CLINICAL STUDIES

(NEW DRUG DISCOVERY & DEVELOPMENT)

PHARMACEUTICAL REGULATORY SCIENCE

ABHISHEK PANIGRAHI
182516100003
B.PHARM 8TH SEM
SCHOOL OF PHARMACY, CUTM
BOLANGIR
 INTRODUCTION

 Development of new drug is very difficult, time consuming & very expensive
process.
 During last 50 years, hundreds of new drugs have been introduced & many older
drugs have been deleted (withdrawn).
 <1% of compounds that go into test eventually become licensed medicines.
 To bring a new drug to market requires a good understanding of drug development
process & integral role preclinical testing plays in that process.
 5000-10000 compounds yield 1new drug to market.
 Overall time required for successful results is 10-12 years.
 In the past most drugs have been discovered either by identifying the active
ingredient from traditional remedies or by serendipitous discovery.
 But now we know disease are controlled at molecular & physiological level.
 Also shape of an molecule at atomic level is well understood information of human
genome.

 New drug; definition under schedule Y-

-New substance , which except during local clinical trials, has not been used ever
before in the country .
-Drug already approved for certain claims but which is new proposed to be marketed
with modified or new claims (indications, dosage, dosage form, route of
administration)
-FDC of two or more drugs proposed to be combined for first time in a fixed ratio.
 CLINICAL STUDIES
 A new drug, which is expected to have some advantage over existing ones, after
pre-clinical testing invitro, short-term & long-term animal testing for safety ,
efficacy & toxicity, after due regulatory & ethics committee permission is
subjected to studies in humans as per the regulatory requirements.
 A clinical studies of new drug development plan is a comprehensive plan designed
to map out the development of a drug compound from early phase-1 studies
through marketing.
 Drug is formulated into a suitable dosage form.
 The clinical trials are done under the guideline of Good clinical practice(GCP) laid
down by international conference on Harmonization(ICH).
HERE ARE SOME SALIENT GUIDELINES TO
DESIGN A PERFECT CLINICAL TRIAL:
1) ETHICS & PATIENT SELECTION-
 Criteria for selection of patient should be well thought out & defined .
 Special care must be taken if more than one doctor is involved in the selection of
patient in the trial specially in multicentric trials.
2) RESPONSE MEASUREMENT-
 The end point should be clearly defined side effect should be carefully observed &
recorded.
3) EXPERIMENTAL DESIGN-
 The design of trial should be preferably a biostatistics should be consulted.
 In general controlled clinical trials must include for safe guards against bias:-
a)Double blind technique, b)Randomization of treatment,
c)Matching of patient, d)Cross over techniques.
PHASES OF CLINICAL TRIALS-
PHASE-1 (Early clinical pharmacology & safety)

PHASE-11 (Therapeutic exploration & dose ranging)

PHASE-111 (Therapeutic confirmation & comparison)

PHASE-1V- (Post marketing surveillance/studies)(PMS)

 PHASES OF CLINICAL TRIALS-
In each phase-

-Exposure to greater numbers of human subject.

-Collection of increasing amounts of data on safety & efficacy of the drug.

 PHASE -1
(EARLY CLINICAL PHARMACOLOGY &
SAFETY)
 Human/clinical pharmacology trials.
 This is open study conducted in healthy human volunteers(20-80).
 In special populations (e.g.,- for anti-cancer drug).
 Carried out in emergency settings.

OBJECTIVES-
 Safety & tolerability.(maximum tolerated dose).
 Pharmacokinetics.
 Pharmacodynamics.
 Measurement of drug activity.
 No blinding, open label.
 Approx. duration 1year.
PHASE-11
(THERAPEUTIC EXPLORATION & DOSE
RANGING)
 Inclusion & exclusion criteria are fixed.
 N=100-500 patients.
 Carried out by trained physician.
 Duration 2-3 years.
 Type; Open label/Blind.
 Venue;2-4 centres.
 Establishment of therapeutic efficacy.
 Dose range for more definitive therapeutic trial identified.
OBJECTIVES-
 Effectiveness of the drug.
 Common short term side effect & risks with I.N.D .
 Determine doses & regimens for phase III trials.
 PK, PD, Safety.
 PHASE-III
(THERAPEUTIC
CONFIRMATION/COMPARISON)
 They are initiated when the data generated shows evidence of efficacy.
 Patients(300-3000).
 Phase III includes multiple sites, hence most expensive & most time
consuming.
 These studies should be intended to provide an adequate basis for marketing
approval.
OBJECTIVES-
 Efficacy & safety profile on a larger no. of population (100+).
 Comparison with current gold standard treatment.
 Identification of the disease subtypes for which drug is effective.
 To provide data for the product package insert.
PHASE-IV
(POST MARKETING SURVEILLANCE PMS)
 Practicing physicians are identified & data collected on a structured perform
regarding –Efficacy, Tolerability & Adverse effects.
 N=4000-5000 patients or more.
 Uncommon rare & long term adverse drug reactions & unsuspected drug
interactions found out.
 Additional indicates.
OBJECTIVES-
 Conform the efficacy & safety profile in large populations during practice.
 Detect the unknown adverse drug reactions.
 Evaluation of over-dosage & concomitant treatments.
 Identification of new indications.
CONCLUSION-
 The drug discovery & development process id a long & complicated process.
 Before any newly discovered drug is placed on the market, it must undergo
extensive testing .
 Each success is built on many , many prior failures.
 Advances in understanding human biology & disease are opening up exciting
new possibilities for breakthrough medicines.