Clinical Trials

Clinical trials A

research study to answer specific question (about drugs or new ways of using known ‘treatments’).

 Used

to determine whether new drugs or treatments are both safe and effective .

DESIGN OF A CONTROLLED TRIAL1  Protocol  Definition

of Study Population  Estimate sample size (n)  Inclusion and Exclusion Criteria

DESIGN OF A CONTROLLED TRIAL2  Randomization  Intervention  Follow-up 

Assessment of outcome

CLINICAL TRIAL- PROTOCOL A

blue print or plan  Consists of all the steps involved in the trial  Objectives of the study  Size of the sample  Procedure for allocation of subjects  Treatment to be applied- when ,where, how, to what kind of patients

CLINICAL TRIAL-PROTOCOL  Standardization

of working procedures and schedules  Fixing responsibilities of the individuals involved in the trial  Aims at preventing bias and to reduce the source of errors in the study .

POPULATION  Geographical

limits  Specific age groups  Sex  Occupational groups  Social groups  Specific diagnostic groups,etc.

ESTIMATION OF SAMPLE SIZE  Proper

sample size saves time, effort and money.

 Size

of the sample depends on precision

 Precision

consists of significance level and allowable error

INCLUSION AND EXCLUSION CRITERIA  Which

subjects are to be included and which to be excluded.

RANDOMISATION  It

is the ‘heart’ of a clinical trial.  Is a process of eliminating “bias”  Every individual gets an equal chance of being allocated into either group  Best done by using a “random number table”.

INTERVENTIOIN

Intervention is an independent variable.

E.g..Drugs , new procedure , vaccine, etc

FOLLOW-UP  Examination

of the study and control

subjects at  A defined interval of time,  In the standard procedure,  Under the same circumstances,  In the same time frame,  Till final assessment.

ASSESSMENT  The

final step

 Outcome

and

of trial in terms of positive

negative results.

POSTIVE RESULTS  Reduced

incidence of the disease

 Reduction  Cost

in severity of the disease

of the health services. etc

NEGATIVE RESULTS  Severity

effects

and frequency of side

 Complications

deaths.

if any , including

ELIMINATION OF BIAS Some of the bias’s  “Allocation bias”  “Subject bias”  “Investigator bias” Randomization eliminates “allocation bias” but does not eliminate “investigator” or Subject’ bias

BLINDING  Elimination

of “investigator” or “subject” bias can be done by a technique called blinding.

 Three

types: Single blind trial Double blind trial triple blind trial

SOME STUDY DESIGNS Completely Randomised designs  Subjects allocated randomly to study and control groups.  Applicable when subjects are homogeneous in nature.

COMPLETELY RANDOMISED DESIGNS LAYOUT OF THE EXPERIMENT TREATMENT A TREATMENT B 02 01 04 03 05 06 09 07 10 08 11 12 15 13 16 14 17 18 20 19

RANDOMISED BLOCK DESIGNS  This

design is applicable when the subjects are heterogeneous in nature. E.g.. When the response is different for different age groups, the age groups are then stratified into blocks. Following this subjects are allocated.

LAYOUT OF THE EXPERIMENT Age groups <30

>or=30

Treatment A 04 05 07 08 10 05 06 07 09 10

Treatment B 01 02 03 06 09 01 02 03 04 08

CROSS OVER DESIGN-PHASE I TREATMENT B

TREATMENT A 02 04 05 09 10 11 15 16 17 20

01 03 06 07 08 12 13 14 18 19

Phase I Clinical Pharmacology (20-50)  Health

Volunteer or Patients  Pharmacokinetics (Absorption, Distribution, Metabolism, Excretion)  Pharmacodynamics (Biological Effects)  Where Practicable, Tolerance, Safety, Efficacy.

Phase 2 Clinical Investigation (50-300)  Patients  PK

and PD  Dose-ranging is expanding; Carefully controlled studies for efficacy and safety.

Phase 3 Formal therapeutic trials (250-1000+)

 Efficacy

on a substantial scale, safety, comparison with other drugs.

Phase 4 Post Licensing (Marketing) studies (200010,000+)

 Surveillance

for safety and efficacy. Further Formal therapeutic trials, including comparisons with other drugs.

CROSS OVER DESIGN – PHASE II TREATMENT B

02 04 05 09 10 11 15 16 17

TREATMENT A

01 03 06 07 08 12 13 14 18

Ethical Considerations  The

research protocol should always contain a statement of ethical considerations involved and should indicate that aspects under Helsinki declaration are complied with.

Ethical Considerations – three principles  Respect

for persons – autonomous individuals – informed consent essential.  Beneficience – minimize risks and maximize benefits.  Justice – benefits and burdens of research be distributed fairly.

Ethical Considerations  An

independent panel of reviewers is given power to monitor preliminary data and to determine whether to terminate the study prematurely.  Such procedures must be explained to subjects during the consent process.

Ethical Considerations  Is

it ethical to plan a trial in which people are not offered a intervention measure ?  Is it ethical not planning a randomized trial ? Failure to do so may result in perpetuation of an ineffective programme. Under the circumstances – protection of safety and rights of participating persons becomes important.

Ethical Considerations  The

process of obtaining informed consent is more important than the subject’s signature on a form.  There is a need to disclose the nature and procedures of the study and the potential risks and benefits.  This will help assure that the participation is voluntary and results confidential.

Ethical Considerations  Investigators

need to set their own standards. Institutional review is most important. Investigators need to set their own standards.

RISK APPROACH & EVALUATION OF CONTROLLED TRIALS

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