Users' Guides to the Medical Literature
Guyatt G, Rennie D, Meade MO, Cook DJ
Part B Therapy
Chapter 6. Therapy (Randomized Trials)
Gordon Guyatt, Sharon Straus, Maureen O. Meade, Regina Kunz, Deborah J. Cook, PJ Devereaux, John Ioannidis
To What Extent Was the Study Blinded?
Topics Discussed:
angina, stable, aspirin, blinded, clopidogrel, control groups, coronary arteriosclerosis, esomeprazole magnesium, follow-up (complete), measures of outcome, peptic ulcer, prognosis, randomization, randomized controlled trials, randomized controlled trials, truncated, relative risk reduction, trial of therapy, truncated studies, upper gastrointestinal bleeding, validity of evidence
Excerpt:
"Consider the question of whether hospital care
prolongs life. A study finds that more sick people die in the hospital
than in the community. We would easily reject the naive conclusion
that hospital care kills because we understand that hospitalized
patients are sicker than patients in the community.The reason that studies in which patient or physician preference
determines whether a patient receives treatment or control (observational
studies) often yield misleading results is that morbidity and mortality
result from many causes, of which treatment is only one. Treatment
studies attempt to determine the impact of an intervention on such
events as stroke, myocardial infarction, and death—occurrences
that we call the trial's target outcomes.
A patient's age, the underlying severity of illness, the presence
of comorbidity, and a host of other factors typically
determine the frequency with which a trial's target
outcome occurs (prognostic factors or determinants
of outcome). If prognostic factors—either
those we know about or those we do not know about—prove
unbalanced between a trial's treatment and control
groups, the study's outcome will be biased,
either underestimating or overestimating the treatment's
effect. Because known prognostic factors often influence
clinicians' recommendations and patients' decisions about
taking treatment, observational studies often yield biased results.If randomization succeeds, treatment and control
groups in a study begin with a similar prognosis. Randomization,
however, provides no guarantees that the 2 groups will remain prognostically
balanced. Blinding is, if possible, the optimal
strategy for maintaining prognostic balance.Ideally, at the conclusion of a trial, you will know the status
of each patient with respect to the target outcome. The
greater the number of patients whose outcome is unknown—patients lost
to follow-up—the more a study's validity is
potentially compromised. The reason is that patients who are lost
often have different prognoses from those who are retained—they
may disappear because they have adverse outcomes or because
they are doing well and so did not return for assessment.26Although it is becoming increasingly popular, stopping trials
early when one sees an apparent large benefit is risky.27 Trials
terminated early will compromise randomization if they
stop at a "random high" when prognostic
factors temporarily favor the intervention group. Particularly
when sample size and the number of events are small, trials
stopped early run the risk of greatly overestimating
the treatment effect (see Chapter 9.3,
Randomized Trials Stopped Early for Benefit)...."
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