Intended for healthcare professionals

Feature Clinical trials

The appeal of large simple trials

BMJ 2013; 346 doi: (Published 28 February 2013) Cite this as: BMJ 2013;346:f1317
  1. Bob Roehr, freelance journalist

Clinical trials have become complex, expensive, and yet are often not large enough to answer questions necessary to optimize treatment for individual patients. One answer might be to have large simple trials. Bob Roehr investigates

Large simple trials are primarily phase IV studies that are embedded in the delivery of care, make use of electronic health records (EHRs), demand little extra effort of physicians and patients, and can be conducted for a relatively modest sum.

Often they are thought of in the context of a learning healthcare system that some of the more integrated systems such as the Veterans Administration and Kaiser Permanente have begun to make part of their operations. Research is a part of care and that information is used to guide a constant refinement of their standard of care, improve outcomes, and often results in net savings.

The criticism of many randomized controlled trials (RCTs) today is that they have become “Ferrari trials,” says Tjeerd-Pieter van Staa, director of research at the UK’s Clinical Practice Research Datalink.

“They have very high internal validity, low measurement error—we are measuring everything, controlling everything.” But as with the high performance race cars he references, “What is our ability to generalize what we saw in this beautiful formula 1 healthcare center to things out there” in a typical clinical practice setting?

“The endpoints are primarily surrogate endpoints, not clinical endpoints,” adds Michael Lauer, director of the Division of Cardiovascular Sciences at the NIH National Heart, Lung, and Blood Institute (NHLBI). “And the setting is a research enterprise where high grade data are created in this parallel universe that is heavily audited and monitored.”

The complexity of surrogate and secondary endpoints opens the door to possible spin by a sponsor seeking to identify some positive association amidst the ocean of data points …

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