Unit V: Clinical Trial Designs

Unit V: Clinical Trial Designs

• Clinical trials aim to determine the effect of an intervention.
• Common errors in clinical trials stem from poor planning.
• Key features of clinical trials 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 to collect data on adverse drug reactions, adverse effects and efficacy for health interventions (e.g., drugs, diagnostics, devices, therapy).
• Clinical research aims to evaluate medical disease in prevention, diagnosis, and treatment.
• Clinical research designs can be categorized as observational or experimental, depending on whether an intervention is used. Further categorization involves whether there is a comparison group, random allocation, if applicable.
• Observational studies include cohort, cross-sectional, and case-control studies.
• Types of clinical trials include treatment, prevention, diagnostic, screening, and quality-of-life trials.
• Drug development involves several phases, starting with preclinical testing and progressing through clinical testing to FDA approval.
• Clinical trials have distinct phases (I-IV) with specific goals and participant numbers relevant for efficacy and safety.
• Parallel design is the most common clinical trial type. Subjects are randomly assigned to different treatment groups.
• Placebo controls use a placebo, which is an inactive substance that looks like the experimental treatment.
• A no-treatment control group compares an experimental treatment to no treatment.
• Active control compares a new treatment to an existing standard treatment.
• Dose-response controls evaluate drug effects at various doses. External controls compare results with other research.
• Crossover design involves participants receiving multiple interventions. A prerequisite for crossover designs is a disease that is chronic.
• Factorial Design examines the effects of two or more interventions simultaneously.
• Randomized withdrawal approach is employed to evaluate the duration of treatment effectiveness.
• Adaptive designs allow modifications during a trial.
• Superiority trials demonstrate a new treatment is better than the control.
• Non-inferiority trials show a new treatment is not significantly worse than the standard.

Key Terms

• Cohort Study: A study following a population over time to estimate disease occurrence.
• Cross-sectional Study: A study measuring the prevalence of a disease in a population at a specific point in time
• Case-Control Study: Observational study comparing patients with a disease to those without to identify possible risk factors.
• Randomized Clinical Trial: An epidemiological experiment where participants are randomly assigned to different treatment groups.
• Non-Randomized Clinical Trial: Participants choose their own treatment group, or researchers assign them.
• Placebo: An inactive substance given to a control group.
• Active Control: an established treatment for comparison to a new treatment.
• Bias: Systematic error that can influence the results of a study.
• External Control: Comparing internal findings to external research to assess the study's reliability.

Declaration of Helsinki

• A set of ethical principles for medical research involving human subjects.
• Key principles include informed consent, beneficence/non-maleficence, scientific validity, and independence/ethics committee review.
• Other considerations like equitable participant selection, privacy/confidentiality, and continuing care also need to be addressed in clinical trials.
• Researchers must respect the fundamental rights, autonomy, and dignity of research participants.

Clinical Trial Design Innovations

• Adaptive Design: Allows modification of trial design after initiation.
• Superiority Trials: Demonstrates a better treatment than the existing one.
• Non-Inferiority Trials: Shows the new treatment is no worse than the standard treatment by a certain margin
• Run-In Design: A preliminary phase for the main study to identify unsuitable participants and better understand how the intervention influences the participants.

Crossover Design

• Participants receive different treatments sequentially with time periods in between each treatment, and serve as a control to themselves.
• A crossover design has prerequisites including; chronic conditions and considerations for wash-out periods, to ensure results are accurate and that carryover effects are not influencing the results.