Clinical Trials

Clinical trial


World Health Organization (WHO) defines a clinical trial as “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes”.    These may be used for prevention, treatment, diagnosis, or for relieving symptoms of a disease. Without clinical trials, we cannot properly determine whether new medicines developed in the laboratory or by using animal models are effective or safe.




Clinical trial




1025- First introduced in Avicenna’s “Canon of Medicine” describes the rule for the testing of the drug.

1573- Ambroise showed that treatment of wounds with Oil of rose + + turpentine + egg yolk heals better & less painful than traditional oil treatment.

1747- James Lind proves lemon juice as a cure for scurvy; it can be called as one of the 1st controlled clinical trials.

1944- Concept of multicentric studies. US Public health service Act passed.

1947- Nuremberg Code establishes 10 points for the protection of patients in clinical trials.

1962- Kefawver-Harris Drug Amendment in the U.S.A. Proof of efficacy in addition to safety, required for new drug approval.

1964- World Medical Association develops the Declaration of Helsinki- Amended 1975, 1983, 1989, 1996, 2000, 2001. (Ethical codes are given)

1986-89- EU sets GCP guidelines

1990- International Conference on Harmonization (ICH) Tri-parties guidelines.

2001- Declaration of Helsinki revised


Phases in Clinical Trials

There are mainly 4 phases in clinical trials.


  • In vivo/ in vitro
  • Wide-ranging doses tested for efficacy, toxicity, and pharmacokinetics
  • Decide scientific merit of candidate drug

Phase O

  • It is also called as ‘Human micro-dosing’ trials (US FDA recommended 2006)
  • Check whether drug behaves in the same way in humans as in pre-clinical trials
  • Single sub-therapeutic doses to a small number of subjects (10-15)
  • Gather preliminary data on pharmacokinetics and pharmacodynamics
  • Does not give data on efficacy and safety
  • This step gives go or no go decision
  • This step is being debated and mostly used in US regions only

Phase I

  • This is the actual 1st stage human trial
  • Healthy individuals about 20-80 participants are taken
  • This step tests safety, tolerability, pharmacokinetics, and pharmacodynamics
  • This step requires preferably in-patient clinic as participants/drug need to be observed until several half-lives of a drug
  • Dose-ranging is also done to find an appropriate therapeutic dose
  • Testing of a fraction of dose that causes harm an animal is also done
  • Participants are paid proportionately to the time spent
  • There are 2 types of Phase 1: SAD (Single Ascending Dose) and MAD (Multiple Ascending Dose)

Phase II

    • This is performed on a little larger group than Phase one (20-300 participants)
    • This requires volunteers and patients
    • Continue assessing the safety and toxic effects
    • If the drug development process is to fail- it happens in this phase
    • Sometimes divided into Phase IIA and Phase IIB

Phase III

  • Randomized Control Trial, Multi- centric.
  • Max number of participants required, about 300-3000
  • Compare with earlier drugs
  • Most expensive prolonged and difficult especially for chronic conditions
  • Obtain additional safety data and support marketing claims
  • Prepare comprehensive document and submit for approval

Phase IV

  • This is a post-marketing surveillance trial
  • This may be required by regulatory authorities or sponsor for competitive and testing interaction with other drugs or special group of the population
  • It detects any long term or rare adverse effects
  • Harmful effects entail the withdrawal of drugs




  3. Notes on Clinical trial by Maj. General Dr. V.W Tilak AVSM, VSM (Retd.)