The document provides an overview of clinical research, including its historical background, key definitions, and processes involved in drug discovery and development. It discusses the significance of clinical trials for participants, various study designs, and stages of drug discovery from synthesis to preclinical studies. Additionally, it outlines methodologies for testing, mechanisms of action, safety assessments, and the documentation required for regulatory approval.

1. CLINICAL RESEARCH
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2. CONTENT
1. GENERAL INTRODUCTION OF CLINICAL RESEARCH
2. KEY POINTS AND CONCEPTUAL DEFINATION
3. DRUG DISCOVERY PROCESS
4. SOURCES OF DRUG DISCOVERY
5. PRECLINICAL STUDY

3. GENERAL INTRODUCTION OF
CLINICAL RESEARCH

4. IN 1754, surgeon James Lane; he discovered
that health save life. Also studied investigation
on SMALL POX, POLIO and YELLOW FEVER.
IN 1946, British Epidemiologist SIR AUSTIN
BRAND HILL; he done trail for TB patient put
patient into experimental and control group
randomly.
First trial with proof which predicts
streptomycin as antituberculatic drug.

5. WHY CLINICAL RESEARCH

6. PEOPLE WHO TAKES PART IN
CLINICAL TRIAL
CAN CONTRIBUTE KNOWLEDGE HOW DISEASE
PROGRESS
 PARICIPANTS HAVE ASSESS TO PROMISSING
APPROACHES OFTEN NOT AVAILABLE OUTSITE
THE TRIAL SETTING

7. PARTICIPANTS RECEIVE CAREFUL MEDICAL
ATTENTION FROM A RESEARCHER TEAM OF
DOCTOR AND OTHER HEALTH PROFESSIONAL.
 PARTICIPANTS MAY BE THE FIRST TO BENEFIT
FROM THE STUDY.
 RESULT FROM THE STUDY MAY HELP OTHERS
FROM STUDY.

8. DRUG, VACCINE OR OTHER INTERVENTION
BEIGN STUDIED MAY BE MORE EFFECTIVE AND/
OR EFFICIOUS THAN STANDARD APPROACH.

9. KEY POINTS AND CONCEPTUAL
DEFINATION
1. CONTROL GROUP
2. RANDOMIZATION
3. BLIND STUDY
4. INCLUSION AND EXCLUSION CRITERIA
5. END POINT
6. SAMPLE SIZE

10. 7. ERROR
8. MULTICETER TRIAL
9. SUBSEQUENTIAL STUDY
10. META ANALYSIS
11. COHORT STUDY
12. CASE CONTROL HISTORY

11. CONTROL GROUP
 A GROUP OF SUNJECTS WHICH RECEIVE
NO TRATMENT, A STADARD TREATMENT
OR PLACEBO.

12. RANDOMIZATION
 A PROCESS OF ASSIGNING TRIAL SUBJECT
TO TREATMENT OR CONTROL GROUPS USING
AN ELEMENT OF CHANCE TO DETERMINE THE
ASSIGMENT IN ORDER TO REDUCE BIAS.

13. BLIND STUDY
 THE STUDY IN CLINICAL TRAIL IN WHICH
INVESTIGATOR, PARTICIPANTS OR ANYONE
ASSESSING THE OUTCOME IS UNWARE OF
TRATMENT ASSIGNMENT.
 IT IS USED TO REDUCE POTENTIAL BIAS.

14. INCLUSION AND EXDLUSION CRITERIA
 INCLUSION CRITERIA IS A PROTOCOL THAT PROSPECTIVE
SUBJECTS MUST TO BE PARTICIPATE IN THE STUDY.
 EXCLUSION CRITERIA IS A PROTOCOL ANY ONE OF WHICH
IS NOT ELIGIBLE FOR THE PARTICIPATION IN STUDY.

15. END POINT
 THE END POINT IS FINAL RESULT FROM THE STUDY.
 END POINT OF STUDY ARE PRIMARY AND SECONDARY.
 WHICH MAY INCLUDES CURE, DEGREE OF IMPROVEMENT,
SYMPTOMS RELEIF, SURROGATE MARKER, AVOIDANCE OF
COMPLICATION, QUALITY OF LIFE, SURVIVAL, ETC.

16. MULTICENTER TRIAL
 A CLINICAL TRIAL CONDUCTED ACCORDING TO
SAME PROTOCOL BUT AT MORE THAN ONE SITE
AND THERE FORE CARRIED OUT BY MORE THAN
ONE INCESTIGATOR.

17. SEQUENTIAL TRIAL
 THIS DESIGN ATTEMPT TO DETECT A SIGNIFICANT RESULT AS SOON AS IT IS ACHIVED, MINIMIZING THE
NUMBER OF SUBJECTS.
 TRIAL CONDUCTED ON MATCHED PAIRE OF SUBJECT AND IS SCORED AS ‘A’ IS BETTER THAN ‘B’ OR ‘B’
IS BETTER THAN ‘A’.
 APPLICABLE TO DRUGS OR DISESASE IN WHICH CLINICAL END POINT IS ACHIVED QUICKLY AND
COMPARISION ARE POSSIBLE.

18. META ANALYSIS
 THIS IS AN EXERCISE IN WHICH DATA FROM SIMILARLY CONDUCTED RANDOMIZED
CONTROL CLINICAL TRIALS WITH SAME DRUG( OR CLASS OF DRUG(S) EXAMINING, THE
SAME CLINICAL END POINT(S) IS POOLED TO BRING OUT OVERALL BALANCE OF EVIDENCE BY
ENLARGING NUMBER OF TEST AND CONTROL SUBJECTS AND INCREASING THE
SIGNIFICANCE AND POWER OF CONCLUSION.

19. COHORT STUDY
 STUDY OF GROUP OF INDIVIDUAL, SOME OF
WHOME ARE EXPOSED TO A VARIABLE OF INTEREST,
IN WHICH SUBJECT ARE FOLLOWED OVERTME.
 COHORT STUDY MAY PROSPECTIVE /
RETROSPECTIVE.

20. CASE CONTROL HISTORY
THIS TYPE OF OBSERVATIONAL STUDY IS USED MAINLY TO
REVEAL ASSOCIAON OF SUSPECTED RARE ADVERSE EVENT
WITH THE USE OF PERTICULAR DRUG.
 CASES OF SUSPECTED ADVERSE EVENT ARE COLLECTED
FROM HOSPITAL RECORD OR DISEASE REGESTRIES.

21. DRUG DISCOVERY PROCESS

22. DRUG
ACCORDING TO USP; “AN ARTICLE INTENDED FOR USE IN DIGNOSI,
TREATMENT, MITIGATION, CURE OR PREVENTION OF DISEASE”.
ACCORDING TO WHO, IN 1996; “DRUG IS ANY SUBSTANCE OR
PRODUCT THAT IS USED OR INTENDED TOMODIFY OR EXPLORE
PHYSIOLOGICAL OR PATHOLOGICAL STATES FOR THE BENEFITS OF
RECIPIENT”.

23. SOURCES OF DRUG DISCOVERY

24. NATURAL SOURCES
1. PLANT
2. MINERAL
3. MICROORGANISM
4. MARINE
5. ANIMAL

25. PLANT SOUCES:
 OLDEST SOURCES OF MEDICINE.
 THIS FIRST NATURAL SOUCES USED AS MEDICINE.
 OBTAINED FROM TRADITIONAL SYSTEM OF
MEDICINE.
AYURVEDIC SYSTEM OF MEDICINE BASED ON
PLANT SOURCES.
 EXAMPLES;
PLANT SOURCE ACTIVE DRUG
OPIUM MORPHINE
EPHEDRA EPHEDRINE
CINCHONA QUININE
BELLADONA ATROPINE

26. MINERALS:
IRON, CALCIUM SALTS ETC ARE THE SOURCES
OBTAINED FROM THE MINERAL SORCES MEDICINE.
MICROORGANISM:
MARINE:
ANIMAL:

27. CHEMICAL SYNTHESIS
 DEBUTE IN 19th CETURY & NOW LARGEST IS
SOURCE.
THIAZIDE DIRUTICS FROM ACETAZOLIMIDE, TRICYCLIC ANTIDEPRESENT
FROM PHENOTHOZINE.
SALBUTAMOL B2 AGONIST B BLOKER BY MODIFYING
STRUCTURE.
EXCEPTION ARE, BARBTURATE AND CPM; SERENDEPITIOUSLY.
 SO NOW BEST APPROACH FORCLINICAL RESEARCH DEVELOPMENT

28. RATIONAL SOURCES
 AIMED AT MITIGATION THE DEARRAGEMENT CAUSED BY
DISEASE.
THIS DEPENDS ON PHYSIOLOGICAL, BIOCHEMICAL,
PATHOLOGICAL AND IDENTIFICATION OF SPECIFIC RECEPTOR
TARGET FOR DRUG ACTION SUCH AS H+K+ATPase ENZYME OR
GLYCOPROTIEN IIa/ IIIb RECEPTOR.
 DOPAMINE DERIVATIVE LEVODOPA IN PARKINSONISM

29. MOLECULAR MODELING
 ADVANCE IN PROTEIN CHEMISTRY AND COMPUTER ADDED
ELUCIDATION OF THREE DIMENTIONAL STRUCTURE OF KEY
RECEPTOR, ENZYME, ETC. HAS PERMITTED DESIGNING OF
TARGETED COPMOUND.
 EXAMPLE; SELECTIVE COX-2 INHIBITOR PROMOTED BY
COMPARATIVE CONFUGARATION OF COX-1 AND COX-2 ENZYME.

30. COMBINATORY CHEMISTRY
 CHEMICAL GROUP ARE COMBINE IN RANDOM
MANNER TO YIELD INNUMERABLE COMPOUND
AND SUBJECTED TO HIGH-THROUGHPUT
SCREENING ON CELLS, GENETICALLY, ENGINEEERED
MICROBES, RECEPTOR, ENZYME, ETC.
 ASK TO SIR?

31. BIOTECHNOLOGY
 SEVERAL DRUG PRODUCED BY RECOMBINANT DNA
TECHNOLOGY.
 EXAMPLE; HUMAN GROWTH HARMONE, HUMAN
INSULIN.
 SOME MONOCLONAL ANTIBODIES HAVE INTRODUCED AS
DRUG.

32. DRUG DISCOVERY STAGES
LOOKING
FOR
NEW

33. SYNTHESIS OF
COMPOUND/
SERENDIPITY
TARGET
IDENTIFICATION
TARGET
VALIDATION
HIGH
THROUGHOUT
SCREENING
LEAD
IDENTIFICATION
LEAD
OPTIMIZATION
DOCUMETION
PRECLINICAL
STUDY
PHASE I
PHASE IIPHASE IIIPHASE IV

34. SYNTHESIS OF COMPOUND
 SERENDIPITY; SUDDENLY DISCOVERY OF MOLECULE
 SYNTHESIS ALSO CARRIED ACCORDING TO SITUATION,
DEMAND.
 SERENDIPITY; PENECILINE
 SYNTHESIS; ZIDOVUDINE

35. TARGET IDENTIFICATION & VALIDATION
 SELECTION OF TARGET SITE FOR WHICH DRUG/ DEVICE IS GOING TO
PREPARE.
 EXAMPLE; HIV(STAGES), CANCER (ORAL---)
 VALIDATION OF PERTICULATE IS CARRIED TO ENSURE.

36. HIGH THROUGHPUT SCREENING
 DEVELOPMENT OF SUBDISCIPLINE OF DRUG DISCOVERY
DEDICATED TO RAPID EVALUATION OF LARGE NUMBER OF
PURE COMPOUND THAT NATURALL PRODUCT EXTRACT FOR
VERY SPECIFIC BIOLOGICAL ACTIVITIES, USUALLY BASED ON
INTERACTION WITH SELECTED ENZYME OR RECEPTOR;
REFERRED AS HTS.

37. LEAD IDENTIFICATION
 ONCE TARGET HAS SELECTED, NEXT STEP IS TO INDETIFICATION
OF NOVEL COMPOUNDS THAT INTERACT WITH ITS HIGH POTENCY,
EFFICACY AND SECTIVITY.
 AFFINITY; ABILTY TO BIND TIGHTLY TO IT’S TARGET.
 EFFICACY; ABILTY OF LIGANDS TO OBTAIN EFFECT ON IT’S
TARGETE, & AND CAN MEASURE AS BIOCHEMICAL AND
PHYSIOLOGICAL RESPONSE.

38. LEAD OPTIMIZATION
 POTENTIAL DRUG REQUIRE MANY ATTRIBUTS.
 BIOAVILABLE, CHEMICALLY STABLE, METABOLICALLY
STABILE.
 FOR INSTACE, ONE MAY ACCEPT COMPOUND WITH LESS
POTENCY THAN OTHER IF IT HAS OTHER
PHARMACOKINETICS PROPERTIES.

39. PRECLINICAL STUDY

40. SCREENING TEST
TEST ON ISOLATED
ORGAN
TEST ON BACTERIAL
CULTURE
ANIMAL TESTING
GENERAL
OBSERVATION TEST
CONFIRMATORY TEST
& ANALOGOUS
ACTIVITIES
MECHANISM OF
ACTION
SYNTHETIC
PHARMACOLOGY
QUANTITATIVE TEST PHARMACOKINETIC TOXICITY DOCUMENTATION
JOURNEY OF PHASE I

41. SCREENING TEST
THESE ARE SIMPLE AND RAPIDLY PERFORM TEST TO
INDICATE PRESENCE OR ABSENCE OF PERTICULAR
PHARMACODYNAMIC ACTIVITY OF THAT IS SOUGHT FOR
 EXAMPLE; ANLAGESIC, ANTITB, ANTIRETROVIRAL, ETC.

42. TEST ON ISOLATED ORGANS, BACTERIAL
CULTURE
THESE ARE ALSO PRILIMINARY TEST PERFORMED ON EITHER
ON ISOLATED ORGAN, BACTERIAL CULTURE OR BOTH TO
DETERMINE THE SPEFIC ACTIVITY OF COMPOUND.
 SUCH AS ANTIHISTAMINIC, VASODILATOR,
ANTIBACTERIAL, ETC.

43. ANIMAL TESTING
THESE ARE THE TEST WHICH PERFORMED ON ANIMAL MODEL.
FOR PERFORMING SUCH TEST APPROVAL OF RELATED
AUTHORITY REQUIRED WHICH PROVIDES THE GOOD LABORATORY
PRACTICES FOR THE TEST.
ANIMAL MODEL USED IN THE TEST ARE; RATS, MOUSE, GENIA
PIG, ETC.

44. GENERAL OBSERVATIONAL TEST
 PERFORMED EITHER IN BEGINNING(IN CASE OF TOTAL NOVEL
COMPOUNDS) OR AFTER DETECTION OF USEFUL ACTIVITY IN
SCREENING TEST, DRUG IS INJECTED TO TRIPLING DOSES TO SMALL
GROUP OF ANIMALS WHICH ARE OBSERVED FOR OVERT EFFECTS.
 PRIMARY CLUES ARE DROWN AT THE PROFILE OF EFFECTS
OBSERVED.

45. CONFIRMATORY TEST AND
ANOLOUGE ACTIVITIES
 COMPOUNDS FOUND ACTIVE ARE TAKEN UP
DETAILED CHARACTERIZE THE ACTIVITY.
 OTHER RELATED ACTIVITIES, EXAMPLE
ANTIPYRETIC AND ANTI- INFLAMATORY
ACTIVITIES IN ANALGESIC.

46. MECHANISM OF ACTION
 THE MECHANISM BY WHICH DRUG ACTS IN THE BODY.
 THESE ATTEMPT ARE MADE TO FIND OUT MECHANISM
OF ACTION OF DRUG WHETHER IT IS AN ANTIHYPERTENSIVE
IS AN ALFA BLOBKER/ BETA BLOKER/ CALCIUM CHANEL
BLOKER/ ACE INHIBITOR/ CENTRALLY ACTING.
THOUGH EXACT MAO OF DRUG IS NOT UNDERSTOOD YET.

47. SYNTHETIC PHARMACOLOGY
 SYNTHETIC PHARMACOLOGY IS BASED ON THE FINDING
OF THE ACTION OF DRUG IN THE SYSTEM OF BODY.
 IRESPECTIVE ACTION OF DRUG, ITS EFFECT ON MAJOR
ORGAN SYSTEMS SUCH AS NERVOUS, CARDIOVASCULAR,
RESPIRATORY, RENAL, GI ARE WORKED OUT.

48. QUANTATIVE TEST
 THE RESPONSE RELATIONSHIP, MAXIMAL
EFFECT AND COMPARATIVE EFFUCACY WITH
EXISTING DRUG IS DETERMINED.

49. PHARMACOKINETICS
 THE STUDY OF ADME; THAT WHAT DRUG DO TO BODY.
 THE ANSORPTION, TISSUE DISTRIBUTION, METABOLISM,
SITE OF EXCREATION, VOLUME OF THE DESTRIBUTION AND
HALF LIFE OF THE DRUG ARE QUANTIFIED.

50. TOXICITY
 TOXICUTY REFERED AS, HARM TO BODY.
AIM IS TO DETERMINE SAFETY OF COMPOUND.
 TOXICITY PRODUCED BY DRUG MAY BE, ACUTE TOXICITY,
CHRONIC TOXICITY, SUB ACUTE TOXICITY, SPECIAL LONG
TERM TOXICITY, REPRODUCTION AND TERATOGENECITY,
CARCINOGENECITY.

51. ACUTE TOXICITY:
 SINGLE ESCALATING DOSE ARE GIVEN TO SMALL GROUPS OF ANIMALS
THAT ARE OBSERVED FOR OVERT EFFECTS AND MORTALITY FOR 1-3
DAYS.
 LD50 IS CALCULATED
SUB ACUTE TOXICITY:
 ORGAN TOXICITY IS EXAMINED BY HISTOPATHOLOGY ON ANIMAL.
REPETATED DOSE ARE GIVEN FOR 2-12 WEEKS DEPENDING ON
DURATION ON INTENDED TREATMENT IN MAN.
 DOSE ARE SELECTED ACCORDING TO ED50 AND LD50.
 ANIMAL ARE EXAMINED FOR OVERT EFFECTS, FOOD INTAKE, BODY
WEIGHT, HAEMATOLOGY, ETC AND ORGAN TOXICITY.
CHRONIC TOXICITY:
 DRUG ARE GIVEN FOR 6-12 MONTHS AND EFFECTS ARE STUDIED AS
SUBACUTE TOXICITY.
 THIS IS UNDERTAKEN CONCURRENTLY WITH EARLY CLINICAL TRIAL.

52. SPECIAL LONG TERM TOXICITY:
 THIS TEST ARE DONE FOR THE DRUG WHICH CROSS PHASE I
CLINICAL TRIAL.
REPRODUCTION AND TERATOGENECITY:
 EFFECTS ON SPERMATOGENESIS, OVULATION, FERTILITY, AND
DEVELOPING FOETUS.
MUTAGENICITY:
 ABILITY OF DRUG TO REDUCE GENERIC DAMAGE IS ASSED IN
BACTERIA (AMES TEST), MAMMILIAN CELL CULTURE AND INTACT
RODENT.
CARCINOGENECITY:
 DRUG IS GIVEN FOR LONG TERM, EVEN WHOLE LIFE OF ANIMAL
AND THEY ARE WATCHED FOR TUMOURS.
 STADERDISE PROCEDURE UNDER “GOOD CLINICAL PRACTICE”
(GLP) HAVE BEEN LAID DOWN.

53. DOCUMENTATION
ALL DATA ARE COLLECTED FROM PRECLINICAL
STUDY AND SENT IT TO REGULATORY AUTHORITY FOR
THE PERMISSION FOR FURTHER STUDY.
DATA ARE RECORDED IN ELECTRONIC AND WRITTEN
FORMAT.

54. JOURNEY
TO
PHASE I