Clinical Trial Designs Unit V

Unit V: Clinical Trial Designs

• Clinical trials aim to determine the effect of an intervention.
• Poor planning is a frequent cause of errors in clinical trials.
• Key features of clinical trial design include randomization (possibly with stratification), adherence to intent-to-treat principles, blinding, prospective evaluation, and use of a control group.
• Clinical trials are procedures in medical research and drug development.
• They collect data on adverse drug reactions, adverse effects, and efficacy for health interventions (e.g., drugs, diagnostics, devices, therapy).
• Clinical research evaluates medical diseases in prevention, diagnosis, and treatment.

Key Terms

• Cohort Study: A study estimating the frequency of diseases or events in a particular population.
• Cross-Sectional Study: An observational study primarily used to determine prevalence.
• Case-Control Study: An observational study comparing patients with diseases to those without.
• Randomized Clinical Trial: An epidemiological experiment assigning subjects randomly to groups (study and control).
• Non-Randomized Clinical Trial: Participants may choose which group to join or be assigned by researchers.

Clinical Trial Types

• Treatment Trials: Test new treatments, combinations of drugs, or new approaches to surgery/radiation therapy.
• Prevention Trials: Identify ways to prevent diseases from developing or recurring (e.g., medicines, vaccines, vitamins, minerals, lifestyle).
• Diagnostic Trials: Find better tests or procedures for diagnosing conditions/diseases.
• Screening Trials: Determine the best ways to detect diseases or health problems.
• Quality of Life Trials (Supportive Care Trials): Improve comfort and quality of life for individuals with chronic illnesses.

Drug Development Stages

• Drug development involves a series of stages: Discovery, Preclinical Testing (Laboratory and Animal Testing), Phase I (20-80 healthy volunteers), Phase II (100-300 patients for efficacy and side effects), Phase III (1000-5000 patients for long-term reactions), Additional Post-Marketing Testing and FDA Review Approval.

Phases of a Clinical Trial

• Phase I: Evaluating safety, determining safe dosage, identifying side effects. (70% of drugs move on).
• Phase II: Testing effectiveness and further evaluating safety. (33% of drugs move on).
• Phase III: Confirming effectiveness, monitoring side effects, comparing to other treatments, collecting information. (25-30% of drugs move on).
• Phase IV: Providing additional information, risk and benefit information, best use.

Clinical Trial Designs

• Parallel Design: Subjects randomly assigned to one of two or more treatment/intervention arms. Each arm receives a different treatment for the duration of the study. This design allows direct comparisons between treatments.

  • Placebo Control: A control group receives an inactive substance that looks like the treatment. Used when no proven treatment exists.
    • When to use placebo: In diseases where no standard therapy exists, in minimal risk, short-term studies, or add-on designs.
  • No Treatment Control: Subjects randomly assigned to either the treatment or no treatment group. Investigators are not blinded to treatment.
  • Active Control: A standard treatment already exists; the "new drug" is compared to the standard treatment, or the standard treatment is compared to a combined therapy involving the standard + "new drug."
  • Dose-Response Control: Examining the relationship between drug dose and response.
  • External Control: External data/sources are used to benchmark research results, to compare findings when no internal control group is feasible.
    • Disadvantages include: no comparability, lack of baseline characteristics, absence of randomization, and bias.
  • Run-In Design: A preliminary phase to identify and exclude unsuitable participants. Subjects get a placebo or standard treatment before the main trial.

• Crossover Design: Participants receive multiple treatments sequentially. Each participant acts as their own control. This design is better for chronic, stable diseases. Requires washout periods between treatments that are long enough for the drug effect to fully disappear; at least 5 half-lives.

  • It is not appropriate for acute conditions or when the immune system is permanently affected. This design is primarily used for bioequivalence studies and Phase I studies.

• Factorial Design: Examines two or more interventions simultaneously. It's useful for studying interactions between interventions.

• Randomized Withdrawal Design: Useful for determining how long a treatment should be continued.

Clinical Trial Innovations

• Adaptive Design: Allows for modifications to trial design after initiation without compromising validity.
• Superiority Trials: Show new treatment is superior to the standard (often compared to a placebo or an existing standard treatment).
• Non-Inferiority Trial: Show a new treatment is not worse than the standard by a significant margin.

Declaration of Helsinki

• A set of ethical principles and guidelines for medical research involving human subjects.
• Based on the principle of informed consent.
• Aims to ensure welfare, rights, and dignity of research participants.
• Key components : informed consent, beneficence and non-maleficence, equitable participant selection, privacy and confidentiality, continuing care, ethical considerations around placebo controls, Publication of results and human rights and dignity involved.

Explore the fundamental concepts of clinical trial designs in Unit V. This quiz covers essential features like randomization, blinding, and control groups, as well as the differences between study types like cohort, cross-sectional, and case-control studies. Test your knowledge on how these elements impact medical research outcomes.