The benefits of including non-comparative observational studies in a systematic review of implantable cardiac monitors in cryptogenic stroke

Article type
Authors
Wakefield V1, Edwards S1, Kew K1, Jhita T1, Cain P1, Marceniuk G1
1BMJ Technology Assessment Group, BMJ
Abstract
Background: cryptogenic strokes (CS) are those with no known cause after standard diagnostic tests. Long-term monitoring of patients with CS using implantable cardiac monitors (ICMs) may detect intermittent atrial fibrillation (AF) and treatments can reduce the risk of further stroke, however there are limited randomized controlled trials (RCTs). Inclusion of non-comparative observational studies would increase the size of the dataset and could enhance the applicability of the results.

Objectives: to assess the diagnostic test accuracy (DTA) and clinical-effectiveness of three ICM devices (BioMonitor 2-AF™, Confirm RX™, and Reveal LINQ™) compared with standard care (i.e. no further electrocardiogram (ECG) monitoring to detect AF in patients with CS after at least 24 hours of external ECG monitoring).

Methods: we conducted a systematic review to identify RCTs addressing the research question. We searched MEDLINE, Embase, CENTRAL, DARE and the HTA databases from inception to September 2018. In the absence of evidence for all devices, we widened study inclusion to find data from non-comparative studies to inform decision making. Two review authors agreed studies for inclusion and performed RCT quality assessment with the Cochrane 'Risk of bias 2' tool.

Results: we identified one RCT comparing an older version of the Reveal LINQ device (CRYSTAL-AF) and no DTA studies met the inclusion criteria. We identified 26 non-comparative observational studies of ICM for AF detection after CS were identified; none studied the BioMonitor 2-AF or Confirm RX devices. The RCT was the highest-quality evidence to answer the research question, however there was a concern that it might not be representative of all the available evidence; there were only 441 participants in the RCT compared to a total of 3414 participants in the non-comparative studies. We therefore compared narratively the outcomes that we captured in both the RCT and non-comparative study datasets to see how consistent the RCT evidence was.

The 26 non-comparative studies demonstrated that even within a CS population, AF detection rates are highly variable but results were broadly consistent with the RCT, which suggested a benefit with ICM. Data for other clinical effectiveness outcomes were also broadly consistent, although some outcomes demonstrated greater variability within the observational data-set compared to other outcomes.
Device-related adverse events (AEs) such as pain and infection were consistently low in all studies reviewed.

Conclusions: pragmatic decisions to amend a systematic review protocol are sometimes required to inform decision making but changes should be stated explicitly. Non-comparative observational evidence can aid answering review questions where RCT data are sparse.

Patient Involvement: this research was initiated by the National Institute for Health and Care Excellence (NICE), which included patient representation from national patient groups in the preparation of the scope of the project.