A large simple trial, or LST, is a medical trial that involves a very large number of patients, typically over 1,000 participants. Because of the large-scale nature of the trial, it’s usually only feasible if it is stripped of all unnecessary complications. Entry requirements are usually very basic.
An example of a large simple trial was the first oral polio vaccine trial (the Salk trial) in 1954. The resoundingly successful trial involved more than a million schoolchildren: 623,972 were injected with either a vaccine or placebo, while the other were “observed” controls. This large simple trial led the way to an end of the polio epidemic.
Importance of Large Simple Trials
Large simple trials are especially important for documenting or testing effects that are significant—or clinically meaningful—but small or medium-sized in range. For instance, a serious side effect that is seen in 1 in a 1000 cases would be a prime focus for a large simple trial; a study which involved only 100 people would likely fail.
Principles of Large Simple Trials
Some essential principles of large simple trials include:
- Simplified Protocol. Since the scope of a large simple trial is so wide, any supplementary details in the protocol are likely to be prohibitively expensive. Often a LST will involve simply a one time-treatment, such as a shot or one-time oral medication, and one or two follow-ups at the patient’s normal clinic or medical practice. Trials in which the outcome of interest is either death or life lend themselves well to large simple trials, as the results are unambiguous and not subject to personal interpretation.
- Normal Care Centers. The large number of patients involved in LSTs mean that the only practical venue for providing both care and reporting is their regular care centers; local clinics, doctors offices or hospital venues. Often a LST will involve care centers and hospitals in many different locations, sometimes in many different countries. The simplified protocol used makes it easy to determine eligibility.
- Electronic Reporting and Risk-Based Monitoring. While modern clinical tools were not available during the first LST, such as Salks in 1954, all large simple trials today are highly dependent on electronic reporting systems (systems such as the Electronic Data Capture and Clinical Trial Management System used in many clinics). Since any study-specific monitoring would be prohibitively expensive, most LSTs rely on risk-based monitoring and clinical records from local medical centers
Foulkes, Mary A. Large Simple Trials. Wiley StatsRef: Statistics Reference Online. Retrieved from https://onlinelibrary.wiley.com/doi/pdf/10.1002/9781118445112.stat07114 on April 12, 2018
Coward, Darwall-Smith, & Schrammel. Shifting the Large Simple Trial Paradigm. Applied Clinical Trials, July 2014. Retrieved from http://www.appliedclinicaltrialsonline.com/shifting-large-simple-trials-paradigm?pageID=1 on April 12, 2018