HMM101 Medical Biotechnology - Clinical Trials and Regulation

Animal Welfare in Biomedical Research

  • 'The Five Freedoms': Freedom from thirst/hunger, discomfort, pain/injury/disease, to express normal behavior, and from fear/distress.
  • 'The Three Rs': Reduction, Refinement, Replacement.
  • Universal Declaration on Animal Welfare (UDAW): A proposed agreement to recognize animal sentience and prevent cruelty.
    • If endorsed by the UN, the UDAW's principles would encourage national governments to improve animal protection legislation.

Clinical Trials

  • Definition (WHO): Research study assigning human participants to health-related interventions to evaluate effects on health outcomes.
  • Purpose:
    • Test new treatments, interventions, or tests to prevent, detect, treat, or manage diseases.
    • Determine if interventions work, are safe, and are better than existing options.
  • Interventions include experimental drugs, biological products, vaccines, medical devices, treatments/procedures, therapies, health service changes and educational interventions.
  • Clinical trials are essential because computer simulation and animal testing cannot fully replicate a living human body's response.
    • Allow testing and monitoring of interventions on a large scale.
    • Lead to improved quality of life (QoL).

Phases of Clinical Trials

  • Phase I: Tests new interventions on a small group (20-80 people) for safety and dosage.
  • Phase II: Studies the intervention in a larger group (hundreds) to determine efficacy and further evaluate safety.
  • Phase III: Studies efficacy in large groups (hundreds to thousands), comparing the intervention to existing standards and monitoring adverse effects.
  • Phase IV: Post-market studies to monitor effectiveness in the general population and collect data on long-term adverse effects.
  • Phase 0/Pilot studies: Exploratory studies before Phase I to test how the body responds to a drug with small doses in a limited number of people.

How Clinical Trials Work

  • Interventions are first tested in the lab and on animals, then moved to clinical trials in humans.
  • New interventions are compared against a control (placebo or established intervention).
  • Governed by national ethics guidelines and codes of conduct, plus Therapeutic Goods Administration (TGA) requirements.

Ethics of Trials

  • Regulated by laws and codes of conduct to protect participants and ensure research integrity.
  • Requires approval by a Human Research Ethics Committee (HREC).
  • Participants must be fully informed about the research objectives, expectations, risks, and potential inconveniences.
  • Trials must follow a controlled protocol and be registered with the Australian New Zealand Clinical Trials Registry (ANZCTR).

Trial Protocols

  • Ensure safety, measure the right things, and produce meaningful results.
  • Comparing a new intervention with standard care or a placebo.

Types of Trial Protocols

  • Comparing a new intervention with a standard intervention.
  • Comparing a new intervention with a placebo.

Placebo Effect

  • Symptoms may improve if you believe you're taking effective medicine.
  • Researchers account for the placebo effect by using sufficiently large sample sizes.

Trial Numbers

  • Interventions must be tested on a large enough group to ensure statistically significant results.
  • Power calculation: determines the sample size needed.

Randomisation

  • Participants are allocated to groups randomly (usually by computer) to avoid bias.

Blinding

  • Single-blind: Participants don't know which intervention they receive, but researchers do.
  • Double-blind: Neither participants nor researchers know who receives which intervention.
  • Blinding reduces bias.

Gold Standard Clinical Trials

  • Double-blind, randomised, placebo-controlled.
  • Orphan drugs (for rare conditions) are often fast-tracked.

Clinical Trial Participants

  • Researchers can be part of hospitals, research groups, universities, or pharmaceutical companies.
  • Teams include doctors, nurses, health care professionals, biostatisticians, and trial coordinators.
  • Participation is voluntary, and participants can withdraw at any time.

Who Takes Part?

  • Trials involve people of all ages and disease stages.
  • Some trials need health participants whereas others need patient participants.

Who Does Not Take Part?

  • Inclusion and exclusion criteria determine eligibility.
  • Criteria can be based on age, gender, disease type/stage, treatment history, etc.

What Happens at The End?

  • Researchers examine all data to determine if the intervention should be further developed.
  • Proven interventions become standard treatment.

Indigenous Health Research

  • Focuses on collaborative partnerships between researchers and local communities including getting consent from local leaders of the community.

Regulation

  • Effective drug regulation ensures the safety, efficacy, and quality of drugs, plus accurate information.
  • Drug laws are updated to keep pace with changes.

Regulation of Drugs: USFDA

  • Responsible for protecting and promoting public health through the regulation and supervision of various products.

Regulation of Drugs: Australia's TGA

  • Regulates therapeutic goods, including medicines, medical devices, and blood products.
  • Evaluates goods before marketing and monitors products post-market.
  • Administers the Therapeutic Goods Act 1989.