Randomized clinical trials (RCTs) are often referred to as the "gold standard" of clinical research. However, in its current state, the U.S. clinical trials enterprise faces substantial challenges to the efficient and effective conduct of research. Streamlined approaches to RCTs, such as large simple trials (LSTs), may provide opportunities for progress on these challenges. Clinical trials support the development of new medical products and the evaluation of existing products by generating knowledge about safety and efficacy in pre- and post-marketing settings and serve to inform medical decision making and medical product development. Although well-designed and -implemented clinical trials can provide robust evidence, a gap exists between the evidence needs of a continuously learning health system, in which all medical decisions are based on the best available evidence, and the reality, in which the generation of timely and practical evidence faces significant barriers.
Large Simple Trials and Knowledge Generation in a Learning Health System is the summary of a workshop convened by the Institute of Medicine's Roundtable on Value & Science-Driven Health Care and the Forum on Drug Discovery, Development, and Translation. Experts from a wide range of disciplines--including health information technology, research funding, clinical research methods, statistics, patients, product development, medical product regulation, and clinical outcomes research--met to marshal a better understanding of the issues, options, and approaches to accelerating the use of LSTs. This publication summarizes discussions on the potential of LSTs to improve the speed and practicality of knowledge generation for medical decision making and medical product development, including efficacy and effectiveness assessments, in a continuously learning health system.
Large Simple Trials and Knowledge Generation in a Learning Health System explores acceleration of the use of LSTs to improve the speed and practicality of knowledge generation for medical decision making and medical product development; considers the concepts of LST design, examples of successful LSTs, the relative advantages of LSTs, and the infrastructure needed to build LST capacity as a routine function of care; identifies structural, cultural, and regulatory barriers hindering the development of an enhanced LST capacity; discusses needs and strategies in building public demand for and participation in LSTs; and considers near-term strategies for accelerating progress in the uptake of LSTs in the United States.
Rapporteurs: Claudia Grossmann, Julia Sanders, and Rebecca A. English.
This activity was supported by contracts between the National Academy of Sciences and
the U.S. Department of Health and Human Services (Contract No. N01-OD-4-2139 TO #203
and HHSN26300023 [Under Base No. HHSN263201200074I] and Contract No. N01-OD-4-2139
TO #276; HHSF22301026T [Under Base No. HHSF223200810020I]), AbbVie Inc., Agency for
Healthcare Research and Quality, American Diabetes Association, American Society for
Microbiology, Amgen Inc., Association of American Medical Colleges, AstraZeneca,
Blue Shield of California, Blue Shield of California Foundation, Bristol-Myers
Squibb, Burroughs Wellcome Fund, Celtic Therapeutics, LLLP, Centers for Medicare
& Medicaid Services, Critical Path Institute, Doris Duke Charitable
Foundation, Eli Lilly and Company, Epic Systems, Inc., FasterCures, Friends of
Cancer Research, GlaxoSmithKline, Gordon and Betty Moore Foundation, Health
Resources and Services Administration, Hospital Corporation of America, Inc.,
Johnson & Johnson, Kaiser Permanente (East Bay Community Foundation), March
of Dimes Foundation, Merck & Co., Inc., Novartis Pharmaceuticals Corporation,
Partners HealthCare, Patient-Centered Outcomes Research Institute, Pfizer Inc.,
Premier, Sanofi, United Health Foundation, and WellPoint, Inc. The views presented
in this publication do not necessarily reflect the views of the organizations or
agencies that provided support for the activity.
IOM (Institute of Medicine). 2013. Large simple trials and knowledge generation in a learning health system: Workshop summary. Washington, DC: The National Academies Press.
NOTICE: The workshop that is the subject of this workshop summary was approved by the
Governing Board of the National Research Council, whose members are drawn from the
councils of the National Academy of Sciences, the National Academy of Engineering,
and the Institute of Medicine.
2013 by the National Academy of Sciences. All rights