OVERVIEW OF CLINICAL TRIAL

Study design Monitoring

Design study documents Patient enrollment
Investigator selection Follow-up visits
Ethics Commitee Review End of trial
Approval letter Data management
Investigator meeting Statistical review
Site initiation Final report

Types of clinical trials

There are different types of clinical trials, including:
1.- Treatment trials to test new treatments, new medicines or combinations of medicines; or other
new therapies such as surgery, the use of new medical devices or new approaches to surgery
2.- Diagnostic or screening trials to evaluate tests or procedures to diagnose and detect diseases
or conditions
3.- Prevention trials to test new ways to prevent disease including medicines, vaccines, vitamins, or
changes to diet, lifestyle or behaviour

ADR : Adverse Drug Reaction IEC : Independent Ethics Committee

AE : Adverse Event IMS : Integrated Medical Safety
AEs of special interest IND : Investigational New Drug Application (USA)
CI : Confidence Interval
CPO : Country Pharma Organization
CR : Complete Response
CRD : Clinical Research and Development
CRF : Case Report/Record Form
CRO : Contract Research Organization
CTA : Clinical Trials Application
CTCAE : Common Terminology Criteria for Adverse
Events
DCR : Disease Control Rate
DDI : Drug-Drug Interaction
DMC : Data Monitoring Committee
ECOG : Eastern Cooperative Oncology Group
EDC : Electronic Data Capture
EMEA : European Medicines Evaluation Agency
EORTC : European Organization for Research and
Treatment of Cancer
EOT : End Of Treatment
FAS : Full Analysis Set
FDA : Food and Drug Administration (USA)
GCP : Good Clinical Practice
GLP : Good Laboratory Practice
HR : Hazard Ratio
HRA : Health Regulatory Authority
IB : Investigators Brochure
IC : Informed Consent
ICH : International Conference on Harmonization
IDMC : Independent Data Monitoring Committee
IRB : Institutional Review Board
IRT (IWRS) : Interactive Response Technology (that includes
Interactive Web Response System)
ITT : Intent-To-Treat
LLN : Lower Limit of Normal
LLOQ : Lower Limit Of Quantification
MAD : Multiple Ascending Dose
MHRA : Medicines and Healthcare Regulatory Agency
MRP : Mutual Recognition Procedure (EU - European Union)
NCCN : National Comprehensive Cancer Network
NCI : National Cancer Institute
NDA : New Drug Application (USA)
PR : Partial Response
PRO : Patient Reported Outcome
PS : Performance Status
QoL : Quality of Life
R & D : Research and Development
RCT: randomized controlled trial (prueba aleatoria controlada)
RECIST : Response Evaluation Criteria in Solid Tumors
REB : Research Ethics Board
SAD : Single Ascending Dose
SAE : Serious Adverse Events
SD : Stable Disease
SEC : Study Evaluation Completion
SOP : Standard Operating Procedure
SPA : Special Protocol Assessment
SSC : Study Steering Committee
TSQM : Treatment Satisfaction Questionnaire for Medication
TTP : Time to Progression
ULN : Upper Limit of Normal
End points:

PFS : Progression Free Survival

OS : Overall Survival
ORR : Objective Response Rate
CBR : Clinical Benefit Rate
Safety

VISIT EVALUATION SCHEDULE

Visit window
Screening
FIRST: Obtain Informed Consent
(ICForm)
SECOND: IRT (Interactive Response
Technology) - Registration (after ICF
signed)
Patient history
1. Demography
2. Inclusion/exclusion criteria
3. Relevant Medical history /
current medical Conditions
4. Diagnosis and extent of cncer
5. Smoking history
6. Prior antineoplastic therapy
(surgery, radiotherapy,
 medications)
7. Prior/concomitant medications
8. Screening log
9. Pre-randomization Form
Randomization
1. IRT (Interactive Response
Technology) - Randomization
2. Physical examination
3. Weight
4. Height
5. Vital signs
6. ECOG (Eastern Cooperative
Oncology Group) - Performance
status
Laboratory assessments
1. Tumor assessments
Safety
1. Adverse events
Biomarkers
1. Collection of archival paraffin
blocks / slides
Patient Reported Outcome (PRO)
1. EORTC (QLQ-C30) European
Organization for Research and
Treatment of Cancer
2. EORTC module
3. TSQM (Treatment Satisfaction
Questionnaire for Medication)
Discontinuation
1. IRT (Interactive Response
Technology) Progression /
discontinuation / death
2. Antineoplastic therapies since
 discontinuation of study treatment
3. Survival Follow-up [At least every
3 months (may be via phone
contact)].

-STUDY DESIGN
1.- Description of study design
Screening Phase
Randomization and treatment phase
Follow-Up phase
2.- Timing of final primary analysis
3.- Definition of end of the study
4.- Early study termination

-POPULATION
Patient population
Inclusion criteria
Exclusion criteria

-TREATMENT
1.- Study treatment
Dosing regimen.
Study drug supply.
 Treatment duration.
2.- Dose modifications
Dose modifications in the management of adverse reactions.
Follow-up for toxicities.
3.- Concomitant medications
Prohibited concomitant therapy and concomitant therapy requiring caution and/or action.
Study drug compliance and accountability.
Disposal and destruction.

-VISIT SCHEDULE AND ASSESSMENTS

1.- Study flow and visit schedule
Screening and Baseline
Treatment period
End of treatment visit including study completion and premature withdrawal
Follow-Up
Survival follow-up
2.- Assessment types
Efficacy assessments
Safety and tolerability assessments
Biomarkers
Patient reported outcomes

-SAFETY MONITORING AND REPORTING

1.- Adverse events
Definitions and reporting
Laboratory test abnormalities
Adverse events of special interest
2.- Serious adverse events
Definitions
Reporting
3.- Emergency unblinding of treatment assignment
4.- Pregnancies
5.- Warnings and precautions
6.- Data Monitoring Committee (DMC)
7.- Study steering Committee (SSC)

-DATA COLLECTION AND MANAGEMENT

1.- Data confidentiality
2.- Site monitoring
Initiation visit or at an investigators meeting (review the protocol and CRFs with the investigators and
their staff).
Completeness of patient records.
The accuracy of entries on the CRFs.
The adherence to the protocol to Good Clinical Practice.
The progress of enrollment.
To ensure that study treatment is being stored, dispensed, and accounted for according to specifications.
All information recorded on CRFs must be traceable to source documents in the patient's file.
The investigator must also keep the original signed informed consent form (a signed copy is given to the patient).
Full verification for the presence of informed consent, adherence to the inclusion/exclusion criteria and documentation of
SAEs.
Checks of the consistency of the source data with the CRFs are performed according to the study-specific monitoring
plan.
Documentation (such as certifications and normal ranges) for all local laboratories used must be collected for data
management.

3.- Database management and quality control

-STATISTICAL METHODS AND DATA ANALYSIS

1.- Analysis sets
Full Analysis Set
Safety Set
Per-Protocol Set
Dose-determining analysis set
2.- Patient demographics/other baseline characteristics
3.- Treatments (study treatment, concomitant therapies, compliance)
Study treatment
 Concomitant therapies
4.- Primary objective
Variable
Statistical model and method of analysis
Handling of missing values / censoring / discontinuations
Supportive analyses
5.- Secondary objectives
Key Secondary Objective
Other secondary objectives
Safety objectives
6.- Sample size calculation

-ETHICAL CONSIDERATIONS AND ADMINISTRATIVE PROCEDURES

1.- Regulatory and ethical compliance
2.- Responsibilities of the investigator and IRB / IEC / REB
3.- Informed consent procedures
4.- Discontinuation of the study
5.- Publication of study protocol and results
6.- Study documentation, record keeping and retention of documents
7.- Confidentiality of study documents and patient records
8.- Audits and inspections
9.- Financial disclosures

-PROTOCOL ADHERENCE
1.- Amendments to the protocol