A QUICK GUIDE TO

CLINICAL TRIALS

What is clinical trial?

Methodological experimentation of investigational drugs or devices (like stents ) in human beings/(volunteers/patients)

Chemistry

Animal Pharmacology

Animal Toxicity (Short / Long term)

Studies in Humans

Drug Authorities

Market

Synthesis & Purification

Formulation

DRUG DEVELOPMENT PROCESS

PHASE I TRIALS 1. Initial studies to determine the metabolism and

pharmacologic actions of drugs in humans, the side effects associated with increasing doses, and to gain early evidence of effectiveness; may include healthy participants and/or patients.

2. In phase I trials, researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

PHASE II TRIALS

1. Controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks.

2. In phase II trials, the experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

PHASE III TRIALS

1. Intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide and adequate basis for physician labeling.

2. In phase III trials, the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.

PHASE IV TRIALS

Post-marketing studies conducted to describe additional information including the drug's risks, benefits, and optimal use.

 

Randomized Controlled Trials

Participants randomly allocated to either study drug OR another like a different drug or placebo

Follow up is for a specified period Analyses in terms of outcomes defined at the outset Objective of randomization is to rule out bias on part of

investigator ( doctor ) for a specific treatment.

1 2 3 4 5 6 7 8 9 10A A B B B A A B B A

Cohort Studies

Two or more groups of people are selected on the basis of their exposure to a particular agent

Subsequently followed up to see how many from each group develop the ‘outcome’

For example: smokers ( one group ) and non-smokers ( other group ) are selected and followed-up for a period of say 5 years to see how many from the smoker group and non-smoker group develop bronchitis( outcome )

Case Control Studies

Patients with a particular disease are identified and matched with controls

Data is collected on past exposure to a possible causal agent

For example, diabetic patients (one group) and non-diabetics (other group ) otherwise matching with each other are selected and evaluated for a risk factor (say obesity) for diabetes.

Cross-sectional Surveys

Data are collected at a single time

e.g. Lipid profiles of 25 year old males in Ahmedabad

Case Reports

Medical history of a single patient Not very reliable as evidence Conveys information which might have

been lost

Terms : Systematic reviews: Summarize primary studies

according to a systematic scientific methodology

Meta-analyses: Integrate numerical data from more than one study/trial on a single product and analyze data

Guidelines: Conclusions from primary studies on clinical decisions For example JNC (Joint National Committee ) VII

Guidelines on hypertension, NCEP ATP III ( National Cholesterol Education Program Adult Treatment Plan ) Guidelines on dyslipidemia management

Terms (Cont…)

Placebo controlled: Subjects in control group receive a placebo whereas subjects in other group receives drug

Treatment controlled: Subjects in control group receive a standard treatment whereas subjects in other group receives drug under investigation.

Single blind: Patients do not know which treatment they are receiving

Double blind: The investigators and the patient both do not know which of the two treatment options is being administered

Terms (Cont…)

Multicenter trial: A clinical trial conducted according to a single protocol at more than one site and thus by more than one investigator

Hierarchy of Evidence:

In terms of clinical evidence ,Systemic reviews & meta-analyses have rated as the highest evidence followed by randomized controlled trials.

Systematic reviews and meta-analyses

Randomized controlled trialsCohort studies

Case-control studiesCross-sectional surveys

Case reports

WORKSHEET – 1

Q.1) What is clinical trial?

ANS :

Q. 2) ………… tops as a scientific evidence in terms of clinical trials.

a) Case reports

b) Case-control study

c) Meta analysis & systemic review

d) None of above

Q. 3) What is randomized placebo-controlled trial?

ANS :

Q. 4) State whether true or false.

1) Case report is considered to be the reliable clinical evidence.

(__________)

Q. 5) What is cohort study?

ANS :

Q. 6) Define the following terms:

Meta-analysis:

Placebo-controlled study

Double-blind study:

Multi-centric study:

P Value

P value: The probability of any particular outcome having arisen by chance.

Arbitrarily a P value of less than 1 in 20 (expressed as P<0.05, odds of 20 to 1) is taken as "statistically significant" and a P value of less than 1 in 100 (P<0.01) as "statistically highly significant”.

Confidence Interval The range of numerical values in which we can be

confident (to a probability, such as 90 or 95%) that the value being estimated will be found.

A 95% CI is the range of values within which we can be 95% sure that the true value for the whole population lies.

RRR=26.9%, 95% CI, Confidence intervals indicate the strength of evidence. The narrower the confidence interval, the more precise is

the estimate of effect. The larger the trial size, the narrower the interval.

WORKSHEET - 2

Q. 3) What is the importance of “p value” in clinical trials?

ANS :

Q.4) P value of …………is considered as statistically significant

a) > 0.5

b) < 1

c) < 0.5

d) none of above