clinical trials Flashcards
It is a systematic process that is intended to find out the safety and
efficacy of a drug/device in treating/preventing/diagnosing a disease or a medical condition.
Clinical Trials
It involves the study of the effect of an investigational drug/any other intervention in a defined population/participant.
Clinical Trials
These are exploratory trial phases
Phase 0
Phase II
It is termed as the non-therapeutic phase
Phase I
It is known as the therapeutic confirmatory phase
Phase III
It is called the post-approval or the post-marketing surveillance phase
Phase IV
Study participants are randomly assigned to a group
Randomized Trial
A type of CT where both study subjects and the researchers are aware of the drug being tested.
Open-label Clinical Trial
In this type of CT, the subject has no idea about the group (test/control) in which they are placed
Single-Blind Clinical Trial
In this CT, the subjects as well as the investigator have no idea about the test/control group.
Double-Blind Clinical Trial
A substance that appears like a drug but has no active moiety
Placebo
An additional drug apart from the clinical trial drug given to a group of study participants
Add-On
A study being carried out at a particular place/location/center
Single-Center
A study is being carried out at multiple places/locations/centers
Multi-Center
Clinical trials are broadly classified into:
Controlled and Uncontrolled Trials
These are potentially biased, and the results of such research are not
considered as equally as the controlled studies.
Uncontrolled Trials
These are considered the most effective clinical trials wherein the bias is minimized, and the results are considered reliable.
Randomized controlled trials (RCTs)
The participants are assigned to a case or a control group based on flipping coin results/computer assignment.
Simple Randomization
Equal and small groups of both cases and controls
Block Randomization
Randomization based on the age of the participant and other covariates
Stratified Randomization
Sequential assignment of a new participant into a group based on the covariates
Co-Variate Adaptive Randomization/Minimization
One intervention is administered to one-half of the body and the comparator intervention is assigned to another half of the body.
Randomization by Body Halves or Paired Organs (Split Body Trials)
Intervention is administered to clusters/groups by randomization to prevent contamination and either active or comparator intervention is administered for each group.
Clustered Randomization
Patients are allocated to one of the two trial arms
Allocation by Randomized Consent (Zelen Trials)
Clinical research design has two major types that include:
Non-Interventional / Observational
Interventional / Experimental
The non-interventional studies may have a comparator group (analytical studies like case-control and cohort studies), or without it (descriptive study). The experimental studies may be either randomized or non-randomized.
This is the most frequent design wherein each arm of the study group is allocated a particular treatment (placebo (an inert substance)/therapeutic drug)
Parallel
The patient in this trial gets each drug and the patients serve as a control themselves. It has a washout period.
Crossover
Two or more interventions on the participants and the study can provide information on the interactions between the drugs
Factorial
This study evaluates the time/duration of the drug therapy
- It uses a placebo to understand the efficacy of a drug in treating the disease
Randomized Withdrawal Approach
Recruit patients with the same characteristics.
• Less Variability
Matched Pairs
It is the most frequently performed clinical research.
This type of research is undertaken to analyze the presence or absence of a disease/condition, potential risk factors,
and prevalence and incidence rates in a defined population.
Cross-Sectional Study Design
Clinical trials may be _____ type depending on the type of intervention
therapeutic or non-therapeutic
This type of clinical trial uses a drug that may be beneficial to the patient.
therapeutic
In this type of clinical trial, the participant does not benefit from the drug. It provide additional knowledge of the drug for future improvements.
non-therapeutic
The clinical trial process involves:
• Protocol Development
• Designing a Case Record/Report Form
• Functioning of Institutional Review Boards
• Data Management
• Monitoring Clinical Trial Site Activities
It is the most significant document in a clinical study. It contains the information collected by the investigator about each subject participating in a clinical study/trial.
Case Record/Report Form (CRF)
The clinical study is conducted by a:
sponsor or a clinical research organization (CRO)
NOTE: The two most important points to consider before the initiation of the clinical trial include whether there is a need for a clinical trial, if there is a need, then one must make sure that the study design and methodology are strong for
the results to be reliable to the people.
Examines too low (1/100th) concentrations (micro-dosing) of the drug for less time. Study the
pharmacokinetics and determine the dose for phase I studies.
Phase 0
• Around less than 50 healthy subjects are recruited.
• Establishes a safe dose range, and the MTD.
• Examines the pharmacokinetic and pharmacodynamic effects.
• Usually single-center studies.
Phase I
Phase IA
Focus: Single Ascending Dose (SAD) and Maximum Tolerated Dose (MTD)
Duration: 1 week to several months
Includes: 6-8 groups of 3-6 participants
Phase IIB
Focus: Multiple Ascending Doses (MAD) and the dose is gradually narrowed down.
Includes: Three groups of 8 individuals each.
• Around 5-100 patients of either sex.
• Examines the effective dosage and the
therapeutic effects on patients.
• It decides the therapeutic regimen and drug-drug interactions.
• Usually, multicentre studies.
Phase II
Decides the drug dosage, includes 20-30 patients, and takes up to weeks/months.
Phase IIA
Studies dose-response relationship, drug-drug interactions, and comparison with a placebo.
Phase IIB
• More than 300 patients (up to 3000) of
either sex are recruited in this study and
are multicentric trials.
• Pre marketing phase examines the efficacy and the safety of the drug.
Phase III
• Comparison of the test drug with the placebo/standard drug.
• Adverse drug reactions/adverse events are noted.
• Initiate the process of NDA with appropriate regulatory agencies like the FDA.
Phase III
• After approval/post-licensure and post-
marketing studies/surveillance studies.
• Following up on the patients for an
exceptionally long time for potential
adverse reactions and drug-drug
interactions.
Phase IV
Phase I CT
• Dose Escalation (SAD)
• Safety Monitoring
• Maximum Tolerated Dose (MTD)
Phase II CT
• Efficacy Evaluation
• Safety Profile
• Dose Optimization
Study Design and Methodology
• Protocol Development
• Randomization
• Blinding
Specific disease characteristics, age
range, and health status for eligibility.
Inclusion Criteria
Conditions or factors that could
interfere with the study or patient
safety.
Exclusion Criteria
Outreach through healthcare providers, patient advocacy groups, and targeted advertising.
Recruitment Strategies
Main outcome measure, such as tumor size reduction or symptom improvement.
Primary Endpoint
Biological indicators used to track treatment response and disease progression.
Biomarkers
Additional measures to support
primary endpoint and gather more data.
Secondary Endpoints
Patient-reported outcomes to assess overall well-being and treatment impact.
Quality of Life
Systematic documentation of any
unexpected medical occurrences during
the trial.
Adverse Event Reporting
Regular checks of blood pressure, heart
rate, and other essential health
indicators.
Vital Signs Monitoring
Periodic blood work and other diagnostic tests to assess organ function.
Laboratory Tests
Phase III CT
• Large Scale Testing
• Comparative Studies
• Long-Term Studies
• Regulatory Submission
Phase III Trial Design and Enrollment
• Protocol Development
• Patient Recruitment
• Randomization
• Treatment Administration
Regulatory Approval Process for Phase III
• Pre-NDA Meeting
• NDA Submission
• FDA Review
• Advisory Committee
Discussion with regulatory agency about submission requirements
Pre-NDA Meeting
Comprehensive application including all clinical and non-clinical data.
NDA Submission
Thorough evaluation of submitted data by expert panels.
FDA Review
Public meeting to discuss benefits and risks of the new treatment.
Advisory Committee
It is a systematic process of evaluating the clinical trial operations at the site. It ensures that the clinical trial process is conducted according to the protocol, and predefined quality system procedures, following GCP guidelines, and according to the requirements of
regulatory authorities.
Audit
• Focuses on safety and feasibility of new drug candidates.
• Preclinical to early clinical trials.
• 30-day FDA review.
Investigational New Drug (IND) Application
• Comprehensive evaluation of efficacy and safety.
• Late-stage clinical trials and manufacturing data.
• 10-month comprehensive FDA
review.
New Drug Application (NDA)
List of objectionable conditons/processes prepared by the FDA Investigator and submitted to the auditee at the end or the inspection
483
The auditors submit their identity proofs and notice of inspections to the clinical investigators and later document their observations
482
This document details the fact that the clinical trial is not initiated before 30 days of submitting the IND to the FDA for approval.
The form confirms that the IRB complies with 21 CFR Part 56. The form details the agreement to follow regulatory requirements and names all the individuals who monitor the conduct and progress of the study and evaluate the safety of the clinical trial
1571
This form details the fact that the study is conducted after ethics approval ensures that the study is carried out according to protocol, informed consent, and IRB approval
1572
Strategies for Successful
NDA Submission
• Effective Communication
• Robust Data
• Meticulous Planning
• Regulatory Compliance
Phase IV Clinical Trials
• Safety Monitoring
• Efficacy Studies
• Population Impact
• Cost Effectiveness
