TOPIC 2: Phases of Clinical Trials

• Clinical trials- are sets of tests and experiments that generates the safety and efficacy data for health interventions in human beings.
• Clinical Trials are conducted if:

  1. Satisfactory information has been gathered on the quality of non-clinical safety.
  2. Health authority/ethics approval has been granted
• Non-clinical safety- assesses the potential adverse effects caused by the drug in relation to its intended use.
• Clinical trials- are the mainstay of bringing in new drugs to the market.
• Drug Review Steps:

  1. Pre-clinical Testing
  2. Investigation New Drug (IND) Application
  3. Clinical Trial Phases: PHASES 1, 2, and 3
  4. Submission of New Drug Application (NDA)
  5. FDA Reviewers
  6. Phase 4 studies.
• Clinical trials- are systematic form of investigation in human subjects in evaluating the safety and effectiveness of a new drug.
• IND Application - outlines the sponsor of a new drug to process the application for human testing.
• The purpose of the IND application is to submit the pre-clinical trial data to determine if the drug is safe for human testing.
• New Drug Application (NDA) Submission - is a formal step asking the FDA to the drug for marketing approval.
• FDA reviewers - approves if the drug is either "approvable" or "not approvable"
• Phase 4 studies - outlines the long-term safety, rare side effects, and the general effectivity of the drug.
• Before a company initiates drug testing, it must need a drug review wherein it involves an extensive pre-clinical and lab research.
• If the approval process prior to human testing is granted, the sponsor will now provide a data to the FDA in order for it to be approved for human testing.
• Pharmacodynamics - is a science that deal on the mechanism of action of drugs. It studies the vivo in animals and in vitro preparation. It also check toxicity studies (adverse effects) of a drug.
• Once the safety and efficacy of the drug is indicated (from pre-clinical trials), an IND application must be filed out with regulating authorities in order to obtain the approval for clinical phases.
• Phase 0 Studies - is the study of new drug in micro doses to derive the pharmacological information in humans before phase I. It also obtains pharmacokinetic data.
• Advantages of Phase O studies:

  • less chances of adverse effects
  • short duration
  • less number of volunteers
  • reduced cost, development and time
• Phase I studies - the first stage of testing in humans
• Phase I study assesses:

  • Safety
  • Tolerability
  • Pharmacokinetic drug
  • Pharmacodynamic drug
• Phase I studies:

  Volunteers: 20-25 healthy individuals.

  Duration: 6-12 months

  Aim: Determine the maximum tolerated dose of a new treatment
• Phase II studies - composed of therapeutic exploratory trials (TET)

  Volunteers: 20-300 subjects

  Duration: 6-several yeas
• In phase II studies, in order to confirm its effectivity. The trial must monitor the side effects and further safety evaluation of the drug.
• In phase II studies, the purpose for this trial is for drugs to be given to patients intended for the drug to treat.
• Types of Phase II Studies:

  • Phase II A - designed to assess the dosing requirements
  • Phase II B - designed to study the efficacy of drugs.
• Phase III studies - is still in TET, but the purpose is to establish the efficacy of drugs against an existing therapy.
• Subtypes of Phase III studies:

  • Phase III A - gets the sufficient and significance of the data.
  • Phase III B - allows to continue treatment, label of expansion, and additional safety data.
• Other name for Phase III B is: Label of Expansion
• Label of expansion - shows that the drug treats other conditions
• At the end of Phase III:

  
  

  FDA (reviewer committee) - reviews the efficacy, safety, and potential sales of the drug. This process involves either "go" or "no go" decision. Which is important to be marketed in phase IV.
• Phase IV studies - is also known as the "Post Marketing Surveillance (PMS)"
• In phase IV studies, there is no fixed duration or patient population. The purpose is to only detect the rare adverse effects, drug interactions, and explore the new uses of the drug.
• In phase IV studies, when the products are sold, the sponsor must provide a Periodic safety Update Reports (PSUR). That is, to be submitted by the manufacturer.

  • For 2 years - every 6 months
  • For marketing approval - annually for the next 2 years
• In phase IV studies, if harmful effects are discovered. The drug may no longer sold or is restricted to certain uses.
• Clinical trials in a nutshell:

  • Approved protocol
  • Investigation selection
  • Approval proces
  • Patient participation and recruitment
  • Data entered and reviewed
  • Statistical analysis
  • Presentation and Publication of report
  • Data fled and registration obtained.