Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06150508 |
| Other study ID # |
IRB No: 2308-183-1463 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 2023 |
| Est. completion date |
December 2024 |
Study information
| Verified date |
November 2023 |
| Source |
Seoul National University Hospital |
| Contact |
Juho Choi, MD |
| Phone |
01072797401 |
| Email |
tmzpdlxld[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Objectives The aim of this intervention is to assess how well and how efficiently the O2O
Service Model works in delivering primary healthcare and managing chronic diseases for
patients living in Pyeongchang-gun at the local government level.
Trial design This is a randomized controlled trial with restricted, batch, blocked and
individual random assignment. Investigators will allocate 1,000 participants from
Pyeongchang-gun into two groups: one with diabetes (and pre-diabetes) and one with
hypertension (including borderline cases), focusing on poorly controlled patients. As
participants visit local health centers, their data will be sent to the research team for
blocked randomization based on disease type, severity, and region. Assignment results will be
communicated back to the centers and patients.
Study setting The intervention will take place in Pyeongchang-gun, Kangwon-do, South Korea.
The Smart Healthcare Center affiliated to Public Medical Center of Pyeongchang will primarily
manage the O2O service by providing necessary education and human resources while receiving
and monitoring data from each participant and local medical centers. The overall study
(including the design of trial) is managed by Seoul National University College of Medicine
while the provision of O2O service and data collection are primarily in charge of Smart
Healthcare Center of Pyeongchang.
Intervention in O2O Service Model:
After initial health exams, each patient gets a custom care plan, classifying their disease
and care level. The Pyeongchang Smart Healthcare Center, with doctors, tracks patients via an
online platform, sending automated health messages. High-risk patients receive a two-week
glucose monitor and guidance on lifestyle adjustments. Doctors access patient health records
through the participant's personal online datastore (POD), with consent, integrating health
and prescription history from national insurance, and can assess heart disease risk.
Sample size The trial's sample size is determined using the MDES(Minimum Detectable Effect
Size), with 1,000 participants divided equally between diabetes and hypertension groups. Each
group is then split into treatment and control subgroups through random allocation. The MDES
calculation, accounting for an explained outcome variation of 50% due to blocking and
controls, and based on 500 subjects per group with equal allocation, aims for a high-accuracy
effect size of 0.216 at a 5% significance level and 80% power.
Assignment of interventions: allocation Participants will be randomly placed into groups by a
computer program. This study uses a specific randomization method that is restricted and
organized by individual characteristics. The research team will tell the centers and patients
about their group assignment via phone and email. Neither the healthcare staff nor the
participants will know the group allocation beforehand. The research team is in charge of the
randomization process and informing everyone involved. The staff at Pyeongchang's Smart
Healthcare Center will sign up participants and manage their placement into the assigned
intervention groups. There will be no blinding after participants are assigned to their
groups.
List of Data For the study, the investigators have created questionnaires and interview
formats to collect various data types, including random assignment records, baseline
information, outcomes, service usage and costs, demographic and health details,
physician-collected health records, life-log data from apps or web, clinical exam results,
and service effectiveness and efficiency from the perspective of medical staff and
administrators.
Statistical methods For the analysis of primary and secondary outcomes, the investigators
will employ ITT(Intention-to-Treat) and Regression-Adjusted Impact Estimate. When data allows
(especially data from control group), the investigators will also conduct timeseries effect
analysis. To investigate the time-series changes in program effects across multiple time
points, the dependent variable (outcome variable) should be measured at each time point to
estimate program effects repeatedly.
Data management and monitoring The data management for the study will be conducted using
electronic systems for secure and accurate data entry, coding, and storage, with robust
checks and backups to ensure data quality, which will be archived for three years in
compliance with bioethics standards before disposal according to privacy regulations.
Participant confidentiality is prioritized through secure data collection and restricted
access, with sharing only to authorized research team members and regulators using password
protection or encryption. Additionally, a dedicated Data Monitoring Committee will oversee
trial progress and adherence to protocols, while the Smart Healthcare Center collaborates
with healthcare workers to manage patient services, with minimal adverse events expected.
Description:
Objectives The objective of this intervention is to evaluate the effectiveness and efficiency
of the Online-to-Offline(O2O) Service Model developed to provide primary healthcare and
management of chronic diseases targeting patients residing in Pyeongchang-gun at the local
government level.
The randomized controlled trial of this intervention will help verifying the model, and
provide valuable information about the effectiveness of an O2O digital healthcare service for
patients with diabetes and hypertension. If the intervention is found to be effective, it has
the potential to improve access to care and self-management for patients, which could lead to
improved health outcomes and reduced healthcare costs. The implications from this study can
also serve as credible evidence for decision making for provision of digital health care
services in other regions of Korea as well.
Trial design This is a randomized controlled trial with restricted, batch, blocked and
individual random assignment. For sampling before randomization, investigators plan to
recruit two target disease groups in Pyeongchang-gun: one group with diabetes patients
(including pre-diabetes patients), and another with hypertension patients (including
borderline hypertension patients). Total 1,000 participants (500 per group) will be
recruited, and the investigators plan to prioritize the poorly controlled patients when
recruiting.
Primary mode of sampling is voluntary based, where patients sign up through the
advertisement, promotional campaign, or information provided by the physicians. Some patients
will be recommended and informed to join this trial by their physicians while
promotional/advertising materials will be posted at participating medical centers((i.e.,
Pyeongchang Public Medical Center and local private clinic, local private medical centres in
Pyeongchang) and the Pyeongchang official website. Flyers will also be distributed through
voluntary village health supporting groups-named Village Health Committee. In the meantime,
for patients who have already diagnosed to have diabetes and hypertension will also be
recruited from participating medical centres in Pyeongchang (i.e., local medical centres,
Pyeongchang Public Medical center).
When eligible patients who are willing to participate in this study visits local health
centre for clinical tests, their data will be periodically sent to the research team to carry
out blocked random assignment (block: disease, severity, region). The assignment results are
notified to the centre/clinic and then to the patients. The allocation ratio is 1:1 for each
disease (hypertension and diabetes).
Study setting The intervention will take place in Pyeongchang-gun, Kangwon-do, South Korea.
(Pyeongchang-gun is a county in the province of Gangwon-do, South Korea. It is in the eastern
part of the province with a population of around 43 thousand people estimated in 2020.) The
Smart Healthcare Center affiliated to Public Medical Center of Pyeongchang will primarily
manage the O2O service by providing necessary education and human resources while receiving
and monitoring data from each participant and local medical centers.
As mentioned, the intervention targets patients (and borderline patients) in Pyeongchang, and
the data is collected from participating patients through the device and application as well
as from the local medical centers when patients participate in (both control and treatment
group) regular follow-ups.
The overall study (including the design of trial) is managed by Seoul National University
College of Medicine while the provision of O2O service and data collection are primarily in
charge of Smart Healthcare Center of Pyeongchang. There are stakeholders to develop and
manage the O2O model (specifically the mobile application, data platform), such as Kangbuk
Samsung Hospital, Huray and DKI, and Seoul National University Hospital as well as XAIMED are
in charge of managing the Public Health HRecord (PHR) data collected from the patients and
local medical centers.
Interventions
Intervention in O2O Service Model:
Following baseline comprehensive health examinations, each participant's primary attending
physician will develop an individualized care plan. This care plan includes identifying the
representative disease group (diabetes, pre-diabetes, hypertension, borderline-hypertension)
and determining the intensity of care (intensive or standard). In cases where participants
have both diabetes and hypertension, they are categorized as diabetes patients. Participants
with poorly controlled diseases (systolic blood pressure exceeding 140 or diastolic pressure
over 90 in the hypertension group, and HbA1c levels exceeding 6.5% in the diabetes group) are
assigned to the intensive care group. However, these classifications can be adjusted as
necessary based on the patient's clinical condition.
The Pyeongchang Smart Healthcare Center, in collaboration with physicians, continuously
monitors and intervenes as needed. Monitoring occurs through the administrator's web page of
the O2O service platform, allowing oversight of the life-log data of the intervention group.
Enrolled patients receive interventions in the form of automated or manual messages.
- Message Delivery through the Application: Personalized Educational Material: The content of
these messages is determined based on the participant's baseline evaluation results. They
consist of publicly available videos produced by reputable organizations, including academic
societies, and are provided via links to YouTube videos.
Health Reports: Sent every three months, these reports provide a comprehensive evaluation of
whether the individual's condition is being well managed based on life-log data from the past
three months.
Manual Messages (Texted Messages): Indicator-based personalized messages are manually
transcribed, evaluating the state of health management over the last two or four weeks based
on life-log data. These messages are primarily drafted by the Pyeongchang Smart Healthcare
Center, using pre-made message templates created by healthcare experts (doctors,
nutritionists, nurses, etc.) suitable for each situation. Messages are sent to patients after
final confirmation by their respective primary physicians. Additional messages can be sent as
needed during the monitoring process, especially if blood pressure or blood glucose levels
are at cautionary or dangerous levels or if data entry is insufficient.
- Continuous Glucose Monitor (Among the Intervention Group): Some diabetes patients in the
intervention group will be provided with a continuous glucose monitor (Freestyle Libre).
Eligibility for this monitor is determined based on their recorded glucose levels not
reaching the normal range in more than half of their recent examinations within the latest 14
days. Patients eligible for the continuous glucose monitor receive notifications via text or
phone call from the Smart Healthcare Center. They are required to attach the device for two
weeks and are advised to self-monitor their glucose variations. During this period, they are
strongly encouraged to manage their glucose levels by adapting their usual lifestyle. Some
patients may receive the monitor again, if needed, two weeks after the detachment of the
device.
- Personal Health Record (PHR) Data: PHR data can be accessed and utilized exclusively by
attending physicians with patient consent through the participant's personal online datastore
(POD) web view in the clinic. POD can import health screening results, medical history, and
prescription history provided by the National Health Insurance Service (NHIS), which is
mandatory for all citizens to enroll in. Additionally, POD contains AI-based retinal image
analysis capable of detecting ophthalmologic abnormalities (e.g., glaucoma, diabetic
retinopathy) and predicting cardiovascular disease (CVD) mortality risk. It also includes
another CVD incidence prediction model developed using national health screening data. With
access to this PHR data, attending physicians can provide comprehensive consultations to
patients regarding their CVD risk.
- Control Group: The control group will receive treatment as usual, which is the typical care
provided to individuals without the additional interventions described above.
Strategies to improve adherence to interventions Patients will be regularly reminded to use
the mobile-app to check up their medical conditions with mobile alarms, notifications and
in-person notification from the Smart Healthcare Center of Pyeongchang Medical Center
Relevant concomitant care permitted or prohibited during the trial Treat of as usual (TAU) is
allowed for both control and treatment group. However, the investigators believe that
patients' participation in alternative services will be the most difficult problem to solve
during the study. The investigators have identified 'participating in another research
program involving smart health technology' as one of the exclusion criteria. will not be
eligible for inclusion in our study. At the same time, the investigators will further prevent
concomitant care (that might be possible during the intervention) through information
provision and by educating the operators who will be in charge of training and informing the
patients for service utilization
Sample size Sample size is calculated using MDES (Minimum Detectable Effect Size) equation.
The sample size for this study is determined with the aim of detecting a meaningful
difference between the treatment and control groups with sufficient statistical power. Given
that the total sample size is 1000 participants, the investigators will divide this cohort
into two main groups: participants with diabetes and those with hypertension. Subsequently,
each of these two groups will be randomly allocated into treatment and control subgroups.
Calculation of MDES is separately carried out for the diabetes and hypertension groups,
taking into account the unique characteristics and expected effect sizes within each group.
Assuming that the variation in the outcome variable that can be explained by blocked random
assignment and control variable is about 50%, and assuming a sample of 500 subjects with a
5:5 allocation ratio, with a statistical significance level of 5% and a power of 80%, the
MDES is 0.216. If the investigators assume that the variation in the outcome variable that
can be explained by blocked random assignment and control variable is about 25%, the MDES is
0.187, which is still high in accuracy. Assuming that the variation in the outcome variable
that can be explained by blocked random assignment and control variable is about 10%, the
MDES is 0.181, which is still high in accuracy. (Note: Cohen (1988) suggested that an MDES of
0.20 is a small effect size, 0.50 is a medium effect size, and 0.80 is a large effect size.)
Therefore, the investigators aim to recruit the sample of 500 participants for each disease
type, and the treatment-to-control ration is 5:5 for each disease group
Recruitment There are two concurrent recruitment procedures, each with slight distinction.
Procedure 1 primarily targets patients previously diagnosed with diabetes, pre-diabetes,
hypertension, or borderline hypertension. Procedure 2 targets respondents who have been
exposed to our promotion and advertisement efforts. For these respondents who voluntarily
asked to enroll, their eligibility will be confirmed when they are either: 1) Previously
diagnosed with diabetes, borderline diabetes, hypertension, or borderline hypertension (with
proof of diagnosis) or 2) Newly diagnosed with any of these conditions through the
comprehensive health check-up included in this intervention procedure.
Assignment of interventions: allocation Sequence generation Participants will be randomized
using a computer-generated randomization sequence. This study will apply a restricted, batch,
blocked, individual random assignment. After screening the participant eligibility, each
eligible participant will be contacted to receive informed consent. For those who consented
to participate will visit the local medical center (or smart healthcare center) for detailed
explanation of service, to physically signed the agreement, receive training to use the
mobile app, and respond the survey. After patients receive clinical tests at the clinic, the
list of patients and test results are periodically sent to the research team. The research
team conducts blocked random assignment periodically based on disease, severity, and region.
The assignment results are notified to the center and clinic and then to the patients by the
research team. Such process is designed to align to the O2O service process.
Concealment mechanism Mechanism of implementing the allocation sequence is using central
telephone and email. The health care staffs and participants won't know the allocation until
the research team inform them.
Implementation The research team will generate the allocation sequence, deliver the
allocation results to the center and patients directly. The staffs of Smart Healthcare Center
of Pyeongchang Public Medical Center will enroll participants and assign participants to
interventions.
Assignment of interventions: Blinding Who will be blinded Once the random assignment is
conducted, no blinding will take place for this study.
Data collection and management Plans for assessment and collection of outcomes
Data Quality Assurance:
To ensure the integrity of our survey data, the investigators have implemented several
processes to promote data quality. First, the investigators plan to employ duplication risk
mitigation measures by cross-referencing participant phone numbers and birth dates. This step
helps identify and rectify any duplicate entries, maintaining the accuracy and uniqueness of
our dataset.
Second, our assessors will be rigorously trained to conduct surveys effectively. The
investigators have developed a comprehensive manual guide to standardize data collection
procedures. This guide serves as a valuable resource for our assessors, ensuring consistency
and adherence to established protocols.
Furthermore, prior to the commencement of the intervention, the assessors will also undergo a
pre-intervention session. During this session, they will receive training on data collection
processes, ensuring their familiarity with survey instruments and questionnaires.
Additionally, our Smart Healthcare Center plays a pivotal role as a call center, promptly
addressing any issues or queries that may arise during data collection. This continuous
support mechanism helps maintain data quality throughout the study.
Study Instruments:
For data collection, the investigators have developed survey questionnaires and interview
guides. These instruments have been meticulously crafted, drawing from health outcome
indicators aligned with clinical guidelines. This alignment ensures that our data collection
tools are both relevant and comprehensive, enabling us to capture essential information
related to our study objectives.
Our commitment to data quality and the robustness of our study instruments underpins the
reliability and validity of the data collected, ensuring the credibility of our research
findings.
List of Data Data to be collected for this study can be categorized into 'Record of Random
'Assignment,' 'Baseline,' 'Outcome,' 'Service Utilization data,' 'Service Cost Data'.
Plans to promote participant retention and complete follow-up
The research team's strategy to retain the completeness of random assignment while managing
any contamination or drop-out is the following:
- Conduct a pilot random assignment for about a week to identify any issues.
- Continuously check the size of Treatment group (T) and Comparison group © considering
the sample size by group to monitor the possibility of non-random assignment.
- Issue of random assignment of ineligible applicants: If found in both T and C, they will
be dropped from the sample; if found only in T, no-show adjustment will be made at the
analysis stage.
- Control group contamination:
1. Identify Contamination by participants vs. contamination by operators
2. Education for operators
3. Minimizing face-to-face contact between operators and participants
4. Direct notification of random assignment results to participants by the research
team
- Cross-over: When the controller applies for random allocation again. Do not remove from
the sample, but handle as no-show adjustment at the analysis stage.
The field operators (i.e., staffs of Smart Healthcare Center and Public Medical Center of
Pyeongchang) will regularly check-up with the patients to remind them to use the mobile
application, while the patients will be automatically notified via app notification and
e-mails for service use. When participants request discontinuation, they will be asked to
fill out the follow-up survey and their medical records (from medical centers and National
Health Insurance Service) will be collected at the point of discontinuation. For deviated
participants, medical records (from medical centers and National Insurance Service) will be
collected when the deviation is identified.
Data management
The data management plan is the following for each process:
Data entry: All data will be entered using electronic data capture (EDC) software. Two
independent operators will perform double data entry for accuracy.
Coding: A coding manual will be created to ensure consistency in coding. All coded data will
be verified by a second operator for accuracy.
Security: Access to the data will be password-protected, and only authorized personnel will
have access. The data will be stored on a secure server that is regularly backed up.
Storage: The data will be stored in an electronic format. The data will be stored on a secure
server located within the research institution.
Data quality processes: Range checks will be performed to ensure that data values fall within
acceptable ranges. Data cleaning procedures will be performed to correct any discrepancies or
missing data. The final dataset will be verified for completeness and accuracy by the
research team before analysis.
Backup and archiving: The data will be regularly backed up to ensure its integrity in case of
system failure or loss. A copy of the final dataset will be archived in a secure location for
future reference. According to Article 15 of the Enforcement Rules of the Bioethics and
Safety Act, all research-related records and data will be archived for three years from the
end of the research.
Data Disposal: Seoul National University, an institution that is in charge of retention, will
dispose of any data and document containing personal information in accordance with Article
16 of Enforcement Decree of the Personal Information Protection Act after three years of
archiving.
Confidentiality
The investigators will collect personal information about potential and enrolled participants
through informed consent forms, medical records, and questionnaires. The investigators will
ensure that all personal information is securely stored and accessed only by authorized
personnel. The investigators will share personal information only with the research team and
regulatory agencies, and the investigators will do so through password-protected access or
encryption to ensure confidentiality.
The specific protocols are as follows:
The participant is provided with sufficient explanation and, if voluntarily agreed, signs a
written consent form to participate in the research.
Confidentiality will be maintained for information that can identify the personal
information.
Information can be provided if the participant inquires about the test results. The
participant's data file will be stored on the server of the data management personnel. This
server is accessible only to the principal investigator, research staff, and co-researchers,
and the file is encrypted. Therefore, access is not possible except for those who
participated in this research.
The data file collected during the research process will be provided to a third party
(National Health Smart Management Research and Development Division under the Ministry of
Health and Welfare, Government of South Korea) and submitted to the data platform (big data
and personal data repository) established by the division. In this process, personal
information is protected by applying the integrated authentication system and DID
(Decentralized Identifier, a distributed identification technology based on blockchain
technology) system developed by the division.
Statistical methods For the analysis of primary and secondary outcomes, the investigators
will employ ITT(Intention-to-Treat) and Regression-Adjusted Impact Estimate.
When data allows (especially data from control group), the investigators will also conduct
timeseries effect analysis. The occurrence of program effects and how these effects change
over time are crucial pieces of information to be derived from this experimental study.
Analysing the temporal trajectory of program effects is essential, as the timing of impact
and the nature of the program can result in diverse patterns of change based on the severity
of disease or behavioural patterns of patients.
In randomized experiments, comparability between randomly assigned program and control groups
remains consistent over time. Therefore, analysing the time-series changes in program effects
can be achieved by applying cross-sectional analysis methods (i.e., Equation (1)) at each
time point. To investigate the time-series changes in program effects across multiple time
points, the dependent variable (outcome variable) should be measured at each time point to
estimate program effects repeatedly. It's important to note that, in Equation (1), the
variables that change over time are the dependent variables only, while program variables and
control variables remain constant. This is because, the distinction between program and
control groups should not change over time, and control variables should be obtained prior to
random allocation.
An important consideration for this analysis is that the "time" mentioned is relative, not
absolute. It is measured relative to the random assignment date, not an absolute calendar
year. Therefore, evaluators will record the random assignment date for all sample members and
integrate it into the analysis dataset. The dependent variables obtained from administrative
statistical databases should also be transformed into relative time variables based on the
random assignment date for analysis.
Methods in analysis to handle protocol non-adherence and any statistical methods to handle
missing data
Defiers in the Treatment Group: In the event that there is non-adherence to the protocol,
particularly if there are individuals who defy the assigned treatment, the investigators will
estimate the Local Average Treatment Effect (LATE). Since the control group will not be
provided with the application, there is no possibility of 'defiers' in the control group.
Therefore, the investigators will simply divide the ITT with the rate of compliers.
LATE= ITT/(Rate of Compliers (in Treatment Group)) To address missing data for variables of
interest, the investigators will use a missing-dummy approach, specifically employing dummy
variable adjustment. This method involves creating dummy variables to account for missing
data and subsequently including these dummy variables in our analysis as covariates. This
approach allows us to compensate for missing data and maintain the completeness of our
analysis while minimizing the impact of missing observations on our results.
Oversight and monitoring Composition of the coordinating centre and trial steering committee
Composition and Roles of Key Entities: The O2O service is orchestrated by a collaborative
effort between the "Smart Healthcare Center" personnel and healthcare professionals situated
at each patient's primary care clinic. The Smart Healthcare Center operates under the
umbrella of the Public Health Center (PHC) of Pyeongchang-gun and comprises our dedicated
team of researchers alongside PHC staff members.
Composition of the data monitoring committee, its role and reporting structure The Data
Monitoring Committee (DMC) comprises members from the evaluation team, ensuring a diverse
range of expertise to oversee the trial's data and processes. The Data Monitoring Committee
plays a pivotal role in maintaining the integrity and quality of trial data. Its
responsibilities include monthly monitoring and feedback sessions to assess the trial's
progress and adherence to protocols. The Data Monitoring Committee reports its findings
directly to the Principal Investigator (PI), providing valuable insights and recommendations
to enhance the trial's efficacy and safety.
Importantly, the Data Monitoring Committee operates independently from the intervention
itself. Its members do not have direct involvement with participating medical centers and the
Pyeongchang Smart Healthcare Center. This independence ensures unbiased evaluation and
decision-making regarding the trial's progress and safety.
Adverse event reporting and harms The likelihood of adverse events or unintended effects
related to trial interventions or trial conduct is not anticipated to be high. However, in
the event that such occurrences do arise, our response protocol is well-established. Any
solicited or spontaneously reported adverse events will be promptly reported to the Principal
Investigator (PI) overseeing the trial. Simultaneously, these events will be reported to the
Seoul National University Hospital (SNUH) Institutional Review Board (IRB) Committee, the
regulatory body responsible for overseeing the ethical and safety aspects of the trial. Upon
notification of an adverse event or unintended effect, relevant and appropriate actions will
be taken in response. These actions may include further investigation, adjustments to trial
conduct, or any necessary modifications to ensure participant safety and the integrity of the
trial.
