Using the Medical Research Council framework for development and evaluation of complex interventions in a low resource setting to develop a theory-based treatment support intervention delivered via SMS text message to improve blood pressure control

We searched PubMed, Cochrane reviews, and Google for systematic reviews and published original studies from 2000 onwards that were written in English. We used search terms including “mobile health, text-message, adherence, high blood pressure, hypertension and adherence”. We revisited the literature and narrowed the focus of our reviews as development of the intervention progressed. We set up automatic alerts to monitor the relevant literature for updates.

There is some evidence that clinical outcomes for treatment of chronic conditions can be modestly improved through targeting adherence behaviour [4, 22], with a number of trials in hypertension [5, 23‐25]. The most effective strategies for improving adherence were complex including combinations of more instructions and health education for patients, disease and treatment-specific adherence counselling, automated and in-person telephone follow-up, and reminders (for pills, appointments, and prescription refills) [22]. In addition some strategies can be costly, for example with case management and pharmacy-based education. These approaches may not be practical in a low-resource setting.

Some studies report that mobile phone messaging interventions may provide benefit in supporting the self-management of long-term illnesses [7, 26], and have the potential to support lifestyle change, including smoking cessation [7, 27]. However randomised trials of the effectiveness of mobile phone messaging in the management of hypertension are few, include additional components (telemonitoring), often focus on high-risk groups such as stroke survivors and renal transplant recipients, and are based in high-resource settings [23, 28‐31].

We set up an expert multi-disciplinary group comprising two specialist general practitioners, two specialist physicians, three biomedical engineers, a health systems researcher, and an epidemiologist. As a team we met formally to agree upon the research problem and the underlying principles guiding the intervention development process. Thereafter we worked in smaller groups to develop the intervention. We maintained written logs of the iterative steps of the intervention development and remained in regular contact with the full group via email and teleconference. When the group met formally we reported on technical progress, resource allocation, implementation issues, and new evidence from the literature or the field.

We used semi-structured interviews and focus groups with three stakeholder groups: (1) Patients with high blood pressure and other chronic diseases (n = 35), (2) primary care health professionals (general practitioners, professional nurses, staff nurses, pharmacists, allied health professionals, reception staff) (n = 12), (3) health care system service providers and subcontractors (provincial health systems managers (n = 5), third party providers of off-site pre-packaged repeat prescription services (n = 3)).

South Africa is a middle-income country with high levels of income inequality and a quadruple burden of disease (HIV/AIDS, maternal and child, non-communicable diseases, violence.) [32, 33] Health care is provided for most South Africans (over 80%) by publicly funded state run facilities the foundation of which are primary care facilities. Medical doctors and nurses (some who have the right to prescribe medications) staff facilities and provide diagnostic, and monitoring services; treatment including all medications is free for patients attending primary care (user fees for primary care were abolished in 1997.) [34] National guidelines for the treatment of high blood pressure exist and are regularly updated [35].There is an essential drugs list and medicines for high blood pressure available in primary care include thiazide and other diuretics, calcium channel blockers, ace-inhibitors, and beta-blockers. Patients maybe prescribed other anti-hypertensive agents like ARBs by specialists. Statins and Aspirin are also available [36].

With the stakeholders described above we explored the problem of high blood pressure and poor control in busy and resource constrained publically-funded primary care facilities. A range of problems were identified that were seen as barriers to providing optimal care and potential targets for intervention. These included organisation of care (failure of systems for referral between primary and secondary care and medication access), service provision (failure of clinicians to adhere to management guidelines), and patient-level factors such as sub-optimal self-management and treatment adherence. From discussion with the various stakeholder groups it emerged that patient-level factors resulting in failure to attend clinic appointments and collect and take medication regularly was both a major concern and a feasible and acceptable potential target for developing an intervention to improve blood pressure control. The underlying hypothesis was that facilitating communication between patients and the health care system might lead to changes in treatment adherence behaviour and improve health outcomes.

We used a causal model to link theoretically relevant behavioural determinants to specific adherence related behaviours. We linked these to health impacts and outcomes along a hypothesised casual pathway [7, 8]. We used validated measures to assess important variables along the causal pathway. (See Fig. 2).

To test assumptions about access to and use of mobile phones we conducted a cross-sectional survey among adult patients attending any one of five community health centres in the Western Cape Metro Health Districts for treatment of hypertension and other chronic diseases. These outpatient facilities provide comprehensive primary care services for people living in the surrounding areas.

At primary health care level, the service is based on prevention by educating people about the benefits of a healthy lifestyle. Every clinic has a staff member who has the skills to diagnose and manage chronic conditions, from young to elderly patients. Patients can see the same nurse for repeat visits if they come regularly on the hypertension, diabetes or asthma clinic day. Counselling, compliance, and health education are also part of usual care. The service is led by clinical nurse practitioners and supported by doctors.

Arrangements are made by the clinic to minimise patient travel (especially by the elderly) by prescribing supplies of drugs that last one to 3 months. Staff often facilitate the initiation of clubs and special support groups for people with chronic diseases. In this way, a patient can get more information on special care and health education pertaining to their condition.

These primary-level services are supported and strengthened by other levels of care, including acute and specialised referral hospitals. If complications arise, patients will be referred to the next level of care [39, 40].

The interviewer-administered questionnaire asked about socio-demographic factors, contact with the clinic, chronic diseases and treatment burdens and about access to and the use of mobile phones. We sampled consecutive consenting adults from outpatient services over a period of 6 weeks. A total of 127 willing and eligible adult patients completed the survey (see Table 3). Mean age (SD) was 53.3 (14) years, 73% were women, and two-thirds had at least some high-school education. Ninety percent of participants reported having regular (daily) access to a mobile phone and 80% reported that their phone was with them most or all of the time. Most participants did not share their phones (76%); women reported sharing more frequently than men (24% versus 13%). Most participants (76%) reported having registered their phone numbers in their name and that they had had the same mobile phone number for two or more years (63%).

70% of participants reported feeling very confident about using their phone to receive an SMS text messages, while fewer participants (55%) were as confident about sending SMS text messages. Most (70%) felt very confident about sending a “Please Call Me” a free service provided by South African telecommunications providers across all local networks. Fewer than 10% of participants reported knowing how to use unstructured supplementary service data (USSD) communication protocol services like mobile-phone banking.

When asked about preferred ways for the clinic to be in touch, more women (74%) than men (47%) preferred SMS text messages to phone calls or other methods like home visits. The majority of participants reported that they would find reminders to attend up-coming clinic appoints (92%), collect medications (94%), and take medications (87%) helpful.

To optimise the intervention and test the technical systems responsible for message delivery we service tested the full intervention package with 19 patients recruited from patient-stakeholder focus groups. We tested the messages in the three languages most commonly used in Cape Town (English, Afrikaans, isiXhosa). Participants were contacted on a weekly basis by a researcher (experienced in qualitative methods) for a semi-structured interview on their experience of the intervention and the SMS text message delivery system. Suggestions were discussed with the intervention development team and changes were made where necessary.

In consultation with the local department of health we identified primary care health centres with high patient loads which might be suitable for a clinical trial to test the intervention. We visited each site to confirm the numbers of patients with high blood pressure using clinic registers, to map out patient flow through the clinic so we could operationalise trial procedures and identify potential challenges and barriers to implementation. One of the requirements for approval from the local department of health for research in public facilities is that normal activities are not interrupted. We therefore selected a health centre with a high caseload of patients with “chronic diseases of lifestyle” where we could recruit, screen, and enrol trial participants without interrupting the usual flow of patients through the clinic services.

We estimated we would be able to screen and recruit between 45 and 120 participants per week based on the functioning of the clinic and the experience of other local researchers [41]. We tested our capacity to recruit and screen participants using a clinical service offering blood pressure measurement to all patients attending the clinical service prior to the start of the trial. We tested trial registration and enrolment procedures including the receipt of an initial SMS text message at the time of enrolment. We collected detailed contact information on participants as well as the details of two next of kin (or similar) to maximise our chances of remaining in contact with participants for the duration of the trial. We monitored recruitment and retention on an ongoing basis.

Adequately powered trials of the effects of m-health interventions on important clinical outcomes are required to develop the evidence base for these approaches [7, 8]. As blood pressure is strongly and directly related to mortality we selected change in mean systolic blood pressure at 12-months from baseline as our primary outcome (clinical). We selected medication adherence (behavioural) as a secondary outcome. We decided not to report these as co-primary outcomes. As there were no previous trials of the effect of adherence support delivered by SMS text on blood pressure measures we used data from published trials of behavioural interventions delivered using other methods to estimate sample size [42]. A decrease in systolic blood pressure of 5 mmHg is associated with clinically important reduction in the relative risk of stroke and coronary heart disease events [43]. Based on a study population similar to that expected for the trial population we used the standard deviation (SD) of systolic blood pressure (22.0 mmHg) to calculate the required sample size [44]. We proposed an intended target sample size of 1215 participants, allowing for 20% loss to follow-up, (at least 405 in each group) to detect an absolute mean difference in SBP of 5 mmHg (SD 22) at 12 months from baseline, with 90% power and 0.05 (two-sided) level of significance. We used an intention to treat (ITT) approach for all analyses.

We decided that the most appropriate design to evaluate the effectiveness of adherence support via SMS text message would be a large single blind (concealed outcome assessment), individually randomised controlled trial. As the effect on clinical outcomes of an informational versus interactive system of SMS text messages was unclear from the published literature we decided to include two interventions; information-only SMS texts, and interactive SMS texts [8, 45]. To try to assess the effects of the behavioural intervention beyond receipt of an SMS text message from the clinic, we decided the control group would receive simple, infrequent text messages (less than one per month) related to the importance of ongoing trial participation [46]. Details of the intervention can be found in the TIDieR checklist (Table 4).

The trial is registered with the South African National Clinical Trials Register number (SANCTR DOH-27-1212-386; 28/12/2012); Pan Africa Trial Register (PACTR201411000724141; 14/12/2013); ClinicalTrials.​gov (NCT02019823; 24/12/2013).

We collected information on the costs of developing and delivering the intervention. The findings from this analysis will be reported separately.

The potential to accumulate evidence of effectiveness and to identify the “active components” in successful m-health interventions depends in part on replication of successful interventions across settings and refining interventions (adding or subtracting elements) using evidence of behaviour change. To facilitate use and adaptation of our intervention we have used recommendations for reporting intervention development to ensure we have described the intervention and its delivery in sufficient detail [13]. We have registered the trial and published the trial protocol [48], and we will publish the trial results (using CONSORT reporting guidelines) in an open access journal. We have also published the findings from the process evaluation [in press]. We have reported findings to participants, health care workers, policy makers, and funders.

We obtained permission to collect routine health data (dispensing and adherence data) from trial participants for a period of 6 months after the trial ended to explore for persistence of effects of the intervention (if any).