CLINICAL TRIALS Flashcards
It is 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 TRIAL
A clinical trial is a systematic process that is intended to find out the safety and efficacy of a drug/device in ___/____/___ a disease or a medical condition.
TREATING/ PREVENTING/ DIAGNOSING
It involves the study of the effect of an investigational drug/any other intervention in a defines population/participant.
CLINICAL TRIAL
The new FDA guidelines include five (5) phases:
PHASE 0 (micro-dosing studies)
PHASE 1
PHASE 2
PHASE 3
PHASE 4
Phase 0 and Phase 2 are called?
EXPLORATORY TRIAL PHASES
Phase 1 is termed the?
NON-THERAPEUTIC PHASE
Phase 3 is knows as the?
THERAPEUTIC CONFIRMATORY PHASE
Phase 4 is called the?
POST-APPROVAL OR POST-MARKETING SURVEILLANCE PHASE
Type of Clinical Trial:
RAMDOMIZED TRIAL
OPEN LABEL
BLINDED (SINGLE BLIND)
DOUBLE-BLINE (DOUBLE-BLIND)
PLACEBO
ADD-ON
SINGLE CENTER
MULTI-CENTER
Study participants are randomly assigned to a group.
RANDOMIZED TRIAL
Both study subjects and the researchers are aware of the drug being tested.
OPEN-LABEL
In____ , the subject has no idea about the group (test/control) in which they are placed
BLINDED (SINGLE-BLIND)
In the ____ study, the subjects as well ad the investigator have no idea about the test/control group.
DOUBLE-BLIND (DOUBLE-BLIND)
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 a particular place/location/center.
SINGLE CENTER
A study is being carried out at multiple places/location/centers.
MULTI-CENTER
Clinical trials are broadly classified into?
CONTROLLED and UNCONTROLLED TRIALS
Are potentially biased, and the results of such research are not considered as equally as the controlled studies.
UNCONTROLLED TRIALS
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 baser on flipping coin results/computer assignment.
SIMPLE RANDOMIZATION
Equal and small group 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 participants 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:
NON-INTERVENTIONAL/OBSERVATIONAL
INTERVENTIONAL/EXPERIMENTAL
It may have a comparator group (analytical studies like case-control and cohort studies), or without it (descriptive study)
NON-INTERVENTIONAL STUDIES
The non-interventional studies may have a _____ (analytical studies like case-control and cohort studies) or without it (descriptive studies)
COMPARATOR GROUP
The experimental studies may be either?
RANDOMIZED OR NON-RANDOMIZED
It may be either randomized or non-randomized?
EXPERIMENTAL STUDIES
It has several types including parallel design, crossover design, factorial design, randomized withdrawal approach, adaptive design, superiority design, and non-inferiority design.
CLINICAL TRIAL DESIGNS
Randomization type:
• SIMPLE RANDOMIZATION
• BLOCK RANDOMIZATION
• STRATIFIED RANDOMIZATION
• CO-VARIATE ADAPTIVE RANDOMIZATION/MINIMIZATION
• RANDOMIZATION BY BODY HALVES OR PAIRED ORGANS (SPLIT BODY TRIALS)
• CLUSTERED RANDOMIZATION
• ALLOCATED BY RANDOMIZED CONSENT (ZELEN TRUALS)
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 - RANDOMIZED
The patient in this trial gets each drug and the patients serve as a control themselves.
CROSSOVER - RANDOMIZED
Two or more interventions on the participants and the study can provide information on the interactions between the drugs.
FACTORIAL - NON-RANDOMIZED
This study evaluates the time/duration of the drug therapy.
RANDOMIZED WITHDRAWAL APPRACH - RANDOMIZED
Recruit patients with the same characteristics.
MATCHED PAIRS - POST APPROVAL STUDY
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 defines population.
OBSERVATIONAL RESEARCH USING CROSS-SECTIONAL STUDY DESIGN
Clinical trials may be ___ or ___ depending on the type of intervention.
THERAPEUTIC or NON-THERAPEUTIC TYPE
The _____ of clinical trial uses a drug that mey be beneficial to the patient
THERAPEUTIC
A ____ clinical trial, the participant does not benefit from the drug. It provide additional knowledge of the drug for future improvements.
NON-THERAPEUTIC TYPE
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)
A clinical study is conducted by a?
SPONSOR or a CLINICAL RESEARCH ORGANIZATION (CRO)
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.
SAFETY ASSESSMEMT
Around <50 healthy subjects are recruiter. Establishes a safe dose range, and the MTD. Examines the pharmacokinetic and pharmacodynamic effects.
PHASE I
Recruiting 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.
PHASE II
More than 300 patients (up to 3000) of either sec are recruited in this study and ate multicentric trials. Premarketing phase examined the efficacy and the safety of the drug. Comparison of the test drug with the placebo/standard drug. Adverse drug reaction/adverse events are noted. Initiate the process of NDA with appropriate regulatory agencies like 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.
PHADE IV
MTD
MAXIMUM TOLERATED DOSE
SAD
SINGLE ASCENDING DOSE
MAD
MULTIPLE ASCENDING DOSE
NDA
NEW DRUG APPLICATION
FDA
FOOD AND DRUGS ADMINISTRATION
Phase I clinical trials:
• DOSE ESCALATION
• SAFETY MONITORING
• MAXIMUM TOLERABLE DOSE
Phase I trials typically start with a very low dose of the investigational product and gradually increase the dose in a controlled manner.
DOSE ESCALATION
Participants are closely monitored for any adverse events or side effects, and the dose is adjusted accordingly.
SAFETY MONITORING
The trial aims to identify the maximum tolerated dose (MTD), which is the highest dose that can be safely administered without causing unacceptable side effects:
MAXIMUN TOLERATED DOSE
Phase II Clinical Trials:
• EFFICACY EVALUATION
• SAFETY PROFILE
• DOSE OPTIMIZATION
Determine if the drug shows promising results in treating the target condition.
EFFICACY EVALUATION
Monitor and assess potential side effects and risks associated with the treatment.
SAFETY PROFILE
Identify the optimal dosage that balances effectiveness and safety for patients.
DOSE OPTIMIZATION
Study Design and Methodology:
• PROTOCOL DEVELOPMENT
• RANDOMIZATION
• BLINDING
Study Design and Methodology:
• PROTOCOL DEVELOPMENT
• RANDOMIZATION
• BLINDING
Create a detailed plan outlining study procedures, endpoints, and statistical methods.
PROTOCOL DEVELOPMENT
Assign participants to treatment groups to minimize bias and ensure statistical validity.
RANDOMIZATION
implement single ir double-blinding to prevent bias in data collection and analysis.
BLINDING
Patient Population and Recruitment:
• INCLUSION CRITERIA
• EXCLUSION CRITERIA
• RECRUITMENT STRATEGIES
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
Outreach through healthcare providers, patient advocacy groups, and targeted advertising.
RECRUITMENT STRATEGIES
Efficacy Endpoints and Assessments
• PRIMARY ENDPOINT
• SECONDARY ENDPOINT
• BIOMARKERS
• QUALITY OF LIFE
Main outcome measure, such as tumor size reduction ot symptom improvement.
PRIMARY ENDPOINT
Additional measures to support primary endpoint and gather more data.
SECONDARY ENDPOINT
Biological indicators used to track treatment response and disease progression.
BIOMARKERS
Patient-reported outcomes to assess overall well-being and treatment impact.
QUALITY OF LIFE
Safety Monitoring and Data Collection
• ADVERSE EVENT REPORTING
• VITAL SIGNS MONITORING
• LABORATORY TESTS
Systematic documentation of any unexpected medical occurrence during the trial.
ADVERSE EVENT REPORTING
Regular checks of blood pressure, heart rate, and other essential health indicators.
VITAL SIGNS MONITORING
Phase III Clinical Trials:
• LARGE-SCALE TESTING
• COMPARATIVE STUDIES
• LONG-TERM EFFECTS
• REGULATORY SUBMISSION
Phase III Trial Design and Enrollment
• PROTOCOL DEVELOPMENT
• PATIENT RECRUITMENT
• RANDOMIZATION
• TREATMENT ADMINISTRATION
Involves hundreds to thousands of patients across multiple centers.
LARGE-SCALE TESTING
Often compares new treatment to current standard of care ot placebo.
COMPARATIVE STUDIES
Monitors for side effects and evaluates long-term efficacy.
LONG-TERM EFFECTS
Data from Phase III trials ate crucial for regulatory approval.
REGULATORY SUBMISSION
Detailed plan outlining trial objectives, design, and methods.
PROTOCOL DEVELOPMENT
Rigorous screening process to ensure eligible participants.
PATIENT RECRUITMENT
Patients randomly assigned to treatment ot control groups.
RANDOMIZATION
Strict adherence to protocol for dosing and follow-up.
TREATMNET 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
Among the most significant aspects of a clinical trial?
AUDIT
A systematic process of evaluating the clinical trial operations at the site.
AUDIT
It ensures that the clinical trial process is conducted according yo the protocol, and predefined quality system procedures, following GCP guidelines, and according to the requirements of regulatory authorities.
AUDIT
The NDA Submission and Review Timeline
• NDA SUBMISSION
• FDA REVIEW
• FDA APPROVAL
The completed NDA us filed with the FDA review.
NDA SUBMISSION
The FDA has 10 months to review the NDA and make a decision.
FDA REVIEW
If approved, the drug can be marketed and sold in the United States.
FDA APPROVAL
Phase IV Clinical Trials:
• SAFETY MONITORING
• EFFICACY STUDIES
• POPULATION IMPACT
• COST-EFFECTIVESS
Continuous tracking of adverse events in real-world settings.
SAFETY MONITORING
Additional research to confirm long-term benefits and risks.
EFFICACY STUDIES
Assessing treatment effects in diverse patient groups.
POPULATION IMPACT
Evaluating economic impacts of the nee treatment.
COST-EFFECTIVENESS
Key differences Between IND and NDA
• FOCUS
• TIMING
• PREVIEW PROCESS
Safety and feasibility of new drug candidate.
IND
Comprehensive evaluation of efficacy ad safety.
NDA
Preclinical to early clinical trials.
IND
Late-stage clinical trials and manufacturing data.
NDA
30-day FDA review
IND
10-month comprehensive FDW review
NDA
Strategies tor Successful NDA submission:
• EFFECTIVE COMMUNICATION
• ROBUST DATA
• METICULOUS PLANNING
• REGULATORY COMPLIANCE
Maintain open dialogue with the FRW throughout the NDA process.
EFFECTIVE COMMUNICATION
Ensure comprehensive and well-organized clinical trial data in the NDA.
ROBUST DATW
Develop a detailed timeline and strategy for NDW preparation and submission.
METICULOUS PLANNING
Adhere to strictly to all FRW guidelines and regulations throughout the process.
REGULATORY COMPLIANCE
identifical in appearance to the treatment drug.
PLACEBO
