3.2

Experimental Units and Treatments

  • Definitions:
    • Individuals on which experiments are conducted:
      • Inanimate objects: Experimental units
      • Animals: Subjects
      • Humans: Participants
    • A specific experimental condition applied to the units is referred to as a treatment.

Example of a Clinical Trial

  • Case Study:
    • A randomized trial evaluating chemoradiotherapy and chemotherapy following the surgical resection of pancreatic cancer, conducted by Neoptolemos et al., published in the New England Journal of Medicine in 2004.
    • Objective: To assess the benefits of radiation therapy and chemotherapy.

Patient Sample and Treatment Groups

  • Study Population:
    • Total of 289 Patients involved in the trial.
  • Treatment Groups:
    • 69 patients received Chemoradiotherapy
    • 73 patients received Chemotherapy
    • 75 patients received both Chemoradiotherapy & Chemotherapy
    • 72 patients were placed in the Observation (Control) group.

Five-Year Survival Rates

  • Survival Rate Statistics for Different Treatments:
    • Observation only: 11%
    • Chemoradiotherapy: 7%
    • Chemotherapy only: 21%
    • Chemoradiotherapy & Chemotherapy: 13%
  • Significance of Randomized Controlled Experiments:
    • Considered the gold standard in health science due to their ability to provide robust evidence for causation.

Nature of the Clinical Trial

  • The described clinical trial exemplifies a comparative experiment.

Control Group

  • Definition:
    • The control group refers to the cohort of patients who did not receive any treatment post-surgery.

Placebo Effect

  • Consideration in Clinical Trials:
    • Acknowledgment that patients might show improvement due to the placebo effect irrespective of the treatment administered.
    • Note: In this specific context, it is deemed unethical to subject cancer patients to a sham treatment placebo.

Experiment Design Elements

  • An experiment is designed based on several key components:
    • Response Variable: The outcome measured in the experiment.
    • Factors: The different treatment conditions being tested.
    • Layout of Treatments: The organization of these factors in the experimental structure.
  • For the clinical trial example:
    • Response Variable: 5-year survival
    • Factors:
      • Radiation therapy
      • Chemotherapy
    • Layout of Treatments: A 2 by 2 factorial experiment is utilized.

Sources of Bias and Randomization

  • Bias in Treatment Assignment:
    • The allocation of experimental units to treatments can introduce bias.
  • Mitigating Bias:
    • Can attempt to match patient characteristics (age, gender, physical condition, etc.), although this is often inadequate.
    • The preferable method is to randomly assign patients to treatment groups.

Randomization

  • Definition:
    • The use of chance to allocate experimental units to treatment groups is termed randomization.
    • Pioneering of Randomization:
      • Introduced by R. A. Fisher in agricultural field trials to enhance crop yields.

Principles of Experimental Design

  • Key Principles:
    • Control the influence of lurking variables on the response by comparing two or more treatments.
    • Randomize the assignment of experimental units to treatment groups.
    • Repeat treatments across numerous units to minimize variation due to chance.

Statistical Significance

  • Definition:
    • An observed effect large enough that it is unlikely to occur by random chance is defined as statistically significant.

Random Number Generation

  • Methods of Randomization:
    • Use a random number generator available on calculators or statistical software.
    • Alternatively, employ a traditional table of random digits.

Types of Experimental Design

  • Completely Randomized Design (CRD):
    • All experimental units are randomly distributed among all treatments.
  • Double-Blind Trials:
    • In such trials, neither the participants nor the medical staff are aware of which treatments have been assigned.
  • Triple-Blind Trials:
    • In addition to the double-blind aspects, the statistician analyzing the data is also unaware of treatment allocation.
    • Requires an additional statistician and at least one medical staff member to track safety, who will know the treatment assignments.

Matched Pairs and Block Designs

  • Matched Pairs Design:
    • Simplest method of utilizing matching, typically involving just two treatments.
  • Block Design:
    • A block is defined as a collection of experimental units known to share common characteristics.
    • In a block design, random assignment of units to treatments is performed separately within each block.