The document discusses the basics of clinical research and clinical trials. It covers the key steps in drug discovery and development including target selection, validation, drug selection, optimization, pre-clinical and clinical testing. Clinical trials are systematic investigations in human subjects to evaluate safety and efficacy of new drugs, and are done in 4 phases. It takes approximately 10-12 years and $800 million to bring a new drug to market. Regulations, stakeholders, essential documents, and infrastructure requirements for clinical trials are also outlined.

1. BASICS OFBASICS OF
CLINICAL RESEARCHCLINICAL RESEARCH
P. K. MitraP. K. Mitra
Manager – Marketing ServicesManager – Marketing Services
Eurodrug Laboratories - IndiaEurodrug Laboratories - India

2. INTRODUCTION
TO
DRUG DISCOVERY

3. Drug Discovery & Development Process involvesDrug Discovery & Development Process involves
1.1. Target SelectionTarget Selection
2.2. Target ValidationTarget Validation
3.3. Drug / Lead SelectionDrug / Lead Selection
4.4. Lead OptimizationLead Optimization
5.5. Pre-Clinical testingPre-Clinical testing
6.6. Clinical TestingClinical Testing

4. INTRODUCTION
TO
CLINICAL TRIAL

5. • A Systematic Investigation in Human SubjectsA Systematic Investigation in Human Subjects
forevaluating the Safety & Efficacy of any Newforevaluating the Safety & Efficacy of any New
Drug.Drug.
• Clinical Trial is the main stay for bringing out NewClinical Trial is the main stay for bringing out New
Drugs to the Market.Drugs to the Market.
• Clinical Trials done in 4 Phases ( I, II, III, IV )Clinical Trials done in 4 Phases ( I, II, III, IV )
• It takes Approx. 10-12 Years & USD 800 Mio toIt takes Approx. 10-12 Years & USD 800 Mio to
bring one New Drug to the Market.bring one New Drug to the Market.
• For Every 10,000 – 30,000 drug moleculesFor Every 10,000 – 30,000 drug molecules
screened, only 1 reaches to the Market.screened, only 1 reaches to the Market.

6. TRIAL REGULATIONSTRIAL REGULATIONS

7. • DCGI under CDSCO has the Prime responsibility
for Regulating CTs in India.
• Declaration of Helsinki by WMA provides Ethical
Guidelines & Principles to the Physicians, Other
Participants & Human Subjects.
• ICMR code includes statement of general &
specific principles on research using human
subjects in biomedical research.

8. • ICH-GCP Guidelines unified standard for EU,
Japan & USA to facilitate the mutual acceptance
of Clinical Data by the Regulatory Authorities in
these Jurisdiction.
• Indian GCP Guidelines are in line with WHO,
ICH, USFDA, and European GCP Guidelines as
well as ICMR Code.
• Drugs & Cosmetics Act 1940, & Schedule Y tells
the requirement and guidelines on Clinical Trials
for Import & Manufacture of New Drug in India

9. TRIAL STAKEHOLDERS

10. Stakeholders of the Clinical Trials are:
• SPONSORS
• Contract Research Organization ( CRO )
• INVESTIGATORS
• ETHICS COMMITTEE
• REGULATORY AUTHORITY
• STUDY SUBJECT ( PATIENTS )

11. • Sponsor takes the responsibility for the Initiation,
Management, and/or financing the Clinical Trial.
• CRO is the Organization Contracted by the Sponsor to
Perform One or More of Sponsor’s Trial related Duties
and Functions.
• Investigator is responsible for the Conduct of a Clinical
Trial at a Site.
• Ethics Committee ensures prtection of Rights, Safety, and
Wellbeing of the Subjects involved and to provide Public
Assurance of the Protection
• Study Subjects ( Patients ) are Individual who Participate
in the Study ( CT ) Voluntarily.

12. ESSENTIAL DOCUMENTS

13. • Essential Clinical Trial Documents individually
and collectively evaluates the conduct of a Trial &
Preserves the integrity of the Data.
• These Documents demonstrate the Compliance
of the Investigators and Sponsors/ CRO with
GCP & all applicable Regulatory Requirements.
• They include, Base Records, Laboratory Data,
CRFs, Randomization Key, Other Investigational
Records, EC-NOC, DCGI-NOC, ICF, CRO-
Sponsor Agreement.

14. CLINICAL TRIAL
IN
INDIA

15. • Clinical Trials are different than routine Medical
Care.
• India became a member of WTO in 1995 and
agreed to adhere to Product & Process Patent
regime from 2005.
• India provides excellent environment for CT:
in terms of Less Cost, Speed, Quality Parameters
of Global Clinical Trials leading to Significant
Growth in Clinical Trial outsourcing to India.

16. STUDY TEAM
AT
TRIAL SITE

17. • Study Team at Trial Site include Investigator, Co-
Investigator, Study Coordinator, Nurse,
Pharmacist.
• Unblinded Personnel
(Coordinator/Nurse/Pharmacist) are required in
blinded Trials for dispensing the Trial Medications
to the Study Subjects
• Clear delegation of duties to the study team
members is essential for the smooth execution of
a clinical Trial.

18. Individual Member of the Study Team can
be delegated specific Trial Duties such as:
• Administration of ICF
• Recruitment of Subjects
• Correspondence with EC / CRO / Sponsors
• Stoarge, Dispensing & Accountability of Drugs
• Completion of Source Documents
• Completion of CRF
• Medical Management of the Trial Subject
• Reporting of SAE ( Adverse Events )
• Escalations, Resolutions, Management of Deviations
• Logistics Management
• Resolution of Data Enquiries
• Patient’s Visit Scheduling, Protocol Compliance & Follow Up
• Maintenance of Site Master File.
• Compliance with GCP & Regulatory Guidelines
• Tracking of Payments / Study Grants

19. REVIEW OF
ETHICS COMMITTEE OPERATIONS

20. • EC must have written SOP on its
Compositions, Functions & Operations.
• The Composition of EC must have 7
Members
• The Chairman of EC should be from outside
of the Institution ( Non Affiliated member ).

21. • The Quorum of EC should have min. 5 Members
( Medical Scientist / Pharmacologist, Clinician,
Theologian / Social Scientist / Ethicist, Legal
Expert, Lay person. )
• No CT should be initiated at any Site without
obtaining written NOC from the respective EC.
• If any Investigator or Study team Member is a
part of EC, they should abstain from voting on
their research proposal.

22. • Version Number of all the essential trial
documents approved by EC should be clearly
mentioned on the approved letter.
• All serious & unexpected ADR should be reported
to EC within 7 working days of their occurrence.
• EC should maintain its records for at least 5 years
after the completion / termination of the study

23. SOURCE DOCUMENTS

24. • Source data/documents refer to the documents
where the informations on patient’s medical
condition and treatment is recorded for the first
time.
• SD should contain accurate, authentic, and
complete information on patient’s medical
condition, laboratory results, treatment
administered, adverse events & corrective
medications.

25. • SD should have proper control & access.
• Should reveal what was done & when
• All the information regarding patient’s Physical
Laboratory, Medical Tests should be kept in one
file with valid signatures & dates of the concerned
personnel.
• SD should be properly archived for preservation
• Electronic data for SD should be ensured for
Security, Validation & Back up control.

26. INFRASTRUCTRUAL
REQUIREMENTS

27. • Space for storing Trial documents & materials
• Communication facility
• Local laboratory facility
• USG / Biopsy / CT-Scan / MRI Scan facility
• Wards / ICU / Operation Theatre facility
• Archival Facility
• SOP
• Lockable Trial Rooms / Storage Cabinets
• Lockable Cabinets, Fridge
• National or Internationally accredited Laboratories
• Well defined Quality control standards

28. ADMINISTRATIVE
POLICIES

29. • Well defined rules & regulations of the site.
• SOP for Trials & Subject recruitment
• Recruit Study Coordinator, Research Staff
• Ensure Storage & Archival facility
• Tripartite / Bipartite Agreement

30. SITE EVALUATION

31. • Ensurance of Non Disclosure of Agreement by the
Site / Invetsigator as per Sponsor / CRO.
• Maintain Confidentiality of Information given by
Sponsor / CRO to the Site / Investigator.
• Sponsor / CRO evaluates the Site, reviews the
Qualification of Study Team Members.
• Evaluates Composition,Operations, EC Operating
System, Source Documentation Practices &
Infrastructures of the Site.

32. PROCESS OF SITE EVALUATION
Sponsor / CRO approaches the investigator site for discussing a
Clinical Trial Proposal
Investigator’s concensus / approval is obtained based on Study
Protocol discussion
NDA is executed between Investigator & Sponsor/CRO
Investigator Provides his details on Study Feasibility Questionnaire
If Investigator’s response is satisfactory & meets the expectations of
Sponsor / CRO, Site Evaluation Visit ensured.
Site is either selected / rejected based on the report of Site Evaluation
done by Sponsor / CRO Representative

33. SITE ACTIVATION

34. Sponsor/CRO forwards the following documents to the
Clinical Investigator for Review & Completion:
1. Study Protocol
2. Patient Information Sheet & PIC (English & Vernacular)
3. Investigator Brochure
4. Case Record Form
5. Insurance / Indemnity Certificate
6. Patient Diaries / Questionnaire
7. Format of Undertaking by Investigator
8. Draft of CTA between Investigator & Sponsor / CRO
9. Regulatory Clearance ( DCGI ) NOC
10. No. of copies of above documents for EC application

35. • Site is selected for CT after successful Evaluation of the
Site by the Sponsor / CRO.
• Careful CTA drafting & Suggestions can avoid issues like,
Payment Delays, Frequent Amendments, Retain
Dedicated Study personnel.
• Investigators Training Meeting is conducted to provide a
uniform understanding of Protocol & process to all the
Participants.

36. SITE INITIATION VISIT

37. Site Initiation Visit by Sponsor verifies that Investigator
& his Team are Trained on the Study Requirements.
1. Essential Trial Documents
2. Roles & Responsibilities of each Team Member
3. Facilities, Role of Sponsor, Study Time lines
4. ICF & CRF
5. SAE / ADR Reporting
6. EC – NOC Application Requirements
7. Source Documents
8. Study Drug Storage / Accounatbility
9. Randomization Procedures
10. Data Management
11. Audits / Inspections & Archival

38. • Performed to evaluate the preparedness of the
Investigator Site for Subject Enrollment.
• It is done after EC-NOC obtained & fulfillment of all the
Protocol Requirements.
• Review the preparedness of the Study Team on all the
Requirements for the Study
• Revisit the Critical Study Supplies for the Study before
Enrollment of the Subjects.
• Opportunity to check the Critical Aspects of The Trial after
initial Training & before implementation Phase.

39. SUBJECT ENROLLMENT
&
ICF ADMINISTRATION

40. • ICF is a procedure to take the consent of the participant
after being completely briefed about the Trial & Outcome,
etc.
• Sponsor has the responsibility to detail all the risks,
regulatory needs & procedures of the Trial in the ICF in
vernacular of the subject.
• ICF must be obtained before non-routine screening
procedures are performed and/or before any change in
the subject’s current medical therapy.
• The subject & the Investigator obtaining the ICF must sign
the ICF with date at the appropriate places.

41. • One copy of the signed ICF should be given to the subject
and ICF should be obtained by the Investigator.
• In case the Subject is illiterate, one impartial person
should be present during ICF discussion & signing.
• Any amendment done in the obtained ICF should be
subjected to EC approval & the subject should be re-
consented.
• Only EC approved ICF should be used for all enrollment.
• Data required in the Protocol should be carefully recorded
in the source documents & later transcribed in the CRF.

42. MAINTENANCE OF
SOURCE DOCUMENTS

43. • Source Documents should tell the complete story of the
trial & aid in reconstruction of total information.
• CRFs as SD refer to Quality of Life Questionnaire,
Evaluation Scales, Patient demographics and it should be
mentioned in the protocol.
• Documentation of all Transactions of the Study Drug
would lead to 100% drug accountability.
• Incomplete & Inappropriate SD can lead to Audit Issues &
well maintained SD helps in reconstruction of the Study at
any point of time.
• All SD are required to be archived for a specific period of
10-15 years after completion of the Study for future Audit.

44. A Good Source Document should be able to
address the following. :
1. ICF Process
2. Pre-existing Conditions & Relevant History
3. Laboratory Reports & Results
4. Efficacy Evaluations
5. Adverse Events & Corrective Medications
6. Drug Accountability
7. Progress Notes
8. Ongoing Patient’s Status

45. THANK YOU