Effects of an Automated System of Pictograms to Facilitate Comprehension of Medical Indications: A Randomised Trial
Phase: NA
Conditions: Asthma Chronic, Adherence, Medication, Primary Health Care
Sponsor: Universidad de Concepcion

Study Protocol and Statistical Analysis Plan 
Protocol Title 
SIMAP: Automatic Association System and Medical Instructions to Pictograms to Facilitate 
Understanding and Retention. 
Sponsor 
University of Concepción n (Chile) 
ClinicalTrials.gov Identifier 
NCT05609760 
Principal Investigator 
Rosa Figueroa  
Version Date 
05-01-2024 
Note 
The text below is excerpted from the Institutional Review Board (IRB) protocols established for 
this study, originally granted approval on November 12, 2019, for implementation in Valparaíso 
city, and later extended to Hualpen and Talcahuano cities in Chile on December 23, 2019. 
Unfortunately, the progression of the COVID-19 health crisis led to the suspension of this study. 
In response to the unprecedented circumstances, the study protocol underwent necessary 
amendments related to COVID-19 before resuming. The revised protocol with amendments 
received approval, and it was registered on the ClinicalTrials.gov platform of the National 
Institutes of Health of the United States under the identifier NCT05609760. 
 
 
 
 
 
 
 
 
 
 

FONDEF ID19I10120 
Study Protocol 
1. Background and objectives 
1.1. Background 
The current shift from paternalistic to participatory models of care emphasizes the role of 
patients and their environment in healthcare decision-making. Effective communication is vital 
for achieving treatment goals, but various factors can impede patients' comprehension and 
retention of information, essential for treatment adherence. During clinical-patient 
communication, especially in post-check-up or discharge instructions, healthcare professionals 
often convey complex information briefly, overwhelming patients. Studies reveal that 40-80% 
of information is immediately forgotten, with up to 50% remembered inaccurately. This not only 
jeopardizes treatment adherence but also exposes patients to risky behaviors. Older adults tend 
to forget a significant percentage (40-80%) of information provided by healthcare personnel. 
Addressing communication challenges is crucial to enhancing patient understanding and, 
consequently, treatment outcomes. 
1.2. Objectives  
1.2.1. General objective 
Develop and evaluate an automatic association system of medical instructions to pictograms to 
positively impact the understanding, retention, and adherence to treatment for patients 
diagnosed with bronchial asthma receiving care at primary health centers. 
1.2.2. Specific Objectives 
• 
Develop the SIMAP system to automatically complement medical instructions with 
pictograms in the context of managing and treating bronchial asthma, ensuring 
interoperability with existing EHRs 
• 
Validate the impact of SIMAP on understanding, retention, and therapeutic adherence 
among patients consulting at an Asthma respiratory Units (ARU) through a randomized 
clinical trial. 
 
2. Research Methodology for Clinical Validation 
2.1 Clinical Trial Description 
In order to determine the effects of implementing a pictogram platform to facilitate 
understanding and therapeutic adherence, a randomized parallel-group, triple-masked clinical 
trial will be conducted with patients recently diagnosed with asthma (<=15 days) who enter the 
Asthma respiratory Units (ARU), hereinafter referred to as ARU, at the Family Health Centers 
(CESFAM) belonging to the Municipal Health Corporations of the cities of Valparaíso, San 
Antonio, Hualpén n, and Talcahuano. This protocol has been drafted in accordance with the 2010 
CONSORT statement (CONSORT 2010). 

2.2 Participants 
2.2.1 Verification of Inclusion and Exclusion Criteria 
All participants in this study will be patients who enter the Asthma respiratory Units (ARU) of 
the CESFAM belonging to the Municipal Corporation of Valparaíso, Municipality of San Antonio, 
Municipal Corporation of Hualpén n, and Health Administration Directorate of the Municipality 
of Talcahuano. The selection criteria for study participants are: 
Inclusion Criteria 
• 
Adult patients aged 18 to 65 years with a recent diagnosis of bronchial asthma (<=15 
days) based on the 2018 criteria from the Global Initiative for Asthma (GINA) (Reddel 
et al., 2015), recommended by the Ministry of Health of Chile. 
• 
Clinically substantiated diagnosis with spirometry results compatible with the 
guidelines of GINA. 
• 
Patients initiating bronchodilator treatment, including at least one inhaled 
corticosteroid and a short-acting bronchodilator. 
 
Exclusion Criteria 
• 
Patients with obstructive bronchial pathology other than bronchial asthma (chronic 
obstructive pulmonary disease, mixed states, etc.), 
• 
Patients who participated in the design phase of the pictograms (Stage 1 of the project), 
• 
Patients with a diagnosis of dementia, harmful alcohol consumption, and other drug-
related diagnoses according to the International Classification of Diseases (ICD-10), 
• 
Patients with significant ophthalmological pathology that hinders the use of pictograms, 
• 
Patients who do not wish to participate in the project. 
2.3 Clinical Intervention 
2.3.1 Recruitment 
A healthcare professional designated by the Director of the CESFAM will be responsible for 
reviewing the selection criteria for patients entering the ARU during the recruitment period. 
Upon the first visit (patient's entry into the ARU), if the patient meets the selection criteria, the 
professional designated by the CESFAM director will introduce the project to the patient and 
inquire if they would like to meet with the researchers for an invitation to participate in the 
project by signing the informed consent form. If the patient agrees, the healthcare professional 
designated by the CESFAM director will inform the project director or a team member 
designated by her. 
Following this, the clinical professional (recruiter) hired by the project will formally invite the 
patient to participate through the reading and signing of the informed consent. After signing the 
informed consent, the clinical professional employed by the project (recruiter) will proceed to 
conduct an interview with the participating patient to obtain a bio-sociodemographic profile, 
including demographic variables such as gender and age, nationality, time with asthma 
symptoms, educational level (categorized as basic, middle, higher, and postgraduate education), 
number of drugs in use, morbidity history as established by the Charlson Comorbidity Index, 

smoking history with the corresponding pack-years index, and drugs in use. The initial 
interview will be conducted by a clinical professional employed by the project. Once the profile 
is completed, the same clinical professional employed by the project will record the level of 
disease control at the beginning of the study (time of patient participation acceptance - T0), 
based on the Asthma Control Test (ACT) questionnaire. This questionnaire has been selected 
based on its diagnostic capabilities, validation in the Spanish language, and widespread use in 
both traditional clinical practice and asthma research in Chile. It is currently recommended in 
national clinical guidelines to establish the level of disease control (Schatz et al., 2006; Vega et 
al., 2007). ACT scores are established based on 5 questions on a 5-point Likert scale, where 
higher scores indicate better disease control. Patients with scores above 19 points are 
considered to have well-controlled asthma. 
2.3.2 Assignment to intervention group A or control group B 
• 
Patients will be randomized using a permuted block method to receive one of two 
possible intervention strategies A or B. 
• 
The permuted block technique aims to ensure a periodic balance in the number of 
subjects assigned to each intervention or control group (Molina et al., 2015). 
• 
The random assignment sequence will be generated by technical staff of the project with 
the support of a statistician. 
Intervention Group A: This intervention involves utilizing a pictogram system named SIMAP 
(Automatic Association System of Medical Instructions to Pictograms), which was developed 
during the initial phase of the study. In essence, SIMAP comprises a series of pictograms 
intended to enhance the understanding of medical instructions provided by the healthcare team 
regarding asthma management. The pictograms will be designed by a panel of experts, as 
detailed in the previous sections of the project, and validated among adult patients consulting 
in the same population where this study will be implemented. The designed pictograms are 
specifically tailored to certain elements within the management of bronchial asthma. 
This intervention entails furnishing the patient with the instruction sheet given by the clinical 
staff of the CESFAM as part of their care, but supplemented with pictograms (automatically 
generated by SIMAP). The provided instructions include images supporting guidance for 
recognizing bronchodilators, indicating their method of use (daily dose, usage schedule, or as 
needed), specifications of bronchodilator families with their functions (disease-controlling and 
symptom-relieving drugs), inhalation technique of bronchodilators, and the use of an inhalation 
chamber in the process. 
The pictograms will be administered by the clinical professional of the CESFAM designated by 
the Director or by the clinical professional hired by the project (recruiter). This depends on the 
care process of the CESFAM participating in this study and the availability of hours of the clinical 
professional of the CESFAM designated by the Director to support the project. 
Control Group B: This corresponds to those patients selected and who agreed to participate in 
the study but will not be assigned to receive the SIMAP system (control group) through the 
randomization method. These patients will receive their medical instructions in the usual 
manner, as established by the healthcare team of the participating clinics. Additionally, these 
patients will receive an informative brochure on bronchial asthma, provided as part of the 

standard education when explaining the disease. These brochures will be crafted using 
everyday language in Spanish, without incorporating pictograms into their content. 
The research team will not intervene in any way in the selection of bronchodilators by the 
healthcare team or in any other decision-making regarding the management of bronchial 
asthma among participating patients. 
2.3.3 Training for those providing interventions A and B 
The clinical and technical team of the SIMAP project will train the clinicians working in the 
participating ARUs of the project in the clinical trial and use of SIMAP. Two training sessions of 
30 minutes each, delivered in groups, are planned. In the first of these sessions, an explanation 
will be provided about the intervention, as well as essential principles regarding how 
pictograms would facilitate users' understanding of the instructions. The second session will 
involve the direct application of these pictograms to simulated patients under the guidance of 
the SIMAP design team. 
 
 
2.3.4 Follow-up (procedure developed in the same way for both Group A and B) 
The follow-up will be conducted according to what is shown in Table I. 
 
Table I: Follow up procedure beginning (t0), 7 days (t1), 30 days (t2) and 60 days (t3) 
 
 
 
 
 
Study Period  
 
 
CESFAM 
Professional 
Clinical 
professional 
hired by the 
project 
(recruiter) 
Clinical 
professional 
hired by the 
project (follow-
up) 
t0 
t1 
t2 
t3 
Recruitment 
Application of 
Eligibility Criteria 
X 
 
 
X 
 
 
 
Informed Consent 
Signature 
 
X 
 
X 
 
 
 
Bio-
sociodemographi
c Profile  
 
X 
 
X 
 
 
 
 
Charlson Index 
 
X 
 
X 
 
 
 
ACT test 
 
X 
 
X 
 
 
 
Intervention A 
Delivery of 
instructions with 
Pictograms 
X 
X 
 
X 
 
 
 
Intervention B 
Delivery of 
informative 
brochure 
 
X 
 
X 
 
 
 
Follow-up 
ACT test 
 
 
X 
 
X 
X 
X 
Inhalation 
 
 
X 
 
X 
X 
X 

Technique 
Adherence 
Guideline 
 
3. Data & Statistical Analysis Plan 
3.1. Outcomes  
The primary outcome of the study consists of the difference in disease control level 60 days 
after the start of the study, as assessed by the ACT questionnaire. As co-primary outcomes, the 
same score difference observed at 7 and 30 days after the intervention has been established, as 
well as adherence to the recommendations provided by the healthcare team regarding the 
correct inhalation technique for bronchodilators and the use of inhalation chambers within the 
same time frames. Secondary outcomes of the study include the recognition of the function of 
bronchodilators. To check adherence to the correct application of the inhalation technique, the 
project clinician will conduct an assessment of the correct use of the prescribed inhalation 
therapy according to a checklist developed 10 months after the start of the project. The checklist 
was developed following the recommendations of national clinical guidelines, the Spanish 
Association of Pediatrics in Primary Care, and a study conducted by Santo Tomás s University on 
inhalation techniques in asthmatic patients (Manríquez et al., 2015).ris 
Additionally, secondary outcomes will include the occurrence of urgent care visits, 
hospitalizations related to the disease, and the need to escalate bronchodilator therapy as per 
GINA guidelines at 60 days. Information regarding these secondary outcomes will be extracted 
from the individual medical records of each patient, as well as during the final follow-up 
interview when the ACT questionnaire is administered. 
3.2. Sample Size 
In this stage, we will be working with new patients entering the ARU. Based on the actual 
population size of adult patients with bronchial asthma recorded from 2019 to 2021 in the 
participating centers of the project, we have considered a minimum sample size of 48 patients, 
with a 10% margin of error and a 95% confidence level. We anticipate recruiting this sample 
within a period of no more than 6 months from the entry of the first patient. The sample 
calculation takes into account the years during which the COVID-19 social and health crisis 
occurred. Additionally, due to the lack of previous literature on the evaluation of pictograms for 
asthma control, it is not feasible to calculate a sample size based on the effect size to be achieved. 
Ideally, we aim for a homogeneous sample according to the a priori population of entries for 
each participating center. However, in case of recruitment difficulties at any health center, the 
sample will be obtained based on the center with the highest availability of patient entries that 
meet the selection criteria. Considering the measurement of the primary and co-primary 
outcomes, we plan to randomize a minimum of 48 patients for Stage 2 of the clinical validation 
of SIMAP. 
3.3. Masking 
The clinical professionals hired by the project who assess patients during follow-up, 
statisticians, and study sponsors will be kept unaware of the treatment assignments. Masking 
of participating patients will be carried out by providing an informative brochure on bronchial 

asthma, given as part of the standard education when explaining the disease. These informative 
brochures will be crafted using everyday language in Spanish, without incorporating 
pictograms into their content. 
3.4. Analysis Strategy 
The statistician hired by the project will conduct the data analysis for Stage 2 of the study. 
Descriptive analysis will initially involve means, standard deviation, absolute and relative 
frequencies. For inferential analysis, either Student's t-tests or Mann-Whitney tests will be 
employed to compare means based on the distribution and variances of the obtained data. The 
Fisher's Exact Test will be used for evaluating qualitative variables. 
The primary outcome will be assessed concerning the difference in mean scores observed in 
bronchial asthma control questionnaires (ACT) between groups at each time point through a 
profile analysis. The secondary outcome will be evaluated based on the proportion of patients 
adhering to recommendations regarding the correct use of bronchodilators between both 
groups. Any intra-group comparisons of qualitative data will be conducted using the ANCOVA 
or Kruskal-Wallis statistic, depending on the distribution of quantitative data. 
 
All analyses will be carried out by a statistician unaware of the treatment assignment of the 
participants. Outcomes will be analyzed on an intention-to-treat basis (intervention or control 
group). In the event of an imbalance in the characteristics of the groups established by the 
randomization process, potential adjustments to the models will be made. Any model generated 
will consider the presence of potential interactions between independent variables during its 
design. Maximum likelihood principles will be ensured based on residual analysis. 
To preserve the intention-to-treat principles, missing data will be handled using multiple 
imputation techniques. All analyses will be performed by a masked statistician using R Project 
software. 
3.5. Data management 
and sensitive data of the patients. To achieve this, the collected information will be managed on 
paper and stored in cabinets kept in the office of the director or alternate director, both of whom 
will have keys. The Director and Alternate Director are considered the custodians of the data 
for the Biobío and Valparaís
so regions, respectively. 
The information collected by the developed system will be encrypted during transfer and 
storage, ensuring the protection of data privacy. Despite lacking patient identification and being 
only a set of instructions filtered by diagnosis, the data obtained from the EHR will also be 
stored on secure servers under a firewall. Project team members with access to this data will 
sign a confidentiality and proper data handling agreement. 
Both the Director and Alternate Director of the project may authorize other team members to 
access the data for the purposes of necessary analyses to fulfill the objectives of this study. Team 
members granted access to the generated data will sign a confidentiality and proper data 
handling agreement. 
 

4. Other Information 
Clinical Trial Registration: Once approved by an Ethical-Scientific Committee, the research 
team of the project will register the study on the ClinicalTrials.gov platform of the National 
Institutes of Health in the United States. 
Funding: This project, which includes the clinical validation of pictograms through a 
randomized clinical trial, is funded by the National Commission for Scientific and Technological 
Research through its FONDEF competition, with approval code ID19I10120. 
 
Figure 1: CONSORT diagram. A blank CONSORT diagram to record the number of participants enrolled, 
number allocated to the treatment arm, number lost to follow-up, and number analyzed   
 
 
 
 
 
 
 
 
 

References 
1. CONSORT TRANSPARENT REPORTING of TRIALS. CONSORT 2010 Documents 
[Internet]. CONSORT  TRANSPARENT REPORTING of TRIALS [Cited Apr 21, 2022]. 
Available from: http://www.consortstatement.org/downloads/extensions. 
2. Reddel HK, Bateman ED, Becker A, Boulet L-P, Cruz AA, Drazen JM, et al. A summary of 
the new GINA strategy: a roadmap to asthma control [Internet]. Vol. 46, European 
Respiratory 
Journal. 
2015. 
p. 
622–39. 
Available 
from: 
http://dx.doi.org/10.1183/13993003.00853-2015. 
3. Schatz M, Sorkness CA, Li JT, Marcus P, Murray JJ, Nathan RA, et al. Asthma Control Test: 
Reliability, validity, and responsiveness in patients not previously followed by asthma 
specialists [Internet]. Vol. 117, Journal of Allergy and Clinical Immunology. 2006. p. 549–
56. Available from: http://dx.doi.org/10.1016/j.jaci.2006.01.011. 
4. Vega JM, Badia X, Badiola C, Lo pez-Vin a A, Olaguí bel JM, Picado C, et al. Validation of the 
Spanish version of the Asthma Control Test (ACT). J Asthma. 2007 Dec;44(10):867–72. 
5. Manrí quez P, Acun a AM, Mun oz L, Reyes A. Estudio sobre la te cnica inhalatoria en 
pacientes asma ticos: diferencias entre pacientes pedia tricos y adultos. J Bras Pneumol. 
2015;405–9.