clinical trials in a nut shell

8/13/2019 Clinical Trials in a Nut Shell

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Clinical Trials in a Nut Shell


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10000-250-5-1


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Clinical Trials

Scientific Aspects

ANDLegal & Procedural Aspects


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Scientific Aspects of Clinical Trial

Phases of Clinical Trial

Phase I : First in mansafety

Phase II : First in patientdose, dosage form

Phase III : Efficacy, ADRs

Post marketing surveillance or Phase IV :Evaluation in the real clinical setting


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Phase I Objectives

1. To assess a safe & tolerated dose

2. To see if pharmacokinetics differ much from animalto man

3. To see if kinetics show proper absorption,bioavailability

4. To detect effects unrelated to the expected action

5. To detect any predictable toxicity

Inclusion criteria Healthy volunteers : Uniformity of subjects: age, sex,

nutritional status [Informed consent a must]

Exception: Patients only for toxic drugs Eg AntiHIV,Anticancer

Exclusion criteria Women of child bearing age, children,


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Phase I contd Methods:

First in Man : Small number of healthy volunteers

First in a small group of 20 to 25 Start with a dose of about 1/10 to 1/5 tolerated

animal dose

Slowly increase the dose to find a safe tolerated

dose If safe in a larger group of up to about 5075

No blinding

Performed by clinical pharmacologists

Centre has emergency care & facility for kineticsstudy

Performed in a single centre

Takes 36 months [ 70% success rate]


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Phase II First in patient [ different from healthy volunteer]

Early phase [20200 patients with relevant disease] Therapeutic benefits & ADRs evaluated

Establish a dose range to be used in late phase

Single blind [Only patient knows] comparison with standarddrug

Late phase [ 50

500] Double blind

Compared with a placebo or standard drug

Outcomes Assesses efficacy against a defined therapeutic endpoint

Detailed P.kinetic & P.dynamic data Establishes a dose & a dosage form for future trials

Takes 6 months to 2 years [ 35% success rate]


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Phase III Large scale, Randomised, Controlled trials

Target population: 250

1000 patients

Performed by Clinicians in the hospital

Minimises errors of phases I and II

Methods

MulticentricEnsures geographic & ethnic variations Diff patient subgroups Eg pediatric, geriatric, renal impaired

Randomised allocation of test drug /placebo / standarddrug

Double blinded:

Cross over design

Vigilant recording of all adverse drug reactions

Rigorous statistical evaluation of all clinical data

Takes a long time: up to 5 years [25% success]


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Cross over design

Group Week 1 Week2 Week3

I Standard Placebo Test

II Placebo Test Standard

III Test Standard Placebo

* A wash out period of a week between two

weeks of therapy


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Phase IV or Post marketing

Surveillance No fixed duration / patient population

Starts immediately after marketing

Report all ADRs

Helps to detect

rare ADRs

Drug interactions

Also new uses for drugs [Sometimes called

Phase V]


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Clinical Trial: Legal & Procedural

aspects

Elements of a Clinical Trial Aim or objective

Protocol : study design

Ethics committee clearance

Regulatory approval whenever required

Informed consent

Implementation of protocol

Collection of data

Compilation of data, analysis and interpretation

Report writing


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Participating Parties in Clinical Trial

1. Patient / Healthy volunteer2. Clinical Pharmacologist, Clinical

Investigator & team: [Qualified andcompetent]

3. Institution where trials are held :[Approval required]

4. Ethical Review Board or InstitutionalEthical Committee:

5. Sponsor

6. Regulatory Authorities:


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Functions of participating parties

[1] Patient / Healthy volunteer : Subjectof the trial

[2] Clinical Pharmacologist, Clinical

Investigator & team: Conducts the clinical trial; reports all

adverse events

[3] Institution where trials are held : Provides all facilities [Approval required]


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Functions of parties contd. [4] Ethical Review Board or Institutional

Ethical Committee: Supervises and monitors every step;

Safeguard the welfare and the rights of theparticipants

[5] Sponsor : Pays for all expenses;

Appoints competent investigators,

Ships all drugs for the trial,

Files all papers to legal / regulatoryauthorities,

[6] Regulatory Authorities:

Legal authority on the outcomes of the trial


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Clinical Trial Protocol Title & Abstract

Introduction General statement of purpose

Complete Preclinical results on animal study

Clinical data if available

Time frame

Goals: Primary & secondary objectives

Study Design: Type of study

Recruitment criteria : Exclusion & Inclusion criteria

Randomisation criteria and Sample size

Duration of study

Data Analysis: Case report forms, Statistical Analysis, Bibliography


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Informed Consent

Informed consent form: Voluntary

Explained in simple nontechnical language

Translated in the native language of the subject

Comprehensive information regarding the trials Benefit of new therapy over existing ones

Alternative treatments available

All possible adverse reactions

Freedom to withdraw from the trial at any time,

without giving any reason


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Institutional Ethical Committee

Independent

Competent

57 members; 5 required for quorum.

Member Sec from same Institution

Others: A mix of medical non-medical,

scientific & non-scientific including lay

public

Multidisciplinary & Multisectorial


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Responsibilities of IEC

1. To protect the dignity, rights & wellbeing of patients / volunteers

2. Ensure a competent review of the

protocol3. Advise on all aspects of welfare &

safety

4. Ensure scientific soundness of theproposal


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The composition of IEC

1. Chairperson2. 1-2 basic medical scientists.

3. 1-2 clinicians from various Institutes

4. One legal expert or retired judge

5. One social scientist / representative of NGO

6. One philosopher / ethicist / theologian

7. One lay person from the community

8. Member Secretary

Individuals from other institutions if required Adequate representation of age, gender,

community,


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Problem areas

Compensation in drug related injuries Mild and Severe

Patient Rights

Confidentiality of data

Right to withdraw

Collection procedures & amount of biologicalmaterial taken

Compensation & Insurance claims Sending bio-material abroad

Selection of Patients

clinical trials in a nut shell

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