CLINICAL DATA MONITORING

INTRODUCTION:
Clinical data monitoring (CDM) is a critical process in clinical research, which leads to
generation of high-quality, reliable, and statistically sound data from clinical trials. Clinical data
management ensures collection, integration and availability of data at appropriate quality and
cost. It also supports the conduct, management and analysis of studies across the spectrum of
clinical research as defined by the National Institutes of Health (NIH). The ultimate goal of CDM
is to ensure that conclusions drawn from research are well supported by the data. Achieving
this goal protects public health and increases confidence in marketed therapeutics.

Clinical trials are a research study that determines the safety and efficacy of the pharmaceutical
product, carried out in humans’ volunteers either in healthy or sick volunteers, this depends on
the pharmacological and pharmacokinetic reactions in human volunteers. These researches are
mainly happened to be aimed at evaluating a medical, surgical, or behavioral intervention of an
investigational product. The study helps in diagnosing, treating, preventing the ailments in
humans. The scientists perform laboratory tests and studies in animals to test a potential
therapy’s safety and efficacy (pre-clinical trials) before the approval to begin a clinical trial by
U.S. Food and Drug Administration (FDA). If these studies show favorable results, the FDA gives
approval for the experiments to be tested in humans. These trials are important for our future
growth.

DATA MONITOPRING PLANS:

The data management plan describes the activities to be conducted in the course of processing
data. Key topics to cover include the SOPs to be followed, the clinical data management
system (CDMS) to be used, description of data sources, data handling processes, data transfer
formats and process, and quality control procedure

CASE REPORT FORM DESIGN:

The case report form (CRF) is the data collection tool for the clinical trial and can be paper or
electronic. Paper CRFs will be printed, often using No Carbon Required paper, and shipped to
the investigative sites conducting the clinical trial for completion after which they are couriered
back to Data Management. Electronic CRFs enable data to be typed directly into fields using a
computer and transmitted electronically to Data Management. Design of CRFs needs to take
into account the information required to be collected by the clinical trial protocol and intended
to be included in statistical analysis. Where available, standard CRF pages may be re-used for
collection of data which is common across most clinical trials e.g. subject demographics. Apart

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from CRF design, electronic trial design also includes edit check programming. Edit checks are
used to fire a query message when discrepant data is entered, to map certain data points from
one CRF to the other, to calculate certain fields like Subject's Age, BMI etc. Edit checks help the
investigators to enter the right data right at the moment data is entered and also help in
increasing the quality of the Clinical trial data.

FUNCTIONS PERFORMED DURING MONITORING:

 Monitors check the Informed Consent Forms (ICFs) completeness, to ensure they have
been duly signed by the patients.
 Verify the eligibility criteria and ensures that all subjects are eligible for the trial.
 Makes sure that all the adverse events are being reported by the site by verifying the
source systems and the reports.
 Verifies the accuracy and completeness of the case report forms with respect to the
source documents.
 Checks whether the dose and treatment modifications done for any specific patients are
accurately documented.

After verification, monitors submit a report after each site visit to the sponsors. These
reports include the following

 Detailed summary of review during visits

 Significant findings if any
 Actions taken and
 Recommendation

FACTORS THAT AFFECT THE SELECTION OF MONITORING TYPE:

The level of scrutiny of monitoring varies across studies based on the risks and nature of the
trial. Below are some of the factors that affect monitoring and the type of monitoring necessary
for the trials.

 First and foremost, the critical factor that affects the complexity of monitoring is the
protocol design. These include duration of treatment, interaction intensity necessary,
the requirement of a special population, etc.
 The therapeutic area under evaluation
 The severity of the treatment
 Number of patients involved in the study
 Number of clinical trial sites
 SOPs
 The phase of the clinical trial.

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 The overall monitoring plan should remain fairly consistent, but the strategy for individual
sites may change considerably depending on study conditions and site performance.

Let’s discuss each monitoring method in detail.

What are different types of monitoring

There are a some of ways in which a clinical trial can be monitored

1. On-site Monitoring
2. Remote Monitoring
3. Risk based Monitoring
4. Centralized Monitoring

A. On-site monitoring- On-site monitoring involves in-person evaluation carried out by

sponsor personnel or representatives at the investigation site. On-site monitoring is a
traditional method of monitoring and provides many advantages.

 The presence of monitors at the site is necessary for some kinds of trials where remote
monitoring is inadequate. In some cases where patient information protection is a
priority, remote access is not possible, and monitors shall physically review the
documents.
 It helps maintain a more effective relationship with both the stakeholders, the
investigator, and the sponsor. When there is a good relationship, it help monitors detect
and resolve any issues in the early stages.
 In physical presence, clinical monitors may provide immediate solutions for a few
problems and can actively involve study teams.
 It helps motivate study teams, which in turn helps attain high-quality data and
compliance in the study end.

B. Centralized monitoring- In multi-center clinical trials, centralized moitoring is a good

option. It ensures patient safety, trial integrity, and data quality.
The centralized monitoring came into action after the publication of regulatory guidance
on risk-based monitoring (RBM). Global regulators recommend centralized monitoring
in conjunction with on-site monitoring to oversee clinical trials. Before implementing
centralized monitoring, it is critical to understand the concept of risk management.

In the centralized monitoring the central coordinating team identifies and reviews key
data at pre-specified time points. The study team can review eligibility criteria, adverse
events, and consent forms centrally to assure the trial team the completeness and
correctness. The central team can also review the drug accountability logs to ensure
that the site has sufficient stock, dosing, and enrolment data.

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 One factor the central monitoring team needs to consider is the internet connection at
the site. Poor internet connection may impact timely data upload and review by the
study team.

Other than these mentioned monitoring, there are several adopted monitoring
techniques such as Safety monitoring, and Risk-based monitoring, Lets understand
them.
C. Risk based Monitoring- Risk-based monitoring is the process of ensuring the quality of
clinical trials by identifying, assessing, monitoring and mitigating the risks that could
affect the quality or safety of a study. Guidance from the US Food and Drug
Administration (FDA) outlines three steps in a risk-based approach to monitoring:

 Identify critical data and processes. To accurately monitor the quality of a study
and the safety of its participants, the sponsor must know which elements are most
important for each particular study – from informed consent to eligibility screening
and tracking of adverse events.
 Perform a risk assessment. A risk assessment involves determining specific
sources of risk and the effect of study errors on those risks.
 Develop a monitoring plan. According to FDA's guidance, a monitoring plan should
"describe the monitoring methods, responsibilities, and requirements of the trial."
The plan is responsible for communicating risks and monitoring procedures to
everyone involved in monitoring the trial.

D. Remote monitoring- Remote Monitoring (RMON) is a standard specification that

facilitates the monitoring of network operational activities through the use of remote
devices known as monitors or probes. RMON assists network administrators (NA) with
efficient network infrastructure control and management.

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TYPES OF MONITORING VISIT: Monitoring is a continuous process conducted before,
during and after the trial. Hence, it is classified into four types of visits:

a) Site Evaluation/ Qualification visit

b) Site Initiation visit
c) Site Monitoring visit/ Interim monitoring visit
d) Site Close-out visit

SAFETY MONITORING: Safety monitoring is another important aspect in clinical trials. The
monitor reviews adverse events and follows up with timely resolution. Monitoring is performed
on regulator basis. An independent physician with relevant expertise monitors safety of a
clinical trial.

Who conducts the safety monitoring?

The monitoring may be conducted by

 sponsor or
 Contract research organization (CRO) staff or
 contractor, and/or
 by the Principal clinical investigator/project manager

CONCLUSION: The Profession of monitor in clinical trials plays a very huge responsible role in
performing his or her tasks as per the situations. The purpose of monitoring should not be
underestimated, it’s a pack of trial design and conduct and process and result. The challenge to
conduct a clinical trial in source-limited settings can be a prominent wonder. But planning the
trial carefully and well-conducted monitoring can be achieved with accurate scientific results
with the respect to the international guidelines and patient’s safety as concerned.

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