness and comprehensiveness of this intervention.

5.
Please provide more details about the SWAT, as it is unclear how the participants will be randomized, whether they will be randomized within each cluster or not.In addition, which objectives of this pilot trial will lead to this SWAT?Need more clarification about the approach; it is confusing to the reader.

6.
Is the rationale for, and objectives of, the study clearly described?

Eimear Morrissey
This is an interesting study to address the non-adherence to antihypertensive medication and prevent further complications.I have added some comments for the improvement of the quality of the article.
We thank the reviewer for taking the time to review our manuscript.The comments have been very useful and we have added our responses below.
Objectives need revision, e.g.objectives 2,3, and 5 do not require "to collect quantitative and qualitative data".Author can directly write "to assess the feasibility outcomes" and how those objectives will be assessed, "Data collection process" can be detailed in the methods section.Rather it's better to mention what are those feasibility outcomes if possible.

1.
We have revised the framing of objectives 2, 3 and 5 in line with this suggestion and agree that the description of objectives is now clearer.The protocol should be registered in a clinical trial registry such as ISRCTN, and the registration number should be provided in the paper.I noticed it is under process, so please provide the number once registered.

1.
As noted, the ISRCTN registration was underway when this manuscript was submitted.Registration has been completed and the registration number is ISRCTN85009436.This has been updated in the manuscript (under section heading 'Aims of the MIAMI cluster pilot RCT).Methods -please provide little details about the characteristics of the study cluster.In addition, it's not compulsory to have power calculation for the sample size in the pilot study, but it is worth mentioning how those 6 clusters and 10 participants in each cluster were decided.Please also specify whether these 10 include only patients or patients and GPs.There is a mismatch in the information provided in the manuscript.

1.
We have added a description of the cluster (under section heading 'Sample size calculations') As mentioned in the manuscript, the number of clusters chosen was governed by pragmatism and to provide a diverse sample (urban and rural practices) from the population of clusters from which data in the definitive trial will be sampled.Our study statistician has estimated that for any future definitive trial, the population mean systolic clinic BP from this sample will be accurate to within +/-7 mmHg and the estimated population standard deviation to within 4 units.However, we are very aware that significant caution is required in applying such figures from pilot to definitive trials, and for this reason consider these estimates to be for illustration only.
The ten participants per cluster in this case refer to patient participants.This is stated in the 'sample size calculations' section.The number of GP participants in each cluster will be dependent on practice size.I am not clear why the acceptability interview with the control arm is needed; what were the objectives of this interview?Please specify.

1.
The objectives of these interviews are to explore the acceptability of being allocated to the 'usual care' arm of a pilot RCT in this context.This is an important aspect to explore, as previous research has shown that study participants can sometimes misunderstand clinical equipoise, and express a preference for intervention arm allocation 1 .These interviews will add important data to the assessment of the overall acceptability of conducting a pilot RCT in primary care in Ireland. 1. Houghton C, Dowling M, Meskell P, et al.Factors that impact on recruitment to randomised trials in health care: a qualitative evidence synthesis.Cochrane Database Syst Rev .2020; (10).
Table 2 provides details about the MIAMI intervention, which is clear.However, the author has indicated in the background that Behavior change and Collective Intelligence methodologies were used to design the intervention, so it is unclear how those models/theories were used and how the intervention was designed.Though the author plans to discuss that in a separate paper, it is very important to provide some details about the intervention design process (MIAMI booklet, Computer guide development etc.) to ensure the robustness and comprehensiveness of this intervention.

1.
As the reviewer has noted, we plan to outline the full development process of the MIAMI intervention in a separate paper, which is currently nearing completion.However, we agree that it is useful to include some detail here and we have added this (under section heading' Introduction'; final paragraph).
Please provide more details about the SWAT, as it is unclear how the participants will be randomized, whether they will be randomized within each cluster or not.In addition, which objectives of this pilot trial will lead to this SWAT?Need more clarification about the approach; it is confusing to the reader.

1.
Thank you for highlighting this, we have now restructured and added more detail to the SWAT section and believe it is much clearer (under section heading 'Study within a trial (SWAT)').
Competing Interests: None to disclose

Introduction•
included a longer description of the development of the intervention • revised framing of objectives 2, 3 and 5 • included ISRCTN registration number Methods • added a description of clusters (under 'Sample size calculations') • restructured and added more detail to the SWAT section (under 'Study Within A Trial')

Figure 1 .
Figure 1.Patient flow through MIAMI intervention arm.

Figure 2 .
Figure 2. Patient flow through the control arm.

Table 2 . MIAMI intervention. GP intervention components Component Details Timing of delivery
Sent relevant text message: YES/NO Text to copy and paste into text messages You can set up text messages to remind you to take your medication at dontforget.ie Information about blood pressure and blood pressure medication is available on the Croí website https://croi.ie/health/heart-conditions/high-blood-pressure/ *All GP practices in this study will be using Socrates software.Dropdown menus are easily integrated into this software and will be done by the research team prior to study beginning.Drop down menu on computer which contains a guide to the consultation.• Discussed ABPM YES/NO • Discussed urine results YES/NO • Made an agreed plan which may include: single pill combinations, 'blister pack' specification: YES/NO • Asked patient to form a habit (pair medication taking with another stable behaviour e.g. a mealtime/brushing teeth/ Coronation Street): YES/NO • Wrote out the agreed plan on the 'MIAMI pre-consultation tool' YES/NP •

Table 3 . Patient outcome measures.
** Ratios are calculated for each patient -based on the medications that could be detected -by dividing the total number of antihypertensive medications detected in spot urine into the total number of detectable antihypertensive medications prescribed, whereby total non-adherence was equal to 0 and perfect adherence was equal to 1 *This outcome will not be captured at baseline in the control arm, due to a concern around the provision of clinical information to GPs without guidance on management.It will be captured at follow up in the control arm, as all GPs will have access to intervention materials at study end.

Table 4 . Stop/go criteria.
*Retention will be defined as availability of final outcome measures.

Version 1
Reviewer Report 10 July 2023 https://doi.org/10.21956/hrbopenres.14939.r34045This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.