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Data Analytics: AS 9 platform

EDC: Oracle CLINICAL, phase forward, medidata solution etc

DOCUMENT management Services:DOCUMENTUM, OPENTEXT, adobe solutions etc.

Data Analytics: AS 9 platform

EDC: Oracle clinical, phase forward, medidata solution etc

Document management Services:Documentum, Opentext, adobe solutions etc.

DOUBLE data ENTRY is the process of entering the same data twice in pass one and pass two, by two different individuals. DDE is important because it helps in reducing the DISCREPANCIES that ARISE due to errors in data entry.

Double data entry is the process of entering the same data twice in pass one and pass two, by two different individuals. DDE is important because it helps in reducing the discrepancies that arise due to errors in data entry.

It is the data which SHOWS that the STUDY was CONDUCTED according to the PROTOCOL. It tells the who, when and why of the entry/changes in data.

It is the also defined as the "DOCUMENTATION that allows reconstruction of the course of events" according to SCDM (Society for Clinical Data Management).

It is the data which shows that the study was conducted according to the protocol. It tells the who, when and why of the entry/changes in data.

It is the also defined as the "Documentation that allows reconstruction of the course of events" according to SCDM (Society for Clinical Data Management).

Common DATA Elements mean the standardized, unique terms and phrases that delineate discreet PIECES of information USED to collect data on a clinical TRIAL.

Common Data Elements mean the standardized, unique terms and phrases that delineate discreet pieces of information used to collect data on a clinical trial.

Here is a list documents that need to be kept at the study site. 
1. Signed FDA form 1572
2. CVs of all investigators
3. Signed approved protocol
4. Informed CONSENTS / all amended informed consents
5. Investigator’s Brochure
6. IRB approval
7. IRB membership
8. Assurance number
9. Drug accountability
10. IND SAFETY reports
11. Annual/interim reports
12. All information given to the subjects
13. CRF s on each subject (signed, dated)
14. AE reports
15. All source documents not kept in Medical record
16. Meeting minutes/correspondence
17. Signature log/equipment logs
18. Laboratory documentation a. Certification
Abnormal range table with dates
19. Specimen handling
a. Instructions/labels/shipping
20. Staff education records
21. Financial agreements
a. Sponsor 
b. Subject
22. study agreement grant
23. Letter of indemnification
24. Advertisements
25. End of study REPORT

Here is a list documents that need to be kept at the study site. 
1. Signed FDA form 1572
2. CVs of all investigators
3. Signed approved protocol
4. Informed consents / all amended informed consents
5. Investigator’s Brochure
6. IRB approval
7. IRB membership
8. Assurance number
9. Drug accountability
10. IND safety reports
11. Annual/interim reports
12. All information given to the subjects
13. CRF s on each subject (signed, dated)
14. AE reports
15. All source documents not kept in Medical record
16. Meeting minutes/correspondence
17. Signature log/equipment logs
18. Laboratory documentation a. Certification
Abnormal range table with dates
19. Specimen handling
a. Instructions/labels/shipping
20. Staff education records
21. Financial agreements
a. Sponsor 
b. Subject
22. study agreement grant
23. Letter of indemnification
24. Advertisements
25. End of study report

Source document means the first recording about the TRIAL subject like original lab REPORTS, PATHOLOGY reports, surgical reports, medical records, LETTERS from referring physicians, participant diary etc.

Source document means the first recording about the trial subject like original lab reports, pathology reports, surgical reports, medical records, letters from referring physicians, participant diary etc.

DATA MEANS Information (facts/figures) which give an accounting of the study.

Data means Information (facts/figures) which give an accounting of the study.

CRF stands for Case Report/Record Form. CRF is perhaps, the most important DOCUMENT after the PROTOCOL since all the clinical TRIAL data is COLLECTED through the CRF.

CRF stands for Case Report/Record Form. CRF is perhaps, the most important document after the protocol since all the clinical trial data is collected through the CRF.

RANDOMIZATION is required in a TRIAL to isolate the DRUG EFFECT.

Randomization is required in a trial to isolate the drug effect.

Informed consent is the VOLUNTARY consent obtained from the RESEARCH subject to participate in the research, after explaining to the person of all the RISKS and benefits involved in the research.

Informed consent is the voluntary consent obtained from the research subject to participate in the research, after explaining to the person of all the risks and benefits involved in the research.

1. Throughvolunteer DATABASE
2. RADIO advertisements
3. NEWS paper advertisements
4. TV advertisements
5. Internet RECRUITMENT
6. By posting notices at the places like to be visited by patients like clinics, PHARMACIES etc

A CLINICAL Trial Protocol is a document that describes the objective(s), design, METHODOLOGY, statistical considerations, and organization of a clinical trial.

• The existence of a clinical trial protocol allows researchers at MULTIPLE locations (in a multi-center trial) to perform the study in exactly the same way, so that their data can be combined as THOUGH They were all working together.
• The protocol also gives the study administrators (often a CONTRACT research organization) as well as the local researchers a common reference document for the researchers' duties and responsibilities During the trial.

A Clinical Trial Protocol is a document that describes the objective(s), design, methodology, statistical considerations, and organization of a clinical trial.

The Investigator's Brochure (IB) is a BASIC document which is required in a clinical trial According to the FDA regulations (Title 21 CFR 312.23), an Investigator's Brochure must contain:

1. Description of the drug substance and the formulation
2. Summary of the pharmacological and toxicological effects
3. Summary of INFORMATION RELATING to its safety and effectiveness in humans
4. Description of possible risks and ADVERSE REACTIONS to be anticipated, and the precautions or special monitoring that the investigator should take.

The Investigator's Brochure (IB) is a basic document which is required in a clinical trial According to the FDA regulations (Title 21 CFR 312.23), an Investigator's Brochure must contain:

CDMS is the TOOL used to ensure that the DATA gathered in the course of the study is: 

1. Accurate
2. Complete
3. Logical
4. Consistent

The trial data collected at the INVESTIGATOR site is STORED in a CDMS

CDMS is the tool used to ensure that the data gathered in the course of the study is: 

The trial data collected at the investigator site is stored in a CDMS

A CTMS DESCRIBES the responsibilities of those INVOLVED in running the TRIAL on a day-to-day BASIS.

A CTMS describes the responsibilities of those involved in running the trial on a day-to-day basis.

The Principal Investigator has the OVERALL responsibility of the design, conduct, analysis and reporting of Clinical TRIAL He has the overall responsibility for the coordination and the day-to-day MANAGEMENT of the trial.

The Principal Investigator has the overall responsibility of the design, conduct, analysis and reporting of Clinical Trial He has the overall responsibility for the coordination and the day-to-day management of the trial.

Unsuspected ADVERSE events are COMMUNICATED from:

1. Sponsor to regulatory AUTHORITIES within 14 days
2. INVESTIGATOR to sponsor within 24 hours
3. Investigator to ETHICS committee in 7 days

Unsuspected adverse events are communicated from:

1. UNRELATED: The AE is clearly not related to the intervention
2. UNLIKELY: The AE is DOUBTFULLY related to the intervention
3. POSSIBLE: The AE is may be related to the intervention
4. Probable: The AE is likely related to the intervention
5. Definite: The AE is clearly related to the intervention

1. Illegal sale of medicines and DRUGS of ABUSE over the internet
2. Increased self medication PRACTICES 
3. Widespread manufacture and sale of COUNTERFEIT and substandard medicines
4. Increased use of traditional medications outside the confines of traditional CULTURE of use
5. Increased use of medications of different systems with potential for drug interactions

1. PATIENTS as the users of medicines
2. DOCTORS, pharmacists, nurses and all other healthcare professionals WORKING with medicines regulatory authorities EMEA and those in the member states RESPONSIBLE for monitoring the safety of medicines
3. Pharmaceutical companies and companies IMPORTING or distributing medicines

The purpose of ICH is to make recommendations on ways to achieve greater harmonization in the interpretation and APPLICATION of technical GUIDELINES and requirements for product registration in order to reduce or obviate the need to duplicate the testing carried out during the research and development of new medicines.

To provide a unified standard for the European UNION (EU), Japan and the United States to FACILITATE the mutual ACCEPTANCE of clinical data by the regulatory authorities in these jurisdictions

The purpose of ICH is to make recommendations on ways to achieve greater harmonization in the interpretation and application of technical guidelines and requirements for product registration in order to reduce or obviate the need to duplicate the testing carried out during the research and development of new medicines.

To provide a unified standard for the European Union (EU), Japan and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions

1. The World Health ORGANIZATION (WHO)
2. The EUROPEAN FREE Trade Area (EFTA), REPRESENTED at ICH by Switzerland
3. CANADA, represented at ICH by Health Canada

1. The clinical trials should be conducted in accordance with the ethical principles based on the declaration of Helsinki and GCP and regulatory requirements
2. Before a trial is INITIATED, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and CONTINUED only if the anticipated benefits justify the risks.
3. The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.
4. Available clinical and non clinical information on the product should adequate to support the proposed clinical trial
5. Trial should be scientifically sound and described in a CLEAR, detailed protocol
6. A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favorable opinion.
7. The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.
8. Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s)
9. Freely given informed consent should be obtained from every subject prior to clinical trial participation.
10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.
11. The confidentiality of records that COULD identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s)
12. Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). Theyshould be used in accordance with the approved protocol.
13. Systems with procedures that assure the quality of every aspect of thetrial should be implemented

The three basic principles of BELMONT report are

1. Respect for persons Respect for persons incorporates at least two ethical convictions:

a. Individuals should be treated as autonomous agents
b. Persons with DIMINISHED autonomy are entitled to protection
c. Informed consent (3 elements)

• Information
• Comprehension
• Voluntary ness

d. Subject should be given opportunity to choose what should and shall not happen to them

2. Beneficence:

• Human subject should not be harmed
• Research should maximize the benefits and minimize the harms 
• Risks and benefits should be assessed
• The nature and SCOPE of risks and benefits must be SYSTEMATICALLY assessed.

3 . Justice:

• The benefits and risks of the research must be distributed uniformly
• Selection of subject: there must be a fair process and outcomes in the selection of research subjects

The three basic principles of Belmont report are

1. Respect for persons Respect for persons incorporates at least two ethical convictions:

a. Individuals should be treated as autonomous agents
b. Persons with diminished autonomy are entitled to protection
c. Informed consent (3 elements)

d. Subject should be given opportunity to choose what should and shall not happen to them

2. Beneficence:

3 . Justice:

Nuremberg CODE (1948) states that the voluntary consent of the human SUBJECT is ABSOLUTELY ESSENTIAL.

Nuremberg code (1948) states that the voluntary consent of the human subject is absolutely essential.

The Declaration of HELSINKI (1964) defines rules for "research combined with clinical care" & "non-therapeutic research" they are

1. Research on human beings should be based on the results from laboratory and ANIMAL experimentations
2. Research protocols should be REVIEWED by an INDEPENDENT committee prior to initiation
3. Informed consent from research participants is necessary
4. Research should be conducted by medically scientifically qualified individuals
5. RISKS should not exceed benefits

The Declaration of Helsinki (1964) defines rules for "research combined with clinical care" & "non-therapeutic research" they are

The three MAIN INCIDENTS are the Thalidomide DISASTER, Tuskegee syphilis STUDY and the Nuremberg WAR prisoner’s incidents.

The three main incidents are the Thalidomide disaster, Tuskegee syphilis study and the Nuremberg war prisoner’s incidents.

USA , EUROPEAN UNION and JAPAN

USA , European Union and Japan

By the SIZE of the TRIAL

By the size of the trial

1. Not APPROVABLE
2. Approvable
3. APPROVAL

1. Detailed reports of pre-clinical studies
2. Detailed reports of clinical studies
3. INFORMATION on composition and manufacture of the drug and on controls and facilities used in manufacture
4. Samples of drug and its labeling
5. Full case reports of the persons who received the drug, needed only in LIMITED circumstances
6. Patient information
7. MATERIAL previously submitted to FDA in the IND application or in periodic reports MUST be included by REFERENCE in the NDA

• The name, CHEMICAL name and structure of the NCE
• Complete list of components of the drug
• Quantitative composition of the drug
• Name and ADDRESS of the supplier of any new drug substance
• Description of synthesis of any new drug substance
• Statement of methods, facilities and controls used in manufacture and packaging of the new drug
• Statement covering all INFORMATION from pre-clinical studies and any clinical studies and experiences With the drug
• Copies of labels for the drug.
• Description of scientific training and experience considered appropriate by the sponsor to qualify the investigator as a suitable expert to investigate the drug 
• Names and curriculum vitae of all the INVESTIGATORS
• An outline of planned methodology to be adopted for the clinical trial

NEW CHEMICAL ENTITY

New Chemical Entity

The AMOUNT of DRUG REQUIRED for its SPECIFIC EFFECT.

The amount of drug required for its specific effect.

The MEASURE of the MAXIMUM STRENGTH of the DRUG

The measure of the maximum strength of the drug

PHASE IIA and Phase IIB

Phase IIA and Phase IIB

Reasons for failure of Phase I trials:

1. Pre-clinical ANIMAL models not equal to behavior in humans
2. Inadequate pre-clinical data
3. CHANGE in drug formulation from pre-clinical testing to clinical testing
4. PK/PD relationship
5. POORLY designed clinical studies
6. Drug too toxic in humans

Reasons for failure in phase II and Phase III trials:

1. Infrequent ADR s
2. Drug-drug interaction
3. Drug-disease interaction 
4. GENETIC
5. Effectiveness insufficient
6. Economic

Reasons for failure of Phase I trials:

Reasons for failure in phase II and Phase III trials:

• SAD(SINGLE Ascending DOSE)
• MAD(Multiple Ascending Dose) and Food Effect

Phase I - 20 to 80

Phase II - 200 - 300

Phase III - 300 to 3000

Phase IV - Thousands of PATIENTS who are being treated

Phase I - 20 to 80

Phase II - 200 - 300

Phase III - 300 to 3000

Phase IV - Thousands of patients who are being treated

Yes. But EXCEPTION is made for the terminally ill PATIENTS who have no ALTERNATIVE therapy available.

Yes. But exception is made for the terminally ill patients who have no alternative therapy available.

USED to assess the expected in-vivo biological EQUIVALENCE of two proprietary PREPARATIONS of DRUG. If two drugs are SAID to be bio equivalent, then they are expected to be for all intent and purpose, same.

Used to assess the expected in-vivo biological equivalence of two proprietary preparations of drug. If two drugs are said to be bio equivalent, then they are expected to be for all intent and purpose, same.

It is the fraction of ADMINISTERED DOSE of UNCHANGED drug that reaches the systemic CIRCULATION.

It is the fraction of administered dose of unchanged drug that reaches the systemic circulation.

ABSORPTION, DISTRIBUTION METABOLISM and EXCRETION

Absorption, Distribution Metabolism and Excretion

Pharmacokinetic parameters DETERMINE the characteristics of thedrug’s ABSORPTION, Distribution, METABOLISM and Excretion (ADME).

Pharmacokinetic parameters determine the characteristics of thedrug’s Absorption, Distribution, Metabolism and Excretion (ADME).

ORPHAN trials AIMED at testing drugs designed to treat diseases affecting less than 200,000 people. Tested only on a small number of participants, Who are so sick that the effect of treatment, if the DRUG really works, is immediately APPARENT.

Orphan trials aimed at testing drugs designed to treat diseases affecting less than 200,000 people. Tested only on a small number of participants, Who are so sick that the effect of treatment, if the drug really works, is immediately apparent.

SUPPORTIVE CARE TRIAL.

Supportive Care Trial.

Double blind is where both the subject and the RESEARCHER do not KNOW which of the treatment the subject is RECEIVING i.e. whether control or the study treatment. In Double dummy, every subject is given both the control and the investigational treatment, for alternating PERIODS.

Double blind is where both the subject and the researcher do not know which of the treatment the subject is receiving i.e. whether control or the study treatment. In Double dummy, every subject is given both the control and the investigational treatment, for alternating periods.

• PHASE I : HUMAN PHARMACOLOGY Trials
• Phase II : Therapeutic exploratory trials 
• Phase III : Therapeutic CONFIRMATORY Trials
• Phase IV : Post marketing Surveillance Trials

There are four major phases in a clinical trial.

Phase I : Human Pharmacology Trials

Phase II : Therapeutic exploratory trials

Phase III : Therapeutic Confirmatory Trials

Phase IV : Post marketing Surveillance Trials

There are different phases of CT

Pre Clinical Studies: They involve in-vitro studies and in-vivo studies on animals. Wide ranging doses are given to animals and the PK, efficacy and toxicity PARAMETERS are studied to determine the viability of further studies. 

Phase 0: Human Micro DOSING Studies (normally the doses are 100 times less than the intended therapeutic doses). Single sub therapeutic doses are administered to a small number of subjects (10-15) PK and PD parameters are derived.Gives no data on safety or efficacy. To support basic go/no go decision making.

Phase I: Human Pharmacology Trials. Size - 20 to 80. May range from several months to a year Usually to TEST one or more of

combination of objectives.

1. Maximum tolerated dose

2. PK

3. PD

4. Early measurement of Drug activity

This phase also includes SAD, MAD and FOOD EFFECT studies.

Phase II:Therapeutic exploratory trials to determine the effective dose and the dosing regimen.May last from 1 to 2 years.Conducted after safety of the drug is confirmed in phase I. Sample size is larger, between 20-300 Sometimes divided into Phase IIA To assess Dosing requirements. Phase IIB to study efficacy.

Phase III: Therapeutic confirmatory trials are randomized, controlled, multicentered trials. Also called pivotal trials because they are crucial to the approval of the drug. May last from 3 to 5 years. Aimed at being definitive assessment of effectiveness of drug in comparison with the current gold standard treatment Sample size 300 – 3000

Phase IV: Post marketing surveillance studies. Either required by the regulatory authorities or UNDERTAKEN by the manufacturer for competitiveness To gather information like use of Drug in children Pregnant women, children Elderly patients Patients with renal or other failures Specific concomitant

There are four major phases in a clinical trial.

Phase I : Human Pharmacology Trials

Phase II : Therapeutic exploratory trials

Phase III : Therapeutic Confirmatory Trials

Phase IV : Post marketing Surveillance Trials

There are different phases of CT

Pre Clinical Studies: They involve in-vitro studies and in-vivo studies on animals. Wide ranging doses are given to animals and the PK, efficacy and toxicity parameters are studied to determine the viability of further studies. 

Phase 0: Human Micro Dosing Studies (normally the doses are 100 times less than the intended therapeutic doses). Single sub therapeutic doses are administered to a small number of subjects (10-15) PK and PD parameters are derived.Gives no data on safety or efficacy. To support basic go/no go decision making.

Phase I: Human Pharmacology Trials. Size - 20 to 80. May range from several months to a year Usually to test one or more of

combination of objectives.

1. Maximum tolerated dose

2. PK

3. PD

4. Early measurement of Drug activity

This phase also includes SAD, MAD and FOOD EFFECT studies.

Phase II:Therapeutic exploratory trials to determine the effective dose and the dosing regimen.May last from 1 to 2 years.Conducted after safety of the drug is confirmed in phase I. Sample size is larger, between 20-300 Sometimes divided into Phase IIA To assess Dosing requirements. Phase IIB to study efficacy.

Phase III: Therapeutic confirmatory trials are randomized, controlled, multicentered trials. Also called pivotal trials because they are crucial to the approval of the drug. May last from 3 to 5 years. Aimed at being definitive assessment of effectiveness of drug in comparison with the current gold standard treatment Sample size 300 – 3000

Phase IV: Post marketing surveillance studies. Either required by the regulatory authorities or undertaken by the manufacturer for competitiveness To gather information like use of Drug in children Pregnant women, children Elderly patients Patients with renal or other failures Specific concomitant

Pre clinical STUDIES are the animal studies that SUPPORT PHASE I SAFETY and tolerance studies. They MUST comply with the GLP guidelines.

Pre clinical studies are the animal studies that support Phase I safety and tolerance studies. They must comply with the GLP guidelines.