Clinical trials designs

Many approaches for the designs of controlled experiments were

adopted from agricultural applications (developed by R.A. Fisher,
1925)
Principles of experimental designs in field trials:
Replication (to estimate variability)
Randomization (for validity)
Local control (the control of all factors except the ones about which we
are investigating)
Clinical trials are simple in design but more complex than other
nonhuman experiments because of ethics, biology, logistics and
execution:
They are constrained by ethical issues regarding involvement of patients
They tend to have a longer study duration needed to observed the
desired endpoint and to achieve needed accrual

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Characteristics of a good clinical trial design

A good design is crucial to ensuring that a clinical trial is able to provide

the answers to the research questions. Below are a few characteristics of a
good clinical trial design:
has an important feasible question to answer
is ethical
uses efficiently the resources
isolates the treatment effect from potential confounders
minimizes bias
minimizes and quantifies random error or uncertainty
is externally valid

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Randomized Controlled Trials

Most trials use the parallel design: Intervention and control groups
are followed simultaneously from the time of allocation, the
assignment being determined by randomization
Controls may be on placebo, no treatment,usual or standard care, or
a specified treatment
Modification of randomized control study: (Zelen, 1979) 1
Randomize eligible participants before enrolling to the study
Only those assigned to active intervention would be asked to participate
The control participants would be monitored
This design have not been widely used; possible ethical concerns not
informing the participants in the control group

1
Zelen M. A new design for randomized clinical trials. N Engl J Med,
1979;300:1242:1245
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Nonrandomized Concurrent control studies

Participants are allocated to one of the two groups (control or

intervention) but the assignment is not a random process
Examples:
Patients treated at two institutions, one institution using a new surgical
procedure and the other institution using the traditional medical care
Patients are offered either of the two treatments and they select the
one they prefer
Advantages: Easier to offer intervention, participants more likely to
participate if they are not randomized
Disadvantages: Potential for bias

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Historical Controls and Databases

A new intervention is used in a series of participants and results are

compared to the outcome in a previous series of comparison
participants
Historical controls are nonrandomized and nonconcurrent
Advantages: All new participants can receive the new intervention, shorter
recruitment time, inexpensive
Limitations: Vulnerable to bias: improvements may stem from a change in
patient population or management rather than the treatment

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