Observational Studies in a Learning Health System Workshop Summary (2013) / Chapter Skim
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4 Generalizing Randomized Clinical Trial Results to Broader Populations
4 Generalizing Randomized Clinical Trial Results to Broader Populations
Pages 31-44
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From page 31... ...
• To maximize the ability of observational studies to generalize the results of RCTs, create a three-dimensional informatics infrastructure comprising electronic health records; high quality, granular, and detailed registries; and patient-reported outcomes. Hernán • Ask the right questions so that comparisons of RCTs and ob servational studies are done with the right analytical tools.
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From page 32... ...
Randomized controlled trials (RCTs) use a rigorous experimental design to evaluate the average overall benefit and risk of a specific therapy when it is used by a narrowly defined, select group of patients treated under carefully controlled conditions.
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From page 33... ...
Califf commented on the way in which the standard of practice in acute cardiac care came to be in the United States, noting that all the foundational studies were conducted by entering patients into clinical trials as soon as they entered the hospital emergency room. This approach led to tens of thousands of people being randomized into clinical trials, and it generated findings that were clear-cut, making it easy to develop clinical practice guidelines.
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From page 34... ...
"We can think of randomized clinical trials as follow-up studies with baseline randomization." If that is the case, he argued, it might be more useful to classify studies according to whether they had baseline randomization, without automatic assignment of greater validity to follow-up studies with baseline randomization. For example, in large simple trials and so-called pragmatic trials, the benefits of baseline randomization can be overshadowed by high rates of noncompliance and loss of patients to follow-up, and typically, data are not collected to adjust for these biases.
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From page 35... ...
. Most observational studies conducted in the 1980s and 1990s had found that women currently on hormone replacement therapy had a 30 percent lower risk of developing heart disease than did women who were not on hormone replacement therapy (Stampfer and Colditz, 1991)
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From page 36... ...
The question asked by the randomized trial was, what is the heart disease risk in women assigned to initiation of hormone therapy compared with women assigned to no initiation of hormone therapy? The observational study asked, what is the heart disease risk in women who are currently taking hormone therapy compared with women who are not?
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From page 37... ...
A target population is the population of all individuals for whom a treatment may be considered for its intended purpose, whereas a trial population is a theoretical population that consists of all individuals who would be eligible to enroll in an RCT. Although it is clear that it is straightforward to generalize about the trial population from the RCT analysis, the key is to define or model how the trial population relates to the target population.
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From page 38... ...
Reweighting schemes include probability sampling methods from the survey sampling research community, such as poststratification or propensitybased standardization. However, patients are not recruited into trials as a weighted sample, given the number of inclusion and exclusion criteria imposed on the trial population, and studies have consistently shown, Kaizar noted, that it is usual for RCTs to include at most half of the target population as a result of eligibility criteria.
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From page 39... ...
In this case, a large observational study of hundreds of thousands of subjects undergoing revascularization showed a survival advantage for those who received drug-eluting stents compared with the survival for those who received bare metal stents, but no difference in repeat revascularization. In contrast, the RCTs showed the opposite: a benefit in terms of revascularization but not in terms of mortality.
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From page 40... ...
Sox asked Kaizar if he understood her correctly that extraction of excluded patients from the target population and comparison of the remaining subjects with those in the RCT provide a more valid estimate of the treatment effect in the target population minus those who were excluded from participating in the RCT. She replied that his understanding was correct.
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From page 41... ...
He also noted that the Health Systems Research Collaboratory of the National Institutes of Health is now conducting seven clinical trials using EHRs in a similar manner. Califf commented that he believes that the field is in transition right now and that as a researcher who conducts clinical trials, he would be dubious about the result of any observational study with an odds ratio of less than 2 to 3.
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From page 42... ...
He cited as an example the Neonatal Intensive Care Unit Network Trial on the effects of oxygen saturation in neonates. The findings of this study were the opposite of those expected from observational studies, and a follow-up showed that mortality among neonates who were not enrolled in the study was higher even than that in the arm of the clinical trial with the worst mortality.
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From page 43... ...
2008. Observational studies analyzed like randomized experiments: An application to postmenopausal hormone therapy and coronary heart disease.
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