A well-controlled clinical trial is much like a well controlled experiment. They are both rooted in the cornerstone of the scientific method. What exactly is a clinical trial? According to clinicaltrials.gov, “In a clinical trial (also called an interventional study), participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or changes to participants' behavior, for example, diet.” In the 21 CFR 314.126, the FDA lays out regulations as to what makes an “Adequate and Well-Controlled study” as one that has:
- A clear statement of the objectives of the investigation and a summary of the proposed methods of analysis in the protocol.
- The study uses a design that permits a valid comparison with a control to provide a quantitative assessment of the effect.
- The method of subject selection that provides adequate assurance that the subject has the disease or condition that the treatment is directed at.
- The method of assigning patients to treatment and control groups minimizes bias and assures comparability of the groups.
- Adequate measures are taken to minimize bias, by the subjects, observers and the data analysts.
- The methods of assessment of subjects’ response are well-defined and reliable.
- There is an analysis of the results of the study that is adequate to assess the effect of the drug or device.
A well-controlled experiment asks a question or a hypothesis. This hypothesis is then tested by the experiment. What characterizes a well-controlled experiment?
- A well-designed experiment is simple and easily replicated. It maintains strict control on all variables.
- The variables in the experiment are designed to prove or disprove a casual relationship between the independent variable and the dependent variable. This would be the drug or device versus the condition of the patient.
- Control is a vital element of a well-designed experiment of the main variables. There needs to be a way to rule out the effects of extraneous variables other than the dependent and independent ones.
A good experiment, like a good clinical trial, often has blind controls or double-blind randomization to compare the end results. The goal for a well-controlled experiment is for it to be repeated many times with the same or statistically similar results. Clinical trials are typically not repeated as much as they are designed with large numbers of subjects to remove the bias that could occur on a study with small subject sampling. This helps to rule out random samples or outliers in the “experiment”.
Many would argue there are other things that go into the makeup of a well-controlled clinical trial, especially once sites and patients get involved. Having a research team with adequate facilities, knowledge of the federal regulations, the time and staff to work on the project is imperative. Additionally, having timely, well-documented data is vital to the trials continued success, which helps ensure the trial is being conducted in a way that will produce relevant results.
What are your thoughts on what makes a well-controlled trial?