Article type
Year
Abstract
Background: Randomized (RCT) or non-randomized controlled trials are regularly used for assessment of certainty of evidence (GRADE) in systematic reviews (SRs) while case series are mostly ignored. For some interventions RCTs are difficult to design, but well-designed case series are available.
Objectives: Studying the influence on conclusion and certainty of evidence (GRADE) by using case series in an SR with only one small RCT.
Method: A systematic literature search in an SR of hypoglossal nerve stimulation (HGNS) in adults with obstructive sleep apnoea (OSA) not tolerating Continuous Positive Airway Pressure treatment resulted in one small RCT (therapy withdrawal design) and seven case series. The case series (n=232) were assessed by a modified checklist (Guo 2013). For the outcome ‘resolution of OSA’, measured by apnoea-hypopnea index (AHI), the conclusion and the certainty of evidence (GRADE) were assessed separately for the RCT and the case-series and then combined.
Results: The RCT evaluated the effect of HGNS switched ‘on’ or ‘off’ during one week, 12 months after implantation, in responders. The intergroup difference in AHI was 11-fold in favour of HGNS ‘on’. The RCT (starting at ++++) was downgraded two steps for study limitations regarding blinding and uncertain directness and precision, resulting in ++OO. The case series (starting at +OOO), several well-designed, were downgraded two steps for some limitations in blinding, inconsistency, and serious indirectness. Then the case series were upgraded one step for > 2-fold AHI reduction at one year, clearly different from the published natural course (AHI increase over time) of OSA, and an additional step due to large upper airway volume increase with immediate resolution of OSA with HGNS, resulting in +OOO. Combined, the certainty of evidence was low (++OO).
Conclusion: Inclusion of case series reduced the estimate of the treatment effect on AHI from 11-fold in the RCT (short term) to 2-fold in long-term, while the certainty of evidence remained at ++OO. Case series may provide additional information in an SR when controlled studies are scarce and the natural course of the condition is known.
Objectives: Studying the influence on conclusion and certainty of evidence (GRADE) by using case series in an SR with only one small RCT.
Method: A systematic literature search in an SR of hypoglossal nerve stimulation (HGNS) in adults with obstructive sleep apnoea (OSA) not tolerating Continuous Positive Airway Pressure treatment resulted in one small RCT (therapy withdrawal design) and seven case series. The case series (n=232) were assessed by a modified checklist (Guo 2013). For the outcome ‘resolution of OSA’, measured by apnoea-hypopnea index (AHI), the conclusion and the certainty of evidence (GRADE) were assessed separately for the RCT and the case-series and then combined.
Results: The RCT evaluated the effect of HGNS switched ‘on’ or ‘off’ during one week, 12 months after implantation, in responders. The intergroup difference in AHI was 11-fold in favour of HGNS ‘on’. The RCT (starting at ++++) was downgraded two steps for study limitations regarding blinding and uncertain directness and precision, resulting in ++OO. The case series (starting at +OOO), several well-designed, were downgraded two steps for some limitations in blinding, inconsistency, and serious indirectness. Then the case series were upgraded one step for > 2-fold AHI reduction at one year, clearly different from the published natural course (AHI increase over time) of OSA, and an additional step due to large upper airway volume increase with immediate resolution of OSA with HGNS, resulting in +OOO. Combined, the certainty of evidence was low (++OO).
Conclusion: Inclusion of case series reduced the estimate of the treatment effect on AHI from 11-fold in the RCT (short term) to 2-fold in long-term, while the certainty of evidence remained at ++OO. Case series may provide additional information in an SR when controlled studies are scarce and the natural course of the condition is known.