Steps in designing and conducting a clinical trial

Conduct of clinical trials in 14 easy steps

LITFL has the dummie's guide to clinical trial design.

• Research the question (is it useful?)
• Define the hypothesis (what do we think the answer is?)
• Review the literature (has anyone else done this?)
• Involve a statistician (how do I design this?)
• Develop inclusion and exclusion criteria
• Calculate the sample size (according to beta value and power)
• Develop methodology (trial protocol)
• Gain ethics approval
• Perform a pilot study (and modify protocol as needed)
• Perform the study (collect data)
• Measure the outcomes
• Analyse the data using appropriate statistical methods
• Compare to null hypothesis (is the difference statistically significant?)
• Consider sources of bias and errors
• Submit for publication

Phases of clinical trials

• In vitro activity
• Animal model
• Phase 1: healthy volunteers
• Phase 2: Patients with the disease of interest
• Phase 3: large scale trial on the patients with the disease
• Phase 4:"post-marketing experience"

Lets say you have some fancy new idea, be it a new drug or some sort of new mechanical technique.

In vitro activity: Cell cultures or whole organs are subjected to the treatment, to determine the mechanism of action at a cellular level.

Animal model: The safety of the treatment is established, and dose-finding experiments are performed. Animal models are also used to determine such things as foetal toxicity of drugs.

Phase 1: healthy volunteers are subjected to the experimental treatment. The data is used to determine pharmacokinetics of the substance in humans.

Phase 2: Patients with the disease of interest are subjected to the experimental treatment. The magnitude of the treatment effect is thus estimated, and this helps determine an appropriate sample size for the next phase of trials (obviously if your treatment effect is very subtle, you will need a massive sample to detect it).

Phase 3: large scale trial on the patients with the disease, powered sufficiently to determine the effect of the treatment on the outcome measure of interest.

Phase 4: This is essentially the gathering of data which occurs after the drug is unleashed on the population at large. Date is collected about this "post-marketing experience". Rare side effects and long term outcomes are usually established by means of Phase 4 research.