Introduction to Clinical Trials

Definition:
Clinical trials are systematic studies of new drugs in humans to assess their safety, efficacy, pharmacokinetics, pharmacodynamics, and adverse effects.

Participation

Participants may gain early access to new treatments and contribute to medical research.
Inclusion/Exclusion Criteria decide eligibility based on factors like age, gender, disease stage, medical history, and prior treatments.
These criteria ensure reliable results and participant safety, not personal rejection.
Trials may involve patients with specific illnesses or healthy volunteers.

Process

Varies by type of trial.
Conducted by a team of doctors, nurses, social workers, and other healthcare professionals.

Clinical Trials – Summary Notes

Process

Health of participants is checked before the trial.
Participants receive instructions, are closely monitored during the trial, and followed up after completion.
Success depends on adherence to protocol and regular contact with the research team.

Informed Consent

Ongoing process of providing trial information before and during participation.
Doctors/nurses explain study details; translation provided if needed.
Consent form covers purpose, duration, procedures, and contacts.
Not a contract – participants may withdraw anytime.

Benefits

Active role in personal health care.
Early access to new treatments.
Expert medical care during trial.
Contribute to advancement of medical research.

Safety

Governed by medical ethics and legal codes.
Federally regulated with safeguards for participant protection.

Clinical Trials – Key Points

Protocol & Reporting

Trials follow a strict study plan (protocol).
Results shared in journals, meetings, and with agencies; participant identities remain confidential.

Information for Subjects

Before joining, participants should ask about:

Purpose, eligibility, prior testing of treatment.
Tests/procedures involved.
Risks, benefits vs. current treatment.
Impact on daily life, duration, need for hospitalization.
Costs and who pays.
Who will manage care.

Ideas for Clinical Trials

Origin: Researchers → lab studies → animal studies → human trials.
Goal: Evaluate safety, risks, and effectiveness of new treatments.

Do you want me to merge all your sections (Intro, Process, Consent, Benefits, Safety, Protocol, etc.) into one complete concise “exam notes” document?

Here’s a brief version of your notes:

Types & Phases of Clinical Trials

Types of Clinical Trials

Treatment Trials – Test new drugs, combinations, surgeries, or radiation.
Prevention Trials – Find ways to prevent diseases or recurrence (drugs, vaccines, lifestyle).
Diagnostic Trials – Develop better diagnostic tests/procedures.
Screening Trials – Improve detection of diseases/conditions.
Quality of Life (Supportive Care) Trials – Enhance comfort and well-being of chronic illness patients.

Phases of Clinical Trials

Phase I (20–80 people): Safety, dosage, side effects.
Phase II (100–300 people): Effectiveness + safety.
Phase III (1000–3000 people): Confirm effectiveness, compare with standard treatment, monitor adverse effects.
Phase IV (Post-marketing): Long-term risks, benefits, and optimal use.

Expanded Access Protocol (Treatment IND)

Allows patients (not eligible for trials) with life-threatening diseases to access investigational drugs.
Provides treatment + additional safety data.
Allowed only if ongoing/completed controlled trials show potential benefit without unreasonable risk.

⭐ Requirements for Conducting Clinical Trials as per Schedule Y

(Complete, combined, easy-to-remember notes)

1️⃣ Pre-Requisites Before Starting a Clinical Trial

Before enrolling any participant, THREE requirements must be fulfilled:

1. DCGI (Drugs Controller General of India) Permission

Mandatory regulatory approval under Schedule Y / NDCTR.
Application through Forms CT-18 + CT-21 or CT-04, with prescribed fee.
Must include all required scientific data.

2. Ethics Committee (EC) Approval

Study must be approved by EC of each site.
EC must be registered with DCGI (validity: 3 years).
No trial can begin without EC approval.

3. CTRI Registration

Mandatory prospective registration on
Clinical Trials Registry of India (CTRI) before enrolling first participant.

2️⃣ Application Requirements (What Sponsor Must Submit)

The application to DCGI must include:

A. Chemical & Pharmaceutical Information

Drug composition
Manufacturing process
Stability data
CMC (Chemistry, Manufacturing & Controls)

B. Preclinical / Animal Data

Animal pharmacology
Animal toxicology (acute, subacute, chronic)
Reproduction toxicity
Genotoxicity
Carcinogenicity (if needed)

C. Clinical Data

Previous human trial data
Safety and efficacy details
Published and unpublished evidence

D. Regulatory Information

Approval status in other countries
Investigational status abroad

3️⃣ Compliance Requirements (How Trials Must Be Conducted)

Trials must follow:

✔ Approved protocol only
✔ Schedule Y guidelines
✔ Good Clinical Practice (GCP) guidelines
✔ New Drugs & Clinical Trials Rules (NDCTR)
✔ All amendments issued by CDSCO

Changes in protocol require prior approval from EC and DCGI.

4️⃣ Responsibilities of Ethics Committee

Protect rights, safety, and wellbeing of participants
Review and approve:

Protocol
Informed consent documents
Compensation rules

Conduct continuing review
Report serious violations to DCGI

EC must be independent and DCGI-registered.

5️⃣ Informed Consent Requirements

Schedule Y mandates:

Written informed consent from each participant
Language understandable to the subject
Clear statements on:

Free medical management for trial-related injury
Financial compensation for injury or death

Investigators must give a copy of signed consent to the participant/attendant
Audio–video recording mandatory for vulnerable participants

6️⃣ Safety Reporting Requirements (SAEs)

Investigators must report Serious Adverse Events (SAEs), including death:

To DCGI, Sponsor, and Ethics Committee
➡ within 24 hours (initial report)
Detailed, causality-assessed report
➡ within 10 calendar days

Sponsor, investigator, and EC share responsibility for timely reporting.

7️⃣ Conduct of Trial – Operational Requirements

Qualified investigator with adequate experience
Adequate site facilities (emergency care, labs, equipment)
IP (Investigational Product) must meet GMP standards
Record keeping must follow GCP
Monitoring and audits must be performed regularly
Maintain:

CRFs
Source documents
Drug accountability logs
EC & DCGI correspondence

Documents must be archived for minimum 5 years after study completion.

8️⃣ Compensation & Medical Management

Schedule Y + Rule 122DAB require:

Free medical care for injury during the study
Financial compensation for:

Trial-related injury
Death
Permanent disability
Congenital anomalies

Sponsor must provide timely compensation after causality assessment.

9️⃣ Trial Registration & Reporting

All clinical trials must be registered in CTRI
Final study report must be submitted to DCGI and EC
Summary results must be made publicly accessible as per CTRI norms

⭐ Super-Short Revision Notes

Schedule Y requires:

DCGI approval + EC approval + CTRI registration
Submission of chemical, preclinical, clinical & regulatory data
Compliance with Schedule Y + GCP + NDCTR
DCGI-registered Ethics Committee review
Detailed informed consent (copy to participant)
SAE reporting in 24 hours, full report in 10 days
Proper trial conduct, monitoring & documentation
Compensation & medical management for injuries
Final report + document archiving for 5 years

🧑‍⚕️ Inclusion and Exclusion Criteria in Clinical Trials

✅ What are Inclusion and Exclusion Criteria?

They are pre-defined rules describing who can participate and who cannot participate in a clinical trial.

These criteria ensure:

Safety of participants
Scientific validity
Homogeneous (similar) study population
Reduction of bias

✅ Inclusion Criteria (Who CAN participate?)

Definition

Inclusion criteria are the essential characteristics that a person must have to join the clinical trial.

Purpose

Ensure subjects have the condition being studied
Ensure correct age, gender, disease severity, and baseline health
Increase accuracy and relevance of results

Examples

For a Type 2 Diabetes trial:

Age 30–65 years
Diagnosed with Type 2 diabetes for ≥ 6 months
HbA1c between 7–10%
BMI 25–40
Willing to give informed consent

For a vaccine trial:

Healthy adults 18–55 years
No prior COVID-19 infection
No vaccination in last 4 weeks

🚫 Exclusion Criteria (Who CANNOT participate?)

Definition

Exclusion criteria are conditions or factors that disqualify a person from participating due to safety concerns or to avoid confounding results.

Purpose

Prevent harm to participants
Eliminate factors that may interfere with the study
Reduce risk
Control variability

Examples

For a Type 2 Diabetes trial:

Type 1 diabetes
Severe kidney or liver disease
Pregnant or breastfeeding
Taking medications that interact with the study drug
History of severe hypoglycemia

For a vaccine trial:

Immunocompromised patients
Allergy to vaccine components
Acute fever or infection
Participation in another trial recently

🔍 Why Are These Criteria Important?

Ensure safety
Minimize variability
Improve validity of results
Protect vulnerable populations
Ensure ethical standards
Meet regulatory requirements (FDA, EMA, CDSCO, ICMR)

⭐ In Simple Words

Inclusion criteria = Who is allowed
Exclusion criteria = Who is not allowed
Both help choose the right participants to get accurate and safe trial results.

🟦 Open Label Trial

✅ Definition

An open label trial is a type of clinical trial where both the researcher (investigator) and the participant know which treatment is being given.

➡️ No blinding is used.
➡️ Everyone is aware of the treatment assignment.

🧪 Why Are Open Label Trials Used?

When blinding is not possible:

Comparing tablet vs surgery
Comparing lifestyle intervention vs drug
Using a treatment with unique effects that cannot be hidden

When it is unethical to blind:

Life-saving treatment
When placebo cannot be justified

For early-phase trials:

Phase 1 safety studies often open label
Dose-finding studies

For post-marketing studies:

Real-world effectiveness
Patient-reported outcomes

📌 Characteristics

No placebo or dummy treatment
Participants know what they receive
Investigator also knows
Can have bias (performance bias, reporting bias)

🩺 Example

Testing a new insulin delivery device:

All patients are given the new device.
Both doctor and patient know what device is used.
Outcomes like glucose control and ease of use are assessed.

➡️ This is an open label trial.

🎯 Advantages

Easy to conduct
Less expensive
Useful when blinding is difficult
Better for patient compliance
Real-world setting

⚠️ Disadvantages

Higher risk of bias

Performance bias
Observation bias
Reporting bias

Results may be less reliable than blinded trials

⭐ In One Line

An open label trial is a clinical study where both the doctor and the participant know which treatment is being given, with no blinding involved.

✅ Definition of Bias

Bias is a systematic error in

the design, conduct, or analysis of a study that leads to an incorrect or distorted estimate of a treatment’s true effect.

👉 It is not random; it consistently pushes results in one direction, making them unreliable.

⭐ Key Points to Remember

Bias causes the study results to differ from the truth
It can occur at any stage: planning, data collection, analysis, or interpretation
It reduces validity of the study
Blinding, randomization, and allocation concealment help reduce bias

✅ Single-Blind Method

Definition

In a single-blind clinical trial, only the participants (subjects) do NOT know which treatment they are receiving.
The researchers/investigators DO know who is receiving which treatment.

Purpose

To reduce participant bias
(e.g., placebo effect, expectations affecting response)

Example

A study testing a new painkiller:

Group A receives the new drug
Group B receives a placebo
Participants do not know whether they got the drug or placebo
But the researcher knows which group each participant is in

This ensures that patient expectations do not influence pain-relief reporting.

✅ Double-Blind Method

Definition

In a double-blind clinical trial, both participants AND the researchers/ investigators do NOT know which participants are getting the test drug or placebo.

Purpose

To reduce participant bias
To reduce researcher bias, especially during:

assessment of outcomes
observation
data collection

Example

A vaccine trial:

Group A receives the new vaccine
Group B receives a placebo injection
Both the participants and the researchers assessing the outcomes do not know who received what
Only an independent data safety monitoring board has the code list

This prevents doctors or participants from being influenced while recording symptoms, side effects, or effectiveness.

🔍 Simple Comparison Table

Feature	Single-Blind	Double-Blind
Participant knows treatment?	❌ No	❌ No
Researcher knows treatment?	✔️ Yes	❌ No
Bias reduced	Participant bias	Participant + researcher bias
Example	Painkiller trial	Vaccine trial

⭐ Quick Tip (Remember easily)

Single blind → 1 group unaware (participants)
Double blind → 2 groups unaware (participants + researchers)

Friday, September 12, 2025