Clinical studies & Pharmacovigilance

Clinical studies & Pharmacovigilance


       Stages of clinical studies

       Pharmacodynamic studies

       Toxicity studies

       Assessment of safety index

At the end of this lecture, student will be able to

       Explain the stages of clinical studies

       Describe Post marketing studies

       Discuss the assessment of safety index

Clinical Studies

Clinical trial is a systemic research of investigating the safety and efficacy of a new drug in human subjects

       Establishing new drugs

       comparing with standard treatments trying in different population

       To study the pharmacological properties of drugs i.e. pharmacokinetic & pharmacodynemic

       To study toxicological properties of drugs

       It represent the scientific way to test individual agents to ensure safety & effectiveness, as well as compare two or more methods.

       It can give information about appropriate route & frequency of administration of drug in human.

Phases of clinical trial

Phase 0

       Phase 0 is a recent designation for exploratory, first-in-human trials conducted in accordance with the U.S. Food and Drug Administration’s (FDA) 2006 Guidance on Exploratory Investigational New Drug (IND) Studies

       Also known as human microdosing studies

       Administration of single sub-therapeutic dose of the study drug to a small number of subjects (10 to 15) to gather preliminary data on the drug’s :

ü  pharmacokinetics (how the body processes the drug)

ü  pharmacodynamics (how the drug works in the body)

                It gives no data on safety/efficacy, as the dose is too low to cause any therapeutic effect


       First time testing

       In a small group of 20-100

       Duration : 6-9 months


        To evaluate safety & tolerability with the initial administration of investigational new drug into human.

       Conducted in healthy volunteers

       Drugs with significant potential toxicity e.g.  Cytotoxic drugs are usually studies.

Studies conducted in phase-1, usually intended to involve one or a combination of following objectives:

       Maximum tolerated dose: to determine the tolerability of the dose range expected to be needed, nature of adverse reaction that can be expectd, in this included both single & multiple dose

       Pharmacokinetics : i.e. characterization of drug’s absorption, disteibution, metabolism, excretion

       Pharmacodynamics: depending on the drug & endpoint studies, studies related to drug blood levels may be conducted into healthy patient or patient with target disease

Phase-2 Therapeutic exploratory trials

Tested in large group of people



       6 month to 3 year

Purpose is to further evaluate

        Effectiveness of a drug for a particular indication in patients with the condition under study to determine the common short term side effects & risk associated with the drug.

       Additional objectives of phase 2 studies can include evaluation of potential study endpoints, therapeutic regimens for further study


       Phase IIA - to assess dosing requirements (how much drug should be given)

       Phase IIB - to study efficacy (how well the drug works at the prescribed dose)  

Phase 3 Therapeutic confirmatory trial


ü  to gather additional information about efficacy and safety  to evaluate overall benefit-risk  ratio of the drug

Sample size

       several hundred to several thousand(1000 to 3000/more)

       Duration : 1 to 4 year


       randomized controlled multicenter (can be multinational also)trials

       sometimes crossover design is also used

Phase-4 Post marketing trial

       Post marketing trial are studies performed after drug approval

       These trials go beyond the prior demonstration of drug’s safety, efficacy.

       These trials may not be considered necessary at the time of new drug approval but may be required by licensing authority for optimizing drug’s use

       Certain  rare ADRs/low frequency effects not manifest in earlier clinical trials because of small study population

       To study increase in frequency or severity of known adverse reactions as population of users expand after drug approval.

       Study population in clinical trial not always representative of normal clinical practices i.e. age, gender, race etc

       To study modifiers of efficacy-concurrent drugs, disease severity, pregnancy, lactation, renal impairment etc.

       To compare the incidence of ADRs in humans treated and not treated with the drug

       Harmful effects discovered by Phase IV trials may result in a drug being no longer sold, or restricted to certain uses.

Post marketing surveillance

After  the approval of the product, new drugs should be closely monitored for their clinical safety once they are in marketed, as per revised Schedule Y, the applicant is required Periodic Safety Update Report(PSURs) every 6 months for the first 2 years after approval of drug.

Structure of PSURs:

       Title page(applicant name data of approval etc)


       Current worldwide market authorization status

       Update of actions taken for safety reasons

       Changes to reference safety reasons

       Estimated patient exposure

       Presentation of individual case history


       Other information

       Overall safety evaluation



Phase 5

       new uses for drugs


       Clinical trials are experiments or observations done in clinical research

        Such prospective biomedical or behavioural research studies on human participants are designed to answer specific questions about biomedical or behavioural interventions, including new treatments

       Clinical trials generate data on safety and efficacy

        They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. 

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