Rodríguez‑Molinero et al.

Trials (2023) 24:797 Trials

https://doi.org/10.1186/s13063-023-07679-1

STUDY PROTOCOL Open Access

Study protocol of a randomized controlled

trial to assess safety of teleconsultation
compared with face‑to‑face consultation:
the ECASeT study
Alejandro Rodríguez‑Molinero1* , Gerard Carot‑Sans2,3, Roser Escrig3, Cristian Tebé4, Jacobo Arce5,
Carlos Pérez‑López1, Silvia Ballesta6, Guillermo Verdejo7, Ángel Cedeño8, Mar Riera‑Pagespetit9,
Sofia Vivas‑Angeles10, Jose L. Alarcon10, Itziar Navarro11, Silvia Toro6, Llorenç Mateo12, Ana J. Torres13,
Gerard Delmás14, Helena Camell7, Antonio Chamero15, Montse Gasol2,3,16, Jordi Piera‑Jiménez2,3,17 and ECASeT
Research Group

Abstract
Background The use of remote consultation modalities has exponentially grown in the past few years, particularly
since the onset of the COVID-19 pandemic. Although a huge body of the literature has described the use of phone
(tele) and video consultations, very few of the studies correspond to randomized controlled trials, and none of them
has assessed the safety of these consultation modalities as the primary objective. The primary objective of this
trial was to assess the safety of remote consultations (both video and teleconsultation) in the follow-up of patients
in the hospital setting.
Methods Multicenter, randomized controlled trial being conducted in four centers of an administrative healthcare
area in Catalonia (North-East Spain). Participants will be screened from all individuals, irrespective of age and sex,
who require follow-up in outpatient consultations of any of the departments involved in the study. Eligibility criteria
have been established based on the local guidelines for screening patients for remote consultation. Participants will
be randomly allocated into one of the two study arms: conventional face-to-face consultation (control) and remote
consultation, either teleconsultation or video consultation (intervention). Routine follow-up visits will be scheduled
at a frequency determined by the physician based on the diagnostic and therapy of the baseline disease (the one
triggering enrollment). The primary outcome will be the number of adverse reactions and complications related
to the baseline disease. Secondary outcomes will include non-scheduled visits and hospitalizations, as well as usabil‑
ity features of remote consultations. All data will either be recorded in an electronic clinical report form or retrieved
from local electronic health records. Based on the complications and adverse reaction rates reported in the literature,
we established a target sample size of 1068 participants per arm. Recruitment started in May 2022 and is expected
to end in May 2024.

*Correspondence:
Alejandro Rodríguez‑Molinero
arodriguez@csapg.cat
Full list of author information is available at the end of the article

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
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Rodríguez‑Molinero et al. Trials (2023) 24:797 Page 2 of 11

Discussion The scarcity of precedents on the assessment of remote consultation modalities using randomized con‑
trolled designs challenges making design decisions, including recruitment, selection criteria, and outcome definition,
which are discussed in the manuscript.
Trial registration NCT05094180. The items of the WHO checklist for trial registration are available in Additional file 1.
Registered on 24 November 2021.
Keywords Remote consultation, Video consultation, Teleconsultation

Roles and responsibilities The rapid implementation of remote consultations in

The ECASeT trial is sponsored by the Consorci Sanitari many healthcare systems of high-income countries has
Alt Penedès—Garraf (CSAPG), a healthcare provider not been accompanied by high-quality evidence regard-
within the Catalan Health System, and funded by the ing its effectiveness and safety. Thus, although thousands
Instituto de Salud Carlos III (ISCIII) through the project of studies have described the benefits and usage of vari-
“PI22/01056” (co-funded by the European Union). Nei- ous types of remote consultation, very few correspond to
ther the sponsor nor the funder agency contributed to randomized-controlled designs, and the assessment of
the trial design; they are not involved in trial conduct and potential harms of remote consultation has been typically
will not be involved in the analysis of the results. listed as secondary—often descriptive—outcomes [13,
The scientific committee, formed by AR-M, GC-S, RE, 14]. We present herein a study protocol of a randomized
CT, JA, CP-L, AT, GD, ACh, MG, and JP-J, was responsi- controlled trial to assess the safety of remote consulta-
ble for key decisions regarding the primary endpoint and tions (both video and teleconsultation) in the follow-up
overall design. The rest of the authors made substantial of patients in the hospital setting.
contributions to the study design and manuscript prepa-
ration, as detailed in the “Declarations” section of the Design
manuscript. The scientific committee is also in charge Study setting and participants
of trial oversight, with AR-M coordinating day-to-day The ECASeT trial (Ensayo Clínico abierto y Aleatorizado
issues. A professional monitor, belonging to the research para valorar la Seguridad de la Teleconsulta, frente a la
support office of the Hospital acting as study sponsor, consulta clínica presencial in Spanish) is aimed at test-
will monitor a subset of all data collected, as described in ing safety of remote consultations, based on its non-
the study protocol. inferiority compared with face-to-face consultation.
The ECASeT trial will be conducted in four centers in
Introduction the healthcare area of Alt Penedès-Garraf in Catalonia
The debut of telemedicine into routine practice stretches (North-East Spain): three secondary hospitals (Hospi-
back over three decades [1]. However, the use of this tal Sant Antoni Abat, Hospital Sant Camil, and Hospital
modality of care delivery has exponentially grown in the Comarcal de l’Alt Penedès) and a rehabilitation center,
past few years, accompanied by a remarkable body of all part of Healthcare Consortium Alt Penedès Garraf
literature reporting the benefits of different types of tel- (CSAPG). All study sites belong to the public network of
emedicine in the management and follow-up of various hospitals and primary care centers of the Catalan Health
chronic and acute conditions [2–6]. Service and provide universal healthcare to a catchment
The concept of telemedicine encompasses multiple population of 247,357 inhabitants. Hospital depart-
information and communication technologies (ICT) ments from all areas (i.e., locomotive, internal medicine,
solutions for monitoring patients remotely [7]. Among surgery, gynecology, and pediatrics) are involved in the
them, video conferencing and phone calls (commonly study.
regarded as video consultation and teleconsultation, Participants will be screened from all individuals, irre-
respectively) are candidates to re-shape care pathways in spective of age and sex, who require follow-up in outpa-
the mid-term, thus mitigating the expected overwhelm- tient consultations of any of the departments involved in
ing of healthcare systems associated with the upcoming the study. Eligibility criteria have been established based
demographic shift [8, 9]. In the past 2 years, the public on the local guidelines for screening patients for remote
health emergency derived from the COVID-19 pandemic consultation [15]. Briefly, to be eligible for remote consul-
has boosted the implementation of remote consultation tation, patients have to have adequate digital literacy at the
systems to avoid crowding of healthcare centers [10–12], physician discretion and technological capacity to use the
thus accelerating the entrance of this modality of care video conferencing software and undergo a type of follow-
delivery in routine practice. up that, due to the moderate complexity of the pathology,
Rodríguez‑Molinero et al. Trials (2023) 24:797 Page 3 of 11

does not require physical examinations. Patients followed Non-scheduled visits will be defined as any contact
up in more than three departments, those with visual or between the patient and the physician that occurs before
hearing impairments that may hamper patient-physician the date established in the previous follow-up visit. Non-
communication, and those enrolled in another clinical scheduled visits will be performed according to the study
trial that requires an experimental intervention during the arm and type of remote consultation (i.e., phone or
follow-up will be excluded from the study. video) in which the patient has been allocated and will be
considered for the analysis.
Interventions
Participants will be randomly allocated into one of the Screening, allocation, and blinding
two study arms: control (i.e., face-to-face consultation) All consecutive patients who visited any of the participat-
and remote consultation (including teleconsultation, and ing departments between May 2022 and May 2024 will
video consultation). All patients, irrespective of the con- be informed about the study design and objective and
sultation type, will receive short text message reminders will be offered to enroll in the trial. Patients who agree
a few days before the visit. to participate will provide their informed consent, which
Participants allocated into the control arm will be will be signed in case of a face-to-face screening visit and
scheduled with face-to-face appointments as usual. All oral in case of a remote visit. Patients who reject enroll-
phone calls (except reminders for scheduled visits) per- ment will be recorded in an anonymous registry. Once
formed by the physician during the study will be noted signed the informed consent, the investigator will assess
in the electronic case report form (eCRF). Per protocol, the eligibility criteria and record them in the eCRF.
participants allocated in the control arm can receive Patients will be randomly allocated in either of the
up to 25% of physician-doctor interactions by phone study arms irrespective of the modality of the screen-
(that is, one phone call allowed for three face-to-face ing visit. Randomization will be balanced by medical
appointments). specialty to prevent biases towards a particular diagno-
Participants allocated in the remote consultation arm sis within study arms. To ensure a minimum number of
will be scheduled remote visits, either phone or video participants who visited through video consultation, par-
consultation. In case of phone visits, the physician will ticipants allocated to the remote consultation arm will be
call the main phone number provided by the patient and, subsequently randomized to either video consultation or
in case of not receiving an answer, other phone numbers remote modality selection at physician discretion at a 3:7
listed as contact numbers. In case of video consultation, ratio.
the participant will receive an additional text message Centralized randomization will be automatically
with the visit link. When clicking the link, a website with conducted by the randomization module of the RED-
the video consultation system embedded will open in the CAP system used for the eCRF. The allocation will be
default browser of the user. The video consultation plat- informed to the administrative service, which will sched-
form of the physician pops up a message indicating that ule all visits indicated by the physician during the inves-
the patient is in the virtual waiting room. Patients will tigated period following the criteria of each study arm.
remain in the virtual waiting room until the physician The health condition for which a patient has attended the
starts the visit. A technical assistance is readily available screening visit will be considered the baseline disease for
for physicians who experience troubles with the system. the study purposes.
In case the patient does not show up to the video con- Although study participants will be informed about the
sultation after a reasonable time, the physician calls the overall study objectives in the patient information sheet,
patient by phone. The date and hour of the phone call they will not be aware of the study endpoints. In addition,
and the reason for the inability to connect are recorded the statisticians performing the analysis will be blinded to
in the eCRF. participant allocation. No rules for unblinding have been
Participants allocated in the remote consultation arm pre-defined in the study protocol.
that require face-to-face visits will be excluded from the
per-protocol analysis, and the reason for the face-to- Data sources
face visit will be recorded in the eCRF. Participants allo- To reduce the workload of participating investigators
cated in the remote consultation arm and scheduled with during visits, variables recorded in the eCRF will be lim-
a phone visit cannot be visited by video, whereas those ited to those that cannot be accurately retrieved from
scheduled for a video consultation can undergo up to electronic health records (EHR), which will include both
25% of phone visits. Phone contacts and their reason in local hospital records and the dataset of the Catalan
patients in the video consultation arm will be recorded in Health Surveillance System (CHSS), a central database
the eCRF. of the Catalan Health System. By the time of submitting
Rodríguez‑Molinero et al. Trials (2023) 24:797 Page 4 of 11

the study protocol to the ethics committee, all four study (G40, G41, R56, O15), diabetes (E100-E108, E110-E118,
sites have separate and different EHRs. Throughout the E120-E128, E130-E138, E140-E148), high blood pres-
following year, all the systems are to be unified into a sin- sure (I10, I119), and iron-deficiency anemia (D501, D508,
gle one and all the data from the different systems will be D509).
migrated. These EHR collect all the data related to the Usability will be assessed by passive and active surveil-
care received in the centers, clinical course, prescrip- lance. Study investigators will record non-attendances, as
tion, diagnostic images, laboratory tests, and adminis- well as all technical incidences that occurred during the
tration, among others. The CHSS systematically collects visit in an unstructured field of the eCRF. For active sur-
and stores healthcare data on health status and resource veillance, a trained interview panel will contact by phone
utilization from all healthcare providers. The CHSS was a subset of 100 participants randomly selected from all
originally designed for healthcare planning and has an patients who have completed the final visit. Interview-
automated validation system to identify internal incon- ers will administer the computer system usability ques-
sistencies between variables. Since the CHSS registries tionnaire (CSUQ), a validated questionnaire aimed at
are used for control of capitation payments, they undergo measuring the users’ satisfaction with the usability of
external audits to ensure provider payment accuracy [16]. computer systems in scenario-based usability studies
[21].
Outcomes and variables The users’ satisfaction with the quality of care received
Table 1 summarizes the definitions and data sources of will be assessed using a validated tool encompassed
primary and secondary outcomes assessed in this trial. within the satisfaction survey plan of the Catalan Health
Complications and adverse reactions will be considered Service [22]. The questionnaire consists of 32 items that
only if related to the baseline disease (i.e., the health con- combine binary and multiple choice questions, 10-point
dition for which the first study visit was scheduled). To assessment scales, and 2 open questions. An inter-
prevent interference with routine practice, the investiga- view panel will administer the questionnaire by phone
tor will have the option of recording the reference disease to a subset of 300 participants (100 per arm), randomly
in a free-text field in the eCRF. The option of completing selected from all participants who have completed the
a field in English or Spanish linked to the ontologies of final visit.
the ICD10 will also be available. If this field is not filled
in, the ICD-10 code will be extracted from the free-text Participant timeline
field. The investigator will also record the stage (if appli- Figure 1 summarizes the participant timeline. All par-
cable) of the baseline disease and its severity. ticipants, irrespective of the study arm, will be scheduled
The follow-up period planned by the investigator for follow-up visits at a frequency determined by the phy-
the baseline disease will be retrieved from the local EHR. sician based on the diagnostic and therapy of the base-
Other variables collected from EHRs at baseline will line disease and will receive a reminder (either SMS or
include sex, age, area of residence, the number of active phone call) before each visit. Physicians can schedule and
prescriptions at the end of the screening visit, and the cancel appointments at their discretion. At least three
comorbidity burden, summarized using the Adjusted visits should be scheduled in the study setting: the base-
Morbidity Groups (AMG). Briefly, the AMG is a case- line visit (i.e., screening visit), intermediate visits (pre-
mix tool that generates a summary index of health defined by the physician based on the follow-up needed
risk by considering all chronic conditions and recent for managing the baseline condition), and the final visit
acute diagnostic codes [17]. The tool allows stratifying (i.e., either the follow-up visit closest to 12 ± 2 months
patients into mutually exclusive health-risk groups and after enrollment or before in case of discharge or early
has shown a high predictive capacity of healthcare and discontinuation).
resource use outcomes, including mortality, hospitaliza- In addition to voluntary withdrawal, the following situ-
tion, visits to primary care, polypharmacy, and overall ations will lead participants in the remote consultation
expenditure [18, 19]. arms to discontinue the study: a change in their clinical
For homogeneity regarding the rate of preventable hos- status that requires face-to-face consultation and not
pitalizations, we considered all hospitalizations due to following the procedures for remote consultation ade-
any of the ICD-10 diagnostic codes listed as ambulatory quately. Patients allocated in the face-to-face arm will
care sensitive conditions [20] managed in the participat- discontinue in case their health status discourages mov-
ing departments, including conditions related to ischemic ing to the hospital for follow-up visits. The reasons for
heart disease (I20, I240, I248, I249), asthma (J45, J46), ending the study will be recorded in the eCRF.
chronic obstructive pulmonary disease (COPD) (J20, J41, The study will be temporarily interrupted if the local
J42, J43, J44, J47), heart failure (I110, I50, J81), seizures authorities or healthcare center managers decide to ban
Table 1 Study outcomes and data sources
Item Domain definition Measure and metrics Data sourcesa

Primary outcome
Rate of ­complicationsb of the baseline disease A secondary disease, an accident, or a negative Measure: events, as recorded in the eCRF. Investigator-reported in the eCRF
reaction (including adverse reactions to treatment) Metrics and aggregation: event rate (i.e., proportion Local EHR.
occurring during the course of the baseline disease of patients experiencing an event within each arm
and usually aggravating the illness. and the follow-up period).
Rodríguez‑Molinero et al. Trials

Secondary outcomes
Rate of severe complications of the baseline illness A complication with significant impact on patient’s Measure: events, as recorded in the eCRF. Investigator-reported in the eCRF
life and/or that require intervention by a healthcare Metrics and aggregation: event rate (i.e., proportion Local EHR.
professional of patients experiencing an event within each arm
and the follow-up period).
(2023) 24:797

Rate of severe adverse reactions related An undesired health event related to a drug adminis‑ Measure: events, as recorded in the eCRF. Investigator-reported in the eCRF
to the treatment of the baseline condition tered to treat the baseline health condition Metrics and aggregation: event rate (i.e., proportion
of patients experiencing an event within each arm
and the follow-up period).
Rate of preventable hospitalizations Hospitalizations due to illnesses secondary Measure: events, as recorded in the eCRF. Local EHR
to the chronic diseases that can be managed Metrics and aggregation: event rate (i.e., proportion
in the outpatient ­settingc of patients experiencing an event within each arm
and the follow-up period).
Non-scheduled medical encounters related The following events will be considered: Measure: events, as recorded in the eCRF. Investigator-reported in the eCRF
to poor control of the baseline disease • Non-scheduled appointments (phone, videoconfer‑ Metrics and aggregation: event rate (i.e., proportion Local EHR
ence, or face-to-face). of patients experiencing an event within each arm
• Visits to primary care services. and the follow-up period).
• Visits to the emergency room.
• Hospital admissions.
Pharmaceutical prescriptions The number of new prescriptions and renewals will Measure: ATC groups prescribed Administrative records.
be collected, along with the type of pharmaceutical Metrics and aggregation: difference in number
prescription: long-term, acute process, or pro re nata. of ATC groups between baseline and last visit;
the outcome will be measured as the mean
and standard deviation, and median and interquartile
range (i.e., ­25th and ­75th percentiles).
Usability Usability parameters will be collected using two Measure: Questionnaire score and number of techni‑ Phone call administration
approaches: cal incidents. by trained interviewers to 10%
• Computer System Usability Questionnaire. Metrics and aggregation: score, expressed of the study sample.
• Technical incidents reported by the investigators. as the mean and standard deviation, and median Investigator report to the eCRF.
and interquartile range (i.e., ­25th and ­75th percentiles).
Cumulative number of incidents.
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 Rodríguez‑Molinero et al. Trials
(2023) 24:797

Table 1 (continued)
Item Domain definition Measure and metrics Data sourcesa

Satisfaction Satisfaction survey CSAPG included in the satisfaction Measure: Questionnaire score. Phone call administration
survey plan of the Catalan Health System. Metrics and aggregation: score, expressed by trained interviewers to 10%
as the mean and standard deviation, and median of the study sample.
and interquartile range (i.e., 25th and 75th percen‑
tiles).
Care provision expenditure Expenses related to each of the interventions. Measure: cost in euros of the year. Administrative records.
Metrics and aggregation: mean and standard devia‑
tion per patient.
EHR electronic health record
a
In outcomes gathered from more than one data source, discrepancies or inconsistencies between data sources will be addressed by the scientific committee before the closure of the database
b
The severity of complications and adverse events will be recorded using a scale with four categories: (a) MILD: does not limit activity and does not require medical follow-up; (b) MODERATE: mild-to-moderate impact on
activity or requires minimal medical intervention or monitoring; (c) SEVERE: significant impact on activity or requires medical care; (d) VERY SEVERE: life-threatening or results in major disability or significant incapacity for
the subject
c
The list of conditions considered has been retrieved from ambulatory care sensitive conditions and include ICD-10 categories related to ischemic heart (I20, I240, I248, I249), asthma (J45, J46), COPD (J20, J41, J42, J43,
J44, J47), heart failure (I110, I50, J81), seizures (G40, G41, R56, O15), diabetes (E100-E108, E110-E118, E120-E128, E130-E138, E140-E148), hypertension (I10, I119), and iron-deficiency anemia (D501, D508, D509)
Page 6 of 11
Rodríguez‑Molinero et al. Trials (2023) 24:797 Page 7 of 11

Fig. 1 Participant timeline

a
The frequency of the follow-up visits will be determined by the physician based on the diagnostic and therapy of the baseline disease and will
receive a reminder (either SMS or phone call) before each visit. bEither the follow-up visit closest to 12 ± 2 months after enrollment or before in case
of discharge or early discontinuation

or limit face-to-face consultations because of the rapid be transferred to a database, which will also contain the
spread of an infectious agent. This interruption can be data extracted from the local EHR and the CHSS regis-
partial in case banning face-to-face consultations does tries. All registries will be linked through the identifica-
not affect all hospital services. The study will resume tion number of the Catalan Health Service.
when face-to-face consultations are restored, and there Data recorded in the eCRF will be monitored for com-
is enough healthcare activity for adequate recruitment pleteness and quality by a professional monitor working
in all study arms. In case of a temporal interruption, the at the research office of the Hospital acting as sponsor.
study will be automatically extended for a time that is at We will schedule periodic visits to assess the adherence
least equivalent to the interruption time. of investigators to the study protocol and good clinical
The independent ethics committee can interrupt the practices. The clinical monitor will release reports at the
study at any time in the advent of risk for participants, end of each visit.
and the study sponsor can do it as well because of finan- A statistical analysis plan, with detailed analyses for
cial issues. each study outcome, will be performed after the last
patient has attended the final visit and before the closure
Data management and analysis of the database.
All data recorded in the eCRF will be stored in a REDCap The primary objective will be assessed using a non-
platform hosted in a local server. The REDCap data will inferiority analysis of the cumulative incidence of
Rodríguez‑Molinero et al. Trials (2023) 24:797 Page 8 of 11

complications of the baseline disease between remote Ethical study conduct

consultation (video and teleconsultation arms) and face- We will collect only the data necessary to achieve the
to-face consultation, using a non-inferiority margin of study objectives. All data will be handled according to the
2%. The analysis will be based on a modified binomial test Spanish Organic Low 03/2018 for the protection of per-
to assess the non-inferiority of an experimental interven- sonal data and assurance of digital rights (LOPD-GDD)
tion vs. a control group in a three-arm trial [23]. The pri- and the General Data Protection Regulation 2016/679
mary analysis will be conducted on a per-protocol study on data protection and privacy for all individuals within
sample, which will include all participants who have fin- the European Union and the local regulatory framework
ished the study and have not been withdrawn because of regarding data protection. No situations classified at high
non-allowed visits using modalities other than scheduled. risk of violation of the rights and freedoms of patients
The intention-to-treat population, used for sensitivity according to the LOPD-GDD are foreseen. Nevertheless,
analyses, will consist of all randomized patients complet- considering that the study will include video conferenc-
ing at least one visit. Since the analysis will be based on ing, we will perform the risk analysis report requested
an event rate, missing data will not be imputed. by the LOPD-GDD. The data generated during the study
The primary analysis will be replicated with patients will be stored for 5 years after the study ends unless the
stratified according to the following characteristics: hospital Independent Ethics Committee or the local regulatory
department, diagnostic, disease duration (chronic vs. acute framework establishes otherwise.
or sub-acute), anatomic-therapeutic treatment groups, The study protocol has been approved by the Inde-
and GMA health risk group. The clinical and demographic pendent Ethics Committee of the Bellvitge Hospital
characteristics of study participants will be described and (L’Hospitalet de Llobregat, Spain) (ref. PR215/21). All
compared between excluded/withdrawn participants. changes made to the study design after protocol approval
The statisticians will be blinded for the allocation arm. will be notified to the Independent Ethics Committee and
The type I error will be set at 2.5% for the primary analysis documented as an amendment in the ClinicalTrials.gov
and 5% for the rest of the analyses. All analyses will be con- registry. The scientific committee and the sponsor are
ducted using R software (version 4.0 or higher) [24]. Data responsible for communicating all amendments that have
collected during the ECASeT trial will not be re-used. been approved by the Independent Ethics Committee to
the rest of the investigators, as well as, patients already
Sample size considerations enrolled in the trial if deemed necessary.
The sample size was estimated based on the primary end- When offered to enter the study, all participants will
point of cumulative incidence of complications related be provided with a patient information sheet (Additional
to the baseline disease. The sample size analysis was file 2). All patients who accept to participate in the study
computed with R software [24], following the approach will provide informed consent before entering the study.
described by Steen A. Julious for non-inferiority trials [25]. In case the first visit is remote, consent will be oral, oth-
Although there is little available information regarding this erwise, written. Participants younger than 18 years will
outcome in the general population of chronic patients, we sign an informed assent, and their legal guardian will
expect 10% of events in face-to-face consultations [26–28] provide the corresponding consent.
and 12% in the remote consultation arm (based on routine The members of the scientific committee commit to
practice of the research team). Assuming a type-I error of public dissemination of the trial results. Therefore, upon
up to 2.5% and a statistical power of 80%, 1068 subjects trial completion and analysis, a report will be submitted
per arm should be analyzed to reject the non-inferiority in a peer-reviewed, open-access journal, regardless of
hypothesis with a non-inferiority margin of 2% and assum- the trial results. The scientific committee will be respon-
ing 10% of participants lost to follow-up. sible for making decisions regarding authorship, which
Altogether, the participating centers schedule 252,000 will be in agreement with the authorship criteria of the
routine follow-up visits during a period equivalent to the International Committee of Medical Journal Editors. The
study, corresponding to 121,400 different patients. There- report will also be sent to local authorities responsible for
fore, the recruitment of the estimated 2136 patients is con- healthcare planning.
sidered within the capabilities of the participating centers.
Owing to the scarcity and heterogeneity of available Discussion
data about the primary endpoint, a blinded interim anal- In this article, we describe the key elements of the design
ysis will be conducted when 50% of the total sample has of an RCT to assess the safety of two modalities of syn-
been recruited to revise the assumptions used to calcu- chronous remote consultations: video consultation and
late the sample size, as proposed in the E9 Guide of the teleconsultation. Trials investigating the benefits and—
ICH on Statistical Principles for Clinical Trials [29]. less frequently—risks of remote consultation typically
Rodríguez‑Molinero et al. Trials (2023) 24:797 Page 9 of 11

focused on a specific clinical condition [30–32]. Alterna- to the local guidelines. Briefly, these guidelines identify as
tively, we seek to address whether remote consultations candidates all patients without severe diseases who are
can be considered overall safe in clinical conditions com- predisposed to contact the physician remotely.
monly followed up in a secondary hospital. While broad- Aside from the little precedent for making decisions on
ening the scope of the research, this approach raises trial design, our study is challenged by the huge sample
notable challenges regarding the study design that are to be enrolled for achieving enough statistical power for
worth being discussed. a primary outcome that is expected to occur in a low fre-
One of these challenges is the selection of the appro- quency. Although the assumptions for sample size calcu-
priate study outcome. Unlike the assessment of safety in lation will be revised in an interim analysis, as proposed
drug therapy, commonly based on the number of adverse by ICH E9 guidelines [29], recruiting such a huge number
events related to the given drug, care delivery through of patients is among the main risks of trial success. The
remote consultation modalities lacks specific pre-defined risk of not reaching a sample size high enough for a pow-
harms that can be monitored. In the context of a particu- ered analysis might be worsened by other aspects aside
lar diagnostic, the safety of a follow-up could be under- from recruitment, including a lower frequency of the
stood as the capacity of the care pathway to prevent an primary outcome than expected, short follow-up periods
unexpected worsening of the disease (e.g., asthma exac- established by the clinician, and high frequency of arm
erbations or cardiac arrest events). However, in our study, switch because of care needs.
which encompasses many chronic conditions, the defi- In summary, the study protocol of this RCT, which is
nition of the safety outcome had to include any possible novel in assessing the safety of remote consultation as a
complication that can be attributed to inadequate control primary endpoint in general consultations and with pow-
of the baseline condition. We considered that listing all ered sample size, provides design insights that will hope-
potential complications associated with the baseline con- fully aid researchers in making decisions in future trials
ditions allowed in the trial would hamper excessively the for assessing remote consultation.
study conduct and constrain the repertoire of possible
complications. Instead, we chose a broad definition of
complication [33]. To prevent unnoticed complications, Trial status
we will complement the investigator’s assessment with a By the time of submitting the manuscript, the trial is recruit-
systematic screening of all events recorded in the EHR ing patients. No interim analyses have been done yet.
within the follow-up period, which are likely to include Current protocol version: 2.0 (07/02/2023).
complications not recorded in the eCRF, such as visits to Recruitment started on November 01, 2021, and was
the emergency room, and primary care services related to interrupted until the protocol amendment on February
the baseline condition. 07, 2023.
The definition of a candidate profile that is suited for Expected date for ending recruitment: February 28,
remote consultation has been identified among the 2025.
important challenges of remote consultation deployment
[34]. In the research setting, this issue results in diffi-
Abbreviations
culty in defining the target population and, therefore, the AMG Adjusted Morbidity Groups
selection criteria for recruitment. In response to the high CHSS Catalan Health Surveillance System
demand for remote consultations in our area during the CSUQ Computer system usability questionnaire
COVID-19 Coronavirus disease
COVID-19 pandemic, the Catalan Health System devel- ECASeT  Ensayo Clínico abierto y Aleatorizado para valorar la Seguridad de la
oped a set of guidelines for helping clinicians and man- Teleconsulta, frente a la consulta clínica presencial
agers of healthcare centers implementing and offering eCRF Electronic case report form
EHR Electronic health records
video and teleconsultation appropriately [15, 35]. These ICD International Classification of Diseases
guidelines, agreed by different stakeholders, recommend ICT Information and communication technologies
offering remote consultation only to patients without
severe or unstable diseases. While these criteria exclude Supplementary Information
patients at higher risk of experiencing complications, The online version contains supplementary material available at https://​doi.​
they are unlikely to be offered remote consultation in the org/​10.​1186/​s13063-​023-​07679-1.
real world. Therefore, including them might result in a
Additional file 1. WHO dataset ECASeT.
biased view of the safety of remote consultation in rou-
Additional file 2. Information sheet.
tine practice. Nevertheless, the applicability of the results
obtained from our study shall be constrained to candi- Additional file 3. SPIRIT Checklist.

dates to be followed up by remote consultation according

Rodríguez‑Molinero et al. Trials (2023) 24:797 Page 10 of 11

Acknowledgements Competing interests

There are no other contributions to declare than those attributed to the article The authors declare that they have no competing interests.
authors.
Author details
1
Version of the protocol and patient information sheet + informed Àrea de Recerca, Consorci Sanitari de L’Alt Penedès I GarrafEspirall, Vilafranca
consent del Penedès, 61 08720 Barcelona, Spain. 2 Catalan Health Service, Barcelona,
2.0 of 07.02.2023. The patient information sheet and informed consent are Spain. 3 Digitalization for the Sustainability of the Healthcare System (DS3),
available in Additional file 2. IDIBELL, Barcelona, Spain. 4 Biostatistics Unit of the Bellvitge Biomedical
Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain. 5 Urol‑
ECASeT Research Group ogy Department, Consorci Sanitari de L’Alt Penedès I Garraf, Vilafranca del
David Benaiges. Endocrinology Department, Consorci Sanitari de l’Alt Penedès Penedès, Barcelona, Spain. 6 Endocrinology Department, Consorci Sanitari de
i Garraf, Vilafranca del Penedès, Barcelona, Spain L’Alt Penedès I Garraf, Vilafranca del Penedès, Barcelona, Spain. 7 Department
Lidia Tikhomirova. Department of Internal Medicine, Consorci Sanitari de l’Alt of Internal Medicine, Consorci Sanitari de L’Alt Penedès I Garraf, Vilafranca del
Penedès i Garraf, Vilafranca del Penedès, Barcelona, Spain Penedès, Barcelona, Spain. 8 Gastroenterology Department, Consorci Sanitari
Vicenç Torrente. Rheumatology Department, Consorci Sanitari de l’Alt Penedès de L’Alt Penedès I Garraf, Vilafranca del Penedès, Barcelona, Spain. 9 Geriatrics
i Garraf, Vilafranca del Penedès, Barcelona, Spain Department, Consorci Sanitari de L’Alt Penedès I Garraf, Vilafranca del Penedès,
Jesús Marimón. Musculoskeletal Area, Consorci Sanitari de l’Alt Penedès i Gar‑ Barcelona, Spain. 10 Department of Surgery, Consorci Sanitari de L’Alt Penedès
raf, Vilafranca del Penedès, Barcelona, Spain I Garraf, Vilafranca del Penedès, Barcelona, Spain. 11 Nefrology Department,
David Saavedra. Department of Surgery, Consorci Sanitari de l’Alt Penedès i Consorci Sanitari de L’Alt Penedès I Garraf, Vilafranca del Penedès, Barcelona,
Garraf, Vilafranca del Penedès, Barcelona, Spain Spain. 12 Musculoskeletal Area, Consorci Sanitari de L’Alt Penedès I Garraf,
Violeta Menendez. Urology Department, Consorci Sanitari de l’Alt Penedès i Vilafranca del Penedès, Barcelona, Spain. 13 Maternal‑Child Area, Consorci
Garraf, Vilafranca del Penedès, Barcelona, Spain Sanitari de L’Alt Penedès I Garraf, Vilafranca del Penedès, Barcelona, Spain.
14
Elisabet Franquet. Neurology Department, Consorci Sanitari de l’Alt Penedès i Innovation Department, Consorci Sanitari de L’Alt Penedès I Garraf, Vilafranca
Garraf, Vilafranca del Penedès, Barcelona, Spain del Penedès, Barcelona, Spain. 15 Anesthesiology Department, Consorci Sanitari
Luis M. Sierra. Urology department, Consorci Sanitari de l’Alt Penedès i Garraf, de L’Alt Penedès I Garraf, Vilafranca del Penedès, Barcelona, Spain. 16 Depart‑
Vilafranca del Penedès, Barcelona, Spain ment of Pharmacology, Therapeutics, and Toxicology, Universitat Autònoma
María López-Diéguez. Department of Internal Medicine, Consorci Sanitari de de Barcelona, Bellaterra, Spain. 17 Faculty of Informatics, Telecommunications
l’Alt Penedès i Garraf, Vilafranca del Penedès, Barcelona, Spain and Multimedia, Universitat Oberta de Catalunya, Barcelona, Spain.
Nuria Rodríguez. Neumology Department, Consorci Sanitari de l’Alt Penedès i
Garraf, Vilafranca del Penedès, Barcelona, Spain Received: 11 July 2023 Accepted: 27 September 2023
Jessica Gonzales. Department of Surgery, Consorci Sanitari de l’Alt Penedès i
Garraf, Vilafranca del Penedès, Barcelona, Spain
Oscar Macho-Pérez. Geriatrics Department, Consorci Sanitari de l’Alt Penedès i
Garraf, Vilafranca del Penedès, Barcelona, Spain
Sandra Huguet. Musculoskeletal Area, Consorci Sanitari de l’Alt Penedès i Gar‑ References
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