Benjamin Djulbegovic1, Iztok Hozo. 1. Interdisciplinary Oncology Programme, H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa 33612, USA. djulbebm@moffitt.usf.edu
Abstract
RATIONALE, AIMS AND OBJECTIVES: Randomized controlled trials (RCTs) have emerged as the most reliable method of assessing the effects of health care interventions in clinical medicine. However, RCTs should be undertaken only if there is substantial uncertainty about which of the trial treatments would benefit a patient most. The purpose of this study is to determine the degree of uncertainty in a research hypothesis before it can empirically be tested in an RCT. METHODS: We integrated arguments from three independent lines of research - on ethics, principles of the design and conduct of clinical trials, and medical decision making - to develop a decision model to help solve the dilemma of under which circumstances innovative treatments should be tested in an RCT. RESULTS: We showed that RCTs are the preferable option to resolve uncertainties about competing treatment alternatives whenever we desire reliable, undisputed, high-quality evidence with a low likelihood of false-positive or false-negative results. CONCLUSIONS: When the expected benefit:risk ratio of a new treatment is small, an RCT is justified to resolve uncertainties over a wide range of prior belief (e.g. 10-90) in the accuracy of the research hypothesis. Randomized controlled trials represent the best means for resolving uncertainties about health care interventions.
RATIONALE, AIMS AND OBJECTIVES: Randomized controlled trials (RCTs) have emerged as the most reliable method of assessing the effects of health care interventions in clinical medicine. However, RCTs should be undertaken only if there is substantial uncertainty about which of the trial treatments would benefit a patient most. The purpose of this study is to determine the degree of uncertainty in a research hypothesis before it can empirically be tested in an RCT. METHODS: We integrated arguments from three independent lines of research - on ethics, principles of the design and conduct of clinical trials, and medical decision making - to develop a decision model to help solve the dilemma of under which circumstances innovative treatments should be tested in an RCT. RESULTS: We showed that RCTs are the preferable option to resolve uncertainties about competing treatment alternatives whenever we desire reliable, undisputed, high-quality evidence with a low likelihood of false-positive or false-negative results. CONCLUSIONS: When the expected benefit:risk ratio of a new treatment is small, an RCT is justified to resolve uncertainties over a wide range of prior belief (e.g. 10-90) in the accuracy of the research hypothesis. Randomized controlled trials represent the best means for resolving uncertainties about health care interventions.