Slide 2

1. Observational Study:

 In this type of study, researchers observe and collect data about participants without
intervening or manipulating any variables.

 The goal is to understand the relationship between different factors without actively
influencing them.

 For example, a researcher might observe the diet and health outcomes of a group of
people to see if there's a correlation between certain dietary habits and the development
of certain diseases.

2. Interventional Study:

 In interventional studies, researchers actively manipulate or intervene in a situation to

see how it affects the participants.

 These are often referred to as "experiments" because the researchers are actively
testing a hypothesis.

 A common example is a clinical trial where a group of participants receives a new

medication, while another group receives a placebo. Researchers then compare the
outcomes in the two groups to see if the medication is effective.

3. Expanded Access:

 Expanded access refers to the use of investigational drugs, biologics, or medical

devices for patients who don't qualify for clinical trials.

 This option is typically considered when standard treatments have failed or are
unavailable.

 Expanded access programs are highly regulated and require approval from the FDA.

In summary:

 Observational studies involve observing and collecting data without intervention.

 Interventional studies involve actively manipulating variables to test a hypothesis.

 Expanded access programs allow patients to access investigational treatments outside
of clinical trials.
Slide 3

his table serves as a crucial tool for documenting the changes made to a research protocol during an
amendment process. It ensures transparency and accountability by clearly outlining the modifications,
their justifications, and the specific sections affected.

Slide 4

Title:

 This is the name given to the research study. It should be clear, concise, and informative,
conveying the essence of the study.

3. Study Description:

 This section provides a brief description of the research study. It might include
information about the study's background, rationale, and overall goals.

4. Objectives:

 These are the specific aims or goals that the researchers hope to achieve through the
study. They are often divided into primary and secondary objectives.
o Primary Objective: The main goal of the study.
o Secondary Objectives: Additional goals that are also important but less central to
the study's primary focus.

5. Endpoints:

 These are the outcomes or measurements that will be used to assess whether the study's
objectives have been met.
o Primary Endpoint: The main outcome measure used to determine the success of
the study.
o Secondary Endpoints: Additional outcome measures that are also important but
less central to the study's primary endpoint.

Slide 5

he image you've provided is a schematic diagram illustrating the timeline and phases of a clinical
trial. Let's break down the different stages:

1. Screening Phase (Week -2 to 0)

  Eligibility Assessment: This is the initial step where potential participants are evaluated
to determine if they meet the inclusion and exclusion criteria for the study.
 Baseline Measurements: If a participant qualifies, various measurements and
assessments are taken to establish their baseline health status before the intervention
begins.

2. Randomization (Week 0)

 This is the point where participants are randomly assigned to one of the study groups. In
the diagram, there are two groups:
o Arm A: Receives the investigational drug (the new treatment being tested).
o Arm B: Receives a placebo (an inactive substance that looks like the real
treatment).
 Randomization helps ensure that the groups are comparable and that any observed
differences are due to the treatment and not pre-existing biases.

3. Treatment Phase (Week 1 to 12)

 This is the core phase of the trial where participants in each group receive their assigned
treatment (drug or placebo).
 Monitoring: Regular monitoring and assessments are conducted at specific intervals
(Weeks 2, 4, 8, and 12) to track the participants' health, response to the treatment, and
any side effects.

4. Follow-Up Phase (Week 12 to 16)

 After the treatment phase ends, participants are followed up for a specific period (in this
case, 4 weeks) to continue monitoring their health and assess any long-term effects of the
treatment.

Overall, this schematic diagram provides a visual representation of the typical phases and
procedures involved in a clinical trial, from the initial screening of participants to the
follow-up period after treatment.

Slide 6

The image contains a clinical trial protocol's schedule of activities. Here's an explanation of the
key sections:

Procedures Overview:

1. Informed Consent: Ensures participants are fully aware of the trial's risks and
procedures before enrollment.
2. Demographics: Collecting participant information like age, gender, etc.
3. Medical History: Recording participants' previous medical conditions and treatments.
4. Randomization: Assignment of participants to study groups, often done after screening.
 5. Administer Study Agent: Indicates when the investigational treatment is given.
6. Concurrent Medications: Monitoring and documenting other medications taken during
the trial.

Assessments and Tests:

 Physical Exam: Conducted at specific visits to assess participants' health status.

 Vital Signs: Regular measurement of parameters like blood pressure and heart rate.
 Height and Weight: Baseline height (usually measured once) and weight are tracked
over time.
 Performance Status: Evaluating the participant's ability to perform daily activities.
 CBC w/diff, Plts: Complete blood count, including differential and platelets, to monitor
blood-related parameters.
 Serum Chemistry: Regular blood tests to check kidney, liver function, and other
biochemical markers.
 Serum Pregnancy Test: Administered for females of childbearing potential at screening
and as needed during the study.
 EKG (as indicated): Electrocardiograms are performed based on clinical indications.
 Adverse Event Evaluation: Regular checks for side effects or negative outcomes of the
study treatment.
 Radiologic Evaluation/Imaging: Imaging studies as needed, often for diagnostics or
monitoring treatment effects.
 Other Tests (as appropriate): Any additional tests determined by the study protocol.

Visit Schedule:

The table outlines when these activities occur:

 Screening (Day -7 to -3): Initial assessments like informed consent, demographics,

medical history, and baseline tests (e.g., CBC, pregnancy test).
 Enrollment/Day 1: Randomization and initial administration of the study agent.
 Study Visits (e.g., Day 8, 15, 29, etc.): Periodic follow-ups for monitoring vital signs,
physical exams, adverse events, and lab tests.
 End of Study: Final assessments, including adverse event evaluations and imaging, if
necessary.

Each "X" marks the procedures or assessments conducted at a specific time point. Dashes (----)
indicate continuous monitoring or activities extending across visits.

Let me know if you'd like a more specific breakdown or further clarification!

When writing sections for an e-clinical trial protocol, the focus should be on clarity,
accessibility, and integration with digital tools. Here's a rephrased version of the study
rationale, background, and risk/benefit assessment tailored for e-clinical formats:
Slide 5

The section you’ve mentioned pertains to the protocols for Study Intervention Discontinuation
and Participant Discontinuation/Withdrawal in a clinical study. Here's a breakdown of what
the section is conveying:

Study Intervention Discontinuation:

 Study intervention discontinuation refers to stopping the study treatment or

intervention for a participant. This could be initiated by either the participant (voluntary
withdrawal) or the Principal Investigator (PI).
 The section should specify which adverse events or circumstances would lead to
stopping the intervention or discontinuing the participant from the study entirely.
 If participants discontinue the intervention, they may still remain in the study for follow-
up, particularly if safety and efficacy data need to be collected.

Participant Discontinuation/Withdrawal:

 Participant discontinuation or withdrawal involves a participant leaving the study,

either voluntarily or due to a decision by the PI, due to various reasons.
 Separate documentation should be required for the study intervention discontinuation
(stopping the treatment) and the participant discontinuation/withdrawal (the
participant exiting the study).
 A Case Report Form (CRF) page should be set up to capture specific details, including
the date and the reason for discontinuation, whether it relates to the intervention or the
participant's overall withdrawal.

"Lost to follow-up" refers to a situation in a clinical study where a participant can no longer be
contacted or tracked during the study period. This means that the participant has not responded to
attempts to reach them for follow-up visits, data collection, or assessments, and their
participation is considered incomplete.

This can happen for several reasons, such as:

 The participant may have moved without leaving contact details.

 The participant may have decided to drop out of the study but didn't formally withdraw.
 The participant may have failed to attend scheduled visits or did not respond to
communication efforts.

In clinical research, participants who are "lost to follow-up" are typically excluded from certain
analyses, particularly those looking at the long-term effects or outcomes, as there is insufficient
data on their progress or status in the study.

Slide 6
This section outlines the detailed procedures and evaluations that will be carried out during a
clinical study to assess efficacy according to the study's primary and secondary objectives. Here's
a concise summary of the key points:

1. Study Procedures & Evaluations:

o All procedures required to determine efficacy (based on the primary and
secondary study objectives) should be listed and described.
o This includes physical exams, imaging tests, biological specimen collection, and
laboratory evaluations.
o The sequence of events during the screening process and eligibility decision
points should be described.
o Specific time frames for screening procedures (e.g., within 28 days prior to
enrollment) must be defined.
o If a separate screening protocol exists, it should be referenced.
2. Special Conditions for Enrollment:
o Outline conditions to be met for enrollment and for the initial administration of
the study intervention (e.g., vital signs, assessments).
o The procedures for administering the study intervention and follow-up
assessments (e.g., vital sign checks) should be explained.
o Any unplanned visits and follow-up visits should be noted.
o Indicate if assessments require qualified professionals (e.g., physicians,
psychologists).
3. Participant Discontinuation:
o For participants who may withdraw early, the rationale for their discontinuation
should be captured at the final visit.
4. Detailed Procedures:
o Specific tests and evaluations, such as physical exams, imaging, lab tests, or
assays, must be listed.
o If using multiple laboratories, specify which tests each lab will handle and ensure
consistency across sites.
o Mention any sensitive procedures (e.g., provocative testing) and provide
justifications.
o The collection, handling, and storage of biological specimens should be
described.
5. Data Privacy & Medical Records:
o Any medical chart data used must comply with regulations like HIPAA or
relevant local laws, with a note on the information obtained from existing records.
6. Questionnaires & Patient-Reported Outcomes:
o Administration of patient-reported outcome measures, like questionnaires or daily
diaries, should be included.

Next section

This section provides an overview of the procedures that will monitor safety and eligibility, as well as
how to handle the study intervention, specimen collection, and follow-up.
Next section

8.3.1 Adverse Event (AE) Definition

Provide the definition of an AE for the clinical trial, typically following FDA regulations (21
CFR 312.32) for IND studies. Definitions from OHRP or ICH GCP may apply in other cases.

8.3.2 Serious Adverse Event (SAE) Definition

Provide the SAE definition, referencing FDA regulations for IND studies. SAE can also include
unanticipated adverse device effects under 21 CFR 812.3(s) for device trials.

8.3.3 Classification of Adverse Events

Subsections discuss how AEs will be classified:

 Severity: Use a defined grading system to assess AE severity.

 Relationship to Study Intervention: Assess the relationship of AEs to the study
intervention, with a binary or scale-based approach.
 Expectedness: Identify if the AE is expected, based on prior data (e.g., Investigator’s
Brochure).

8.3.4 Event Assessment and Follow-Up

Describe procedures for identifying and following AEs and SAEs until resolved or stable,
including solicited and unsolicited events, and the follow-up period (e.g., 1 week, 2 months).

8.3.5 AE Reporting
Outline the AE reporting process, including timeframes, responsibilities, and which events do
not need standard reporting, if applicable.

8.3.6 SAE Reporting

Define SAE reporting procedures, including timeframes and responsibilities, and reporting
serious events to the Data Coordinating Center (DCC), safety committees, and regulatory bodies.

8.3.7 Reporting Events to Participants

Describe how participants will be informed about AEs, SAEs, and study-related results.

8.3.8 Events of Special Interest

List other events (e.g., secondary malignancies, cardiovascular incidents, medical device
malfunctions) requiring reporting to sponsors, leadership, IRB, and regulatory agencies.

8.3.9 Pregnancy Reporting

Explain the study's pregnancy-related policy and reporting mechanisms, including modifications
to procedures if pregnancy occurs during the study.

Slide 7
Unanticipated Problem (UP) reporting involves the process of identifying and reporting any
unexpected issues that could pose risks to the participants or others in a research study. This
section outlines the responsibilities of the investigators and the procedures for reporting these
problems.

 Reporting Procedures: Investigators must have a clear plan in place to report these
issues. This plan should include when and how the events are reported to various
oversight groups, like the Data Safety Monitoring Board (DSMB), and regulatory
authorities. The study team should know who is responsible for filling out and signing the
UP reports.
 Institutional Requirements: If the study is funded or supported by the U.S. Department
of Health and Human Services (DHHS), the institution conducting the research must
have written procedures to ensure these problems are reported quickly to the Institutional
Review Board (IRB), relevant officials, and DHHS departments. Additionally, if the
research is covered under a specific federal assurance, the institution must inform the
Office for Human Research Protections (OHRP) about any unanticipated problems.

In short, researchers are required to follow a clear reporting procedure to ensure that any
unexpected issues that may affect participant safety are communicated quickly to the proper
authorities.

Slide 8

9.4.1 General Approach:

This section outlines how data will be analyzed, including the types of data (categorical,
continuous) and the statistical methods to be used. It also explains the handling of assumptions,
missing data, and covariates.

9.4.2 Primary Efficacy Endpoint Analysis:

This focuses on the primary outcomes of the study, detailing how they are measured, what
statistical tests will be used, and how the results will be presented. It includes handling missing
data, assumptions, and adjustments for multiple primary endpoints.

9.4.3 Secondary Endpoint Analysis:

This describes how secondary outcomes will be analyzed, based on the results of the primary
endpoints. It includes similar details as for primary endpoints, with attention to covariates,
missing data, and statistical methods.

9.4.4 Safety Analyses:

Safety endpoints are analyzed through summary statistics and adverse event (AE) reporting. It
outlines how AEs are coded, calculated, and presented, including specific details like severity
and relationship to the study intervention.

9.4.5 Baseline Descriptive Statistics:

This section compares baseline characteristics between intervention groups, including
demographics and lab data, using descriptive statistics or inferential statistics if needed.
9.4.6 Planned Interim Analyses:
Describes any planned interim analyses, including timing, who will review the results, and
criteria for halting the study due to safety or efficacy concerns. It also covers adjustments to
sample size and impact on final analyses.

9.4.7 Sub-Group Analyses:

Explains how the primary and secondary endpoints will be analyzed based on sub-groups like
age, sex, and ethnicity, or justifies why such analyses are not needed.

9.4.8 Tabulation of Individual Participant Data:

This section specifies whether individual participant data will be provided for each measure and
time point.

9.4.9 Exploratory Analyses:

Exploratory analyses are supplementary and cannot be used for regulatory proof. They should be
defined in the protocol but are not the primary focus of the study.

Skide 9

10.1.1 Informed Consent Process

This section outlines the procedures for obtaining and documenting informed consent from study
participants. It must comply with applicable regulations (e.g., 45 CFR Part 46, 21 CFR Part 50,
21 CFR Part 56) and adhere to ICH GCP. The investigator must ensure IRB approval of the
protocol and informed consent documents before starting the trial.

10.1.1.1 Consent/Assent and Other Informational Documents

Provide a list of consent and assent forms and other materials, ensuring all required regulatory
elements are included.

10.1.1.2 Consent Procedures and Documentation

Describe the informed consent process, including waivers, special circumstances, and consent for
non-English speakers or those unable to consent themselves. Include re-consent for children who
become adults during the study.

10.1.2 Study Discontinuation and Closure

Explain possible reasons for study termination or suspension (e.g., PI decision, safety concerns)
and how participants will be informed.

10.1.3 Confidentiality and Privacy

Describe how participant confidentiality will be maintained, including access to records, security
measures, and situations where personal information may be shared.
10.1.4 Future Use of Stored Specimens and Data
Describe how specimens and data may be used in future studies, consent procedures, storage
locations, and confidentiality protections.

10.1.5 Key Roles and Study Governance

List the Principal Investigator and Medical Monitor, and describe study leadership committees
and governance roles.

10.1.6 Safety Oversight

Outline safety monitoring procedures, including committees, interim data reviews, and roles in
ensuring participant safety and data integrity.

10.1.7 Clinical Monitoring

Describe site monitoring to ensure participant safety, data accuracy, and protocol compliance,
including the monitoring plan and any independent audits.

10.1.8 Quality Assurance and Quality Control

Explain quality management processes, including data and specimen evaluation, staff training,
and audits to ensure protocol compliance.

10.1.9 Data Handling and Record Keeping

Describe the data collection and management processes, responsibilities for data handling, and
the retention of clinical records, ensuring compliance with applicable regulations and standards.

Next 10,2

The phrase you're referring to means that this section of the protocol should address any
additional factors or requirements that are not already mentioned in the main body of the
protocol. These could include:

1. Institutional Requirements: Specific rules or policies that the institution where the
research is being conducted might have. For example, certain institutions may have
additional safety protocols, specific documentation requirements, or unique reporting
procedures for research involving human participants.
2. IRB-related Requirements: The Institutional Review Board (IRB) is responsible for
reviewing and approving research protocols to ensure the ethical treatment of human
subjects. If the IRB has specific expectations or additional conditions that need to be
followed for the research to proceed, these should be included here. For example, the IRB
may request certain modifications to the consent process or additional participant
protections.

In short, this section should clarify anything not already covered by the standard protocol that
must be adhered to in relation to the institution or IRB to ensure full compliance with all ethical
and regulatory standards.

Next 10.4
This section provides instructions for documenting the history of any amendments (changes)
made to an IRB-approved protocol. Here's what it means:

1. Protocol Amendment History Table: This table is meant to record any revisions or
updates made to the protocol after the initial IRB approval. Each amendment should be
listed with:
o Description of the Change: A brief explanation of what was altered in the
protocol (e.g., changes to the study design, participant criteria, data collection
methods).
o Rationale for the Change: An explanation of why the amendment was
necessary. This could include reasons like new scientific findings, changes in the
regulatory environment, or feedback from the IRB.
2. Summary of Changes Table: The "Summary of Changes" is a separate table that
appears on the protocol's title page, providing a quick overview of the most recent
changes made in the current amendment. It helps readers quickly see what has been
updated without having to read through the entire document.

In short, the protocol amendment history section tracks the evolution of the research protocol,
ensuring transparency and allowing the IRB and other stakeholders to understand how and why
the protocol has been modified over time.