Hierarchical modeling: variation between current vs.Power priors: historical control discounted when added to.Test then pool: test if controls sufficiently similar for pooling.
#CONTROL ARM TRIAL#
Performance criterion for current, treated-only trial to beat
The first step of creating a synthetic control arm is to harmonize the source data. Therapy (e.g., blood pressure, tumor size), have no internal control and are thus So-called baseline controlled studies, in which subjects' status on therapy is compared with status before Uncontrolled) because general impressions are so often inaccurate. This latter comparator is particularly treacherous (such trials are usually considered The external control may be defined (a specific group of patients) or nondefined (a comparator group based on general medical knowledge of outcome). (historical control) or a group treated during the same time period but in another The external control can be a group of patients treated at an earlier time Treatment with a group of patients external to the study, rather than to an internalĬontrol group consisting of patients from the same population assigned to a different The external control here is not the same as synthetic control.ġ.3.5 External Control (Including Historical Control)Īn externally controlled trial compares a group of subjects receiving the test
ICH E10 " CHOICE OF CONTROL GROUP AND RELATED ISSUES IN CLINICAL TRIALS" included "External Control (including Historical Control)" as one of the options as the control groups in clinical trials.
The source data must be the subject-level data, not the summary or aggregate data. The source data for constructing synthetic control can be the data from previous RCT clinical trials, real-world data, registry data, data from natural history studies, electronic health records. Just like the meta-analysis is also called research synthesis and requires the statistical approaches to combine the results from multiple scientific studies, the 'synthetic' control also requires the use of statistical approaches to process the data from multiple sources to form a control group to replace the concurrent control in traditional RCT clinical trials. With 'synthetic' control arms, the term 'synthetic' implies there are some selection, manipulation, derivation, matching, pooling, borrowing from the source data. However, I think that there are subtle differences between these two terms. It is important to note that using control data from historical RCTs still results in a nonrandomized comparison but has the advantage of standardized data collection in a trial setting and patients who enroll in clinical trials may have more similar characteristics than those who do not. Pooled data from historical RCTs can serve as external controls depending on the availability of selected “must have” data, similarity of patients, recency and relevancy of experimental treatments that were tested, availability and similarity of relevant endpoints (eg, operational definitions and assessments), and similarity of other important study procedures that were conducted in these historical trials. For example, external control arms can be established using aggregated or pooled data from placebo/control arms in completed RCTs or using RWD (Real World Data) and pharmacoepidemiological methods. In a paper by Thorlund et al " Synthetic and External Controls in Clinical Trials – A Primer for Researchers", they stated that synthetic control arms are external control arms - two terms can be used interchangeably: External control arms are also called “synthetic” control arms as they are not part of the original concurrent patient sample that would have been randomized into the experimental or the control treatment arms as in a traditional RCT.