Tipos de estudios

Se incluyeron los ensayos controlados aleatorios (ECA) de diseño de grupos paralelos que asignaron al azar por participante o por grupos. No se incluyeron los ensayos cruzados porque este diseño no sería apropiado para evaluar los efectos sobre los eventos cardiovasculares o la mortalidad, debido a la naturaleza irreversible de estos eventos. Solo se incluyeron los ensayos con un seguimiento mínimo de un año para que las medidas de resultado se relacionaran con los comportamientos y los resultados de adherencia a la medicación mantenidos a más largo plazo. Se incluyeron los estudios publicados como texto completo y solamente como resumen, así como los datos no publicados.

Tipos de participantes

Se incluyeron adultos (18 años de edad en adelante) a los que se les habían prescrito fármacos para la prevención primaria de las EC. Como esta revisión se centró en la prevención primaria de las EC, solo se incluyeron los estudios en los que se reclutaron participantes que no habían tenido un evento previo de EC, definido como: infarto de miocardio anterior, accidente cerebrovascular, procedimiento de revascularización (injerto de derivación de arterias coronarias o intervención coronaria percutánea), pacientes con angina y pacientes con cardiopatía coronaria definida mediante angiografía. Cuando se identificaron ensayos que incluyeron un subconjunto de participantes elegibles, se estableció contacto con los autores para solicitarles datos solamente de los participantes de interés. Cuando no fue posible acceder a dichos datos, se aplicó un punto de corte mediante el cual solo se incluyeron los ensayos en los que al menos el 75% de los participantes cumplieron con los criterios para la prevención primaria.

Tipos de intervenciones

Se incluyeron los ensayos de intervenciones proporcionadas completa o parcialmente por teléfonos móviles para mejorar la adherencia a los fármacos cardiovasculares prescritos para la prevención primaria de las EC. Se incluyeron las intervenciones dirigidas a la adherencia de fármacos antihipertensivos (diuréticos similares a tiazida, inhibidores de la enzima convertidora de angiotensina, bloqueadores de los canales de calcio, betabloqueantes); fármacos para reducir los lípidos (estatinas); y fármacos antiplaquetarios (aspirina a dosis baja, fármacos antiplaquetarios que no son aspirina). Solo se incluyeron los ensayos dirigidos a la adherencia de al menos uno de estos fármacos. También se incluyeron los ensayos de intervenciones dirigidas a la adherencia a la medicación junto con otras modificaciones del estilo de vida.

Tipos de medida de resultado

Búsquedas electrónicas

We identified trials through systematic searches of the following bibliographic databases:

• Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 6);

• Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, MEDLINE Daily and MEDLINE (Ovid, 1946 to 21 June 2017);

• Embase (Ovid, 1980 to 2017 week 25);

• CINAHL Plus (EBSCOhost, 1937 to 21 June 2017);

• Conference Proceedings Citation Index‐Science (CPCI‐S) on Web of Science (Thomson Reuters, 1990 to 21 June 2017).

The search strategies are presented in Appendix 1. The Cochrane sensitivity‐precision maximising RCT filter was applied to MEDLINE (Ovid) and adaptations of it to the other databases, except CENTRAL (Lefebvre 2011).

We carried out a search of ClinicalTrials.gov (www.ClinicalTrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal (apps.who.int/trialsearch/) for ongoing or unpublished trials on 14 July 2017.

We imposed no restriction on date or language of publication.

We did not perform a separate search for adverse effects of mobile phone‐based interventions targeting medication adherence. We considered adverse effects described in included studies only.

Búsqueda de otros recursos

We checked the reference lists of all included studies and reviewed relevant articles for additional references. We also examined relevant retraction statements and errata for included studies.

Selección de los estudios

Two review authors (MP and SB) independently screened the titles and abstracts of all identified potential studies to decide whether to retrieve the full text (eligible or potentially eligible/unclear studies) or to discard the study. Two review authors (MP and SB) independently screened the retrieved full texts to identify studies for inclusion and identify and record reasons for exclusion of the ineligible studies in the Characteristics of excluded studies table. We resolved any disagreements though discussion, and where necessary, a third review author (CF) arbitrated. We excluded any duplicates. We collated multiple reports of the same RCT into a single entry. We completed a PRISMA flow diagram (Liberati 2009).

Extracción y manejo de los datos

We used a standardised, prepiloted form to extract data from the included studies for assessment of study quality and evidence synthesis. We contacted chief investigators for additional information where necessary. We extracted the following information.

• Methods: study design; total duration of study; study setting and date of study.

• Participants: number randomised; number lost to follow‐up/withdrawn; number analysed; mean age; age range; gender; proportion meeting criteria of 'primary prevention'; and inclusion criteria and exclusion criteria.

• Interventions: intervention; comparison; concomitant medications; excluded medications; intervention delivery mechanism (text messages/MMS/mobile application/combined); how intervention was developed; behaviour change technique(s) employed; if intervention was personalised; and frequency and duration of intervention receipt.

• Outcomes: primary and secondary outcomes specified and collected; adverse effects; and time points reported.

• Notes: funding for trial and notable conflicts of interest of trial authors.

Two review authors (MP and SB) independently extracted data and resolved any differences by returning to the original study reports and discussion with a third review author (CF) where necessary. One review author (MP) transferred data into the Review Manager 5 (Review Manager 2014). To ensure that there were no errors in data entry, one review author (SB) checked that the data entered into Review Manager 5 were consistent with those in the data extraction form.

Evaluación del riesgo de sesgo de los estudios incluidos

Two review authors (MP and SB) independently assessed the risk of bias for each study using the criteria detailed in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). For each of the following domains, we graded the potential bias as high, low or unclear.

• Random sequence generation.

• Allocation concealment.

• Blinding of participants and personnel.

• Blinding of outcome assessment.

• Incomplete outcome data.

• Selective outcome reporting.

• Other biases.

We resolved disagreements by discussion. Where necessary, we consulted a third review author (CF) to arbitrate. We constructed a 'Risk of bias' table including justifications for our judgements. Where information relating to the risk of bias came from unpublished data or correspondence with an author, we noted this. We summarised the risk of bias judgements across different studies for each of the domains listed. When considering treatment effects, we accounted for the risk of bias for the studies that contributed to that outcome.

Given the nature of the interventions included in this review, it is likely that blinding of participants and personnel would be impossible, therefore, we expected trials to be categorised at high risk of bias on this domain. For the overall study assessment, we categorised a trial as being at low risk of bias if it was rated as low risk in all the domains listed above (with the exception of blinding of participants and personnel). Trials that were at high or unclear risk of bias on any of the domains (except blinding of participants and personnel) were categorised as being at high risk of bias.

Medidas del efecto del tratamiento

We planned to analyse dichotomous outcome data as risk ratios (RR) with 95% confidence intervals (CI). We planned to analyse continuous outcome data as mean differences (MD) with 95% CIs, or if a continuous outcome had been measured in multiple ways, as a standardised mean difference (SMD) with 95% CIs. If it had been applicable, we would have entered data presented as a scale with a consistent direction of effect. If it had been applicable, we would have reported any skewed data identified as medians and interquartile ranges.

Cuestiones relativas a la unidad de análisis

We did not carry out a meta‐analysis because of the heterogeneity of the included studies' intervention content and delivery mechanisms; as a result, we had no unit of analysis issues. Had we conducted meta‐analyses, we would have included RCTs with a parallel design, and if we had identified any cluster randomised trials, we would have analysed the data accounting for clustering using the intracluster coefficient. If we had identified multi‐arm trials for inclusion in meta‐analyses, where there was more than one relevant intervention arm but only one control arm, we would have pooled the intervention arms for a single pair‐wise comparison as recommended by the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We planned to exclude intervention arms not appropriate for this review.

Manejo de los datos faltantes

We contacted investigators to obtain further information where necessary (e.g. when the study included a mixed population of participants who met the criteria for primary prevention and participants who met the criteria for secondary prevention, and when only a subset of participants had been prescribed CVD preventive medication). We also planned to contact investigators or study sponsors to obtain missing data (e.g. when a study was identified as abstract only). We planned that where this was not possible, and the missing data were considered a potential source of serious bias, we would conduct a sensitivity analysis to explore the impact of including such studies in the overall assessment of results.

Evaluación de la heterogeneidad

We considered the included trials to be too methodologically heterogeneous to pool the data in a meta‐analysis. Therefore, we described the studies narratively. We planned to use the I² statistic to measure heterogeneity across the trials for the analysis of each outcome. In constructing the narrative forest plots for those outcomes reported by multiple studies, we calculated the I² statistic and reported this. Had we considered the trials methodologically similar enough to pool, and had we identified there to be moderate to substantial heterogeneity (an I² statistic between 30% and 100%), we would have reported it and examined possible causes according to our prespecified subgroup analyses, subject to having a sufficient number of studies.

Evaluación de los sesgos de notificación

We did not use a funnel plot to explore possible small‐study biases for the primary outcomes as we only included four studies which were too heterogeneous to pool in a meta‐analysis. We planned that if the results from more the 10 trials could be pooled, we would use a funnel plot to explore possible small‐study biases for the primary outcomes.

Síntesis de los datos

We planned to carry out meta‐analyses only if it was meaningful to do so (i.e. if the interventions, participants and outcome measures were similar enough for pooling to make sense). We did not undertake meta‐analyses as the included studies were too heterogeneous in the content and delivery of their interventions. We presented the effect estimates for outcomes reported by multiple studies on forest plots (without pooling); it should be noted that in transferring effect estimates from papers into Review Manager 5 using the generic inverse variance method, some CIs differed from those reported in the original paper by a decimal place.

Should more studies become available in future updates of this review which enable meaningful meta‐analyses, we plan to use fixed‐effect models. In the presence of heterogeneity (an I² statistic in excess of 30%), we plan to examine whether this heterogeneity can be explained through our prespecified subgroup analyses. If these analyses account for the heterogeneity, we would only present the subgroup pooled effect estimates. If these subgroup analyses did not explain the heterogeneity, we would present results narratively. We intended to use fixed‐effect meta‐analysis and apply a conservative I² threshold to identify heterogeneity in this review to avoid overweighting smaller studies. This is because we consider that the heterogeneity observed in these behaviour change trials will primarily be a result of differences in the content of the interventions and differences in risk of bias.

Análisis de subgrupos e investigación de la heterogeneidad

We had planned to conduct the following subgroup analyses for the primary outcome of adherence to treatment if there had been sufficient studies:

• income region (by World Bank income group) (World Bank 2017);

• how text messages were developed (i.e. theory‐based, incorporating user views and based on evidence relating to factors influencing behaviour‐targeted versus other);

• intervention content (number behaviour change technique employed coded according to the taxonomy developed by Michie and colleagues (Michie 2015));

• delivery mechanisms (i.e. mobile phone messaging only, mobile applications only, combined mobile phone messaging and application, combined application and other).

Due to the limited number of studies, we were unable to conduct subgroup analyses. Should more trials become available for future updates of this review, we will re‐examine the planned subgroup analyses.

Análisis de sensibilidad

We planned to carry out a sensitivity analysis by only including studies with low risk of bias. As we were unable to carry out a meta‐analysis, no sensitivity analysis was conducted.