Users' Guides to the Medical Literature
Guyatt G, Rennie D, Meade MO, Cook DJ
Part B Therapy
Chapter 11.4. Surrogate Outcomes
Heiner C. Bucher, Regina Kunz, Deborah J. Cook, Anne Holbrook, Gordon Guyatt
For example, ecologic studies such as the Seven Countries Study16 suggested a strong...
angiotensin-converting enzyme inhibitors, anti-arrhythmia agents, coronary heart disease, diabetes mellitus, type 2, diabetic nephropathy, drug class effects, health outcomes, osteoporosis, patient-important outcome, randomized controlled trials, sodium fluoride, statins, surrogate outcomes, target endpoints, validity of evidence
"When we consider the validity of a surrogate endpoint,
we must address 2 issues. First, a surrogate outcome will
be consistently reliable only if there is a causal connection between
change in surrogate and change in the patient-important outcome.
Thus, the surrogate must be in the causal pathway of the disease
process. For instance, LDL must be a cause of atherosclerotic cardiac
and cerebral events to act as a valid surrogate for those events.
Second, we must be confident that change in the surrogate captures
all critical influences on patient-important outcomes.9 For
instance, if the treatment affects either positively or negatively
(as turned out to be the case for fibrates13) the
morbidity or mortality independent of its effect on LDL, the validity
of the surrogate is threatened.To function as a valid substitute for an important target
outcome, the surrogate endpoint must be associated
with that target outcome. Often, researchers choose surrogate endpoints
because they have found a correlation between a surrogate outcome
and a target outcome in observational studies. Their understanding
of biologic characteristics gives them confidence that changes in
the surrogate will invariably lead to changes in the important outcome.
The stronger the association, the more likely the causal link between
the surrogate and the target. The strength of an association is
reflected in statistical measures such as the relative
risk (RR) or the odds
ratio (see Chapter 7, Does Treatment
Lower Risk? Understanding the Results)...."
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